tbuckley/cabot-search huggingface dataset:
Trends in US Pediatric Hospital Admissions in 2020 Compared With the Decade Before the COVID-19 Pandemic
Authors: Jonathan H. Pelletier, Jaskaran Rakkar, Alicia K. Au, Dana Fuhrman, Robert S. B. Clark, Christopher M. Horvat
Journal: JAMA Network Open (2021)

<h3>Importance</h3> In early 2020, the United States declared a public health emergency in response to coronavirus disease 2019 (COVID-19) and implemented a variety of social distancing measures. The association between the COVID-19 pandemic and the number of pediatric admissions is unclear. <h3>Objective</h3> To determine the changes in patterns of pediatric admissions in 2020 compared with the prior decade. <h3>Design, Setting, and Participants</h3> This cross-sectional study included 49 US hospitals contributing to the Pediatric Health Information Systems database. Inpatient admissions were transformed into time-series data, and ensemble forecasting models were generated to analyze admissions across a range of diagnoses in 2020 compared with previous years. The setting was inpatient admissions. All patients discharged between January 1, 2010, and June 30, 2020, from an inpatient hospital encounter were included. <h3>Main Outcomes and Measures</h3> Number of hospital admissions by primary diagnosis for each encounter. <h3>Results</h3> Of 5 424 688 inpatient encounters among 3 372 839 patients (median [interquartile range] age, 5.1 [0.7-13.3] years; 2 823 748 [52.1%] boys; 3 171 224 [58.5%] White individuals) at 49 hospitals, 213 571 (3.9%) were between January 1, 2020, and June 30, 2020. There was a decrease in the number of admissions beginning in March 2020 compared with the period from 2010 to 2019. At the nadir, admissions in April 2020 were reduced 45.4% compared with prior years (23 798 in April 2020 compared with a median [interquartile range] of 43 550 [42 110-43 946] in April 2010-2019). Inflation-adjusted hospital charges decreased 27.7% in the second quarter of 2020 compared with prior years ($4 327 580 511 in 2020 compared with a median [interquartile range] of $5 983 142 102 [$5 762 690 022-$6 324 978 456] in 2010-2019). Seasonal patterns were evident between 2010 and 2019 for a variety of common pediatric conditions, including asthma, atrial septal defects, bronchiolitis, diabetic ketoacidosis, Kawasaki syndrome, mental health admissions, and trauma. Ensemble models were able to discern seasonal patterns in admission diagnoses and accurately predicted admission rates from July 2019 until December 2019 but not from January 2020 to June 2020. All diagnoses except for birth decreased below the model 95% CIs between January 2020 and June 2020. <h3>Conclusions and Relevance</h3> In this cross-sectional study, pediatric admissions to US hospitals decreased in 2020 across an array of pediatric conditions. Although some conditions may have decreased in incidence, others may represent unmet needs in pediatric care during the COVID-19 pandemic.
Genome-wide CRISPR/Cas9 knockout screening uncovers a novel inflammatory pathway critical for resistance to arginine-deprivation therapy
Authors: Cheng-Ying Chu, Yi-Ching Lee, Cheng-Han Hsieh, Chi-Tai Yeh, Tsu-Yi Chao, Po-Hung Chen, I-Hsuan Lin, Tsung-Han Hsieh, Jing-Wen Shih, Chia-Hsiung Cheng, Che-Chang Chang, Ping-Sheng Lin, Yuan-Li Huang, Tsung-Ming Chen, Yun Yen, David K. Ann, Hsing-Jien Kung
Journal: Theranostics (2021)

