tbuckley/cabot-search huggingface dataset:
Loss of MAT2A compromises methionine metabolism and represents a vulnerability in H3K27M mutant glioma by modulating the epigenome
Authors: Brian J. Golbourn, Matthew E. Halbert, Katharine Halligan, Srinidhi Varadharajan, Brian Krug, Nneka E. Mbah, Nisha Kabir, Ann-Catherine J. Stanton, Abigail L. Locke, Stephanie M. Casillo, Yanhua Zhao, Lauren M. Sanders, Allison Cheney, Steven J. Mullett, Apeng Chen, Michelle Wassell, Anthony Andren, Jennifer Perez, Esther P. Jane, Daniel R. David Premkumar, Robert F. Koncar, Shideh Mirhadi, Lauren H. McCarl, Yue-Fang Chang, Yijen L. Wu, Taylor A. Gatesman, Andrea F. Cruz, Michal Zapotocky, Baoli Hu, Gary Kohanbash, Xiuxing Wang, Alenoush Vartanian, Michael F. Moran, Frank Lieberman, Nduka M. Amankulor, Stacy G. Wendell, Olena M. Vaske, Ashok Panigrahy, James Felker, Kelsey C. Bertrand, Claudia L. Kleinman, Jeremy N. Rich, Robert M. Friedlander, Alberto Broniscer, Costas Lyssiotis, Nada Jabado, Ian F. Pollack, Stephen C. Mack, Sameer Agnihotri
Journal: Nature Cancer (2022)
Table of contents
Authors: Jonathan Rick, Lindsay Strowd, Helena Pasieka, Karl Saardi, Robert Micheletti, Megan Zhao, Daniela Kroshinsky, Michi Shinohara, Alex Ortega-Loayza, Thomas Bettuzzi, Marie Jachiet, Emilie Sbidian, Laure Frumholtz, Florence Cordoliani, Luc Mouthon, Romain Paule, Jean-David Bouaziz, Ic Guillevin, Benjamin Terrier, Selim Aractingi, Nicolas Dupin, Alexis Re ´gent, Anouk Soenen, Morgane Vourc'h, Amir Khammari, Jean-Michel Nguyen, ´line Bossard, Marie Denis Musquer, Brigitte Dre ´no, Alessandra Condorelli, Francesca Farnetani, Silvana Ciardo, Johanna Chester, Shaniko Kaleci, Ignazio Stanganelli, Laura Mazzoni, Serena Magi, Victor Mandel, Marica Mirra, Riccardo Pampena, Margherita Raucci, Caterina Longo, Giovanni Pellacani, Marta Van Beek, Robert Swerlick, Barbara Mathes, Margo Reeder, Toni Kaye, Arik Aninos, Mason Totaro, Alyssa Burns, Matthew Fitzgerald, Caryn Etkin, Jeffrey Jacobs, Gregory Phillips, Amy Huang, Bret Augsburger, Laura Kaplan, Kathleen Peoples, Anna Bruckner, Phuong Khuu, Jean Tang, Irene Lara-Corrales, Elena Pope, Karen Wiss, Laura Levin, Kimberly Morel, Kristen Hook, Amy Paller, Lawrence Eichenfield, Catherine Mccuaig, Julie Powell, Leslie Castelo-Soccio, Moise Levy, Harper Price, Lawrence Schachner, John Browning, Marla Jahnke, Tor Shwayder, Susan Bayliss, Anne Lucky, Sharon Glick, Joseph Mathew, Anita Bowman, Jad Saab, Klaus Busam, Kishwer Nehal, Melissa Pulitzer
Journal: Journal of the American Academy of Dermatology (2022)
Restored Ketosis Drives Anticancer Immunity in Colorectal Cancer
Authors: David C. Montrose, Lorenzo Galluzzi
Journal: Cancer Research (2022)

