tbuckley/cabot-search huggingface dataset:
Contact Precautions to Prevent Pathogen Transmission—Reply
Authors: Michael A. Rubin, Matthew H. Samore, Anthony D. Harris
Journal: JAMA (2018)

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Environmental Tobacco Smoke and Coronary Heart Disease in the American Cancer Society CPS-II Cohort
Authors: KyleSteenland, MichaelThun, CathyLally, ClarkHeath
Journal: Circulation (1996)

Background Thirteen of 14 epidemiological studies have shown an increased risk of ≈20% for coronary heart disease (CHD) for never-smokers exposed to environmental tobacco smoke (ETS), but this association remains controversial. If true, ETS might account for an estimated 35 000 to 40 000 heart disease deaths per year in the United States. Methods and Results We have conducted the largest study to date, a prospective study of 353 180 female and 126 500 male never-smokers enrolled in 1982 in the American Cancer Society's Cancer Prevention Study II and followed through 1989. Analyses focused on subcohorts of 309 599 married pairs and of 135 237 subjects concordant for self-reported exposure and exposure reported by each one's spouse. More than 2800 CHD deaths (ICD 410-414) occurred among married pairs; 10% of married men and 28% of married women were married to currently smoking spouses, while 10% and 32%, respectively, were married to former smokers. After controlling for many cardiovascular risk factors, w...
Abstract 17839: Transcatheter Annuloplasty Ring Multicentre Trial Report
Authors: Karl-Heinz Kuck, Alec Vahanian, Georg Nickenig, Ottavio Alfieri, Antonio Colombo, Stephan Baldus, Francesco Maisano
Journal: Circulation (2015)

Aim: Cardioband system enables percutaneous implantation of an adjustable “surgical-like” mitral annuloplasty ring using a transseptal approach. The aim of this study was to evaluate the feasibility, safety and up to 12 month outcome of Cardioband in patients with functional mitral regurgitation (FMR) in a multicentre study. Methods and Results: Between February 2013 and March 2015, 40 high-risk patients with significant FMR were enrolled at 6 sites in Europe. After a Heart Team evaluation all patients were screened by echocardiography and cardiac CT to assess feasibility. Echocardiographic data were analysed by an independent core-lab. Mean age was 72±7 years, thirty patients were males (75%). Mean EuroScore II 9.0%±7.02% and median STS score 7.2 % (1.0%-34.0%). At baseline 93% of patients were in NYHA class III-IV with mean EF of 33.3±10% (15%-57%). Device implantation was feasible in all patients (100%). Acute procedural success (device successfully implanted with acute reduction of MR &lt;2+) was achieved in 92% of the patients (37/40. After cinching of the device, an average of 20% reduction of the septo-lateral diameter was observed (from 37±5 mm to 29±5 mm; p&lt;0.01). Thirty-day mortality was 5.0% (adjudicated unrelated to the device). At 6 months follow up (n=20) 80% of patients were in NYHA class I-II with significant improvement in quality of life (MLWHFQ from 38 to 18; p&lt;0.05) and 85% of patients had MR≤2+. At 12 months follow up (n=14), 93% of patients had MR&lt;2+). Conclusions: Transseptal direct annuloplasty with an adjustable “surgical-like” ring is feasible, with a comparable safety profile similar to other transcatheter mitral procedures. Effective reduction in MR severity is observed in most patients related to a significant septo-lateral dimension reduction. MR reduction is stable and consistent up to 12 months, with clinical benefit.
Boys in England to get HPV vaccine from next year
Authors: Zosia Kmietowicz
Journal: BMJ (2018)

The government has given the go ahead for boys aged between 12 and 13 in England to be given the vaccine against the human papilloma virus (HPV) and aims to roll out vaccination next autumn.

