tbuckley/cabot-search huggingface dataset:
Five-Year Follow-up of Nonfibrotic Scars in the Comparison of Age-Related Macular Degeneration Treatments Trials
Authors: Ebenezer Daniel, Gui-shuang Ying, Benjamin J. Kim, Cynthia A. Toth, Frederick Ferris, Daniel F. Martin, Juan E. Grunwald, Glenn J. Jaffe, Joshua L. Dunaief, Wei Pan, Maureen G. Maguire
Journal: Ophthalmology (2018)
Phosphatidylinositol 3-Kinase, Growth Disorders, and Cancer
Authors: Marcus D. Goncalves, Benjamin D. Hopkins, Lewis C. Cantley
Journal: New England Journal of Medicine (2018)

Phosphatidylinositol 3-kinase (PI3K) is involved in multiple cell processes, including insulin signaling, cell growth, immunity, and brain development. It is activated in a wide variety of cancers and is being targeted as a treatment, with notable success in lymphoma.
Trajectory of Excess Medical Expenditures 10 Years Before and After Diabetes Diagnosis Among U.S. Adults Aged 25–64 Years, 2001–2013
Authors: Sundar S. Shrestha, Ping Zhang, Israel A. Hora, Edward W. Gregg
Journal: Diabetes Care (2018)

OBJECTIVE We assessed the excess medical expenditures for adults newly diagnosed with diabetes, for up to 10 years before and after diabetes diagnosis. RESEARCH DESIGN AND METHODS Using the 2001–2013 MarketScan data, we identified people with newly diagnosed diabetes among adults aged 25–64 years (diabetes cohort) and matched them with people who did not have diagnosed diabetes (control cohort) using 1:1 propensity score matching. We followed these two cohorts up to ±10 years from the index date, with annual matched cohort sizes ranging from 3,922 to 39,726 individuals. We estimated the yearly and cumulative excess medical expenditures of the diabetes cohorts before and after the diagnosis of diabetes. RESULTS The per capita annual total excess medical expenditure for the diabetes cohort was higher for the entire 10 years prior to their index date, ranging between $1,043 in year −10 and $4,492 in year −1. Excess expenditure spiked in year 1 ($8,109), declined in year 2, and then increased steadily, ranging from $4,261 to $6,162 in years 2–10. The cumulative excess expenditure for the diabetes cohort during the entire 20 years of follow-up was $69,177 ($18,732 before and $50,445 after diagnosis). CONCLUSIONS People diagnosed with diabetes had higher medical expenditures compared with their counterparts, not only after diagnosis but also up to 10 years prior to diagnosis. Managing risk factors for type 2 diabetes and cardiovascular disease before diagnosis, and for diabetes-related complications after diagnosis, could alleviate medical expenditure in people with diabetes.
Blocking HIV-1 replication: are Fc–Fcγ receptor interactions required?
Authors: Donald Forthal, Andrés Finzi
Journal: Journal of Clinical Investigation (2018)

Interactions between IgG Fc and its receptors (FcγRs) have been shown to augment broadly neutralizing Ab-mediated (BnAb-mediated) protection from simian-human immunodeficiency virus (SHIV) challenge. In the current issue of the JCI, Parsons and collaborators compared the BnAb PGT121 with a version engineered to have impaired FcγR binding for their ability to protect macaques from an intravenous challenge with SHIV-infected cells as well as to treat already infected animals. Unexpectedly, and in contrast to previous studies, both versions of the Ab were equally able to prevent infection and decrease viral loads in infected animals. Thus, FcγR engagement does not always improve the in vivo antiviral activity of BnAbs.
<i>FLI1</i> Exonic Circular RNAs as a Novel Oncogenic Driver to Promote Tumor Metastasis in Small Cell Lung Cancer
Authors: Lingyu Li, Wei Li, Naifei Chen, Haixin Zhao, Guang Xu, Yijing Zhao, Xin Pan, Xiaoying Zhang, Lei Zhou, Dehai Yu, Ailing Li, Ji-Fan Hu, Jiuwei Cui
Journal: Clinical Cancer Research (2018)