Abstract Dietary interventions including alterations in the amount or type of specific macronutrients have been shown to mediate antineoplastic effects in preclinical tumor models, but the underlying mechanisms are only partially understood. In this issue of Cancer Research, Wei and colleagues demonstrate that restoring ketogenesis in the colorectal cancer microenvironment decreases the KLF5-dependent synthesis of CXCL12 by cancer-associated fibroblasts, ultimately enhancing tumor infiltration by immune effector cells and increasing the therapeutic efficacy of an immune checkpoint inhibitor specific for PD-1. These findings provide a novel, therapeutically actionable link between suppressed ketogenesis and immunoevasion in the colorectal cancer microenvironment. See related article by Wei et al., p. 1575
Artificial intelligence and machine learning for early detection and diagnosis of colorectal cancer in sub-Saharan Africa
Authors: Akbar K Waljee, Eileen M Weinheimer-Haus, Amina Abubakar, Anthony K Ngugi, Geoffrey H Siwo, Gifty Kwakye, Amit G Singal, Arvind Rao, Sameer D Saini, Andrew J Read, Jessica A Baker, Ulysses Balis, Christopher K Opio, Ji Zhu, Mansoor N Saleh
Journal: Gut (2022)
Mediterranean Diet or Mindfulness-Based Stress Reduction and Prevention of Small-for-Gestational-Age Birth Weights in Newborns—Reply
Authors: Francesca Crovetto, Fàtima Crispi, Eduard Gratacós
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
SMAD4 TGF-β–independent function preconditions naive CD8+ T cells to prevent severe chronic intestinal inflammation
Authors: Ramdane Igalouzene, Hector Hernandez-Vargas, Nicolas Benech, Alexandre Guyennon, David Bauché, Célia Barrachina, Emeric Dubois, Julien C. Marie, Saïdi M’Homa Soudja
Journal: Journal of Clinical Investigation (2022)

SMAD4, a mediator of TGF-β signaling, plays an important role in T cells to prevent inflammatory bowel disease (IBD). However, the precise mechanisms underlying this control remain elusive. Using both genetic and epigenetic approaches, we revealed an unexpected mechanism by which SMAD4 prevents naive CD8+ T cells from becoming pathogenic for the gut. Prior to the engagement of the TGF-β receptor, SMAD4 restrains the epigenetic, transcriptional, and functional landscape of the TGF-β signature in naive CD8+ T cells. Mechanistically, prior to TGF-β signaling, SMAD4 binds to promoters and enhancers of several TGF-β target genes, and by regulating histone deacetylation, suppresses their expression. Consequently, regardless of a TGF-β signal, SMAD4 limits the expression of TGF-β negative feedback loop genes, such as Smad7 and Ski, and likely conditions CD8+ T cells for the immunoregulatory effects of TGF-β. In addition, SMAD4 ablation conferred naive CD8+ T cells with both a superior survival capacity, by enhancing their response to IL-7, as well as an enhanced capacity to be retained within the intestinal epithelium, by promoting the expression of Itgae, which encodes the integrin CD103. Accumulation, epithelial retention, and escape from TGF-β control elicited chronic microbiota-driven CD8+ T cell activation in the gut. Hence, in a TGF-β-independent manner, SMAD4 imprints a program that preconditions naive CD8+ T cell fate, preventing IBD.
Delivery of sorafenib by myofibroblast-targeted nanoparticles for the treatment of renal fibrosis
Authors: Hui-Teng Cheng, Hsi-Chien Huang, Tsung-Ying Lee, Yu-Hui Liao, Yi-Hua Sheng, Pei-Ru Jin, Kuan-Wei Huang, Ling-Hsuan Chen, Yi-Ting Chen, Zi-Yan Liu, Tzu-Chieh Lin, Hsueh-Cheng Wang, Cheng-Han Chao, I. Pu Juang, Chi-Ting Su, Kuo-How Huang, Shuei-Liong Lin, Jane Wang, Yun-Chieh Sung, Yunching Chen
Journal: Journal of Controlled Release (2022)
Fluconazole-resistant Candida parapsilosis clonally related genotypes: first report proving the presence of endemic isolates harbouring the Y132F ERG11 gene substitution in Spain
Authors: Eva Alcoceba, Ana Gómez, Paula Lara-Esbrí, Antonio Oliver, Adrián Ferre Beltrán, Ignacio Ayestarán, Patricia Muñoz, Pilar Escribano, Jesús Guinea
Journal: Clinical Microbiology and Infection (2022)
Effects of Metoprolol on Exercise Hemodynamics in Patients With Obstructive Hypertrophic Cardiomyopathy
Authors: Anne M. Dybro, Torsten B. Rasmussen, Roni R. Nielsen, Bertil T. Ladefoged, Mads J. Andersen, Morten K. Jensen, Steen H. Poulsen
Journal: Journal of the American College of Cardiology (2022)
Life course socioeconomic conditions and multimorbidity in old age – A scoping review
Authors: Cornelia Wagner, Cristian Carmeli, Arnaud Chiolero, Stéphane Cullati
Journal: Ageing Research Reviews (2022)