Arginine synthesis deficiency due to the suppressed expression of ASS1 (argininosuccinate synthetase 1) represents one of the most frequently occurring metabolic defects of tumor cells. Arginine-deprivation therapy has gained increasing attention in recent years. One challenge of ADI-PEG20 (pegylated ADI) therapy is the development of drug resistance caused by restoration of ASS1 expression and other factors. The goal of this work is to identify novel factors conferring therapy resistance. Methods: Multiple, independently derived ADI-resistant clones including derivatives of breast (MDA-MB-231 and BT-549) and prostate (PC3, CWR22Rv1, and DU145) cancer cells were developed. RNA-seq and RT-PCR were used to identify genes upregulated in the resistant clones. Unbiased genome-wide CRISPR/Cas9 knockout screening was used to identify genes whose absence confers sensitivity to these cells. shRNA and CRISPR/Cas9 knockout as well as overexpression approaches were used to validate the functions of the resistant genes both in vitro and in xenograft models. The signal pathways were verified by western blotting and cytokine release. Results: Based on unbiased CRISPR/Cas9 knockout screening and RNA-seq analyses of independently derived ADI-resistant (ADIR) clones, aberrant activation of the TREM1/CCL2 axis in addition to ASS1 expression was consistently identified as the resistant factors. Unlike ADIR, MDA-MB-231 overexpressing ASS1 cells achieved only moderate ADI resistance both in vitro and in vivo, and overexpression of ASS1 alone does not activate the TREM1/CCL2 axis. These data suggested that upregulation of TREM1 is an independent factor in the development of strong resistance, which is accompanied by activation of the AKT/mTOR/STAT3/CCL2 pathway and contributes to cell survival and overcoming the tumor suppressive effects of ASS1 overexpression. Importantly, knockdown of TREM1 or CCL2 significantly sensitized ADIR toward ADI. Similar results were obtained in BT-549 breast cancer cell line as well as castration-resistant prostate cancer cells. The present study sheds light on the detailed mechanisms of resistance to arginine-deprivation therapy and uncovers novel targets to overcome resistance. Conclusion: We uncovered TREM1/CCL2 activation, in addition to restored ASS1 expression, as a key pathway involved in full ADI-resistance in breast and prostate cancer models.
Quantifying the Long-term Survival Benefit of Pembrolizumab for Patients With Advanced Gastric Cancer—Reply
Authors: Kohei Shitara, Josep Tabernero
Journal: JAMA Oncology (2021)

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 Oncology 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 Oncology journal
Studies on Cardiac Dimensions in Intact, Unanesthetized Man
Authors: DONALD C. HARRISON, GERALD GLICK, ALLAN GOLDBLATT, EUGENE BRAUNWALD
Journal: Circulation (1964)

The effects on ventricular dimensions of intact, unanesthetized patients of isoproterenol, a drug that stimulates beta adrenergic receptors, and of methoxamine, an agent that stimulates alpha adrenergic receptors, were studied by means of a cineradiographic technic. The administration of isoproterenol to 13 patients consistently resulted in a decline in the end-systolic dimensions of both ventricles. A smaller and less consistent decrease in ventricular end-diastolic dimensions was noted. In contrast, the administration of methoxamine resulted in an increase of ventricular end-diastolic dimensions in all 10 patients studied. Left ventricular end-systolic dimensions increased during methoxamine infusion in the eight patients in whom the measurements were made, but changes in right ventricular end-systolic dimensions were inconsistent. The alterations in heart rate induced by isoproterenol and methoxamine could account only in part for the observed changes in ventricular dimensions. It is anticipated that the experimental approach used in this study, that is, the measurement of ventricular dimensions in intact, unanesthetized human subjects, will help to provide a more complete analysis of the action of drugs on the circulation of man.
Molecular Pathology of Poorly Differentiated and Anaplastic Thyroid Cancer: What Do Pathologists Need to Know?
Authors: Marco Volante, Alfred K. Lam, Mauro Papotti, Giovanni Tallini
Journal: Endocrine Pathology (2021)