Abstract Purpose: The aberrantly upregulated Friend leukemia virus integration 1 (FLI1) is closely correlated with the malignant phenotype of small cell lung cancer (SCLC). It is interesting to note that the CRISPR gene knockout by Cas9 gRNAs that target the FLI1 coding region and the posttranscriptional knockdown by shRNAs that target the 3′ region of FLI1 mRNA yielded distinct antimetastasis effects in SCLC cells. This study attempts to examine if FLI1 exonic circular RNAs (FECR) function as a new malignant driver that determines the metastatic phenotype in SCLC. Experimental Design: The clinical relevance of FECRs was examined in 56 primary SCLC tissues and 50 non–small cell lung cancer (NSCLC) tissues. The prognostic value of FECRs was examined by measuring serum exosomal FECRs in a longitudinal cohort of patients with SCLC. The oncogenic activity of FECRs was investigated in both SCLC cell lines and animal xenograft studies. Finally, we explored the molecular mechanisms underlying these noncoding RNAs as a malignant driver. Results: Therapeutic comparison of CRISPR Cas9 knockout and shRNA knockdown of FLI1 identified FECRs as a new noncanonical malignant driver in SCLC. Using RNA FISH and quantitative PCR, we found that FECR1 (exons 4-2-3) and FECR2 (exons 5-2-3-4) were aberrantly upregulated in SCLC tissues (P &amp;lt; 0.0001), and was positively associated with lymph node metastasis (P &amp;lt; 0.01). Notably, serum exosomal FECR1 was associated with poor survival (P = 0.038) and clinical response to chemotherapy. Silencing of FECRs significantly inhibited the migration in two highly aggressive SCLC cell lines and reduced tumor metastasis in vivo. Mechanistically, we uncovered that FECRs sequestered and subsequently inactivated tumor suppressor miR584-3p, leading to the activation of the Rho Associated Coiled-Coil Containing Protein Kinase 1 gene (ROCK1). Conclusions: This study identifies FLI1 exonic circular RNAs as a new oncogenic driver that promotes tumor metastasis through the miR584–ROCK1 pathway. Importantly, serum exosomal FECR1 may serve as a promising biomarker to track disease progression of SCLC.
Quantitative Analysis of the Whole-Body Metabolic Fate of Branched-Chain Amino Acids
Authors: Michael D. Neinast, Cholsoon Jang, Sheng Hui, Danielle S. Murashige, Qingwei Chu, Raphael J. Morscher, Xiaoxuan Li, Le Zhan, Eileen White, Tracy G. Anthony, Joshua D. Rabinowitz, Zoltan Arany
Journal: Cell Metabolism (2018)
Impact of pneumococcal conjugate vaccines introduction on antibiotic resistance of Streptococcus pneumoniae meningitis in children aged 5 years or younger, Israel, 2004 to 2016
Authors: Shalom Ben-Shimol, Noga Givon-Lavi, David Greenberg, Michal Stein, Orli Megged, Avihu Bar-Yochai, Shahar Negari, Ron Dagan
Journal: Eurosurveillance (2018)

