tbuckley/cabot-search huggingface dataset:
Changing prevalence of current asthma and inhaled corticosteroid treatment in the UK: population-based cohort 2006–2016
Authors: Chloe I. Bloom, Sejal Saglani, Johanna Feary, Debbie Jarvis, Jennifer K. Quint
Journal: European Respiratory Journal (2019)

Asthma is the most common respiratory disorder in the UK, yet we have incomplete knowledge on the prevalence of current disease, treatment and exacerbations.We used UK electronic healthcare records, 2006-2016, to estimate the prevalence of current asthma by year, sex and age (<5, 5-11, 12-17, 18-24, 25-54 and ≥55 years), and the proportion prescribed inhaled corticosteroids (ICS) and additional asthma therapy, treated for exacerbations and other asthma care markers.Overall current asthma prevalence was 6.5% in 2016 (7.2% in 2006). Prevalence fell in those aged <45 years. The lowest prevalence and largest absolute decrease was in children aged <5 years. In 2016, 80% of current asthma patients were managed on ICS (65% in 2006); this increase occurred in all age groups, primarily due to an increase in low-dose ICS. During this time there was an increase in all age groups in the proportion prescribed additional asthma therapy, treated for an exacerbation within primary care and given an annual asthma review or management plan. Hospitalised exacerbations showed minimal change over time.Asthma remains highly prevalent and a significant healthcare burden. In those with a diagnosis, there was an increase in ICS prescriptions and treatment of exacerbations across all age groups. This may reflect a trend towards more aggressive asthma management within primary care. An apparent decline in prevalence was observed in those aged <45 years, particularly in children aged <5 years.
Improve scheduling to perform an extra 291 000 elective operations a year, trusts are told
Authors: Jacqui Wise
Journal: BMJ (2019)

Theatre time lost to late starts, early finishes, and delays between operations could have been used by hospitals in England to carry out 291 327 more elective operations a year (a 16.8% increase), according to NHS Improvement.1

In a report, the agency calls on NHS trusts to consider a raft of new measures to improve the scheduling of non-urgent operations such as hip replacements and cataract surgery.

The NHS performs around five million elective operations a year but has been struggling to meet its target to treat 92% of patients within 18 weeks. The number of patients having to wait over a year has grown in recent months with the …
Assessment of Radiotherapy-Associated Angiosarcoma After Breast Cancer Treatment in a Dutch Population-Based Study
Authors: Anouk J. M. Rombouts, Jonathan Huising, Niek Hugen, Sabine Siesling, Philip Martin Poortmans, Iris D. Nagtegaal, Johannes H.W. de Wilt
Journal: JAMA Oncology (2019)

Angiosarcoma After Breast Cancer Treatment in a Dutch Population-Based StudyRadiotherapy-associated angiosarcoma (RAAS) has been reported as a rare, but serious late complication of radiotherapy (RT) for breast cancer. 1,2This study describes the incidence, latency period, and outcomes of RAAS using the prospective database from the nationwide Netherlands Cancer Registry.Methods | Patients who were treated with or without RT for stages I to III primary breast cancer from January 1, 1989, through December 31, 2015, with follow-up completed January 31, 2017, were retrospectively studied.A competing risk model (according to Fine and Gray 3 ) was used to determine the incidence and predictive factors of RAAS.Survival after treatment of RAAS was analyzed using Kaplan-Meier curves.The Cox proportional hazards regression model was used for multivariable analysis.Follow-up was defined as the time from incidence of RAAS until the date of death or the last date of follow-up.Statistical significance was defined as 2-sided P < .05.Data were analyzed from January 1, 1989, through January 1, 2017.Following good clinical practice rules in the Netherlands, one does not need to ask ethical approval for the use of anonymized cohort data.
A KRAS mutation is associated with an immunosuppressive tumor microenvironment in mismatch-repair proficient colorectal cancer.
Authors: Michael Marco, Ching-Tung Chen, Seo-Hyun Choi, Raphael Pelossof, Jinru Shia, Julio Garcia-Aguilar
Journal: Journal of Clinical Oncology (2019)

