tbuckley/cabot-search huggingface dataset:
Association of MicroRNAs and YRNAs With Platelet Function
Authors: Dorothee Kaudewitz, Philipp Skroblin, Lukas H. Bender, Temo Barwari, Peter Willeit, Raimund Pechlaner, Nicholas P. Sunderland, Karin Willeit, Allison C. Morton, Paul C. Armstrong, Melissa V. Chan, Ruifang Lu, Xiaoke Yin, Filipe Gracio, Katarzyna Dudek, Sarah R. Langley, Anna Zampetaki, Emanuele de Rinaldis, Shu Ye, Timothy D. Warner, Alka Saxena, Stefan Kiechl, Robert F. Storey, Manuel Mayr
Journal: Circulation Research (2015)

Rationale: Platelets shed microRNAs (miRNAs). Plasma miRNAs change on platelet inhibition. It is unclear whether plasma miRNA levels correlate with platelet function. Objective: To link small RNAs to platelet reactivity. Methods and Results: Next-generation sequencing of small RNAs in plasma revealed 2 peaks at 22 to 23 and 32 to 33 nucleotides corresponding to miRNAs and YRNAs, respectively. Among YRNAs, predominantly, fragments of RNY4 and RNY5 were detected. Plasma miRNAs and YRNAs were measured in 125 patients with a history of acute coronary syndrome who had undergone detailed assessment of platelet function 30 days after the acute event. Using quantitative real-time polymerase chain reactions, 92 miRNAs were assessed in patients with acute coronary syndrome on different antiplatelet therapies. Key platelet-related miRNAs and YRNAs were correlated with platelet function tests. MiR-223 ( r p =0.28; n=121; P =0.002), miR-126 ( r p =0.22; n=121; P =0.016), and other abundant platelet miRNAs and YRNAs showed significant positive correlations with the vasodilator-stimulated phosphoprotein phosphorylation assay. YRNAs, miR-126, and miR-223 were also among the small RNAs showing the greatest dependency on platelets and strongly correlated with plasma levels of P-selectin, platelet factor 4, and platelet basic protein in the population-based Bruneck study (n=669). A single-nucleotide polymorphism that facilitates processing of pri-miR-126 to mature miR-126 accounted for a rise in circulating platelet activation markers. Inhibition of miR-126 in mice reduced platelet aggregation. MiR-126 directly and indirectly affects ADAM9 and P2Y 12 receptor expression. Conclusions: Levels of platelet-related plasma miRNAs and YRNAs correlate with platelet function tests in patients with acute coronary syndrome and platelet activation markers in the general population. Alterations in miR-126 affect platelet reactivity.
Mitochondrial DNA-LL-37 Complex Promotes Atherosclerosis by Escaping from Autophagic Recognition
Authors: Zhiye Zhang, Ping Meng, Yajun Han, Chuanbin Shen, Bowen Li, Md Abdul Hakim, Xuguang Zhang, Qiumin Lu, Mingqiang Rong, Ren Lai
Journal: Immunity (2015)
Young adults with hemophilia in the U.S.: demographics, comorbidities, and health status
Authors: Randall Curtis, Judith Baker, Brenda Riske, Megan Ullman, Xiaoli Niu, Kristi Norton, Mimi Lou, Michael B. Nichol
Journal: American Journal of Hematology (2015)