The decision follows a recommendation from the Joint Committee on Vaccination and Immunisation last week to extend the current programme for girls to include boys.1 A new modelling method …
Diffuse erythema with ‘angel wings’ sign in Japanese patients with anti-small ubiquitin-like modifier activating enzyme antibody-associated dermatomyositis
Authors: S. Inoue, N. Okiyama, M. Shobo, S. Motegi, H. Hirano, Y. Nakagawa, A. Saito, Y. Nakamura, Y. Ishitsuka, Y. Fujisawa, R. Watanabe, M. Fujimoto
Journal: British Journal of Dermatology (2018)
Genome-scale CRISPR-Cas9 screen identifies druggable dependencies in <i>TP53</i> wild-type Ewing sarcoma
Authors: Björn Stolte, Amanda Balboni Iniguez, Neekesh V. Dharia, Amanda L. Robichaud, Amy Saur Conway, Ann M. Morgan, Gabriela Alexe, Nathan J. Schauer, Xiaoxi Liu, Gregory H. Bird, Aviad Tsherniak, Francisca Vazquez, Sara J. Buhrlage, Loren D. Walensky, Kimberly Stegmaier
Journal: The Journal of Experimental Medicine (2018)

Ewing sarcoma is a pediatric cancer driven by EWS-ETS transcription factor fusion oncoproteins in an otherwise stable genomic background. The majority of tumors express wild-type TP53, and thus, therapies targeting the p53 pathway would benefit most patients. To discover targets specific for TP53 wild-type Ewing sarcoma, we used a genome-scale CRISPR-Cas9 screening approach and identified and validated MDM2, MDM4, USP7, and PPM1D as druggable dependencies. The stapled peptide inhibitor of MDM2 and MDM4, ATSP-7041, showed anti-tumor efficacy in vitro and in multiple mouse models. The USP7 inhibitor, P5091, and the Wip1/PPM1D inhibitor, GSK2830371, decreased the viability of Ewing sarcoma cells. The combination of ATSP-7041 with P5091, GSK2830371, and chemotherapeutic agents showed synergistic action on the p53 pathway. The effects of the inhibitors, including the specific USP7 inhibitor XL-188, were rescued by concurrent TP53 knockout, highlighting the essentiality of intact p53 for the observed cytotoxic activities.
Internet-Based Cognitive Behavioral Therapy for Chronic Stress: A Randomized Controlled Trial
Authors: Elin Lindsäter, Erland Axelsson, Sigrid Salomonsson, Fredrik Santoft, Kersti Ejeby, Brjánn Ljótsson, Torbjörn Åkerstedt, Mats Lekander, Erik Hedman-Lagerlöf
Journal: Psychotherapy and Psychosomatics (2018)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Prolonged exposure to stress can lead to substantial suffering, impairment and societal costs. However, access to psychological treatment is limited. Internet-based cognitive behavioral therapy (ICBT) can be effective in reducing symptoms of stress, but little is known of its effects in clinical samples. The aim of this study was to investigate the efficacy of ICBT for patients suffering from chronic stress, operationalized as adjustment disorder (AD) and exhaustion disorder (ED). &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; A total of 100 adults diagnosed with AD or ED were randomly assigned to a 12-week ICBT (&lt;i&gt;n =&lt;/i&gt; 50) or waitlist control condition (&lt;i&gt;n =&lt;/i&gt; 50). Primary outcome was the level of perceived stress (PSS). Secondary outcomes included several mental health symptom domains as well as functional impairment and work ability. All outcomes were assessed at baseline, after treatment and at the 6-month follow-up. The study was preregistered at Clinicaltrials.gov: NCT02540317. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Compared to the control condition, patients in the ICBT group made large and significant improvements on the PSS (&lt;i&gt;d =&lt;/i&gt; 1.09) and moderate to large improvements in secondary symptom domains. Effects were maintained at the 6-month follow-up. There was no significant between-group effect on functional impairment or work ability. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; A relatively short ICBT is indicated to be effective in reducing stress-related symptoms in a clinical sample of patients with AD and ED, and has the potential to substantially increase treatment accessibility. Results must be replicated, and further research is needed to understand the relationship between symptom reduction, functional impairment and work ability.
Prospective Serial FDG PET/CT During Treatment of Extrapulmonary Tuberculosis in HIV-Infected Patients
Authors: Charlotte Martin, Catherine Castaigne, Irina Vierasu, Camilo Garcia, Chloe Wyndham-Thomas, Stéphane de Wit
Journal: Clinical Nuclear Medicine (2018)