Background Empiric treatment of pneumococcal meningitis includes ceftriaxone with vancomycin to overcome ceftriaxone resistant disease. The addition of vancomycin bears a risk of adverse events, including increased antibiotic resistance. We assessed antibiotic resistance rates in pneumococcal meningitis before and after pneumococcal conjugate vaccine (PCV) implementation. Methods All pneumococcal meningitis episodes in children aged 5 years and younger, from 2004 to 2016, were extracted from the nationwide bacteremia and meningitis surveillance database. For comparison purposes, we defined pre-PCV period as 2004–2008 and PCV13 period as 2014–2016. Minimal inhibitory concentration (MIC) &gt; 0.06 and &gt; 0.5 μg/mL were defined as penicillin and ceftriaxone resistance, respectively. Results Overall, 325 episodes were identified. Pneumococcal meningitis incidence rates declined non-significantly by 17%, comparing PCV13 and pre-PCV periods. Throughout the study, 90% of isolates were tested for antibiotic susceptibility, with 26.6%, 2.1% and 0% of isolates resistant to penicillin, ceftriaxone and vancomycin, respectively. Mean proportions (± SD) of meningitis caused by penicillin-resistant pneumococci were 40.5% ± 8.0% and 9.6% ± 7.4% in the pre-PCV and the PCV13 periods, respectively, resulting in an overall 83.9% reduction (odd ratio:0.161; 95% confidence interval: 0.059–0.441) in penicillin resistance rates. The proportions of meningitis caused by ceftriaxone resistant pneumococci were 5.0% ± 0.8% in the pre-PCV period, but no ceftriaxone resistant isolates were identified since 2010. Conclusions PCV7/PCV13 sequential introduction resulted in &gt; 80% reduction of penicillin- resistant pneumococcal meningitis and complete disappearance of ceftriaxone resistant disease. These trends should be considered by the treating physician when choosing an empiric treatment for pneumococcal meningitis.
Gene expression profiling of cultured squamous cell carcinoma keratinocytes identifies a pattern of gene expression which predicts invasive capacity
Authors: A. P. South, C. Pourreyron, J. Foerster, X. Mao, K. Purdie, C. Hogan, C. Mein, L. Bruckner-Tuderman, C. M. Proby, B. Young, D. P. Kelsell, J. A. McGrath, I. M. Leigh
Journal: British Journal of Dermatology (2008)
Ethics of Psychosurgery
Authors: Walter Freeman
Journal: New England Journal of Medicine (1953)

SURGICAL operations on the brain for the treatment of functional mental disorder continue to disturb the conscience of many thoughtful and sympathetic persons, physicians and others. It is timely and proper, therefore, that the ethics of psychosurgery should be discussed. Enough factual material is available for a fairly precise postoperative picture of the patient to be presented and compared with the ideal of human attainment. This was not so in the beginning of psychosurgery. Indeed, Burckhardt presented the moral problem as long ago as 1890. His words seem to have a particular relevance to the present discussion:Doctors are different . . .
Corrigendum to ‘Role of cardiopulmonary exercise testing in clinical stratification in heart failure. A position paper from the Committee on Exercise Physiology and Training of the Heart Failure Association of the European Society of Cardiology’ [Eur J Heart Fail 2018;20:3–15]
Authors: Ugo Corrà, Pier Giuseppe Agostoni, Stefan D. Anker, Andrew J.S. Coats, Maria G. Crespo Leiro, Rudolph A. de Boer, Veli‐Pekka Harjola, Loreena Hill, Mitja Lainscak, Lars H. Lund, Marco Metra, Piotr Ponikowski, Jillian Riley, Petar M. Seferović, Massimo F. Piepoli
Journal: European Journal of Heart Failure (2018)
Immune checkpoint inhibitor-related acral vasculitis
Authors: Thibault Comont, Vincent Sibaud, Loïc Mourey, Pierre Cougoul, Odile Beyne-Rauzy
Journal: Journal for ImmunoTherapy of Cancer (2018)

Commentary on « Ipilimumab induced vasculitis » by Padda A. et al., J Immunother Cancer. 2018;6:12. The authors diagnosed a small vessel vasculitis following treatment with anti-CTLA-4 (ipilimumab) for a resected stage III B/C melanoma. We report a similar case of acral vasculitis occurring with a combination of anti-CTLA-4 (tremelimumab) and anti-PD-L1 (durvalumab) prescribed for the management of a metastatic urothelial bladder cancer. In contrast to Padda A. et al., we observed a significant improvement with oral corticosteroids.
Follow the trail: Using insights from the growth of palliative care to propose a roadmap for cancer rehabilitation
Authors: Kathleen D. Lyons, Lynne S. Padgett, Timothy F. Marshall, Joseph A. Greer, Julie K. Silver, Vishwa S. Raj, David S. Zucker, Jack B. Fu, Mackenzi Pergolotti, Alix G. Sleight, Catherine M. Alfano
Journal: CA A Cancer Journal for Clinicians (2018)