Improvements in hemophilia care over the last several decades might lead to expectations of a near‐normal quality of life for young adults with hemophilia. However, few published reports specifically examine health status indicators in this population. To remedy this knowledge gap, we examined the impact of hemophilia on physical and social functioning and quality of life among a national US cohort of 141 young men with hemophilia aged 18–34 years of age who received care at 10 geographically diverse, federally funded hemophilia treatment centers in 11 states between 2005 and 2013 and enrolled in the Hemophilia Utilization Group Studies. Indicators studied included educational achievement, employment status, insurance, health‐related quality of life, and prevalence of the following comorbidities: pain, range of motion limitation, overweight/obesity, and viral status. The cohort was analyzed to compare those aged 18–24 to those aged 25–34 years. When compared to the general US adult population, this nationally representative cohort of young US adults with hemophilia experienced significant health and social burdens: more liver disease, joint damage, joint pain, and unemployment as well as lower high‐school graduation rates. Nearly half were overweight or obese. Conversely, this cohort had higher levels of health insurance and equivalent mental health scores. While attention has typically focused on newborns, children, adolescents, and increasingly, on older persons with hemophilia, our findings suggest that a specific focus on young adults is warranted to determine the most effective interventions to improve health and functioning for this apparently vulnerable age group. Am. J. Hematol. 90:S11–S16, 2015. © 2015 Wiley Periodicals, Inc.
Dengue cases in India doubled in 2014-15
Authors: Cheryl Travasso
Journal: BMJ (2015)

While the number of malaria cases in India fell from 1 102 205 in 2014 to 792 234 in 2015 (to September), the number of dengue cases doubled from 40 571 to 84 391 over much the same period (to 15 November).1

A large increase in dengue cases in the past year was seen in several states and territories including Delhi (up from 995 to 15 531), Punjab (472 to 12 628), Haryana (214 to 8021), and West Bengal (3934 to 5703). In other states the number of cases fell, including in Odisha (6433 to 2167) and Maharashtra (8573 to 3461).

Cases of malaria dropped …
Crizotinib Synergizes with Chemotherapy in Preclinical Models of Neuroblastoma
Authors: Kateryna Krytska, Hannah T. Ryles, Renata Sano, Pichai Raman, Nicole R. Infarinato, Theodore D. Hansel, Monish R. Makena, Michael M. Song, C. Patrick Reynolds, Yael P. Mossé
Journal: Clinical Cancer Research (2015)

The presence of an ALK aberration correlates with inferior survival for patients with high-risk neuroblastoma. The emergence of ALK inhibitors such as crizotinib has provided novel treatment opportunities. However, certain ALK mutations result in de novo crizotinib resistance, and a phase I trial of crizotinib showed a lack of response in patients harboring those ALK mutations. Thus, understanding mechanisms of resistance and defining circumvention strategies for the clinic is critical.The sensitivity of human neuroblastoma-derived cell lines, cell line-derived, and patient-derived xenograft (PDX) models with varying ALK statuses to crizotinib combined with topotecan and cyclophosphamide (topo/cyclo) was examined. Cultured cells and xenografts were evaluated for effects of these drugs on proliferation, signaling, and cell death, and assessment of synergy.In neuroblastoma murine xenografts harboring the most common ALK mutations, including those mutations associated with resistance to crizotinib (but not in those with wild-type ALK), crizotinib combined with topo/cyclo enhanced tumor responses and mouse event-free survival. Crizotinib + topo/cyclo showed synergistic cytotoxicity and higher caspase-dependent apoptosis than crizotinib or topo/cyclo alone in neuroblastoma cell lines with ALK aberrations (mutation or amplification).Combining crizotinib with chemotherapeutic agents commonly used in treating newly diagnosed patients with high-risk neuroblastoma restores sensitivity in preclinical models harboring both sensitive ALK aberrations and de novo-resistant ALK mutations. These data support clinical testing of crizotinib and conventional chemotherapy with the goal of integrating ALK inhibition into multiagent therapy for ALK-aberrant neuroblastoma patients.
Classification of antituberculosis drugs: a new proposal based on the most recent evidence
Authors: Jose A. Caminero, Anna Scardigli
Journal: European Respiratory Journal (2015)

