tbuckley/cabot-search huggingface dataset:
Notch signaling dynamically regulates adult β cell proliferation and maturity
Authors: Alberto Bartolome, Changyu Zhu, Lori Sussel, Utpal B. Pajvani
Journal: Journal of Clinical Investigation (2018)

Notch signaling regulates differentiation of the pancreatic endocrine lineage during embryogenesis, but the role of Notch in mature β cells is unclear. We found that islets derived from lean mice show modest β cell Notch activity, which increases in obesity and in response to high glucose. This response appeared maladaptive, as mice with β cell-specific-deficient Notch transcriptional activity showed improved glucose tolerance when subjected to high-fat diet feeding. Conversely, mice with β cell-specific Notch gain of function (β-NICD) had a progressive loss of β cell maturity, due to proteasomal degradation of MafA, leading to impaired glucose-stimulated insulin secretion and glucose intolerance with aging or obesity. Surprisingly, Notch-active β cells had increased proliferative capacity, leading to increased but dysfunctional β cell mass. These studies demonstrate a dynamic role for Notch in developed β cells for simultaneously regulating β cell function and proliferation.
Abstract 12716: Is Pre Existing Atrial Fibrillation a Risk Factor for Contrast Induced Nephropathy After Cardiac Catheterization?
Authors: Yub Raj Sedhai, Tatvam Choksi, Ankush Asija, Waseem Ahangar, David Gevorgyan, Reshma Golamari, Madhura Borikar, Jose Missri
Journal: Circulation (2016)

Introduction: Identifying patients at risk is an important step in preventing contrast-induced nephropathy (CIN). Several risk factors have been previously identified. We investigated to determine the association of pre-existing atrial fibrillation (AF) with the development of CIN after cardiac catheterization. Methods: A retrospective chart review of 513 patients who underwent cardiac catheterization from June to December 2014 was done. Patients with end-stage renal disease (n=38) &amp; without pre-procedural serum creatinine (n=57) were excluded. Serum creatinine before the procedure &amp; each day for three days after the procedure was recorded. CIN was defined as an increase in serum creatinine by ≥25% or ≥0.5mg/dl from the pre-procedural value within 72 hours of contrast exposure. Chronic kidney disease (CKD) was defined as eGFR &lt;60ml/min calculated by modified diet in renal disease equation. Use of ICD 9 codes for atrial fibrillation &amp; congestive heart failure (CHF) in admission medical records was defined as pre-existing AF &amp; CHF. Results: A total of 418 patients (mean age 69.1 ± 13.8, 55% male and 45% female) were included in the study. 13% of patients had pre-existing AF, 27.9% had CHF &amp; 19.6% had CKD. 16 patients of the total 418 developed CIN. The mean incidence of CIN in the population studied was 3.8%. Higher incidence of CIN was seen in AF, CHF &amp; CKD groups when tested by univariate analysis &amp; chi-squared test. The incidence of CIN was 13.8% in AF group Vs. 2.3% in non-AF group (p&lt;0.001), 8.6% in CHF group Vs. 1.9% in non-CHF group (p&lt;0.01) &amp; 8.9% CKD group Vs. 2.4 % in non-CKD group (p&lt;0.002). In multivariate logistic regression analysis, development of CIN was strongly associated with pre-existing AF. AF had odds ratio (OR) 4.11, 95% confidence interval (CI) 1.40-12.07, p=0.01. CHF had OR = 2.67, 95% CI, 0.89-7.98, p=0.08. CKD had OR=3.94, 95% CI, (1.56-9.98), p=0.04. Conclusions: Pre-existing atrial fibrillation may have an association with higher risk of CIN after cardiac catheterization in addition to conventional risk factors.
Highly Diverse Hepatitis C Strains Detected in Sub‐Saharan Africa Have Unknown Susceptibility to Direct‐Acting Antiviral Treatments
Authors: Chris Davis, George S. Mgomella, Ana da Silva Filipe, Eric H. Frost, Genevieve Giroux, Joseph Hughes, Catherine Hogan, Pontiano Kaleebu, Gershim Asiki, John McLauchlan, Marc Niebel, Ponsiano Ocama, Cristina Pomila, Oliver G. Pybus, Jacques Pépin, Peter Simmonds, Joshua B. Singer, Vattipally B. Sreenu, Clara Wekesa, Elizabeth H. Young, Donald G. Murphy, Manj Sandhu, Emma C. Thomson
Journal: Hepatology (2018)