Abstract Despite research explicating the benefits of cancer rehabilitation interventions to optimize physical, social, emotional, and vocational functioning, many reports document low rates of referral to and uptake of rehabilitation in oncology. Cancer rehabilitation clinicians, researchers, and policy makers could learn from the multidisciplinary specialty of palliative care, which has benefited from a growth strategy and has garnered national recognition as an important and necessary aspect of oncology care. The purpose of this article is to explore the actions that have increased the uptake and integration of palliative care to yield insights and multimodal strategies for the development and growth of cancer rehabilitation. After examining the history of palliative care and its growth, the authors highlight 5 key strategies that may benefit the field of cancer rehabilitation: 1) stimulating the science in specific gap areas; 2) creating clinical practice guidelines; 3) building clinical capacity; 4) ascertaining and responding to public opinion; and 5) advocating for public policy change. Coordinated and simultaneous advances on these 5 strategies may catalyze the growth, utilization, and effectiveness of patient screening, timely referrals, and delivery of appropriate cancer rehabilitation care that reduces disability and improves quality of life for cancer survivors who need these services.
Long-Term Prognostic Value of Myocardial Fibrosis in Patients With Chagas Cardiomyopathy
Authors: Tiago Senra, Barbara M. Ianni, Ana C.P. Costa, Charles Mady, Martino Martinelli-Filho, Roberto Kalil-Filho, Carlos E. Rochitte
Journal: Journal of the American College of Cardiology (2018)
Research waste is still a scandal—an essay by Paul Glasziou and Iain Chalmers
Authors: Paul Glasziou, Iain Chalmers
Journal: BMJ (2018)

Progress has been made towards reducing the 85% of wasted effort in medical research—and the huge amounts of money misspent and harm caused to patients—but there's still a long way to go, say <b>Paul Glasziou</b> and <b>Iain Chalmers</b>
Abstract 15256: Genetic Modifiers of Heritable Thoracic Aortic Aneurysms in Marfan Syndrome
Authors: Cassandra Malecki, Yaxin Lu, Donna Lai, Elizabeth Robertson, Murat Kekic, Stephanie Portelli, Brett D Hambly, Richmond Jeremy
Journal: Circulation (2017)

Introduction: Heritable thoracic aortic aneurysms (TAA) are potentially life threatening, with timely intervention essential to the survival of patients. The development of these aneurysms is the main cause of death in Marfan syndrome (MFS) patients. The phenotypic presentation of TAA’s is highly variable in MFS patients, suggesting a substantial complexity associated with the pathogenesis of this disease. Altered TGF-β signalling is thought to play an essential role in the development of TAA’s seen in MFS. Therefore, variable expression in the key proteins associated with this pathway may be critical to understanding the variable severity associated with this syndrome. Hypothesis: That functional single nucleotide polymorphisms (SNPs) in genes coding for these key proteins may alter the phenotypic presentation of MFS aneurysm. Methods: Through pyrosequencing technology, the genotypes of three relevant SNPs (MMP-9 C1562T, TGF-beta C509T, MMP-9 A8202G) were determined in a group of MFS patients and analyse...
Atezolizumab + bevacizumab in hepatocellular carcinoma (HCC): Safety and clinical activity results from a phase Ib study
Authors: K.-H. Lee, C.-H. Hsu, M.S. Lee, B.-Y. Ryoo, W. Verret, A.R. He, A. Kwan, B. Liu, K. Iizuka, S. Stein
Journal: Annals of Oncology (2018)
Histone Demethylase KDM4B Promotes DNA Damage by Activating Long Interspersed Nuclear Element-1
Authors: Ying Xiang, Kai Yan, Qian Zheng, Haiqiang Ke, Jie Cheng, Wenjun Xiong, Xin Shi, Lei Wei, Min Zhao, Fei Yang, Ping Wang, Xing Lu, Li Fu, Xuemei Lu, Feng Li
Journal: Cancer Research (2018)

