tbuckley/cabot-search huggingface dataset:
PAD-2-mediated citrullination of nucleophosmin provides an effective target for tumor immunotherapy
Authors: Ruhul H Choudhury, Peter Symonds, Samantha J Paston, Ian Daniels, Katherine W Cook, Mohamed Gijon, Rachael L Metheringham, Victoria A Brentville, Lindy G Durrant
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background The enzymatic conversion of arginine to citrulline is involved in gene and protein regulation and in alerting the immune system to stressed cells, including tumor cells. Nucleophosmin (NPM) is a nuclear protein that plays key roles in cellular metabolism including ribosome biogenesis, mRNA processing and chromatin remodeling and is regulated by citrullination. In this study, we explored if the same citrullinated arginines within NPM are involved in gene regulation and immune activation. Methods HLA-DP4 and HLA-DR4 transgenic mice were immunized with 22 citrullinated NPM overlapping peptides and immune responses to the peptides were assessed by ex vivo ELISpot assays. Antitumor immunity of NPM targeted vaccination was assessed by challenging transgenic mice with B16F1 HHDII/iDP4, B16F1 HHDII/PAD2KOcDP4, B16F1 HHDII and Lewis lung carcinoma cells/cDP4 cells subcutaneously. Peripheral blood mononuclear cells isolated from healthy donors were stimulated with NPM266-285cit peptides with/without CD45RO+memory cell depletion to assess if the responses in human were naïve or memory. Results In contrast to NPM regulation, which is mediated by peptidylarginine deiminase (PAD4) citrullination of arginine at position 197, only citrullinated NPM266-285 peptide induced a citrulline-specific CD4 T cell response in transgenic mice models expressing human HLA-DP4 or HLA-DR4. Vaccinations with the NPM266-285cit peptide stimulated antitumor responses that resulted in dramatic tumor therapy, greatly improved survival, and protected against rechallenge without further vaccination. The antitumor response was lost if MHCII expression on the tumor cells was knocked out demonstrating direct presentation of the NPM266-285cit epitope in tumors. This antitumor response was lost in B16 tumors lacking PAD2 enzyme indicating NPM266cit is citrullinated by PAD2 in this model. Assessment of the T cell repertoire in healthy individuals and patients with lung cancer also showed CD4 T cells that respond to NPM266-285cit. The proliferative CD4 responses displayed a Th1 profile as they were accompanied with increased IFNγ and granzyme B expression. Depletion of CD45RO+ memory cells prior to stimulation suggested that responses originated from a naïve population in healthy donors. Conclusion This study indicates PAD2 can citrullinate the nuclear antigen NPM at position 277 which can be targeted by CD4 T cells for antitumor therapy. This is distinct from PAD4 citrullination of arginine 197 within NPM which results in its transport from the nucleoli to the nucleoplasm.
Fine-Scale Genetic Structure in the United Arab Emirates Reflects Endogamous and Consanguineous Culture, Population History, and Geography
Authors: Katherine S Elliott, Marc Haber, Hinda Daggag, George B Busby, Rizwan Sarwar, Derek Kennet, Michael Petraglia, Lawrence J Petherbridge, Parisa Yavari, Frauke U Heard-Bey, Bindu Shobi, Tariq Ghulam, Dalia Haj, Alia Al Tikriti, Alshafi Mohammad, Suma Antony, Maitha Alyileili, Shatha Alaydaroos, Evelyn Lau, Mark Butler, Arash Yavari, Julian C Knight, Houman Ashrafian, Maha T Barakat
Journal: Molecular Biology and Evolution (2022)