Abstract The molecular characterization of poorly and anaplastic thyroid carcinomas has been greatly improved in the last years following the advent of high throughput technologies. However, with special reference to genomic data, the prevalence of reported alterations is partly affected by classification criteria. The impact of molecular pathology in these tumors is multifaceted and bears diagnostic, prognostic, and predictive implications although its use in the clinical practice is not completely assessed. Genomic profiling data claim that genetic alterations in poorly differentiated and anaplastic thyroid carcinomas include “Early” and “Late” molecular events, which are consistent with a multi-step model of progression. “Early” driver events are mostly RAS and BRAF mutations, whereas “Late” changes include above all TP53 and TERT promoter mutations, as well as dysregulation of gene involved in the cell cycle, chromatin remodeling, histone modifications, and DNA mismatch repair. Gene fusions are rare but represent relevant therapeutic targets. Epigenetic modifications are also playing a relevant role in poorly differentiated and anaplastic thyroid carcinomas, with altered regulation of either genes by methylation/deacetylation or non-coding RNAs. The biological effects of epigenetic modifications are not fully elucidated but interfere with a wide spectrum of cellular functions. From a clinical standpoint, the combination of genomic and epigenetic data shows that several molecular alterations affect druggable cellular pathways in poorly differentiated and anaplastic thyroid carcinomas, although the clinical impact of molecular typing of these tumors in terms of predictive biomarker testing is still under exploration.
Incidence And Risk Factors of Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema: A Large Case-Control Study
Authors: Juan Garcia-Saucedo, Ismael Carrillo-Martin, Jorge Trejo-Gutierrez, Matthew Rank, Gerald Volcheck, Miguel Park, Alexei Gonzalez-Estrada
Journal: Journal of Allergy and Clinical Immunology (2021)
Abstract 15463: Occupational Health Hazards of Working in the Interventional Laboratory: A Large Case-Control Study
Authors: Nicholas M Orme, Charanjit S Rihal, David R Holmes, Ryan J Lennon, Bradley R Lewis, Kent R Thielen, Ian R McPhail, Sorin V Pislaru, Gurpreet S Sandhu, Singh Mandeep
Journal: Circulation (2014)

Introduction: An increase in PCI volumes, complexity, and procedure times has led to both an increase in physical stresses related to wearing protective lead aprons and operator radiation exposure. The effects of such occupational hazards remain poorly understood as available studies have limitations such as poor survey response rates, lack of age-matched controls, and subjective pain assessment.

Methods: We surveyed 1541 Mayo Foundation employees within the departments of cardiology and radiology (1042 without and 499 with radiation exposure) for pain, cancer, thyroid disease, cataract, and nephrolithiasis and stratified them based on their exposure to radiation. Multiple logistic regression was used to estimate adjusted associations between radiation exposure and endpoints.

Results: The response rate was 57%. The average age was 43 years; 33% were male. The associations between pain and medical diagnoses with radiation exposure are summarized in the Table.

Conclusions: In personnel exposed to radiation working in laboratories, there is a higher prevalence of musculoskeletal pain but the prevalence of cancer, cataract, thyroid problems and nephrolithiasis are similar. There was a trend towards a higher incidence of composite endpoints. Larger studies are needed to confirm this association.

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Continued Increases in Overdose Deaths Related to Synthetic Opioids
Authors: Grant T. Baldwin, Puja Seth, Rita K. Noonan
Journal: JAMA (2021)