Abstract The histone demethylase KDM4B is frequently overexpressed in various cancer types, and previous studies have indicated that the primary oncogenic function of KDM4B is its ability to demethylate H3K9me3 in different tumors, resulting in altered gene expression and genome instability. A genome-wide analysis to evaluate the effect of KDM4B on the global or local H3K9me3 level has not been performed. In this study, we assess whole-genome H3K9me3 distribution in cancer cells and find that H3K9me3 is largely enriched in long interspersed nuclear element-1 (LINE-1). A significant proportion of KDM4B-dependent H3K9me3 was located in evolutionarily young LINE-1 elements, which likely retain retrotransposition activity. Ectopic expression of KDM4B promoted LINE-1 expression, while depletion of KDM4B reduced it. Furthermore, KDM4B overexpression enhanced LINE-1 retrotransposition efficacy, copy number, and associated DNA damage, presumably via the histone demethylase activity of KDM4B. Breast cancer cell lines expressing high levels of KDM4B also exhibited increased LINE-1 expression and copy number compared with other cell lines. Pharmacologic inhibition of KDM4B significantly reduced LINE-1 expression and DNA damage in breast cancer cells with excessive KDM4B. Our study not only identifies KDM4B as a novel regulator of LINE-1, but it also suggests an unexpected oncogenic role for KDM4B overexpression in tumorigenesis, providing clues for the development of new cancer prevention strategies and therapies. Significance: The histone demethylase KDM4B promotes tumorigenesis by inducing retrotransposition and DNA damage.
Abstract 20172: A Novel Mutation in Hif1α in Sprague Dawley Rats is Associated With Hyper-Responsiveness to Su5416 and Severe Pulmonary Arterial Hypertension
Authors: Ketul R Chaudhary, Yupu Deng, Anli Yang, Edwin Cuppen, Duncan J Stewart
Journal: Circulation (2016)

Introduction: Our lab has identified a unique sub-strain of SD rats that is hyper-responsive (HR) to SU5416 (SU) alone and develops severe progressive PAH in response to single injection of SU, eve...
Bictegravir/Emtricitabine/Tenofovir Alafenamide: A Review in HIV-1 Infection
Authors: Emma D. Deeks
Journal: Drugs (2018)

Bictegravir is a new integrase strand transfer inhibitor (INSTI) with a high genetic barrier to the development of HIV-1 resistance. The drug is co-formulated with the nucleos(t)ide reverse transcriptase inhibitors emtricitabine and tenofovir alafenamide (AF) in a single-tablet regimen (STR) for the once-daily treatment of HIV-1 infection in adults (bictegravir/emtricitabine/tenofovir AF; Biktarvy®). In phase 3 trials, bictegravir/emtricitabine/tenofovir AF was noninferior to dolutegravir-based therapy (dolutegravir/abacavir/lamivudine or dolutegravir plus emtricitabine/tenofovir AF) in establishing virological suppression in treatment-naïve adults through 96 weeks' treatment and, similarly, was noninferior to ongoing dolutegravir/abacavir/lamivudine or boosted elvitegravir- or protease inhibitor (PI)-based therapy in preventing virological rebound over 48 weeks in treatment-experienced patients. No resistance emerged to any of the antiretrovirals in the STR. Bictegravir/emtricitabine/tenofovir AF is generally well tolerated, requires no prior HLA-B*5701 testing (making it more suitable for 'rapid start' treatment), fulfils the antiretroviral regimen requirement for patients with hepatitis B virus (HBV) co-infection (i.e. contains tenofovir AF and emtricitabine, both of which are active against HBV) and can be used in renally impaired patients with creatinine clearance (CRCL) ≥ 30 mL/min. Thus, although cost-effectiveness analyses would be beneficial, current data indicate that bictegravir/emtricitabine/tenofovir AF is a convenient initial and subsequent treatment option for adults with HIV-1 infection, including those co-infected with HBV, and provides the first non-pharmacologically boosted, INSTI-based, triple-combination STR suitable for patients with CRCL 30-50 mL/min.
Abstract 18270: Acarbose Attenuates Age-Associated Declines in Motor and Cardiac Function
Authors: Sean Louzon, Jonathan Herrera, Jaime Yob, Kimber Converso, Richard Miller, Sharlene Day
Journal: Circulation (2017)