The indigenous population of the United Arab Emirates (UAE) has a unique demographic and cultural history. Its tradition of endogamy and consanguinity is expected to produce genetic homogeneity and partitioning of gene pools while population movements and intercontinental trade are likely to have contributed to genetic diversity. Emiratis and neighboring populations of the Middle East have been underrepresented in the population genetics literature with few studies covering the broader genetic history of the Arabian Peninsula. Here, we genotyped 1,198 individuals from the seven Emirates using 1.7 million markers and by employing haplotype-based algorithms and admixture analyses, we reveal the fine-scale genetic structure of the Emirati population. Shared ancestry and gene flow with neighboring populations display their unique geographic position while increased intra- versus inter-Emirati kinship and sharing of uniparental haplogroups, reflect the endogamous and consanguineous cultural traditions of the Emirates and their tribes.
THE PHYSIOLOGY OF MASSAGE
Journal: JAMA (1925)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
INTRAPERITONEAL ADMINISTRATION OF SULFANILAMIDE
Journal: JAMA (1942)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Giant Viruses Encode Actin-Related Proteins
Authors: Violette Da Cunha, Morgan Gaia, Hiroyuki Ogata, Olivier Jaillon, Tom O Delmont, Patrick Forterre
Journal: Molecular Biology and Evolution (2022)

Abstract The emergence of the eukaryotic cytoskeleton is a critical yet puzzling step of eukaryogenesis. Actin and actin-related proteins (ARPs) are ubiquitous components of this cytoskeleton. The gene repertoire of the Last Eukaryotic Common Ancestor (LECA) would have therefore harbored both actin and various ARPs. Here, we report the presence and expression of actin-related genes in viral genomes (viractins) of some Imitervirales, a viral order encompassing the giant Mimiviridae. Phylogenetic analyses suggest an early recruitment of an actin-related gene by viruses from ancient protoeukaryotic hosts before the emergence of modern eukaryotes, possibly followed by a back transfer that gave rise to eukaryotic actins. This supports a coevolutionary scenario between pre-LECA lineages and their viruses, which could have contributed to the emergence of the modern eukaryotic cytoskeleton.
Good News About Endometriosis and Preterm Delivery
Authors: Liisu Saavalainen, Oskari Heikinheimo
Journal: JAMA Network Open (2022)

Louis Marcellin, MD, PhD; Francois Goffinet, MD, PhD; Elie Azria, MD, PhD; Anne Thomin, MD; Charles Garabedian, MD, PhD; Jeanne Sibiude, MD, PhD; Eric Verspyck, MD, PhD; Martin Koskas, MD, PhD; Pietro Santulli, MD, PhD; Jessica Rousseau, PhD; Pierre-Yves Ancel, MD, PhD; Charles Chapron, MD
Calcium Channel Antagonists and Gingival Hyperplasia
Authors: Ruth Steele
Journal: Annals of Internal Medicine (1994)

Letters15 October 1994Calcium Channel Antagonists and Gingival HyperplasiaRuth Steele, PharmD, Arthur A. Schuna, MD, and Ronald Schreiber, MDRuth Steele, PharmDSearch for more papers by this author, Arthur A. Schuna, MDSearch for more papers by this author, and Ronald Schreiber, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-121-8-199410150-00021 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Drs. Mathis and Scheetz raise some interesting questions regarding the dosage form of calcium antagonist and gingival hyperplasia. Because most of our patients received sustained-release preparations of calcium antagonists, we could not do a subgroup analysis with adequate numbers of patients receiving prompt-release dosage forms to do statistical comparisons. We did not assess blood levels or compliance in this prevalence survey; however, previous reports found no relation between the dosage of the calcium antagonist and the development of gingival hyperplasia [1, 2]. We found no statistical differences in age between patients with and without hyperplasia. Our patient population ...REFERENCE1. Barclay S, Thomason JM, Idle JR, Seymour RA. The incidence and severity of nifedipine-induced gingival overgrowth. J Clin Periodontol. 1992; 19:311-4. Google Scholar2. Veraldi S, Piferi M, Marini D. Gingival hyperplasia following nifedipine therapy (Letter). Clin Exp Dermatol. 1989; 14:93. Google Scholar3. Hancock RH, Swan RH. Nifedipine-induced gingival overgrowth: report of a case treated by controlling plaque. J Clin Periodontol. 1992; 19:12-4. Google Scholar4. Modeer T, Dahllof G. Development of phenytoin-induced gingival overgrowth in non-institutionalized epileptic children subjected to different plaque control programs. Acta Odontol Scand. 1987; 45:81-5. Google Scholar5. Pihlstrom BL, Carlson JF, Smith QT, Bastien SA, Keenan KM. Prevention of phenytoin associated gingival enlargement—a 15-month longitudinal study. J Periodontol. 1980; 51:311-7. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 October 1994Volume 121, Issue 8Page: 624-625KeywordsCalciumCalcium antagonist therapyCalcium channel blockerForecastingGeriatricsHemorrhageHygieneInflammationPeriodontal diseasesRacial and ethnic issues ePublished: 15 August 2000 Issue Published: 15 October 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Chinese Medical Journal, Peking
Journal: JAMA (1964)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Hippocampal-amygdala memory circuits govern experience-dependent observational fear
Authors: Joseph I. Terranova, Jun Yokose, Hisayuki Osanai, William D. Marks, Jun Yamamoto, Sachie K. Ogawa, Takashi Kitamura
Journal: Neuron (2022)