The global plan to eradicate hepatitis C virus (HCV) led by the World Health Organization outlines the use of highly effective direct‐acting antiviral drugs (DAAs) to achieve elimination by 2030. Identifying individuals with active disease and investigation of the breadth of diversity of the virus in sub‐Saharan Africa (SSA) is essential as genotypes in this region (where very few clinical trials have been carried out) are distinct from those found in other parts of the world. We undertook a population‐based, nested case‐control study in Uganda and obtained additional samples from the Democratic Republic of Congo (DRC) to estimate the prevalence of HCV, assess strategies for disease detection using serological and molecular techniques, and characterize genetic diversity of the virus. Using next‐generation and Sanger sequencing, we aimed to identify strains circulating in East and Central Africa. A total of 7,751 Ugandan patients were initially screened for HCV, and 20 PCR‐positive samples were obtained for sequencing. Serological assays were found to vary significantly in specificity for HCV. HCV strains detected in Uganda included genotype (g) 4k, g4p, g4q, and g4s and a newly identified unassigned g7 HCV strain. Two additional unassigned g7 strains were identified in patients originating from DRC (one partial and one full open reading frame sequence). These g4 and g7 strains contain nonstructural (ns) protein 3 and 5A polymorphisms associated with resistance to DAAs in other genotypes. Clinical studies are therefore indicated to investigate treatment response in infected patients. Conclusion : Although HCV prevalence and genotypes have been well characterized in patients in well‐resourced countries, clinical trials are urgently required in SSA, where highly diverse g4 and g7 strains circulate.
THU0540 Increased work capacity in chronic low back pain patients after a multidimensional program associated with decrease in fear and apprehension
Authors: M. Norberg, L. Belgrand
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Chronic low back pain has a high burden in our society. Almost 85% of he population would be affected from low back pain. Less than 10% would be chronic but they have an important economic impact since they have the highest costs. According to Vlayen, the kinesiophobia (avoidance of movement) is the most important prognostic factor when evaluating the return to work <h3>Objectives</h3> To study the importance of kinesiophobia, fear and anxiety in the chronic low back (CLB) pain patient and their relationship to workability after a multidimensional intensive treatment program. <h3>Methods</h3> We included 850 patients who had followed an outpatient program of functional restoration during 3 weeks. The program was composed of physical exercises, occupational therapy and psychological group discussions. They were followed over 1 year. Using different questionnaires (TSK -Tampa scale of Kinesiophobia, FABQ, Pact -subjective work capacity-, Phoda, SF 36), physical performances tests (muscular endurance: Shirado, Biering-Sörensen, Bruce; lumbar mobility, Pile lifting test) we analysed the important factors for their work capacity. <h3>Results</h3> There were a clear relationship between a decrease in kinesiophobia and an increase of work capacity. Globally, the work capacity increased from 41.2% to 79%. There were no long standing increases in muscular performances, but the important change appeared in the decrease in the physical part of FABQ (14 to 9/24) and the SF36 limitations physical health/emotional problems (19.4% to 51.8%/36 to 65.7%). <h3>Conclusions</h3> A multidimensional intensive program including approaches on fear and apprehension has an important impact on work capacity. This observation is important to take into count in creating functional restoration programs <h3>Disclosure of Interest</h3> None declared
Child and adolescent health in Europe: monitoring implementation of policies and provision of services
Authors: Aixa Y Alemán-Díaz, Sophia Backhaus, Lisa L Siebers, Obiora Chukwujama, Friederike Fenski, Christoph N Henking, Karolina Kaminska, Aigul Kuttumuratova, Martin W Weber
Journal: The Lancet Child & Adolescent Health (2018)
Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities
Authors: Mathew Suji Eapen, Philip M. Hansbro, Anna-Karin Larsson‑Callerfelt, Mohit K. Jolly, Stephen Myers, Pawan Sharma, Bernadette Jones, Md Atiqur Rahman, James Markos, Collin Chia, Josie Larby, Greg Haug, Ashutosh Hardikar, Heinrich C. Weber, George Mabeza, Vinicius Cavalheri, Yet H. Khor, Christine F. McDonald, Sukhwinder Singh Sohal
Journal: Drugs (2018)
PIK3CA, AKT1 MUTATION AND HER2 AMPLIFICATION GENE SIGNATURES (GS) SUGGEST PREDOMINANTLY NEGATIVE FEEDBACK INHIBITION OF PI3K/AKT PATHWAY IN HUMAN BREAST CANCER (BC).
Authors: S. Loi, B. Haibe-Kains, F. Lallemand, L. Pusztai, A. Tutt, C. E. Gillett, M. Piccart, W. A. Phillips, G. McArthur, C. Sotiriou
Journal: Annals of Oncology (2009)
Parents in science
Authors: Emily Perry, Kristin Tessmar-Raible, Florian Raible
Journal: Genome biology (2018)

