tbuckley/cabot-search huggingface dataset:
Tumor cell membrane-camouflaged responsive nanoparticles enable MRI-guided immuno-chemodynamic therapy of orthotopic osteosarcoma
Authors: Liwen Fu, Weiying Zhang, Xiaojun Zhou, Jingzhong Fu, Chuanglong He
Journal: Bioactive Materials (2022)

Osteosarcoma is a refractory bone disease in young people that needs the updating and development of effective treatment. Although nanotechnology is widely applied in cancer therapy, poor targeting and inadequate efficiency hinder its development. In this study, we prepared alendronate (ALD)/K7M2 cell membranes-coated hollow manganese dioxide (HMnO2) nanoparticles as a nanocarrier to load Ginsenoside Rh2 (Rh2) for Magnetic Resonance imaging (MRI)-guided immuno-chemodynamic combination osteosarcoma therapy. Subsequently, the ALD and K7M2 cell membranes were successively modified on the surface of HMnO2 and loaded with Rh2. The tumor microenvironment (TME)-activated Rh2@HMnO2-AM nanoparticles have good bone tumor-targeting and tumor-homing capabilities, excellent GSH-sensitive drug release profile and MRI capability, and attractive immuno-chemodynamic combined therapeutic efficiency. The Rh2@HMnO2-AM nanoparticles can effectively trigger immunogenic cell death (ICD), activate CD4+/CD8+ T cells in vivo, and upregulate BAX, BCL-2 and Caspase-3 in cellular level. Further results revealed that Rh2@HMnO2-AM enhanced the secretion of IL-6, IFN-γ and TNF-α in serum and inhibited the generation of FOXP3+ T cells (Tregs) in tumors. Moreover, the Rh2@HMnO2-AM treatment significant restricted tumor growth in-situ tumor-bearing mice. Therefore, Rh2@HMnO2-AM may serve as an effective and bio-friendly nanoparticle platform combined with immunotherapy and chemodynamic therapy to provide a novel approach to osteosarcoma therapy.
The effects of pantoprazole vs. placebo on 1-year outcomes, resource use and employment status in ICU patients at risk for gastrointestinal bleeding: a secondary analysis of the SUP-ICU trial
Authors: Christine Marie Bækø Halling, Morten Hylander Møller, Søren Marker, Mette Krag, Jakob Kjellberg, Anders Perner, Dorte Gyrd-Hansen
Journal: Intensive Care Medicine (2022)
Circulating Fatty Acids and Genetic Predisposition to Type 2 Diabetes: Gene-Nutrient Interaction Analysis
Authors: Pan Zhuang, Xiaohui Liu, Yin Li, Haoyu Li, Lange Zhang, Xuzhi Wan, Yuqi Wu, Yu Zhang, Jingjing Jiao
Journal: Diabetes Care (2022)

To assess the relationship of circulating fatty acids (FA) with risk of type 2 diabetes (T2D) and potential interactions with genetic risk.A total of 95,854 participants with complete data on plasma FA from the UK Biobank were enrolled between 2006 and 2010 and were followed up to the end of 2020. Plasma concentrations of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA) were analyzed by a high-throughput nuclear magnetic resonance-based biomarker profiling platform. The genetic risk scores (GRS) were calculated on the basis of 424 variants associated with T2D. Pathway-specific GRS were calculated based on robust clusters of T2D loci.There were 3,052 instances of T2D documented after an average follow-up of 11.6 years. Plasma concentrations of SFA and MUFA were positively associated with T2D risk, while plasma PUFA were inversely associated. After adjustment for major risk factors, hazard ratios (95% CI) of T2D for 1-SD increment were 1.03 (1.02-1.04) for SFA, 1.03 (1.02-1.05) for MUFA, 0.62 (0.56-0.68) for PUFA, 0.67 (0.61-0.73) for n-6 PUFA, 0.90 (0.85-0.95) for n-3 PUFA, and 1.01 (0.98-1.04) for n-6-to-n-3 ratio. Plasma MUFA had significant interactions with the overall GRS and GRS for proinsulin and liver/lipid clusters on T2D risk. The protective associations of n-3 PUFA with T2D risk were weaker among individuals with higher obesity GRS (P interaction = 0.040) and liver/lipid GRS (P interaction = 0.012). Additionally, increased plasma n-3 PUFA concentration was associated with more reductions in T2D risk among participants carrying more docosapentaenoic acid-associated alleles (P interaction = 0.007).Plasma concentrations of SFA and MUFA were associated with a higher T2D risk, whereas plasma PUFA and n-6 and n-3 PUFA were related to a lower risk. Circulating MUFA and n-3 PUFA had significant interactions with genetic predisposition to T2D and FA-associated variants.
Hyperthermia-induced doxorubicin delivery from thermosensitive liposomes via MR-HIFU in a pig model
Authors: Lukas Christian Sebeke, Juan Daniel Castillo Gómez, Edwin Heijman, Pia Rademann, Alexandra Claudia Simon, Sandra Ekdawi, Susan Vlachakis, Dennis Toker, Ben Lasse Mink, Claudia Schubert-Quecke, Sin Yuin Yeo, Patrick Schmidt, Christina Lucas, Susanne Brodesser, Martin Hossann, Lars H. Lindner, Holger Grüll
Journal: Journal of Controlled Release (2022)
Antibodies to Cartilage Oligomeric Matrix Protein Are Pathogenic in Mice and May Be Clinically Relevant in Rheumatoid Arthritis
Authors: Changrong Ge, Dongmei Tong, Erik Lönnblom, Bibo Liang, Weiwei Cai, Cecilia Fahlquist‐Hagert, Taotao Li, Alf Kastbom, Inger Gjertsson, Doreen Dobritzsch, Rikard Holmdahl
Journal: Arthritis & Rheumatology (2022)