Multidrug-resistant (MDR) tuberculosis (TB) (resistance to at least isoniazid and rifampicin), with >480 000 cases in 2013, 10% of them being affected by extensively drug-resistant (XDR)-TB (MDR-TB with additional resistance to any fluoroquinolone, and to injectable second-line drugs (SLDs) (capreomycin, kanamycin or amikacin)), continues to represent a real threat to TB control [1–4]. In some high MDR-TB burden countries, the prevalence of MDR-TB among new cases exceeds 20% and among retreatment cases, reaches almost 50% [1, 5]. The classification of the anti-TB drugs should probably be modified to optimise the use old and new compounds <http://ow.ly/QbDSP> The authors wish to thank R. Centis and L. D'Ambrosio (WHO Collaborating Centre for TB and Lung Disease, Tradate, Italy) for their editorial and technical support. The authors alone are responsible for the views expressed in this publication and they do not necessarily represent the decisions or policies of their institutions.
The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia
Authors: M Díaz-Beyá, S Brunet, J Nomdedéu, A Cordeiro, M Tormo, L Escoda, J M Ribera, M Arnan, I Heras, D Gallardo, J Bargay, M P Queipo de Llano, O Salamero, J M Martí, A Sampol, C Pedro, M Hoyos, M Pratcorona, J J Castellano, M Nomdedeu, R M Risueño, J Sierra, M Monzó, A Navarro, J Esteve
Journal: Blood Cancer Journal (2015)

Abstract Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (⩾60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC , its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival ( P =0.0025), shorter leukemia-free survival ( P =0.026) and higher cumulative incidence of relapse ( P =0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers ( P =0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML.
Developing a Risk Model for In-Hospital Adverse Events Following Implantable Cardioverter-Defibrillator Implantation
Authors: John A. Dodson, Matthew R. Reynolds, Haikun Bao, Sana M. Al-Khatib, Eric D. Peterson, Mark S. Kremers, Michael J. Mirro, Jeptha P. Curtis
Journal: Journal of the American College of Cardiology (2013)
Bendamustine plus rituximab versus fludarabine plus rituximab for patients with relapsed indolent and mantle-cell lymphomas: a multicentre, randomised, open-label, non-inferiority phase 3 trial
Authors: Mathias Rummel, Ulrich Kaiser, Christina Balser, Martina Stauch, Wolfram Brugger, Manfred Welslau, Norbert Niederle, Christoph Losem, Hans-Peter Boeck, Eckhart Weidmann, Ulrich von Gruenhagen, Lothar Mueller, Michael Sandherr, Lars Hahn, Julia Vereshchagina, Frank Kauff, Wolfgang Blau, Axel Hinke, Juergen Barth
Journal: The Lancet Oncology (2015)
Ipilimumab-Induced Hypophysitis and Uveitis in a Patient With Metastatic Melanoma and a History of Ipilimumab-Induced Skin Rash
Authors: Neelima N. Nallapaneni, Rajesh Mourya, Vijaya Raj Bhatt, Sakshi Malhotra, Apar Kishor Ganti, Ketki K. Tendulkar
Journal: Journal of the National Comprehensive Cancer Network (2014)

Ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen-4, leading to enhanced T-cell activation and proliferation, is associated with improved overall survival in melanoma. Its use can result in immune-related adverse events, the most common of which are skin rash, diarrhea, and colitis. Ipilimumab-induced hypophysitis is uncommon, mostly involves anterior pituitary, and is associated with abnormalities in pituitary MRI, whereas uveitis has been rarely reported. These immune-related adverse events occur during therapy. This report describes a patient who developed uveitis and hypophysitis involving both anterior and posterior pituitary, without MRI findings more than 3 weeks after the fourth dose of ipilimumab. This case illustrates the unusual presentation of and diagnostic challenges associated with ipilimumab-induced immune-related adverse events.
Delayed Initiation of Adjuvant Chemotherapy Among Patients With Breast Cancer
Authors: Mariana Chavez-MacGregor, Christina A. Clarke, Daphne Y. Lichtensztajn, Sharon H. Giordano
Journal: JAMA Oncology (2015)

Adjuvant chemotherapy improves outcomes of patients with breast cancer. However, the optimal timing of chemotherapy initiation is unknown. Delayed administration can decrease the benefit of cytotoxic systemic therapies.
Mind the Gap: Why Closing the Doughnut Hole Is Insufficient for Increasing Medicare Beneficiary Access to Oral Chemotherapy
Authors: Stacie B. Dusetzina, Nancy L. Keating
Journal: Journal of Clinical Oncology (2015)