As part of our Q&A series, Genome Biology spoke to four scientists about their personal experiences as parents in their careers to highlight the challenges of researchers having children and the support they need in this regard. Our participants also included a couple (Kristin Tessmar-Raible and Florian Raible), as we were interested to know whether both parents being active researchers can have an impact. One of our participants wishes to remain anonymous.
Development and validation of a renal risk score in ANCA-associated glomerulonephritis
Authors: Silke R. Brix, Mercedes Noriega, Pierre Tennstedt, Eik Vettorazzi, Martin Busch, Martin Nitschke, Wolfram J. Jabs, Fedai Özcan, Ralph Wendt, Martin Hausberg, Lorenz Sellin, Ulf Panzer, Tobias B. Huber, Rüdiger Waldherr, Helmut Hopfer, Rolf A.K. Stahl, Thorsten Wiech
Journal: Kidney International (2018)
Abstract 17654: The Soluble VEGF Receptor sFlt-1 Contributes to Impaired Neovascularization in Aged Mice
Authors: Guangxian Zhao, Limei Piao, Aiko Inoue, Masafumi Kuzuya, Xian Wu Cheng
Journal: Circulation (2017)

Introduction: The mechanism by which angiogenesis declines with aging is not fully understood. Soluble vascular endothelial growth factor receptor 1 (VEGFR1) form (sFlt1) contributes to endothelial...
Combination cancer immunotherapy targeting PD-1 and GITR can rescue CD8 <sup>+</sup> T cell dysfunction and maintain memory phenotype
Authors: Bei Wang, Wen Zhang, Vladimir Jankovic, Jacquelynn Golubov, Patrick Poon, Erin M. Oswald, Cagan Gurer, Joyce Wei, Ilyssa Ramos, Qi Wu, Janelle Waite, Min Ni, Christina Adler, Yi Wei, Lynn Macdonald, Tracey Rowlands, Susannah Brydges, Jean Siao, William Poueymirou, Douglas MacDonald, George D. Yancopoulos, Matthew A. Sleeman, Andrew J. Murphy, Dimitris Skokos
Journal: Science Immunology (2018)

Synergistic CD8 + T cell activation by antibodies to PD-1 and GITR in cancer immunotherapy depends on the CD226 costimulatory pathway.
Commentary regarding “on-orbit sleep problems of astronauts and countermeasures”
Authors: Joseph John Bevelacqua, Seyed Mohammad Javad Mortazavi
Journal: Military Medical Research (2018)