Objective Cartilage oligomeric matrix protein (COMP) is an autoantigen in rheumatoid arthritis (RA) and experimental models of arthritis. This study was undertaken to investigate the structure, function, and relevance of anti‐COMP antibodies. Methods We investigated the pathogenicity of monoclonal anti‐COMP antibodies in mice using passive transfer experiments, and we explored the interaction of anti‐COMP antibodies with cartilage using immunohistochemical staining. The interaction of the monoclonal antibody 15A11 in complex with its specific COMP epitope P6 was determined by x‐ray crystallography. An enzyme‐linked immunosorbent assay and a surface plasma resonance technique were used to study the modulation of calcium ion binding to 15A11. The clinical relevance and value of serum IgG specific to the COMP P6 epitope and its citrullinated variants were evaluated in a large Swedish cohort of RA patients. Results The murine monoclonal anti‐COMP antibody 15A11 induced arthritis in naive mice. The crystal structure of the 15A11–P6 complex explained how the antibody could bind to COMP, which can be modulated by calcium ions. Moreover, serum IgG specific to the COMP P6 peptide and its citrullinated variants was detectable at significantly higher levels in RA patients compared to healthy controls and correlated with a higher disease activity score. Conclusion Our findings provide the structural basis for binding a pathogenic anti‐COMP antibody to cartilage. The recognized epitope can be citrullinated, and levels of antibodies to this epitope are elevated in RA patients and correlate with higher disease activity, implicating a pathogenic role of anti‐COMP antibodies in a subset of RA patients.
Severe Angina Pectoris
Authors: Tinsley R. Harrison
Journal: JAMA (1973)

Among the giants of internal medicine of the 20th century, James B. Herrick stands tall. Few physicians have described and clearly delineated a disease as important as myocardial infarction. Very few indeed have also opened the door for the understanding of an entirely different but, when considered on a world-wide basis, perhaps equally important group of diseases: the hemoglobinopathies. Therefore, Dr. Herrick's description of sickle cell anemia was also an epochal contribution to clinical medicine. It was my good fortune to meet Dr. Herrick while I was still a fledgling, an intern. His week's sojourn at the Peter Bent Brigham Hospital as visiting professor was an inspiration to the entire house staff. His kindness to us and his compassion for patients indicated that he agreed with the statement of Benjamin Franklin: "... when I am employed in serving others I do not look on myself as conferring favors but paying debts."
The Slowing Rate of CpG Depletion in SARS-CoV-2 Genomes Is Consistent with Adaptations to the Human Host
Authors: Akhil Kumar, Nishank Goyal, Nandhini Saranathan, Sonam Dhamija, Saurabh Saraswat, Manoj B Menon, Perumal Vivekanandan
Journal: Molecular Biology and Evolution (2022)