Orally administered anticancer medications are among the fastest growing components of cancer care. These medications are expensive, and cost-sharing requirements for patients can be a barrier to their use. For Medicare beneficiaries, the Affordable Care Act will close the Part D coverage gap (doughnut hole), which will reduce cost sharing from 100% in 2010 to 25% in 2020 for drug spending above $2,960 until the beneficiary reaches $4,700 in out-of-pocket spending. How much these changes will reduce out-of-pocket costs is unclear.We used the Medicare July 2014 Prescription Drug Plan Formulary, Pharmacy Network, and Pricing Information Files from the Centers for Medicare & Medicaid Services for 1,114 stand-alone and 2,230 Medicare Advantage prescription drug formularies, which represent all formularies in 2014. We identified orally administered anticancer medications and summarized drug costs, cost-sharing designs used by available plans, and the estimated out-of-pocket costs for beneficiaries without low-income subsidies who take a single drug before and after the doughnut hole closes.Little variation existed in formulary design across plans and products. The average price per month for included products was $10,060 (range, $5,123 to $16,093). In 2010, median beneficiary annual out-of-pocket costs for a typical treatment duration ranged from $6,456 (interquartile range, $6,433 to $6,482) for dabrafenib to $12,160 (interquartile range, $12,102 to $12,262) for sunitinib. With the assumption that prices remain stable, after the doughnut hole closes, beneficiaries will spend approximately $2,550 less.Out-of-pocket costs for Medicare beneficiaries taking orally administered anticancer medications are high and will remain so after the doughnut hole closes. Efforts are needed to improve affordability of high-cost cancer drugs for beneficiaries who need them.
Neural constraints and flexibility in language processing
Authors: Christian R. Huyck
Journal: Behavioral and Brain Sciences (2016)

Abstract Humans process language with their neurons. Memory in neurons is supported by neural firing and by short- and long-term synaptic weight change; the emergent behaviour of neurons, synchronous firing, and cell assembly dynamics is also a form of memory. As the language signal moves to later stages, it is processed with different mechanisms that are slower but more persistent.
Communicating With Patients—The Other Side of the Conversation
Authors: Anne Micheaux Akwari
Journal: JAMA Internal Medicine (2015)

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 Internal Medicine 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 Internal Medicine journal
Effect of a Single Dose of N-Diethylnitrosamine on the Rat Kidney
Authors: U. Mohr, J. Hilfrich
Journal: JNCI Journal of the National Cancer Institute (1972)

Journal Article Effect of a Single Dose of N-Diethylnitrosamine on the Rat Kidney Get access U. Mohr, U. Mohr Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Hilfrich J. Hilfrich Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 49, Issue 6, December 1972, Pages 1729–1731, https://doi.org/10.1093/jnci/49.6.1729 Published: 01 December 1972 Article history Received: 23 May 1972 Revision received: 06 September 1972 Accepted: 08 September 1972 Published: 01 December 1972
Length of hospital stay after hip fracture and risk of early mortality after discharge in New York state: retrospective cohort study
Authors: Lucas E Nikkel, Stephen L Kates, Michael Schreck, Michael Maceroli, Bilal Mahmood, John C Elfar
Journal: BMJ (2015)