The empathic ability to vicariously experience the other's fearful situation, a process called observational fear (OF), is critical to survive in nature and function in society. OF can be facilitated by both prior similar fear experience in the observer and social familiarity with the demonstrator. However, the neural circuit mechanisms of experience-dependent OF (Exp OF) remain unknown. Here, we demonstrate that hippocampal-basolateral amygdala (HPC-BLA) circuits in mice without involving the anterior cingulate cortex, considered a center of OF, mediate Exp OF. Dorsal HPC neurons generate fear memory engram cells in BLA encoding prior similar fear experiences, which are essential for Exp OF. On the other hand, ventral HPC neurons respond to the familiar demonstrator's aversive situation during Exp OF, which reactivates the fear memory engram cells in BLA to elicit Exp OF. Our study provides new insights into the memory engram-dependent perception-action coupling that underlies empathic behaviors like Exp OF.
Therapeutics: Its Principles and Practice.
Journal: JAMA (1901)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Faecal microbiome and metabolic signatures in rectal neuroendocrine tumors
Authors: Wei Hu, Ze Min Chen, Xia Xi Li, Lan Lu, Gen Hua Yang, Zheng Xia Lei, Li Juan You, Xiao Bing Cui, Si Cun Lu, Zhi Yong Zhai, Zhi Yu Zeng, Ye Chen, Si Lin Huang, Wei Gong
Journal: Theranostics (2022)

Background:The prevalence of rectal neuroendocrine tumors (RNET) has increased substantially over the past decades.Little is known on mechanistic alteration in the pathogenesis of such disease.We postulate that perturbations of human gut microbiome-metabolome interface influentially affect the development of RNET.The study aims to characterize the composition and function of faecal microbiome and metabolites in RNET individuals.Methods: We performed deep shotgun metagenomic sequencing and untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomic profiling of faecal samples from the discovery cohort (18 RNET patients, 40 controls), and validated the microbiome and metabolite-based classifiers in an independent cohort (15 RNET participants, 19 controls).Results: We uncovered a dysbiotic gut ecological microenvironment in RNET patients, characterized by aberrant depletion and attenuated connection of microbial species, and abnormally aggregated lipids and lipid-like molecules.Functional characterization based on our in-house and Human Project Unified Metabolic Analysis Network 2 (HUMAnN2) pipelines further indicated a nutrient deficient gut microenvironment in RNET individuals, evidenced by diminished activities such as energy metabolism, vitamin biosynthesis and transportation.By integrating these data, we revealed 291 robust associations between representative differentially abundant taxonomic species and metabolites, indicating a tight interaction of gut microbiome with metabolites in RNET pathogenesis.Finally, we identified a cluster of gut microbiome and metabolite-based signatures, and replicated them in an independent cohort, showing accurate prediction of such neoplasm from healthy people.Conclusions: Our current study is the first to comprehensively characterize the perturbed interface of gut microbiome and metabolites in RNET patients, which may provide promising targets for microbiome-based diagnostics and therapies for this disorder.
Safety and Efficacy of Mesenchymal Stromal Cells and Other Cellular Therapeutics in Rheumatic Diseases in 2022: A Review of What We Know So Far
Authors: Gary S. Gilkeson
Journal: Arthritis & Rheumatology (2022)