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
Pregnancy and infant outcomes among pregnant women with Chronic Spontaneous Urticaria (CSU) treated with omalizumab: a descriptive analysis from the EXPECT pregnancy registry
Authors: Jennifer Namazy, Angela Scheuerle, Vic Spain, Pranathi Janampally, Ayesha Ahmed, Sachin Gupta, Cecile Holweg, Nayla Mumneh, Cristine Radojicic
Journal: Journal of Allergy and Clinical Immunology (2021)
First-line treatment and survival of newly diagnosed primary plasma cell leukemia patients in the Netherlands: a population-based study, 1989-2018
Authors: Mirian Brink, Otto Visser, Sonja Zweegman, Pieter Sonneveld, Annemiek Broyl, Niels W.C.J. van de Donk, Avinash G. Dinmohamed
Journal: Blood Cancer Journal (2021)
Communication and ethical considerations for fertility preservation for patients with childhood, adolescent, and young adult cancer: recommendations from the PanCareLIFE Consortium and the International Late Effects of Childhood Cancer Guideline Harmonization Group
Authors: Renée L Mulder, Anna Font-Gonzalez, Eline van Dulmen-den Broeder, Gwendolyn P Quinn, Jill P Ginsberg, Erik A H Loeffen, Melissa M Hudson, Karen C Burns, Hanneke M van Santen, Claire Berger, Tamara Diesch, Uta Dirksen, Aleksander Giwercman, Clarisa Gracia, Sarah E Hunter, Joanne F Kelvin, James L Klosky, Joop S E Laven, Barbara A Lockart, Sebastian J C M M Neggers, Michelle Peate, Bob Phillips, Damon R Reed, Eva Maria E Tinner, Julianne Byrne, Margreet Veening, Marleen van de Berg, Chris M Verhaak, Antoinette Anazodo, Kenny Rodriguez-Wallberg, Marry M van den Heuvel-Eibrink, Ogechukwu A Asogwa, Alexandra Brownsdon, W Hamish Wallace, Daniel M Green, Roderick Skinner, Riccardo Haupt, Lisa B Kenney, Jennifer Levine, Marianne D van de Wetering, Wim J E Tissing, Norbert W Paul, Leontien C M Kremer, Julia Inthorn, Richard A Anderson, Anke Barnbrock, Joern D Beck, Annelies M E Bos, Gabriele Calaminus, Louis S Constine, Isabelle Demeestere, Christian Denzer, Desiree Grabow, Natascia di Iorgi, Holly R Hoefgen, Kirsi Jahnukainen, Peter Kaatsch, Rejin Kebudi, Cornelis Lambalk, Thorsten Langer, Jacqueline Loonen, Armando Lorenzo, Lillian R Meacham, Andreas Meissner, Rod T Mitchell, Leena Nahata, Andreas Ranft, Marij Dinkelman-Smit, Catharyn Stern, Eveline Stutz-Grunder, Herman Tournaye, Wendy van Dorp, Ans M M van Pelt, Andrica de Vries, Richard Yu
Journal: The Lancet Oncology (2021)
Long-term Outcomes of Children After Fetal Surgery for Spina Bifida—Toward Sustainability
Authors: Martin Meuli, Ueli Moehrlen
Journal: JAMA Pediatrics (2021)

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 Pediatrics 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 Pediatrics journal
Mutations in the RAS/MAPK Pathway Drive Replication Repair–Deficient Hypermutated Tumors and Confer Sensitivity to MEK Inhibition
Authors: Brittany B. Campbell, Melissa A. Galati, Simone C. Stone, Alexandra N. Riemenschneider, Melissa Edwards, Sumedha Sudhaman, Robert Siddaway, Martin Komosa, Nuno M. Nunes, Liana Nobre, A. Sorana Morrissy, Matthew Zatzman, Michal Zapotocky, Lazar Joksimovic, Sangeetha N. Kalimuthu, David Samuel, Gary Mason, Eric Bouffet, Daniel A. Morgenstern, Melyssa Aronson, Carol Durno, David Malkin, John M. Maris, Michael D. Taylor, Adam Shlien, Trevor J. Pugh, Pamela S. Ohashi, Cynthia E. Hawkins, Uri Tabori
Journal: Cancer Discovery (2021)

The RAS/MAPK pathway is an emerging targeted pathway across a spectrum of both adult and pediatric cancers. Typically, this is associated with a single, well-characterized point mutation in an oncogene. Hypermutant tumors that harbor many somatic mutations may obscure the interpretation of such targetable genomic events. We find that replication repair-deficient (RRD) cancers, which are universally hypermutant and affect children born with RRD cancer predisposition, are enriched for RAS/MAPK mutations (P = 10-8). These mutations are not random, exist in subclones, and increase in allelic frequency over time. The RAS/MAPK pathway is activated both transcriptionally and at the protein level in patient-derived RRD tumors, and these tumors responded to MEK inhibition in vitro and in vivo. Treatment of patients with RAS/MAPK hypermutant gliomas reveals durable responses to MEK inhibition. Our observations suggest that hypermutant tumors may be addicted to oncogenic pathways, resulting in favorable response to targeted therapies. SIGNIFICANCE: Tumors harboring a single RAS/MAPK driver mutation are targeted individually for therapeutic purposes. We find that in RRD hypermutant cancers, mutations in the RAS/MAPK pathway are enriched, highly expressed, and result in sensitivity to MEK inhibitors. Targeting an oncogenic pathway may provide therapeutic options for these hypermutant polyclonal cancers.This article is highlighted in the In This Issue feature, p. 1307.
Microarray patches enable the development of skin-targeted vaccines against COVID-19
Authors: Emrullah Korkmaz, Stephen C. Balmert, Tina L. Sumpter, Cara Donahue Carey, Geza Erdos, Louis D. Falo
Journal: Advanced Drug Delivery Reviews (2021)