Depletion of CpG dinucleotides in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genomes has been linked to virus evolution, host-switching, virus replication, and innate immune responses. Temporal variations, if any, in the rate of CpG depletion during virus evolution in the host remain poorly understood. Here, we analyzed the CpG content of over 1.4 million full-length SARS-CoV-2 genomes representing over 170 million documented infections during the first 17 months of the pandemic. Our findings suggest that the extent of CpG depletion in SARS-CoV-2 genomes is modest. Interestingly, the rate of CpG depletion is highest during early evolution in humans and it gradually tapers off, almost reaching an equilibrium; this is consistent with adaptations to the human host. Furthermore, within the coding regions, CpG depletion occurs predominantly at codon positions 2-3 and 3-1. Loss of ZAP (Zinc-finger antiviral protein)-binding motifs in SARS-CoV-2 genomes is primarily driven by the loss of the terminal CpG within the motifs. Nonetheless, majority of the CpG depletion in SARS-CoV-2 genomes occurs outside ZAP-binding motifs. SARS-CoV-2 genomes selectively lose CpGs-motifs from a U-rich context; this may help avoid immune recognition by TLR7. SARS-CoV-2 alpha-, beta-, and delta-variants of concern have reduced CpG content compared to sequences from the beginning of the pandemic. In sum, we provide evidence that the rate of CpG depletion in virus genomes is not uniform and it greatly varies over time and during adaptations to the host. This work highlights how temporal variations in selection pressures during virus adaption may impact the rate and the extent of CpG depletion in virus genomes.
IL-6 Revisited: From Rheumatoid Arthritis to CAR T Cell Therapy and COVID-19
Authors: Tadamitsu Kishimoto, Sujin Kang
Journal: Annual Review of Immunology (2022)

The diverse biological activity of interleukin-6 (IL-6) contributes to the maintenance of homeostasis. Emergent infection or tissue injury induces rapid production of IL-6 and activates host defense through augmentation of acute-phase proteins and immune responses. However, excessive IL-6 production and uncontrolled IL-6 receptor signaling are critical to pathogenesis. Over the years, therapeutic agents targeting IL-6 signaling, such as tocilizumab, a humanized anti-IL-6 receptor antibody, have shown remarkable efficacy for rheumatoid arthritis, Castleman disease, and juvenile idiopathic arthritis, and their efficacy in other diseases is continually being reported. Emerging evidence has demonstrated the benefit of tocilizumab for several types of acute inflammatory diseases, including cytokine storms induced by chimeric antigen receptor T cell therapy and coronavirus disease 2019 (COVID-19). Here, we refocus attention on the biology of IL-6 and summarize the distinct pathological roles of IL-6 signaling in several acute and chronic inflammatory diseases.
Symptom Free Days In Patients With Severe Chronic Rhinosinusitis with Nasal Polyps Treated with Dupilumab
Authors: Claus Bachert, Claire Hopkins, Joseph Han, Wytske Fokkens, Leda Mannent, Asif Khan, Jérôme Msihid, Urvi Mujumdar, Siddhesh Kamat, Scott Nash, Shahid Siddiqui, Paul Rowe, Yamo Deniz, Juby Jacob-Nara
Journal: Journal of Allergy and Clinical Immunology (2022)
Circulating microbiome in patients with portal hypertension
Authors: Rolandas Gedgaudas, Jasmohan S Bajaj, Jurgita Skieceviciene, Greta Varkalaite, Gabija Jurkeviciute, Sigita Gelman, Irena Valantiene, Romanas Zykus, Andrius Pranculis, Corinna Bang, Andre Franke, Christoph Schramm, Juozas Kupcinskas
Journal: Gut Microbes (2022)

