tbuckley/cabot-search huggingface dataset:
Concise report: a minimal-invasive method to retrieve and identify entheseal tissue from psoriatic arthritis patients
Authors: Milena L Pachowsky, Maria Gabriella Raimondo, Cong Xu, Simon Rauber, Koray Tascilar, Hannah Labinsky, Mario Vogg, Mina Saad Aziz Saad, David Simon, Juergen Rech, Alina Soare, Lars Braeuer, Arnd Kleyer, Georg Schett, Andreas Ramming
Journal: Annals of the Rheumatic Diseases (2022)

Objectives To establish a minimally invasive biopsy technique for the analysis of entheseal tissue in patients with psoriatic arthritis (PsA). Methods Human cadavers were used for establishing the technique to retrieve tissue from the lateral humeral epicondyle enthesis (cadaveric biopsies). After biopsy, the entire enthesis was surgically resected (cadaveric resections). Biopsies and resections were assessed by label-free second harmonic generation (SHG) microscopy. The same technique was then applied in patients with PsA with definition of entheseal tissue by SHG, staining of CD45+immune cells and RNA extraction. Results Entheseal biopsies from five cadavers allowed the retrieval of entheseal tissue as validated by the analysis of resection material. Microscopy of biopsy and resection sections allowed differentiation of entheseal, tendon and muscle tissue by SHG and definition of specific intensity thresholds for entheseal tissue. In subsequent entheseal biopsies of 10 PsA patients: the fraction of entheseal tissue was high (65%) and comparable to cadaveric biopsies (68%) as assessed by SHG microscopy. Furthermore, PsA biopsies showed immune cell infiltration and sufficient retrieval of RNA for further molecular analysis. Conclusion Entheseal biopsy of the lateral epicondyle is feasible in patients with PsA allowing reliable retrieval of entheseal tissue and its identification by SHG microscopy.
Targeted Disruption of a Proximal Tubule–Specific TMEM174 Gene in Mice Causes Hyperphosphatemia and Vascular Calcification
Authors: Shinobu Miyazaki-Anzai, Audrey L. Keenan, Judith Blaine, Makoto Miyazaki
Journal: Journal of the American Society of Nephrology (2022)

The proximal tubules play a critical role in phosphate (Pi) homeostasis by reabsorbing Pi
To go or not to go? Biological logic gating engineered T cells
Authors: Rebecca C Abbott, Hannah E Hughes-Parry, Misty R Jenkins
Journal: Journal for ImmunoTherapy of Cancer (2022)

Genetically engineered T cells have been successfully used in the treatment of hematological malignancies, greatly increasing both progression-free and overall survival in patients. However, the outcomes of patients treated with Chimeric Antigen Receptor (CAR) T cells targeting solid tumors have been disappointing. There is an unmet clinical need for therapies which are specifically designed to overcome the challenges associated with solid tumors such as tumor heterogeneity and antigen escape. Genetic engineering employing the use of biological logic gating in T cells is an emerging and cutting-edge field that may address these issues. The advantages of logic gating include localized secretion of anti-tumor proteins into the tumor microenvironment, multi antigen targeting of tumors and a potential increase in safety when targeting tumor antigens which may not be exclusively tumor specific. In this review, we introduce the concept of biological logic gating and how this technology addresses some of the challenges of current CAR T treatment. We outline the types of logic gating circuits and finally discuss the application of this new technology to engineered T cells, in the treatment of cancer.
Immune disease variants modulate gene expression in regulatory CD4+ T cells
Authors: Lara Bossini-Castillo, Dafni A. Glinos, Natalia Kunowska, Gosia Golda, Abigail A. Lamikanra, Michaela Spitzer, Blagoje Soskic, Eddie Cano-Gamez, Deborah J. Smyth, Claire Cattermole, Kaur Alasoo, Alice Mann, Kousik Kundu, Anna Lorenc, Nicole Soranzo, Ian Dunham, David J. Roberts, Gosia Trynka
Journal: Cell Genomics (2022)