Purpose The aim of this study was to prospectively describe evolution of 18 F-FDG uptake of extrapulmonary tuberculosis (TB) throughout the course of TB treatment in HIV patients to evaluate 18 F-FDG PET/CT as a monitoring tool of treatment response. Methods We performed baseline FDG PET/CT, PET-2 after 2 months, and PET-3 at the end of TB treatment in 18 HIV/TB patients. We correlated evolution of FDG uptake with clinical outcome of patients. Results After 2 months of treatment, 78% of the patients had a significant metabolic response. Lymph node (LN) metabolic response was heterogeneous, with 57% of LN sites showing decreased SUVmax and 41% showing unchanged FDG uptake. Organs other than LNs showed more homogeneous response. The FDG PET/CT performed at the end of TB treatment showed a complete response of all infected organs and a drastic response in terms of active LNs in 95% of the patients (SUVmax mean decrease = 85%, median = 100%). A complete metabolic response after TB treatment was seen in only 47% of patients. Conclusions In difficult-to-treat entities such as extrapulmonary TB in HIV patients, FDG PET/CT is a potential tool in monitoring TB treatment response and should be explored in larger studies.
Abstract 19668: Caspase Recruitment Domain-Containing Protein 9 Knockout Rescues Heart Function by Reducing Fibrosis and Hypertrophy in a Pressure-Overload Model of Murine Heart Failure
Authors: Matt Peterson, Samantha Haller, Kayla Wilson, D. Paul Thomas, Guanglong He
Journal: Circulation (2016)

Introduction:  Nearly 1 in 3 adults aged over 20 in the US presents with hypertension, which can lead to left ventricular hypertrophy, hypertensive heart disease, and heart failure. The progressions of each are tied closely to elevated systemic and local inflammation. Caspase Recruitment Domain-containing Protein 9 (CARD9), a cytosolic protein expressed in macrophages and neutrophils, mediates secretion of inflammatory cytokines by these cells, which infiltrate the myocardium after injury and perpetuate a sustained inflammatory response. We recently reported rescued myocardial function by knockout of CARD9 (CARD9 -\- ) in high-fat diet feeding. Macrophage deletion has been reported to ameliorate the progression of TAC-induced left ventricular hypertrophy and fibrosis. Combined, these findings suggest that CARD9 may be a valuable target in a TAC model of heart failure.   Hypothesis:  We hypothesized that knockout of CARD9 would rescue progression of TAC pressure-overload induced hypertrophy, fibrosis, and failure.   Methods:  C57BL/6 wild-type (WT) and CARD9 -\-  mice were assigned to thoracic aortic constriction (TAC) or to sham (CONT). To assess heart function, fractional shortening (FS), was measured by echocardiogram 1, 2, and 3 months post-surgery.   Results:  FS was compromised in WT-TAC compared to WT-CONT at 1 (35.2 vs. 47.8; p -\- TAC at any time point. At 3 months, mice were sacrificed. Heart weight/tibia length was elevated in WT-TAC compared to WT-CONT (11.7 vs. 6.7; p -\- TAC. Histological results of Masson’s trichrome stain suggested hypertrophy in both TAC groups, but revealed less fibrosis in CARD9 -\- TAC than in WT-TAC.   Conclusion:  CARD9 is a novel target for TAC-induced cardiac dysfunction, at least in part through reductions in fibrosis and hypertrophy. Further study is needed to investigate signaling transduction involved, as well as the extent to which CARD9 -\-  may be protective in order to determine if it is a potential target for intervention in hypertensive heart disease.
Abstract 18590: Hypoxic Liver Injury at Admission as a Predictor of In-hospital Death in Patients With ST-Elevation Myocardial Infarction Undergone Primary Percutaneous Coronary Intervention: Data From the INTERSTELLAR Cohort
Authors: Hyun Woo Park, Jon Suh, Jeonggeun Moon, Pyung Chun Oh, Ho-Jun Jang, Tae-Hoon Kim, Sang-Don Park, Sung Woo Kwon, Woong Chol Kang
Journal: Circulation (2015)