Portal hypertension (PH) in liver cirrhosis leads to increased gut permeability and the translocation of bacteria across the gut-liver axis. Microbial DNA has recently been detected in different blood compartments; however, this phenomenon has not been thoroughly analyzed in PH. This study aimed to explore circulating bacterial DNA signatures, inflammatory cytokines, and gut permeability markers in different blood compartments (peripheral and hepatic veins) of patients with cirrhosis and PH. The 16S rRNA blood microbiome profiles were determined in 58 patients with liver cirrhosis and 46 control patients. Taxonomic differences were analyzed in relation to PH, liver function, inflammatory cytokines, and gut permeability markers. Circulating plasma microbiome profiles in patients with cirrhosis were distinct from those of the controls and were characterized by enrichment of Comamonas, Cnuella, Dialister, Escherichia/Shigella, and Prevotella and the depletion of Bradyrhizobium, Curvibacter, Diaphorobacter, Pseudarcicella, and Pseudomonas. Comparison of peripheral and hepatic vein blood compartments of patients with cirrhosis did not reveal differentially abundant taxa. Enrichment of the genera Bacteroides, Escherichia/Shigella, and Prevotella was associated with severe PH (SPH) in both blood compartments; however, circulating microbiome profiles could not predict PH severity. Escherichia/Shigella and Prevotella abundance was correlated with IL-8 levels in the hepatic vein. In conclusion, we demonstrated a distinct circulating blood microbiome profile in patients with cirrhosis, showing that specific bacterial genera in blood are marginally associated with SPH, Model for End-Stage Liver Disease score, and inflammation biomarkers; however, circulating microbial composition failed to predict PH severity.
G.M.C. Annual Retention Fee
Authors: S. S. Barker, A. J. T. Bateson, T. Baynes, J. D. Carroll, R. H. Curties, G. F. Falconer, B. Leppard, G. B. May, W. Mercer, C. S. N. Nagara, M. W. J. Older, P. Bowen-Simpkins, P. R. Shires, P. J. Stiles, R. L. Strickland, J. S. Taylor, M. P. Thakur, C. P. Wallace, G. L. Way, W. S. White, D. O. Williams
Journal: BMJ (1970)
Forensic Neuropathology
Authors: Milton G. Bohrod
Journal: JAMA (1988)

Only a few times does a reviewer of books come across one that is almost thoroughly satisfying in subject matter and mode of presentation and at the same time a pleasure to read. Such a book is this one. From "The Neuropathologist's Role in Forensic Pathology" to the final chapter on "Complex Neural Dysfunction," covering such matters as epilepsy and dementia, the author and four associates traverse almost the entire field of neuropathology, including areas that at first blush seem far removed from forensic medicine. But their relevance is never left unexplored. The section of more than 20 pages on brain tumors, for instance, is begun by a six-page essay on "Brain Tumors and the Forensic Pathologist." The six-page gem on Alzheimer's disease is preceded by a discussion of the concerns of forensic pathologists in degenerative diseases. The usual matters of trauma and its differentiation from spontaneous disturbances of nervous
INTRACRANIAL ABSCESS.
Authors: HAL C. WYMAN
Journal: JAMA (1897)

Recent improvements in surgical technique enable surgeons to open the cranial cavity with much less danger than formerly attended operations of this class. Anesthesia, antisepsis, better instruments and more knowledge of surgical history and news, make the foundation on which this improvement rests. The art of diagnosis keeps pace with the advance in surgical methods. The general forward movement along the whole line of medicine has helped to crowd the cranial cavity with industrious investigators. The bony envelope of the brain is no longer a Chinese wall against research and discovery concerning the function and aberrations of the organs of the mind. The common cause of abscess, infection, operates on the same principle in the cranial cavity, but under different conditions from those which obtain in other parts of the body. For example, the swelling incident to an infection of the knee-joint occurs in consequence of the yielding character of
Dr. William MacDermott
Journal: BMJ (1923)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Dr. William MacDermott Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Extending Drug Monopolies by Patenting Safe Drug Use
Authors: Doni Bloomfield, Bryan S. Walsh, Aaron S. Kesselheim
Journal: JAMA Internal Medicine (2022)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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 Internal Medicine journal
Interaction between peripheral T helper cells and CD11c+CD21- B cells underlies the pathogenesis of IgG4-related disease
Authors: Ryuta Kamekura, Motohisa Yamamoto, Keisuke Yamamoto, Hiroki Takahashi, Kenichi Takano, Shingo Ichimiya
Journal: Journal of Allergy and Clinical Immunology (2022)

IgG4-related disease (IgG4-RD) is a chronic fibroinflammatory disease characterized by elevated serum IgG4 concentration and infiltration of IgG4+ plasma cells in various affected organs. However, the underlying immunological mechanisms involved in IgG4-RD remain unclear. In this study, we examined circulating peripheral T helper (Tph) cells and CD11c+CD21- B cells, which are known as age-associated B cells, in IgG4-RD to address this issue.
The methyl-CpG-binding domain 2 facilitates pulmonary fibrosis by orchestrating fibroblast to myofibroblast differentiation
Authors: Yi Wang, Lei Zhang, Teng Huang, Guo-Rao Wu, Qing Zhou, Fa-Xi Wang, Long-Min Chen, Fei Sun, Yongman Lv, Fei Xiong, Shu Zhang, Qilin Yu, Ping Yang, Weikuan Gu, Yongjian Xu, Jianping Zhao, Huilan Zhang, Weining Xiong, Cong-Yi Wang
Journal: European Respiratory Journal (2022)