Identifying cellular functions dysregulated by disease-associated variants could implicate novel pathways for drug targeting or modulation in cell therapies. However, follow-up studies can be challenging if disease-relevant cell types are difficult to sample. Variants associated with immune diseases point toward the role of CD4+ regulatory T cells (Treg cells). We mapped genetic regulation (quantitative trait loci [QTL]) of gene expression and chromatin activity in Treg cells, and we identified 133 colocalizing loci with immune disease variants. Colocalizations of immune disease genome-wide association study (GWAS) variants with expression QTLs (eQTLs) controlling the expression of CD28 and STAT5A, involved in Treg cell activation and interleukin-2 (IL-2) signaling, support the contribution of Treg cells to the pathobiology of immune diseases. Finally, we identified seven known drug targets suitable for drug repurposing and suggested 63 targets with drug tractability evidence among the GWAS signals that colocalized with Treg cell QTLs. Our study is the first in-depth characterization of immune disease variant effects on Treg cell gene expression modulation and dysregulation of Treg cell function.
When I use a word . . . . Medical hyacinths
Authors: Jeffrey K Aronson
Journal: BMJ (2022)

The word "vaccinia" refers not only to the orthopoxvirus used in vaccination against smallpox; it is also the plural of the Latin word "vaccinium," originally used in English to describe purplish-black berries from a variety of plants. "<i>Vaccinium</i>" nowadays refers to various species of plants, such as <i>Vaccinium myrtillus</i>, bilberries, in the family of Ericaceae, "Hyacinthaceae" is the name given to a different family of plants, and "Hyacinthoides" is the name of a genus of plants in the family Asparagaceae. However, in these cases there may be an etymological connection with "<i>Vaccinium,</i>" via a Cretan form of the Greek name of the youth Hyacinth, whose blood, spilt when he died during a game of quoits with the god Apollo, turned into a plant with purple flowers, thought to be a form of iris or larkspur, but nowadays called hyacinth. Potential medical uses of the pyrrolizidine compound hyacinthacine have been proposed, but, so far at least, its therapeutic applications seem to be less powerful than the myth.
Effect of Intramuscular vs Intra-articular Glucocorticoid Injection on Pain Among Adults With Knee Osteoarthritis
Authors: Qiuke Wang, Marianne F. Mol, P. Koen Bos, Desirée M. J. Dorleijn, Marijn Vis, Jacobijn Gussekloo, Patrick J. E. Bindels, Jos Runhaar, Sita M. A. Bierma-Zeinstra
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Intra-articular (IA) glucocorticoid injection is widely used in patients with knee osteoarthritis (OA), but the safety of this technique is in question among physicians. Intramuscular (IM) glucocorticoid injection could be an alternative approach. <h3>Objective</h3> To investigate whether an IM glucocorticoid injection is noninferior to an IA glucocorticoid injection in reducing knee pain for patients with knee OA in primary care. <h3>Design, Setting, and Participants</h3> The KIS trial, a multicenter, open-label, randomized clinical noninferiority trial including patients with symptomatic knee OA, was conducted in 80 primary care general practices in the southwest of the Netherlands. The study was conducted from March 1, 2018, to July 28, 2020. <h3>Interventions</h3> Patients were randomly allocated to receive an injection of triamcinolone acetonide, 40 mg, either IM in the ipsilateral ventrogluteal region or IA in the knee joint. All patients were followed up for 24 weeks. <h3>Main Outcomes and Measures</h3> The pain score at 4 weeks measured with Knee Injury and Osteoarthritis Outcome Score (range, 0-100; 0 indicates extreme pain), with a noninferiority margin of −7 (IM minus IA). A per-protocol analysis was prespecified as the primary analysis. <h3>Results</h3> A total of 145 patients (94 women [65%]; mean [SD] age, 67 [10] years) were included; of these, 138 patients (IM, 72; IA, 66) were included in the per-protocol analysis. Clinically relevant improvements in knee pain were reached up to 12 weeks after the injection in both groups. At 4 weeks, the estimated mean difference in the Knee Injury and Osteoarthritis Outcome Score between the 2 groups was −3.4 (95% CI, −10.1 to 3.3). Noninferiority could not be declared because the lower limit exceeded the noninferiority margin. Intramuscular injection was noninferior to IA injection at 8 (mean difference, 0.7; 95% CI, −6.5 