609 Background: KRAS-mutant (KRAS mut ) colorectal cancers (CRCs) are associated with worse prognosis and resistance to therapy. We have previously shown that KRAS mut CRCs have different transcriptomic signature of stromal and immune-related genes compared to KRAS-wild type (KRAS wt ) tumors. Here, we validated the immune-related changes in the tumor microenvironment associated with the KRAS mutation in CRC to guide the design of novel immunotherapy strategies. Methods: The expression of different immune markers (T cells, B cells, macrophages, natural killer cells, and immune check ligands) were assessed using multiplex immunofluorescence (M-IF) technique in both tumor core (TC) and invasive margin (IM). Sequential slides were cut from paraffin blocks of CRC resected at our institute. Each slide was stained with 4 immune markers using M-IF technique. The stained slides were scanned, and quantification of immune cells was done using ImageJ software. Student’s t test was used for statistical analyses. DNA was extracted from each tumor and profiled for 420 cancer genes using targeted exome-capture sequencing (MSK-IMPACT assay). DNA mismatch-repair (MMR) proteins deficiency were analyzed by immunohistochemistry. Only MMR-proficient (pMMR) tumors were included. Results: A total of 39 patients with pMMR CRC were included. AJCC stages (I-III) were not different between KRAS mut (n = 15) and KRAS wt (n = 25) tumors. M2-macrophages (CD68+CD163+ cells) and IL-17-producing cells (IL17+ cells) were significantly higher (p = 0.002, and 2.9e-6 respectively), while T-helper cells (CD3+CD4+cells) were significantly lower (p = 3.9e-4) in TC of KRAS mut tumors compared to KRAS wt . Treg (CD3+CD4+FOXP3+cells) were significantly higher in IM of KRAS mut tumors (p = 0.01). KRAS mut tumors had significantly higher ratios of Treg:T-helper cells, and Treg:T cytotoxic cell (p = 0.008, and p = 0.04; respectively). Conclusions: KRAS oncogene is associated with more pro-tumorigenic (M2 macrophages, IL17 and Treg) and less anti-tumorigenic (CD4 T-helper) immune cells in CRC. These results can be used to guide further research to design novel immunotherapy strategies against KRAS mut CRC.
Vertebral augmentation in osteoporosis: common procedures for spinal fractures show no benefit
Authors: Owen Dyer
Journal: BMJ (2019)

Two common surgical interventions for spinal fractures caused by osteoporosis are no more effective than placebo or sham surgery in bringing lasting relief from pain and disability, a taskforce of the American Society for Bone and Mineral Research has concluded from a meta-analysis of existing studies.1

About 750 000 patients have such a fracture each year in the United States, and roughly a third of these experience acute pain and disability, although this often resolves after several months.

Over 30 000 patients a year are treated with “vertebral augmentation” therapies: mostly percutaneous vertebroplasty, where bone cement is injected into the vertebra; or kyphoplasty, where a balloon or bone tamp is introduced into …
Should Physicians Recommend Replacing Opioids With Cannabis?
Authors: Keith Humphreys, Richard Saitz
Journal: JAMA (2019)

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
Abstract 15543: Long Term Prospective Follow up of Ablation of Ventricular Tachycardia in Adult Congenital Heart Disease
Authors: Michael Brunnquell, Wendy Tzou, William Sauer, Joseph D Kay, Duy T Nguyen
Journal: Circulation (2017)

Introduction: Adult patients with congenital heart disease (ACHD) both repaired and unrepaired, are at risk for ventricular arrhythmias (VAs). Despite the increasing use of radiofrequency (RF) ablation in treating VAs, there is a paucity of data regarding its safety and efficacy in ACHD patients. Objective: To describe characteristics and prospectively follow outcomes for a large, diverse cohort of ACHD patients undergoing RF ablation for ventricular arrhythmias. Methods: A prospective cohort was followed for all ablation procedures of ventricular arrhythmias performed at University of Colorado from 2010 - present. Of over 600 ablation procedures, 29 (5%) consecutive ACHD patients were identified. Patient characteristics, indications, procedural details, complications, and follow up were collected. Results: Of 29 ACHD patients undergoing ablation, 25 (86.2%) had prior surgical repair. The cohort included those with tetralogy of Fallot, single ventricle physiology, transposition of the great arteries, and ...
High Incidence of Hepatitis B Viral Reactivation in Chronic Myeloid Leukemia Patients Treated with Tyrosine Kinase Inhibitors
Authors: Jieun Uhm, Sung-Hyun Kim, Sukjoong Oh, Dae Young Zang, Young Rok Do, Won Sik Lee, Myung Hee Chang, Sung-Eun Lee, Dong-Wook Kim
Journal: Blood (2018)
The eye as a novel imaging site in diabetes research
Authors: Shao-Nian Yang, Per-Olof Berggren
Journal: Pharmacology & Therapeutics (2019)