Although DNA methylation has been recognised in the pathogenesis of idiopathic pulmonary fibrosis (IPF), the exact mechanisms are yet to be fully addressed. Herein, we demonstrate that lungs originated from IPF patients and mice after bleomycin (BLM)-induced pulmonary fibrosis are characterised by altered DNA methylation along with overexpression in myofibroblasts of methyl-CpG-binding domain 2 (MBD2), a reader responsible for interpreting DNA methylome-encoded information. Specifically, depletion of Mbd2 in fibroblasts or myofibroblasts protected mice from BLM-induced pulmonary fibrosis coupled with a significant reduction of fibroblast differentiation. Mechanistically, transforming growth factor (TGF)-β1 induced a positive feedback regulatory loop between TGF-β receptor I (TβRI), Smad3 and Mbd2, and erythroid differentiation regulator 1 (Erdr1). TGF-β1 induced fibroblasts to undergo a global DNA hypermethylation along with Mbd2 overexpression in a TβRI/Smad3 dependent manner, and Mbd2 selectively bound to the methylated CpG DNA within the Erdr1 promoter to repress its expression, through which it enhanced TGF-β/Smad signalling to promote differentiation of fibroblast into myofibroblast and exacerbate pulmonary fibrosis. Therefore, enhancing Erdr1 expression strikingly reversed established pulmonary fibrosis. Collectively, our data support that strategies aimed at silencing Mbd2 or increasing Erdr1 could be viable therapeutic approaches for prevention and treatment of pulmonary fibrosis in clinical settings.
Endoscopic ultrasound-guided radiofrequency ablation of recurrent cervical cancer in the pelvis untreatable by radiation therapy
Authors: Vanda Salutari, Mario Gagliardi, Gianenrico Rizzatti, Francesca Ciccarone, Eugenia D’Angeli, Giovanni Scambia, Alberto Larghi
Journal: Endoscopy (2022)

A 75-year-old woman with a history of squamous cell carcinoma of the cervix (FIGO staging IIa: T2a, N0, M0) was treated with neoadjuvant platinum-based chemotherapy, followed by laparoscopic bilateral hysteroannessiectomy and bilateral pelvic lymphadenectomy. One year later, recurrent disease at the vaginal dome was detected and treated with cisplatin chemotherapy and radiotherapy (4500 Gy total), with a complete response. After 2 years, she developed additional lesions at the right iliac fossa for which cisplatin and topotecan were administered, with a partial response. The patient was subsequently enrolled in an experimental trial and received 10 cycles of atezolizumab and tiragolumab. One year later, two solid lesions were detected close to the posterior (25 mm) and lateral (35 mm) bladder walls. The former lesion was treated with radiation therapy, but the second lesion could not be treated owing to close proximity to the bladder ([Fig. 1 a, b]).
This Week in JAMA
Journal: JAMA (2002)

A Piece of My Mind"For the Haitian poor, the folklore of the loup garou can help to explain the unexplainable, to deal with the fear, the guilt, and the helplessness generated by the loss of a child."From "Beyond Folklore." SEE PAGE 2791 Contempo UpdatesA review of bariatric surgical procedures and outcomes for patients with severe obesity.
Editorial: Plasma proteins in cancer surveillance.
Journal: BMJ (1975)

organized ambulance service can relieve the hospital service of providing a team of doctors and nurses just at the time when their skills are most needed in the hospital.Control of nearly every disaster fails because of inadequate communication and co-ordination at all levels of every emer- gency service.With modern radiotelephonic techniques it is possible to connect a radio link into a telephone switchboard, and the provision of this means of communication between every casualty receiving hospital and ambulance control is long overdue.There are still many difficulties in disaster planning, and the ultimate responsibility for maintaining the readiness of hospital and community plans, both local and national, remains unresolved.Hospitals in the United Kingdom are ill-prepared to deal with disasters.This needs knowledge, will, and money.The knowledge is already available.
First Aid and Ambulance for Factories
Journal: JAMA (1941)

Occupiers of factories in Great Britain are instructed by means of this pamphlet about the makeup and location of first aid boxes, instruction of workers in first aid technic, construction and equipment of dispensary facilities in factories, the value of good accident records and the importance of setting up the system under medical guidance. Samples of forms used for recording accidents are included. The varying requirements of factories of various sizes are recognized, and suitable recommendations are made regarding necessary supplies and floor plans for the accident rooms.