to 7.8) and 24 (mean difference, 1.6; 95% CI, −5.7 to 9.0) weeks. No significant difference was found among all the secondary outcomes. These results were similar for the sensitivity analysis in an intention-to-treat population. The most frequently reported adverse events were hot flush (IM, 7 [10%] vs IA, 14 [21%]) and headache (IM, 10 [14%] vs IA, 12 [18%]), and all events were classified as nonserious. <h3>Conclusions and Relevance</h3> Based on the findings of this trial, among patients with knee OA in primary care, IM glucocorticoid injection could present an inferior effect in reducing pain at 4 weeks compared with IA injection. Noninferiority of an IM injection was observed at 8 and 24 weeks after injection. This trial provides data for shared decision-making, taking into account the advantages and disadvantages of both types of injections. <h3>Trial Registration</h3> Dutch Trial Registry:NTR6968
Cost-effectiveness of Installing Barriers at Bridge and Cliff Sites for Suicide Prevention in Australia
Authors: Piumee Bandara, Jane Pirkis, Angela Clapperton, Sangsoo Shin, Lay San Too, Lennart Reifels, Sandersan Onie, Andrew Page, Karl Andriessen, Karolina Krysinska, Anna Flego, Marisa Schlichthorst, Matthew J. Spittal, Cathrine Mihalopoulos, Long Khanh-Dao Le
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Installation of barriers has been shown to reduce suicides. To our knowledge, no studies have evaluated the cost-effectiveness of installing barriers at multiple bridge and cliff sites where suicides are known to occur. <h3>Objective</h3> To examine the cost-effectiveness of installing barriers at bridge and cliff sites throughout Australia. <h3>Design, Setting, and Participants</h3> This economic evaluation used an economic model to examine the costs, costs saved, and reductions in suicides if barriers were installed across identified bridge and cliff sites over 5 and 10 years. Specific and accessible bridge and cliff sites across Australia that reported 2 or more suicides over a 5-year period were identified for analysis. A partial societal perspective (including intervention costs and monetary value associated with preventing suicide deaths) was adopted in the development of the model. <h3>Interventions</h3> Barriers installed at bridge and cliff sites. <h3>Main Outcomes and Measures</h3> Primary outcome was return on investment (ROI) comparing cost savings with intervention costs. Secondary outcomes included incremental cost-effectiveness ratio (ICER), comprising the difference in costs between installation of barriers and no installation of barriers divided by the difference in reduction of suicide cases. Uncertainty and sensitivity analyses were undertaken to examine the association of changes in suicide rates with barrier installation, adjustments to the value of statistical life, and changes in maintenance costs of barriers. <h3>Results</h3> A total of 7 bridges and 19 cliff sites were included in the model. If barriers were installed at bridge sites, an estimated US $145 million (95% uncertainty interval [UI], $90 to $160 million) could be saved in prevented suicides over 5 years, and US $270 million (95% UI, $176 to $298 million) over 10 years. The estimated ROI ratio for building barriers over 10 years at bridges was 2.4 (95% UI, 1.5 to 2.7); the results for cliff sites were not significant (ROI, 2.0; 95% UI, −1.1 to 3.8). The ICER indicated monetary savings due to averted suicides over the intervention cost for bridges, although evidence for similar savings was not significant for cliffs. Results were robust in all sensitivity analyses except when the value of statistical life-year over 5 or 10 years only was used. <h3>Conclusions and Relevance</h3> In an economic analysis, barriers were a cost-effective suicide prevention intervention at bridge sites. Further research is required for cliff sites.
Cross-reactivity of anti-modified protein antibodies is also present in predisease and individuals without rheumatoid arthritis
Authors: Sanne Reijm, Astrid S Brehler, Solbritt Rantapää-Dahlqvist, Atsushi Kawakami, Takahiro Maeda, Shin-ya Kawashiri, Mami Tamai, Diane van der Woude, René E M Toes
Journal: Annals of the Rheumatic Diseases (2022)
Imaging biomarkers of TERT or GABPB1 silencing in TERT-positive glioblastoma
Authors: Noriaki Minami, Donghyun Hong, Nicholas Stevers, Carter J Barger, Marina Radoul, Chibo Hong, Lee Chen, Yaewon Kim, Georgios Batsios, Anne Marie Gillespie, Russel O Pieper, Joseph F Costello, Pavithra Viswanath, Sabrina M Ronen
Journal: Neuro-Oncology (2022)