Multimorbidity disproportionally affects individuals exposed to socioeconomic disadvantage. It is, however, unclear how adverse socioeconomic conditions (SEC) at different periods of the life course predict the occurrence of multimorbidity in later life. In this scoping review, we investigate the association between life course SEC and later-life multimorbidity, and assess to which extent it supports different life course causal models (critical period, sensitive period, accumulation, pathway, or social mobility). We identified four studies (25,209 participants) with the first measure of SEC in childhood (before age 18). In these four studies, childhood SEC was associated with multimorbidity in old age, and the associations were partially or fully attenuated upon adjustment for later-life SEC. These results are consistent with the sensitive period and the pathway models. We identified five studies (91,236 participants) with the first measure of SEC in young adulthood (after age 18), and the associations with multimorbidity in old age as well as the effects of adjustment for later-life SEC differed from one study to the other. Among the nine included studies, none tested the social mobility or the accumulation models. In conclusion, SEC in early life could have an effect on multimorbidity, attenuated at least partly by SEC in adulthood.
Incidental Diagnosis of Right Renal Subcapsular Urinoma on an 18F-FDG PET/CT Scan Performed for Staging of Cervical Cancer
Authors: Weiting Liu, Xilan Yao, Xiaohong Ou
Journal: Clinical Nuclear Medicine (2022)

Abstract A 53-year-old woman with cervical cancer underwent FDG PET/CT staging, which demonstrated an avid cervical mass with right parametrial involvement and presence of bilateral lymph node metastases. The right ureter was encased, resulting in obstruction and renal pelvic dilatation. Avid right renal subcapsular lesions were also noted, which were hyperintense on T2-weighted imaging compatible to encapsulated fluid collections. These lesions were diagnosed as subcapsular urinoma due to transmitted back pressure caused by obstruction of the right ureter.
Inhibition of <i>METTL3</i> attenuates renal injury and inflammation by alleviating <i>TAB3</i> m6A modifications via IGF2BP2-dependent mechanisms
Authors: Jia-nan Wang, Fang Wang, Jing Ke, Zeng Li, Chuan-hui Xu, Qin Yang, Xin Chen, Xiao-yan He, Yuan He, Xiao-guo Suo, Chao Li, Ju-tao Yu, Ling Jiang, Wei-jian Ni, Juan Jin, Ming-ming Liu, Wei Shao, Chen Yang, Qian Gong, Hai-yong Chen, Jun Li, Yong-gui Wu, Xiao-ming Meng
Journal: Science Translational Medicine (2022)

The role of N6-methyladenosine (m6A) modifications in renal diseases is largely unknown. Here, we characterized the role of N6-adenosine-methyltransferase-like 3 (METTL3), whose expression is elevated in renal tubules in different acute kidney injury (AKI) models as well as in human biopsies and cultured tubular epithelial cells (TECs). METTL3 silencing alleviated renal inflammation and programmed cell death in TECs in response to stimulation by tumor necrosis factor-α (TNF-α), cisplatin, and lipopolysaccharide (LPS), whereas METTL3 overexpression had the opposite effects. Conditional knockout of METTL3 from mouse kidneys attenuated cisplatin- and ischemic/reperfusion (I/R)-induced renal dysfunction, injury, and inflammation. Moreover, TAB3 [TGF-β-activated kinase 1 (MAP3K7) binding protein 3] was identified as a target of METTL3 by m6A methylated RNA immunoprecipitation sequencing and RNA sequencing. The stability of TAB3 was increased through binding of IGF2BP2 (insulin-like growth factor 2 binding protein 2) to its m6A-modified stop codon regions. The proinflammatory effects of TAB3 were then explored both in vitro and in vivo. Adeno-associated virus 9 (AAV9)-mediated METTL3 silencing attenuated renal injury and inflammation in cisplatin- and LPS-induced AKI mouse models. We further identified Cpd-564 as a METTL3 inhibitor that had better protective effects against cisplatin- and ischemia/reperfusion-induced renal injury and inflammation than S-adenosyl-l-homocysteine, a previously identified METTL3 inhibitor. Collectively, METTL3 promoted m6A modifications of TAB3 and enhanced its stability via IGF2BP2-dependent mechanisms. Both genetic and pharmacological inhibition of METTL3 attenuated renal injury and inflammation, suggesting that the METTL3/TAB3 axis is a potential target for treatment of AKI.
Safety and immunogenicity of SpikoGen®, an Advax-CpG55.2-adjuvanted SARS-CoV-2 spike protein vaccine: a phase 2 randomized placebo-controlled trial in both seropositive and seronegative populations
Authors: Payam Tabarsi, Nassim Anjidani, Ramin Shahpari, Masoud Mardani, Araz Sabzvari, Babak Yazdani, Khashayar Roshanzamir, Behnam Bayatani, Ali Taheri, Nikolai Petrovsky, Lei Li, Saghar Barati
Journal: Clinical Microbiology and Infection (2022)
Breast tumor microenvironment structures are associated with genomic features and clinical outcome
Authors: Esther Danenberg, Helen Bardwell, Vito R. T. Zanotelli, Elena Provenzano, Suet-Feung Chin, Oscar M. Rueda, Andrew Green, Emad Rakha, Samuel Aparicio, Ian O. Ellis, Bernd Bodenmiller, Carlos Caldas, H. Raza Ali
Journal: Nature Genetics (2022)