Introduction: Recently, hypoxic liver injury (HLI) has been proposed as a novel prognostic marker for ST-elevation myocardial infarction (STEMI) in small study. So, we evaluated the prognostic implication of HLI at admission in patients with STEMI who underwent primary percutaneous coronary intervention (PCI) in large cohort. Methods: From 2007 to 2014, a total of 1540 consecutive patients (1221 males, mean age 61±13 years old) with STEMI underwent primary PCI were analyzed retrospectively. HLI was defined as ≥ 2-fold increase of serum alanine aminotransferase (ALT) above upper normal limit at the time of presentation. Primary endpoint was in-hospital death. Results: Of all patients, the HLI was noted in 7.7% patients. Compared to patients without HLI, the patients with HLI were younger (58±14 vs. 61±13 years, p=0.043), had lower ejection fraction (43±15 vs. 48±17%, p=0.002). A total of 89 in-hospital death (5.8%) were occurred. Compared to patients without in-hospital death, those patients were older (69±11 vs. 60±13 years old, p&lt;0.001), had higher ALT (65±69 vs. 36±40 IU/L, p&lt;0.001) at the time of presentation and had lower left ventricular ejection fraction (49±12 vs. 27±19, p&lt;0.001). The HLI at the presentation was associated with high in-hospital death (p &lt;0.001) and was an independent predictor of in-hospital death (HR 5.69, CI 3.12-10.38, p&lt;0.001) after adjusted by age, diabetes, sex and shock. Conclusions: The HLI is an independent predictor of in-hospital death in patients with STEMI underwent primary PCI.
Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations. Section 9. t(14;18) with BCL2-IGH rearrangement.
Authors: P. A. S. Evans, Benedict Jon Milner, C. Bastard, E. Delabesse, E. A. Macintyre, P. Wijers-Koster, E. Schuuring, E. Moreau, D. González, K. I. Mills, B. A. Jennings, D. Bloxham, P. Starostik, M. H. Delfau-Larue, G. Salles, G. J. Morgan
Journal: Leukemia (2003)
A genome-wide siRNA screen identifies a druggable host pathway essential for the Ebola virus life cycle
Authors: Scott Martin, Abhilash I. Chiramel, Marie Luisa Schmidt, Yu-Chi Chen, Nadia Whitt, Ari Watt, Eric C. Dunham, Kyle Shifflett, Shelby Traeger, Anne Leske, Eugen Buehler, Cynthia Martellaro, Janine Brandt, Lisa Wendt, Andreas Müller, Stephanie Peitsch, Sonja M. Best, Jürgen Stech, Stefan Finke, Angela Römer-Oberdörfer, Allison Groseth, Heinz Feldmann, Thomas Hoenen
Journal: Genome Medicine (2018)

The 2014–2016 Ebola virus (EBOV) outbreak in West Africa highlighted the need for improved therapeutic options against this virus. Approaches targeting host factors/pathways essential for the virus are advantageous because they can potentially target a wide range of viruses, including newly emerging ones and because the development of resistance is less likely than when targeting the virus directly. However, systematic approaches for screening host factors important for EBOV have been hampered by the necessity to work with this virus at biosafety level 4 (BSL4). In order to identify host factors involved in the EBOV life cycle, we performed a genome-wide siRNA screen comprising 64,755 individual siRNAs against 21,566 human genes to assess their activity in EBOV genome replication and transcription. As a screening platform, we used reverse genetics-based life cycle modelling systems that recapitulate these processes without the need for a BSL4 laboratory. Among others, we identified the de novo pyrimidine synthesis pathway as an essential host pathway for EBOV genome replication and transcription, and confirmed this using infectious EBOV under BSL4 conditions. An FDA-approved drug targeting this pathway showed antiviral activity against infectious EBOV, as well as other non-segmented negative-sense RNA viruses. This study provides a minable data set for every human gene regarding its role in EBOV genome replication and transcription, shows that an FDA-approved drug targeting one of the identified pathways is highly efficacious in vitro, and demonstrates the power of life cycle modelling systems for conducting genome-wide host factor screens for BSL4 viruses.
ERS/EACTS statement on the management of malignant pleural effusions
Authors: Anna C. Bibby, Patrick Dorn, Ioannis Psallidas, Jose M. Porcel, Julius Janssen, Marios Froudarakis, Dragan Subotic, Phillippe Astoul, Peter Licht, Ralph Schmid, Arnaud Scherpereel, Najib M. Rahman, Giuseppe Cardillo, Nick A. Maskell
Journal: European Respiratory Journal (2018)