<b>Study question</b> Can the length of hospital stay for hip fracture affect a patient's risk of death 30 days after discharge? <b>Methods</b> In a retrospective cohort study, population based registry data from the New York Statewide Planning and Research Cooperative System (SPARCS) were used to investigate 188 208 patients admitted to hospital for hip fracture in New York state from 2000 to 2011. Patients were aged 50 years and older, and received surgical or non-surgical treatment. The main outcome measure was the mortality rate at 30 days after hospital discharge. <b>Study answer and limitations</b> Hospital stays of 11-14 days for hip fracture were associated with a 32% increased odds of death 30 days after discharge, compared with stays lasting one to five days (odds ratio 1.32 (95% confidence interval 1.19 to 1.47)). These odds increased to 103% for stays longer than 14 days (2.03 (1.84 to 2.24)). Other risk factors associated with early mortality included discharge to a hospice facility, older age, metastatic disease, and non-surgical management. The 30 day mortality rate after discharge was 4.5% for surgically treated patients and 10.7% for non-surgically treated patients. These findings might not be generalizable to populations in other US states or in other countries. The administrative claims data used could have been incomplete or include inaccurate coding of diagnoses and comorbid conditions. The database also did not include patient socioeconomic status, which could affect access to care to a greater extent in New York state than in European countries. Specific cause of death was not available because few autopsies are performed in this population. <b>What this study adds</b> By contrast with recent findings in Sweden, decreased length of hospital stay for hip fracture was associated with reduced rates of early mortality in a US cohort in New York state. This could reflect critical system differences in the treatment of hip fractures between Europe and the USA. <b>Funding, competing interests, data sharing</b> University of Rochester grant from the Clinical Translational Science Institute for statistical analyses used in this work (National Institutes of Health (UL1 TR000042)) and the National Institutes of Health (K-08 AR060164-01A). No competing interests declared. Data may be obtained through SPARCS at https://www.health.ny.gov/statistics/sparcs/access/.
Time for a quality check before recruiting patients
Authors: Knut A Holtedahl, Eivind Meland
Journal: BMJ (2007)

We select the letters for these pages from the rapid responses posted on bmj.com favouring those received within five days of publication of the article to which they refer.Letters are thus an early selection of rapid responses on a particular topic.Readers should consult the website for the full list of responses and any authors' replies, which usually arrive after our selection. DeciDing on caesarean section Vaginal birth after a caesarean is not always beneficialThe study by Montgomery et al and the accompanying editorial are based on the premise that vaginal delivery after one caesarean section is necessarily a beneficial and desirable objective or outcome. 1 2 However, the box shows the risks and benefits as published in the recent RCOG (Royal College of Obstetricians and Gynaecologists) guidelines. 3 Given that most women in developed countries are unlikely to have more than two to three babies, the value of promoting vaginal delivery after one caesarean section is highly questionable.Women with a breech presentation are no longer offered a choice between vaginal delivery and caesarean section on the basis of the results of the term breech trial. 4 Must we wait for such a trial to recognise that vaginal delivery after one caesarean section costs lives and caesarean section saves lives?Women should have a choice, but this should not come before safety.To promote a process that is known to be associated with greater mortality and morbidity, or consider such a process as beneficial or desirable seems inappropriate irrespective of the reduction in women's anxiety.
Antigen-specific T cells conditioned with MDSC display a surprising increased anti-tumor activity after adoptive T cell-based immunotherapy
Authors: Patrick Raber, Paul Thevenot, Rosa Sierra, Paulo C Rodriguez
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The success of adoptive T cell-based immunotherapy (ACT) in cancer is limited in part by the accumulation of myeloid-derived suppressor cells (MDSC), which block several T cell functions, including proliferation and expression of effector mediators. Paradoxically, inhibition of
Expanding Phenotypic Spectrum of<i>NKX2-1</i>–Related Disorders—Mitochondrial and Immunologic Dysfunction
Authors: Elizabeth A. Coon, J. Eric Ahlskog, Marc C. Patterson, Zhiyv Niu, Margherita Milone
Journal: JAMA Neurology (2015)

NKX2-1-related disorders.Recurrent fevers in NKX2-1 are considered a hypothalamic symptom, but our patient had evidence of meningitis.Additionally, her history of IgA nephropathy and Henoch-Schönlein purpura suggests an immunologic dysfunction.NKX2-1 regulates inflammatory pathways in the lung 6 and could similarly affect inflammatory responses in the brain.NKX2-1 also represses NR1D1, which may be involved in regulating metabolic and inflammatory processes, offering potential mechanisms for immunologic dysfunction.In this family, whole-exome sequencing was an effective tool to diagnose a multisystem disorder, broadening the phenotypic spectrum of NKX2-1 mutations.