Diabetes develops due to deficient functional β cell mass, insulin resistance, or both. Yet, various challenges in understanding the mechanisms underlying diabetes development in vivo remain to be overcome owing to the lack of appropriate intravital imaging technologies. To meet these challenges, we have exploited the anterior chamber of the eye (ACE) as a novel imaging site to understand diabetes basics and clinics in vivo. We have developed a technology platform transplanting pancreatic islets into the ACE where they later on can be imaged non-invasively for long time. It turns out that the ACE serves as an optimal imaging site and provides implanted islets with an oxygen-rich milieu and an immune-privileged niche where they undergo optimal engraftment, rich vascularization and dense innervation, preserve organotypic features and live with satisfactory viability and functionality. The ACE technology has led to a series of significant observations. It enables in vivo microscopy of islet cytoarchitecture, function and viability in the physiological context and intravital imaging of a variety of pathological events such as autoimmune insulitis, defects in β cell function and mass and insulin resistance during diabetes development in a real-time manner. Furthermore, application of the ACE technology in humanized mice and non-human primates verifies translational and clinical values of the technology. In this article, we describe the ACE technology in detail, review accumulated knowledge gained by means of the ACE technology and delineate prospective avenues for the ACE technology.
Shared Ancient Sex Chromosomes in Varanids, Beaded Lizards, and Alligator Lizards
Authors: Michail Rovatsos, Ivan Rehák, Petr Velenský, Lukáš Kratochvíl
Journal: Molecular Biology and Evolution (2019)

Sex determination in varanids, Gila monsters, beaded lizards, and other anguimorphan lizards is still poorly understood. Sex chromosomes were reported only in a few species based solely on cytogenetics, which precluded assessment of their homology. We uncovered Z-chromosome-specific genes in varanids from their transcriptomes. Comparison of differences in gene copy numbers between sexes across anguimorphan lizards and outgroups revealed that homologous differentiated ZZ/ZW sex chromosomes are present in Gila monsters, beaded lizards, alligator lizards, and a wide phylogenetic spectrum of varanids. However, these sex chromosomes are not homologous to those known in other amniotes. We conclude that differentiated sex chromosomes were already present in the common ancestor of Anguimorpha living in the early Cretaceous or even in the Jurassic Period, 115-180 Ma, placing anguimorphan sex chromosomes among the oldest known in vertebrates. The analysis of transcriptomes of Komodo dragon (Varanus komodoensis) showed that the expression levels of genes linked to anguimorphan sex chromosomes are not balanced between sexes. Besides expanding our knowledge on vertebrate sex chromosome evolution, our study has important practical relevance for breeding and ecological studies. We introduce the first, widely applicable technique of molecular sexing in varanids, Gila monsters, and beaded lizards, where reliable determination of sex based on external morphology is dubious even in adults.
Tyrosine kinase inhibitor discontinuation in patients with chronic myeloid leukemia: a single-institution experience
Authors: Kamal Chamoun, Hagop Kantarjian, Rami Atallah, Graciela Nogueras Gonzalez, Ghayas C. Issa, Mary Beth Rios, Guillermo Garcia-Manero, Gautam Borthakur, Farhad Ravandi, Nitin Jain, Naval Daver, Marina Konopleva, Courtney D. DiNardo, Tapan Kadia, Naveen Pemmaraju, Elias Jabbour, Jorge Cortes
Journal: Journal of Hematology & Oncology (2019)