TERT promoter mutations are observed in 80% of wild-type IDH glioblastoma (GBM). Moreover, the upstream TERT transcription factor GABPB1 was recently identified as a cancer-specific therapeutic target for tumors harboring a TERT promoter mutation. In that context, noninvasive imaging biomarkers are needed for the detection of TERT modulation.
Systemic Corticosteroid Use for COVID-19 in US Outpatient Settings From April 2020 to August 2021
Authors: Marie C. Bradley, Silvia Perez-Vilar, Yoganand Chillarige, Diane Dong, Ashley I. Martinez, Andrew R. Weckstein, Gerald J. Dal Pan
Journal: JAMA (2022)

This study uses 2 large US health care claims databases (Medicare fee-for-service and the US Food and Drug Administration’s Sentinel System) to examine systemic corticosteroid use among nonhospitalized patients with COVID-19.
Prion protein monoclonal antibody (PRN100) therapy for Creutzfeldt–Jakob disease: evaluation of a first-in-human treatment programme
Authors: Simon Mead, Azadeh Khalili-Shirazi, Caroline Potter, Tzehow Mok, Akin Nihat, Harpreet Hyare, Stephanie Canning, Christian Schmidt, Tracy Campbell, Lee Darwent, Nicola Muirhead, Nicolette Ebsworth, Patrick Hextall, Madeleine Wakeling, Jacqueline Linehan, Vincenzo Libri, Bryan Williams, Zane Jaunmuktane, Sebastian Brandner, Peter Rudge, John Collinge
Journal: The Lancet Neurology (2022)
Error in Figure
Authors: Francesca Crovetto, Fàtima Crispi, Eduard Gratacós, S Shah
Journal: JAMA (2022)

Wayne A. Ray, PhD; Cecilia P. Chung, MD, MPH; C. Michael Stein, MB, ChB; Walter Smalley, MD, MPH; Eli Zimmerman, MD; William D. Dupont, PhD; Adriana M. Hung, MD, MPH; James R. Daugherty, MS; Alyson Dickson, MA; Katherine T. Murray, MD
Comparison of switching to 6-week dosing of natalizumab versus continuing with 4-week dosing in patients with relapsing-remitting multiple sclerosis (NOVA): a randomised, controlled, open-label, phase 3b trial
Authors: John F Foley, Gilles Defer, Lana Zhovtis Ryerson, Jeffrey A Cohen, Douglas L Arnold, Helmut Butzkueven, Gary Cutter, Gavin Giovannoni, Joep Killestein, Heinz Wiendl, Karen Smirnakis, Shan Xiao, George Kong, Robert Kuhelj, Nolan Campbell, Anneke van der Walt, Christopher Dwyer, Katherine Buzzard, Judith Spies, John Parratt, Vincent van Pesch, Barbara Willekens, Gaetano Perrotta, Emmanuel Bartholomé, Francois Grand'Maison, Francois Jacques, Paul Giacomini, Reza Vosoughi, Jean-Marc Girard, Jerome de Seze, Christine Lebrun Frenay, Aurelie Ruet, David-Axel Laplaud, Gerd Reifschneider, Bert Wagner, Sebastian Rauer, Refik Pul, Maria Seipelt, Achim Berthele, Luisa Klotz, Boris-Alexander Kallmann, Friedemann Paul, Anat Achiron, Giacomo Lus, Diego Centonze, Francesco Patti, Luigi Grimaldi, Raymond Hupperts, Stephan Frequin, Jiske Fermont, Sara Eichau Madueno, Ana Maria Alonso Torres, Lucienne Costa-Frossard França, Jose Eustasio Meca-Lallana, Luis Brieva Ruiz, Owen Pearson, David Rog, Nikolaos Evangelou, Azza Ismail, Ellen Lathi, Edward Fox, Thomas Leist, Jacob Sloane, Gregory Wu, Bhupendra Khatri, Brian Steingo, Ben Thrower, Mark Gudesblatt, Jonathan Calkwood, Daniel Bandari, John Scagnelli, Christopher Laganke, Derrick Robertson, Lucas Kipp, Martin Belkin, Stanley Cohan, Lawrence Goldstick, Ardith Courtney, Wendy Vargas, Andrew Sylvester, Jayshri Srinivasan, Meena Kannan, Maryann Picone, Jeffrey English, Salvatore Napoli, Roumen Balabanov, Islam Zaydan, Jacqueline Nicholas, Jeffrey Kaplan, Fred Lublin, Emily Riser, Tamara Miller, Enrique Alvarez, Sibyl Wray, Jeffrey Gross, Siddharama Pawate, Carrie Hersh, Lucas McCarthy, Heidi Crayton, Jennifer Graves
Journal: The Lancet Neurology (2022)
Modeling Effects of Immunosuppressive Drugs on Human Hearts Using Induced Pluripotent Stem Cell–Derived Cardiac Organoids and Single-Cell RNA Sequencing
Authors: Karim Sallam, Dilip Thomas, Sadhana Gaddam, Nicole Lopez, Aimee Beck, Leila Beach, Albert J. Rogers, Hao Zhang, Ian Y. Chen, Mohamed Ameen, William Hiesinger, Jeffrey J. Teuteberg, June-Wha Rhee, Kevin C. Wang, Nazish Sayed, Joseph C. Wu
Journal: Circulation (2022)
Current State of Pediatric Reference Intervals and the Importance of Correctly Describing the Biochemistry of Child Development
Authors: Alicia N. Lyle, Fidelia Pokuah, Dennis J. Dietzen, Edward C. C. Wong, Amy L. Pyle-Eilola, John S. Fuqua, Alison Woodworth, Patricia M. Jones, Lara J. Akinbami, Luigi R. Garibaldi, Hubert W. Vesper
Journal: JAMA Pediatrics (2022)