Background: Age is a primary risk factor for chronic conditions including cardiovascular diseases. With inflation in the aged population over the last century, there is a growing need for interventions that directly target aging. Acarbose, an alpha-glucosidase inhibitor, is a promising aging intervention that increases lifespan in male and female mice by 22% and 5%, respectively. Acarbose is an FDA approved anti-diabetic drug with a limited side effect profile. We hypothesized that, in addition to lengthening lifespan, Acarbose would also diminish the effects of aging on motor and cardiac function. Methods and Results: Outbred male and female F1 mice that were a cross of 4 strains were treated with Acarbose (ACA, 1000 ppm) or a control diet from 8 months to 22 months of age. Both groups of aged 22 month old mice were compared to 4 month control mice in motor performance and echocardiography. Grip strength, a strong predictor of all cause and cardiovascular mortality in humans, was reduced with age (0.511 ...
Failure to Accurately Disclose Conflicts of Interest in Articles Published in <i>JAMA Oncology</i>
Authors: José Baselga
Journal: JAMA Oncology (2018)

Roberto Salgado, MD, PhD; Carsten Denkert, MD, PhD; Christine Campbell, MSc; Peter Savas, MD; Paolo Nuciforo, MD; Claudia Aura, MD; Evandro de Azambuja, MD, PhD; Holger Eidtmann, MD; Catherine E. Ellis, PhD; José Baselga, MD; Martine J. Piccart-Gebhart, MD, PhD; Stefan Michiels, PhD; Ian Bradbury, PhD; Christos Sotiriou, MD, PhD; Sherene Loi, MD, PhD
Abstract 20022: Mobile Phone-Based Cardiac Rehabilitation Program Improves Exercise Capacity and Clinical Outcomes in Chinese Revascularized Patients
Authors: Jing Ma, Cheng Ge, Yajun Shi, Yong Xu, Chenghui Zhao, Chunxue Liu, Ling Gao, Sidney C Smith, Yundai Chen
Journal: Circulation (2017)

Background: Previous studies have documented a favorable effect of cardiac rehabilitation (CR) on patients undergoing percutaneous coronary intervention (PCI). However, participation in CR is sub-optimal, especially in China. Innovative models of CR are needed to improve participation. The present study assessed the effect of a mobile phone-based CR (MBCR)program on exercise capacity and clinical outcomes in patients undergoing PCI. Methods: Totally 212 patients following PCI referred to the CR clinic of Chinese PLA General Hospital, between Jul, 2015 and Apr, 2016, were divided into 2 groups, to participate in MBCR (n=107) or usual care program (control, n=105). Individualized exercise prescription and educational materials were sent to the participants in the MBCR group by the App named “Heartguard” regularly. Cardiopulmonary exercise testing and adverse events were evaluated at baseline and after 12 months. Results: There is no statistical difference of the baseline demographic, clinical, and functiona...
Softening Our Approach to Discussing Prognosis
Authors: Joshua R. Lakin, Juliet Jacobsen
Journal: JAMA Internal Medicine (2018)

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First clinical experiences with Gemtuzumab ozogamicin (GO, Mylotarg (c)) in CD33 positive relapsed/refractory leukemia in children
Authors: CM Zwaan, D Reinhardt, S Corbacioglu, H Jurgens, Ulf Samuelsson, A Biondi, OP Smith, Jpm Bokkerink, Wje Tissing, U Creutzig, Gjl Kaspers
Journal: Leukemia (2003)
A Nationwide Survey on Chronic Active Epstein-Barr Virus Infection in Japan Based on New Diagnostic Criteria: Clinical Features and Treatment Strategies
Authors: Ayako Arai, Ichiro Yonese, Chizuko Sakashita, Ken-Ichi Imadome, Tohru Kobayashi, Akihisa Sawada, Yoshinori Ito, Shouichi Ohga, Hiroshi Kimura, Shigeyoshi Fujiwara
Journal: Blood (2018)