Patients with CML treated with TKI can have a life expectancy comparable to that of the general population. Due to the extended duration of TKI administration, treatment discontinuation has been increasingly sought. Medical records of 100 patients with CML who were in MR4.5 and discontinued their TKI outside clinical trials were reviewed. After a median follow-up of 30 months (range, 5–112 months) after discontinuation, 35% and 17% lost MR4.5 and major molecular response (MMR), respectively. Only six patients lost MMR 12 months or more after discontinuation. Loss of MR4.5 was observed in 29% and 7% of patients with sustained MR4.5 duration of more than 2 and 6 years before discontinuation, respectively. By univariate analysis, there was a higher risk of loss of MR4.5 for patients who were treated for less than 87 months, received second or subsequent line TKI, never received interferon, or those with sustained MR4.5 for less than 6 years. By multivariate analysis, sustained MR4.5 for 6 years or more was the only significant predictor for durable response. Overall, 30% of patients who discontinued while in MR4.5 were retreated with 93% regaining MR4.5 at a median of 5 months. These results demonstrate that under proper conditions, treatment discontinuation is feasible outside of clinical trial setting. MR4.5 duration of 6 years or more before discontinuation is associated with very low risk of loss of MR4.5.
Antibacterial Coatings: Responsive and Synergistic Antibacterial Coatings: Fighting against Bacteria in a Smart and Effective Way (Adv. Healthcare Mater. 3/2019)
Authors: Ting Wei, Qian Yu, Hong Chen
Journal: Advanced Healthcare Materials (2019)

In article number 1801381, Qian Yu and co-workers summarize the recent development of three types of responsive and synergistic antibacterial coatings, including self-defensive antibacterial coatings that are responsive to the bacterial microenvironment, synergetic antibacterial coatings that possess two or more killing mechanisms which interact synergistically, and smart "kill-and-release" antibacterial coatings that have triggered-cleaning capability.
Lessons from antineoplaston
Authors: Sally Tweddle, Nicholas James
Journal: The Lancet (1997)

Your March 15 editorial,1Editorial.Lessons from antineoplaston.Lancet. 1997; 349: 741Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar calls for practitioners to recognise patients' needs for, and rights to, information about complementary as well as conventional cancer treatments. Articulate and literate patients will always succeed in finding information that is in the public domain, whatever the views of their own practitioners. On behalf of all patients, particularly those who are less skilled at handling information, we endorse the call. We would, however, qualify it. Patients need accessible, timely, relevant, and appropriate information about cancer treatments. As a supplement to their interactions with medical teams, patients should have access to a range of texts: print, televisual, and computer-based. They should also be in a position to choose the information that best suits their purposes, skills, and preferences. The quality of such texts should be as carefully researched, and their development and provision as seriously funded as any treatment intervention. For as with orthodox oncology, not everything in cancer information is perfect.
Dysregulated activation of fetal liver programme in acute liver failure
Authors: Jeongeun Hyun, Seh-Hoon Oh, Richard T Premont, Cynthia D Guy, Carl L Berg, Anna Mae Diehl
Journal: Gut (2019)

Objective Uncertainty about acute liver failure (ALF) pathogenesis limits therapy. We postulate that ALF results from excessive reactivation of a fetal liver programme that is induced in hepatocytes when acutely injured livers regenerate. To evaluate this hypothesis, we focused on two molecules with known oncofetal properties in the liver, Yes-associated protein-1 (YAP1) and Insulin-like growth factor-2 RNA-binding protein-3 (IGF2BP3). Design We compared normal liver with explanted livers of patients with ALF to determine if YAP1 and IGF2BP3 were induced; assessed whether these factors are upregulated when murine livers regenerate; determined if YAP1 and IGF2BP3 cooperate to activate the fetal programme in adult hepatocytes; and identified upstream signals that control these factors and thereby hepatocyte maturity during recovery from liver injury. Results Livers of patients with ALF were massively enriched with hepatocytes expressing IGF2BP3, YAP1 and other fetal markers. Less extensive, transient accumulation of similar fetal-like cells that were proliferative and capable of anchorage-independent growth occurred in mouse livers that were regenerating after acute injury. Fetal reprogramming of hepatocytes was YAP1-dependent and involved YAP1-driven reciprocal modulation of let7 microRNAs and IGF2BP3, factors that negatively regulate each other to control fate decisions in fetal cells. Directly manipulating IGF2BP3 expression controlled the fetal-like phenotype regardless of YAP1 activity, proving that IGF2BP3 is the proximal mediator of this YAP1-directed fate. Conclusion After acute liver injury, hepatocytes are reprogrammed to fetal-like cells by a YAP1-dependent mechanism that differentially regulates let7 and IGF2BP3, identifying novel therapeutic targets for ALF.
Validation of the NCI Colorectal Cancer Risk Assessment Tool for baseline advanced neoplasia in a veterans cohort.
Authors: Laura W. Musselwhite, Thomas S. Redding, Elizabeth R. Hauser, David A. Lieberman, Dawn T. Provenzale
Journal: Journal of Clinical Oncology (2019)