Appropriately established pediatric reference intervals are critical to the clinical decision-making process and should reflect the physiologic changes that occur during healthy child development. Reference intervals used in pediatric care today remain highly inconsistent across a broad range of common clinical biomarkers.This narrative review assesses biomarker-specific pediatric reference intervals and their clinical utility with respect to the underlying biological changes occurring during development. Pediatric reference intervals from PubMed-indexed articles published from January 2015 to April 2021, commercial laboratory websites, study cohorts, and pediatric reference interval books were all examined. Although large numbers of pediatric reference intervals are published for some biomarkers, very few are used by clinical and commercial laboratories. The patterns, extent, and timing of biomarker changes are highly variable, particularly during developmental stages with rapid physiologic changes. However, many pediatric reference intervals do not capture these changes and thus do not accurately reflect the underlying biochemistry of development, resulting in significant inconsistencies between reference intervals.There is a need to correctly describe the biochemistry of child development as well as to identify strategies to develop accurate and consistent pediatric reference intervals for improved pediatric care.
Prediction models of hepatocellular carcinoma recurrence after liver transplantation: A comprehensive review
Authors: Sang Jin Kim, Jong Man Kim
Journal: Clinical and Molecular Hepatology (2022)

Liver transplantation (LT) is one of the most effective treatments for hepatocellular carcinoma (HCC). Although LT eliminates HCC and greatly reduces recurrence, some patients experience recurrence after LT. Criteria and models for screening patients with a high probability of HCC recurrence after LT, starting with the Milan criteria, have been published. These models have changed over time, but a standard has not been established. We summarized HCC prediction models after LT by focusing on the application of radiologic, serologic, and pathologic factors and recent trends. This review will look at studies that are based on living donor LT and deceased donor LT, as well as studies that downstaging procedures have been performed preoperatively. This ultimately aims to help make decisions for evaluating the HCC state and selecting candidates for LT according to the circumstances of each transplantation center.
Major Concerns Remain With Gestational Weight Gain and Pregnancy Burden
Authors: Minjing Luo, Yuting Feng, Yutong Fei
Journal: JAMA Internal Medicine (2022)

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Empagliflozin Improves Quality of Life in HFpEF
Authors: Anita Slomski
Journal: JAMA (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 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