Abstract The functions of the tumor microenvironment (TME) are orchestrated by precise spatial organization of specialized cells, yet little is known about the multicellular structures that form within the TME. Here we systematically mapped TME structures in situ using imaging mass cytometry and multitiered spatial analysis of 693 breast tumors linked to genomic and clinical data. We identified ten recurrent TME structures that varied by vascular content, stromal quiescence versus activation, and leukocyte composition. These TME structures had distinct enrichment patterns among breast cancer subtypes, and some were associated with genomic profiles indicative of immune escape. Regulatory and dysfunctional T cells co-occurred in large ‘suppressed expansion’ structures. These structures were characterized by high cellular diversity, proliferating cells and enrichment for BRCA1 and CASP8 mutations and predicted poor outcome in estrogen-receptor-positive disease. The multicellular structures revealed here link conserved spatial organization to local TME function and could improve patient stratification.
Trends in Mortality Due to Myocardial Infarction, Stroke, and Pulmonary Embolism in Patients Receiving Dialysis
Authors: Gurbey Ocak, Rianne Boenink, Marlies Noordzij, Willem Jan W. Bos, Bjorn E. Vikse, Aleix Cases, Julia Kerschbaum, Jaakko Helve, Maurizio Nordio, Mustafa Arici, Lucile Mercadal, Christoph Wanner, Runolfur Palsson, Kristine Hommel, Johan De Meester, Myrto Kostopoulou, Rafael Santamaria, Emilio Rodrigo, Helena Rydell, Samira Bell, Ziad A. Massy, Kitty J. Jager, Anneke Kramer
Journal: JAMA Network Open (2022)

During the past decades, improvements in the prevention and management of myocardial infarction, stroke, and pulmonary embolism have led to a decline in cardiovascular mortality in the general population. However, it is unknown whether patients receiving dialysis have also benefited from these improvements.To assess the mortality rates for myocardial infarction, stroke, and pulmonary embolism in a large cohort of European patients receiving dialysis compared with the general population.In this cohort study, adult patients who started dialysis between 1998 and 2015 from 11 European countries providing data to the European Renal Association Registry were and followed up for 3 years. Data were analyzed from September 2020 to February 2022.Start of dialysis.The age- and sex-standardized mortality rate ratios (SMRs) with 95% CIs were calculated by dividing the mortality rates in patients receiving dialysis by the mortality rates in the general population for 3 equal periods (1998-2003, 2004-2009, and 2010-2015).In total, 220 467 patients receiving dialysis were included in the study. Their median (IQR) age was 68.2 (56.5-76.4) years, and 82 068 patients (37.2%) were female. During follow-up, 83 912 patients died, of whom 7662 (9.1%) died because of myocardial infarction, 5030 (6.0%) died because of stroke, and 435 (0.5%) died because of pulmonary embolism. Between the periods 1998 to 2003 and 2010 to 2015, the SMR of myocardial infarction decreased from 8.1 (95% CI, 7.8-8.3) to 6.8 (95% CI, 6.5-7.1), the SMR of stroke decreased from 7.3 (95% CI, 7.0-7.6) to 5.8 (95% CI, 5.5-6.2), and the SMR of pulmonary embolism decreased from 8.7 (95% CI, 7.6-10.1) to 5.5 (95% CI, 4.5-6.6).In this cohort study of patients receiving dialysis, mortality rates for myocardial infarction, stroke, and pulmonary embolism decreased more over time than in the general population.
Dose-Limiting Bone Marrow Toxicities After Peptide Receptor Radionuclide Therapy Are More Prevalent in Women Than in Men
Authors: Noémie S. Minczeles, Wouter W. de Herder, Mark W. Konijnenberg, Richard A. Feelders, Tessa Brabander, Johannes Hofland
Journal: Clinical Nuclear Medicine (2022)