This commentary addresses the article by Wu et al. entitled “On-orbit sleep problems of astronauts and countermeasures”. In this article, the authors discussed the sleep problems of astronauts. Despite its challenging topic, the paper authored by Wu et al. has at least one major shortcoming. This issue is related to the observation that the sleep pattern of astronauts can be disturbed by light flash phenomenon. Since the first report by astronaut E.E. Aldrin in 1969, many astronauts have reported light flashes. These visually perceived flashes of light occurred in different shapes but they apparently moved across the visual field of astronauts and possibly caused, at least to some extent, sleep problems. Moreover, the countermeasures proposed by the authors may improve astronauts’ sleep pattern, but they do not address the root cause of the light flashes (i.e., heavy ion interactions outside the shielding provided by the Earth’s magnetosphere). A possible approach to reducing light flashes is available using the fact that much of the galactic cosmic radiation (GCR) spectrum is composed of ions that can be diverted from the spacecraft using electromagnetic fields. Possible design parameters and the requisite electric and magnetic field strengths to successfully deflect GCR radiation are outlined.
Redistributing Investment in Health and Social Services—The Evolving Role of Managed Care
Authors: William H. Shrank, Donna J. Keyser, John G. Lovelace
Journal: JAMA (2018)

This Viewpoint discusses the increasing investments managed care organizations are making in social services to improve members' health and decrease costs, and argues that the trend could free up resources for investment in the health of groups not covered by managed care plans.
An airway epithelial IL-17A response signature identifies a steroid-unresponsive COPD patient subgroup
Authors: Stephanie A. Christenson, Maarten van den Berge, Alen Faiz, Kai Inkamp, Nirav Bhakta, Luke R. Bonser, Lorna T. Zlock, Igor Z. Barjaktarevic, R. Graham Barr, Eugene R. Bleecker, Richard C. Boucher, Russell P. Bowler, Alejandro P. Comellas, Jeffrey L. Curtis, MeiLan K. Han, Nadia N. Hansel, Pieter S. Hiemstra, Robert J. Kaner, Jerry A. Krishnanm, Fernando J. Martinez, Wanda K. O’Neal, Robert Paine, Wim Timens, J. Michael Wells, Avrum Spira, David J. Erle, Prescott G. Woodruff
Journal: Journal of Clinical Investigation (2018)

BACKGROUND. Chronic obstructive pulmonary disease (COPD) is a heterogeneous smoking-related disease characterized by airway obstruction and inflammation. This inflammation may persist even after smoking cessation and responds variably to corticosteroids. Personalizing treatment to biologically similar "molecular phenotypes" may improve therapeutic efficacy in COPD. IL-17A is involved in neutrophilic inflammation and corticosteroid resistance, and thus may be particularly important in a COPD molecular phenotype.
Primary lung cancer in patients with previous malignancies: a nationwide study
Authors: Onno M Mets, Cornelia M Schaefer-Prokop, Pim A de Jong
Journal: Thorax (2018)

Overall survival of patients with cancer continues to increase and so they receive more frequent CT imaging, making oncological patients a growing population that effectively receives lung cancer screening in the course of daily practice. However, it is currently uncertain how early lung cancer detection in this subgroup of patients should be optimally managed. We describe the relationship between primary lung cancer and prior malignancies in a nationwide cohort, in an attempt to identify possible areas of improvement in nodule management. We found that a substantial number of subjects with lung cancer suffered from a prior malignancy; however, with the exception of otorhinolaryngeal malignancies, they did not show a high absolute risk for lung cancer. Future research should provide more data on how to handle this subgroup of patients in clinical and screening setting.
Multicenter, randomized, double-blind, placebo-controlled clinical trial of vital wheat gluten oral immunotherapy
Authors: Anna Nowak-Węgrzyn, Robert A. Wood, Kari C. Nadeau, Jacqueline A. Pongracic, Alice K. Henning, Robert W. Lindblad, Kirsten Beyer, Hugh A. Sampson
Journal: Journal of Allergy and Clinical Immunology (2018)
Alternative State-Level Financing for Hepatitis C Treatment—The “Netflix Model”
Authors: Mark R. Trusheim, William M. Cassidy, Peter B. Bach
Journal: JAMA (2018)

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
Upfront allogeneic hematopoietic cell transplantation (HCT) versus remission induction chemotherapy followed by allogeneic HCT for acute myeloid leukemia with multilineage dysplasia: A propensity score matched analysis
Authors: Takaaki Konuma, Kaito Harada, Satoshi Yamasaki, Shohei Mizuno, Naoyuki Uchida, Satoshi Takahashi, Makoto Onizuka, Hirohisa Nakamae, Michihiro Hidaka, Takahiro Fukuda, Kazuteru Ohashi, Akio Kohno, Akiko Matsushita, Heiwa Kanamori, Takashi Ashida, Junya Kanda, Yoshiko Atsuta, Shingo Yano
Journal: American Journal of Hematology (2018)