521 Background: Tailoring screening strategy to colorectal cancer (CRC) risk may improve efficiency for all stakeholders. We applied the National Cancer Institute (NCI) CRC Risk Assessment Tool, which calculates 5-10-year, and 20-year absolute risk of colorectal cancer to determine whether it could be used to predict baseline risk of colorectal cancer precursors in a Veterans cohort undergoing first screening colonoscopy. Methods: This was a prospective evaluation of whether the NCI CRC Risk Assessment Tool which offers an absolute risk over time, could be used to estimate baseline cancerous precursors (advanced neoplasia) in Veterans undergoing first screening colonoscopy. Family, medical, dietary and physical activity histories were collected at the time of screening colonoscopy and used to calculate absolute 5, 10, and 20-year CRC risk, and to compare estimated CRC risk to observed AN. Sensitivity analyses were performed. Results: Of 3,121 Veterans undergoing screening colonoscopy, 94% had complete data available to calculate risk (N = 2,934, median age 63 years, 100% men, and 15% minorities). 11% (N = 313) were diagnosed with AN on baseline screening colonoscopy. The area under the curve for predicting AN was 0.60 (95% CI; 0.57-0.63, p &lt; 0.0001) at 5 years, 0.60 (95% CI, 0.57-0.63, p &lt; 0.0001) at 10 years and 0.58 (95% CI, 0.54-0.61, p &lt; 0.0001) at 20 years. At 5 years, we calculated the sensitivity (0.18, 95% CI; 0.14-0.22), specificity (0.91, 95% CI; 0.90-0.92) positive predictive value (0.19, 95% CI; 0.15-0.24) and negative predictive value (0.90, 95% CI; 0.89-0.91) considering the top 10 th percentile of risk tool scores as a positive result. Conclusions: The NCI CRC Risk Assessment Tool had modest discriminatory function for predicting AN risk at 5, 10 and 20 years. The Tool’s specificity and negative predictive value were quite good, highlighting its usefulness in risk prediction. This tool may beused to inform the benefit-risk assessment of screening colonoscopy for patients with competing comorbidities.
A Phase 2 Study of Ruxolitinib with Chemotherapy in Children with Philadelphia Chromosome-like Acute Lymphoblastic Leukemia (INCB18424-269/AALL1521): Dose-Finding Results from the Part 1 Safety Phase
Authors: Sarah K. Tasian, Albert Assad, Deborah S Hunter, Yining Du, Mignon L. Loh
Journal: Blood (2018)
Abstract 19539: The Joining Region in Junctophilin-2 Modulates Excitation-contraction Coupling in Cardiomyocytes
Authors: Polina Gross, Jaslyn Johnson, Timothy S Gross, Xiongwen Chen, Steven Houser
Journal: Circulation (2017)

Background: Junctophilin-2 (JPN2) is a structural protein that stabilizes the cardiac dyads in the transverse tubules (T-T) by maintaining the precise space between plasma membrane (PM) and sarcopl...
Abstract IA04: Identification of new vulnerabilities in fusion-driven pediatric cancers with functional and chemical genomic approaches
Authors: Kimberly Stegmaier
Journal: Cancer Research (2018)

Abstract Fusion-driven pediatric cancers remain a therapeutic challenge. On one hand, the genomic simplicity of these malignancies and the tumor selectivity of their expressed fusion oncoproteins represent a therapeutic opportunity. These fusion oncoproteins, however, are typically transcription factors, and make for particularly challenging drug targets. Novel approaches to targeting these malignancies are needed. The EWS/ETS-driven pediatric solid tumor Ewing sarcoma is one exemplary childhood cancer. Our laboratory is integrating next-generation sequencing, functional genomic screening (shRNA and CRISPR/Cas9), and chemical genomic screening to identify, validate, and mechanistically dissect new targets in Ewing sarcoma. Emerging data from these efforts will be presented. Citation Format: Kimberly Stegmaier. Identification of new vulnerabilities in fusion-driven pediatric cancers with functional and chemical genomic approaches [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr IA04.
Targeting β3 Integrin Psi Domain Inhibits Both Platelet Aggregation and Blood Coagulation: Two Birds with One Stone
Authors: Tyler W. Stratton, Guangheng Zhu, Yiming Wang, Pingguo Chen, Miguel A. D. Neves, Reid C. Gallant, Peter A. A. Norris, John J. Freedman, Heyu Ni
Journal: Blood (2018)