Purpose Peptide receptor radionuclide therapy (PRRT) can cause dose-limiting toxicities (DLTs) of the bone marrow, liver, and kidneys. It is yet unknown whether women and men are equally at risk of these DLTs. Methods Neuroendocrine tumor patients treated with 177 Lu-DOTATATE between 2000 and 2015 in our phase II trial with available laboratory data were included. For all DLTs, the highest Common Terminology Criteria for Adverse Events (version 4.03) grades that occurred from the start of PRRT until 3 months after the last cycle were scored. Results At baseline, women (n = 439) had a significantly lower body mass index, Karnofsky Performance Score, hemoglobin level, and creatinine clearance and a significantly higher platelet level than men (n = 534). Both groups received a median activity of 29.6 GBq (800 mCi). After the start of PRRT, women more frequently developed grade ≥2 thrombocytopenia compared with men (25% vs 18%, P = 0.004) due to a significant increase in grade ≥3 thrombocytopenia (11% vs 6%, P = 0.008). Furthermore, the incidence of grade ≥3 anemia was higher in women (7% vs 3%, P = 0.002). In the multivariable regression model, female sex (odds ratio, 2.50; 95% confidence interval, 1.67–3.74) was confirmed to be an independent risk factor for grade ≥2 thrombocytopenia, among baseline platelet count, bone metastases, uptake on 111 In-DTPA-octreotide scan, Karnofsky Performance Score, alkaline phosphatase, lymphocytes, albumin, and renal function. Conclusions Female neuroendocrine tumor patients more often experienced PRRT-induced toxicities of platelets and hemoglobin than males, but this did not lead to a lower cumulative activity.
Few Black Individuals Are Becoming Surgeons
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
Intermittent prednisone treatment in mice promotes exercise tolerance in obesity through adiponectin
Authors: Mattia Quattrocelli, Michelle Wintzinger, Karen Miz, Manoj Panta, Ashok D. Prabakaran, Grant D. Barish, Navdeep S. Chandel, Elizabeth M. McNally
Journal: The Journal of Experimental Medicine (2022)

The fat-muscle communication regulates metabolism and involves circulating signals like adiponectin. Modulation of this cross-talk could benefit muscle bioenergetics and exercise tolerance in conditions like obesity. Chronic daily intake of exogenous glucocorticoids produces or exacerbates metabolic stress, often leading to obesity. In stark contrast to the daily intake, we discovered that intermittent pulses of glucocorticoids improve dystrophic muscle metabolism. However, the underlying mechanisms, particularly in the context of obesity, are still largely unknown. Here we report that in mice with diet-induced obesity, intermittent once-weekly prednisone increased total and high-molecular weight adiponectin levels and improved exercise tolerance and energy expenditure. These effects were dependent upon adiponectin, as shown by genetic ablation of the adipokine. Upregulation of Adipoq occurred through the glucocorticoid receptor (GR), as this effect was blocked by inducible GR ablation in adipocytes. The treatment increased the muscle metabolic response of adiponectin through the CAMKK2-AMPK cascade. Our study demonstrates that intermittent glucocorticoids produce healthful metabolic remodeling in diet-induced obesity.
Targeted screening in the UK: A narrow concept with broad application
Authors: Anna Bobrowska, Molly Murton, Farah Seedat, Cristina Visintin, Anne Mackie, Robert Steele, John Marshall
Journal: The Lancet Regional Health - Europe (2022)

A recent report on screening in the UK proposed that the responsibility for recommendations on population and targeted screening programmes should be held by one new integrated advisory body. There is no wide international consensus on the definition of targeted screening. Our review identified and compared the defining components of screening terms: targeted, population, selective, and cascade screening, and case finding. Definitions of targeted screening and population screening were clearly demarcated by the eligible population; targeted and selective screening were found to be conceptually interchangeable; cascade screening, whilst conceptually similar to targeted screening across several components, was only used within the context of genetic diseases. There was little consensus between different definitions of case finding. These comparisons contributed to an updated definition of targeted screening. Considerable overlap between definition components across terms implies that a broad range of disease areas may fall into the remit of the new advisory body.
Oncogenic inspiration for programmable activators
Authors: David Ichikawa, Marcus Noyes
Journal: Cell Genomics (2022)

The discovery of regulatory domains has been limited to the investigation of transcription factors and homologous protein sequences. In this issue of Cell Genomics, motivated by an oncogenic protein fusion, Tak et al.1 direct the regulatory potential of a nontraditional effector domain to novel genomic loci with fusions to programmable DNA-binding domains.