The COVID-19 pandemic is a serious threat to global health and the global economy. The ongoing race to develop a safe and efficacious vaccine to prevent infection by SARS-CoV-2, the causative agent for COVID-19, highlights the importance of vaccination to combat infectious pathogens. The highly accessible cutaneous microenvironment is an ideal target for vaccination since the skin harbors a high density of antigen-presenting cells and immune accessory cells with broad innate immune functions. Microarray patches (MAPs) are an attractive intracutaneous biocargo delivery system that enables safe, reproducible, and controlled administration of vaccine components (antigens, with or without adjuvants) to defined skin microenvironments. This review describes the structure of the SARS-CoV-2 virus and relevant antigenic targets for vaccination, summarizes key concepts of skin immunobiology in the context of prophylactic immunization, and presents an overview of MAP-mediated cutaneous vaccine delivery. Concluding remarks on MAP-based skin immunization are provided to contribute to the rational development of safe and effective MAP-delivered vaccines against emerging infectious diseases, including COVID-19.
Acute BAF perturbation causes immediate changes in chromatin accessibility
Authors: Sandra Schick, Sarah Grosche, Katharina Eva Kohl, Danica Drpic, Martin G. Jaeger, Nara C. Marella, Hana Imrichova, Jung-Ming G. Lin, Gerald Hofstätter, Michael Schuster, André F. Rendeiro, Anna Koren, Mark Petronczki, Christoph Bock, André C. Müller, Georg E. Winter, Stefan Kubicek
Journal: Nature Genetics (2021)
Erythromycin loaded by tetrahedral framework nucleic acids are more antimicrobial sensitive against Escherichia coli (E. coli)
Authors: Yue Sun, Yuhao Liu, Bowen Zhang, Shirong Shi, Tao Zhang, Dan Zhao, Taoran Tian, Qirong Li, Yunfeng Lin
Journal: Bioactive Materials (2021)

Erythromycin is a commonly used broad-spectrum antibiotic, but resistance to this antibiotic makes its use less effective. Considerable efforts, beside finding alternatives, are needed to enhance its antimicrobial effect and stability against bacteria. Tetrahedral framework nucleic acids (tFNAs), a novel delivery vehicle with a three-dimensional nanostructure, have been studied as a carrying platform of antineoplastic drugs. In this study, the use of tFNAs in delivering erythromycin into
Chemical pancreatectomy: an unconventional approach to preventing autodigestion in pancreatitis
Authors: Rodger A. Liddle
Journal: Journal of Clinical Investigation (2021)

Due to progressive inflammation, chronic pancreatitis destroys both the exocrine and endocrine pancreas and sensitizes pancreatic nerves, leading to unremitting pain. Unfortunately, there are no treatments for pancreatic inflammation and approaches to ameliorate pain are suboptimal. Pancreatic inflammation is particularly problematic because damage to acinar cells causes local release of digestive enzymes, which initiate pancreatic autodigestion. The combination of autodigestion and inflammation is unique to pancreatitis and undoubtedly contributes to the difficulty in devising effective treatments. In this issue of the JCI, Saleh et al. describe a nonsurgical technique to ablate pancreatic acinar cells, thus eliminating the source of digestive enzymes and preventing autodigestion. In mice and a nonhuman primate model, this approach effectively reduced inflammation and pain while preserving islet cell function. These findings support the concept that ongoing acinar cell damage is at the root of chronic pancreatitis and provide a possible strategy for clinical treatment.