Although a number of new immunosuppressive agents and biologics have been approved for treating various autoimmune inflammatory rheumatic diseases, there remains a substantial number of patients who have no clinical response or limited clinical response to these available treatments. Use of cellular therapies is a novel approach for the treatment of autoimmune inflammatory rheumatic diseases, with perhaps enhanced efficacy and less toxicity than current therapies. Autologous hematopoietic stem cell transplants were the first foray into cellular therapies, with proven efficacy in scleroderma and multiple sclerosis. Newer, yet unproven, cellular therapies include allogeneic mesenchymal stromal cells, which have been shown to be effective in graft‐versus‐host disease and in healing Crohn's fistulas. Chimeric antigen receptor T cells are effective in various malignancies, with possible application in rheumatic diseases, as shown in preclinical studies in murine lupus and recently in human lupus. Treg cells are one of the master controllers of the immune response and are decreased in number and/or effectiveness in specific autoimmune diseases. Expansion of autologous Treg cells is an attractive approach to controlling autoimmunity. There are a number of other regulatory cells in the immune system, including Breg cells, dendritic cells, macrophages, and other T cell types, that are in early stages of development as treatments. In this review, the current evidence for the efficacy and mechanisms of actions of cellular therapies already in use or in clinical trials in human autoimmune diseases will be discussed, including the limitations of these therapies and potential side effects.
THE ETIOLOGY OF TETANUS.
Journal: JAMA (1900)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Next-generation sequencing of cerebrospinal fluid for clinical molecular diagnostics in pediatric, adolescent and young adult brain tumor patients
Authors: Alexandra M Miller, Luca Szalontay, Nancy Bouvier, Katherine Hill, Hamza Ahmad, Johnathan Rafailov, Alex J Lee, M Irene Rodriguez-Sanchez, Onur Yildirim, Arti Patel, Tejus A Bale, Jamal K Benhamida, Ryma Benayed, Maria E Arcila, Maria Donzelli, Ira J Dunkel, Stephen W Gilheeney, Yasmin Khakoo, Kim Kramer, Sameer F Sait, Jeffrey P Greenfield, Mark M Souweidane, Sofia Haque, Audrey Mauguen, Michael F Berger, Ingo K Mellinghoff, Matthias A Karajannis
Journal: Neuro-Oncology (2022)

Abstract Background Safe sampling of central nervous system tumor tissue for diagnostic purposes may be difficult if not impossible, especially in pediatric patients, and an unmet need exists to develop less invasive diagnostic tests. Methods We report our clinical experience with minimally invasive molecular diagnostics using a clinically validated assay for sequencing of cerebrospinal fluid (CSF) cell-free DNA (cfDNA). All CSF samples were collected as part of clinical care, and results reported to both clinicians and patients/families. Results We analyzed 64 CSF samples from 45 pediatric, adolescent and young adult (AYA) patients (pediatric = 25; AYA = 20) with primary and recurrent brain tumors across 12 histopathological subtypes including high-grade glioma (n = 10), medulloblastoma (n = 10), pineoblastoma (n = 5), low-grade glioma (n = 4), diffuse leptomeningeal glioneuronal tumor (DLGNT) (n = 4), retinoblastoma (n = 4), ependymoma (n = 3), and other (n = 5). Somatic alterations were detected in 30/64 samples (46.9%) and in at least one sample per unique patient in 21/45 patients (46.6%). CSF cfDNA positivity was strongly associated with the presence of disseminated disease at the time of collection (81.5% of samples from patients with disseminated disease were positive). No association was seen between CSF cfDNA positivity and the timing of CSF collection during the patient’s disease course. Conclusions We identified three general categories where CSF cfDNA testing provided additional relevant diagnostic, prognostic, and/or therapeutic information, impacting clinical assessment and decision making: (1) diagnosis and/or identification of actionable alterations; (2) monitor response to therapy; and (3) tracking tumor evolution. Our findings support broader implementation of clinical CSF cfDNA testing in this population to improve care.