The efficacy of induction chemotherapy before allogeneic hematopoietic cell transplantation (HCT) for patients with acute myeloid leukemia with multilineage dysplasia (AML-MLD) is unclear. Some patients with AML-MLD have received upfront HCT without prior induction chemotherapy. To compare the transplant outcomes between patients who received upfront HCT and those who received induction chemotherapy followed by allogeneic HCT for AML-MLD, we retrospectively analyzed the Japanese registration data of 1445 adult patients who had received allogeneic HCT between 2007 and 2016. Propensity score matching identified 269 patients in each cohort. There were no significant differences in overall survival between the two groups. The cumulative incidence of leukemia-related mortality was significantly lower in patients who received upfront HCT than those who received induction chemotherapy before HCT. In the subgroup analyses, upfront HCT had a significantly reduced incidence of leukemia-related mortality among patients aged between 60 and 70 years, those with a lower white blood cell count at diagnosis (<3000/μL), and poor cytogenetic risk, and those who received myeloablative conditioning and cord blood transplantation. Our results suggested that induction chemotherapy before HCT did not have any benefits of survival after HCT for AML-MLD. Upfront HCT contributed to the reduced incidence of leukemia-related mortality after HCT. Upfront HCT should be considered for patients with AML-MLD who are eligible for allogeneic HCT.
Compulsory community treatment to reduce readmission to hospital and increase engagement with community care in people with mental illness: a systematic review and meta-analysis
Authors: Phoebe Barnett, Hannah Matthews, Brynmor Lloyd-Evans, Euan Mackay, Stephen Pilling, Sonia Johnson
Journal: The Lancet Psychiatry (2018)

Compulsory community treatment (CCT) aims to reduce hospital readmissions among people with mental illness. However, research examining the usefulness of CCT is inconclusive. We aimed to assess the effectiveness of CCT in reducing readmission and length of stay in hospital and increasing community service use and treatment adherence.For this systematic review and meta-analysis, we searched three databases (PsycINFO, MEDLINE and Embase) for quantitative studies on CCT published in English between Jan 1, 1806, and Jan 4, 2018. We included both randomised and non-randomised designs that compared CCT with no CCT, and pre-post designs that compared patients before and after CCT. Studies were eligible if they had been peer-reviewed, if 50% or more of patients had severe mental illness, and if CCT was the intervention. Trials in which CCT was used in response to a criminal offence were excluded. We extracted data on study characteristics and length of follow-up, patient-level data on diagnosis, age, sex, race, and admission history, and outcomes of interest (readmission to hospital, inpatient bed-days, community service use, and treatment adherence) for meta-analysis, for which we extracted summary estimates. We used a random-effects model to compare disparate outcome measures and convert effect size statistics into standardised mean differences. This systematic review is registered with PROSPERO, number CRD42018086232.Of 1931 studies identified, 41 (2%) met inclusion criteria and had sufficient data for analysis. Before and after CCT comparisons showed significant large effects on readmission to hospital (standardised mean difference 0·80, 95% CI 0·53-1·08; I2=94·74), use of community services (0·83, 0·46-1·21; I2=87·26), and treatment adherence (2·12, 1·69-2·55; I2=0), and a medium effect on inpatient bed-days (0·66, 0·46-0·85; I2=94·12). Contemporaneous controlled comparison studies (randomised and non-randomised) showed no significant effect on readmission, inpatient bed-days, or treatment adherence, but a moderate effect on use of community services (0·38, 0·19-0·58; I2=96·92). A high degree of variability in study quality was found, with observational study ratings ranging from three to nine. Bias most frequently centred on poor comparability between CCT and control participants.We found no consistent evidence that CCT reduces readmission or length of inpatient stay, although it might have some benefit in enforcing use of outpatient treatment or increasing service provision, or both. Future research should focus on why some people do not engage with treatment offered and on enhancing quality of the community care available. Shortcomings of this study include high levels of variability between studies and variation in study quality.National Institute for Health Research.