Malignant pleural effusions (MPE) are a common pathology, treated by respiratory physicians and thoracic surgeons alike. In recent years, several well-designed randomised clinical trials have been published that have changed the landscape of MPE management. The European Respiratory Society (ERS) and the European Association for Cardio-Thoracic Surgery (EACTS) established a multidisciplinary collaboration of clinicians with expertise in the management of MPE with the aim of producing a comprehensive review of the scientific literature.Six areas of interest were identified, including the optimum management of symptomatic MPE, management of trapped lung in MPE, management of loculated MPE, prognostic factors in MPE, whether there is a role for oncological therapies prior to intervention for MPE and whether a histological diagnosis is always required in MPE.The literature revealed that talc pleurodesis and indwelling pleural catheters effectively manage the symptoms of MPE. There was limited evidence regarding the management of trapped lung or loculated MPE. The LENT score was identified as a validated tool for predicting survival in MPE, with Brims' prognostic score demonstrating utility in mesothelioma prognostication. There was no evidence to support the use of oncological therapies as an alternative to MPE drainage, and the literature supported the use of tissue biopsy as the gold standard for diagnosis and treatment planning.
Bullous disorders associated with anti–PD-1 and anti–PD-L1 therapy: A retrospective analysis evaluating the clinical and histopathologic features, frequency, and impact on cancer therapy
Authors: Jacob Siegel, Mariam Totonchy, William Damsky, Juliana Berk-Krauss, Frank Castiglione, Mario Sznol, Daniel P. Petrylak, Neal Fischbach, Sarah B. Goldberg, Roy H. Decker, Angeliki M. Stamatouli, Navid Hafez, Earl J. Glusac, Mary M. Tomayko, Jonathan S. Leventhal
Journal: Journal of the American Academy of Dermatology (2018)
Evaluation of EGFR diagnostic testing and treatment patterns in advanced NSCLC patients over time.
Authors: Victor C Wang, Karl Rudeen, Angelique Russell, Gabriel S Eichler, Jennifer O. Nwankwo, Robert Fair, Faith DeFreitas, Douglas Terrell, Jeffrey Kaufman, Thomas Brasington, Edward J. Stepanski, Brigham Hyde
Journal: Journal of Clinical Oncology (2018)

e21030 Background: Diagnostic testing is essential for implementation of targeted therapy. Rates of adoption of therapeutically relevant diagnostic tests in advanced NSCLC is evolving. Tyrosine kinase inhibitors (TKIs) are now approved for first line use in EGFR+ patients. Our aim is to define the testing rates, and subsequent use of TKIs in EGFR+ NSCLC patients. Methods: A manually curated dataset of 11,655 stage III/IV NSCLC patients diagnosed between 2009 and 2016, was obtained from the ASCO CancerLinQ Discovery™ EMR database. We evaluated the rates of EGFR mutation testing in advanced NSCLC patients prior to initiation of first line therapy, and the use of EGFR TKIs in those patients. Results: In our cohort, the rate of EGFR mutation testing increased from 8% to 35% between 2009 and 2016. Of the stage III/IV NSCLC patients who tested positive for an EGFR-sensitizing mutation, 47-66% of patients were treated with targeted EGFR TKI, and 17-34% of patients were treated with chemotherapy as their first line therapy. Conclusions: We demonstrated that EGFR testing rates in patients prior to first line systemic therapy increased for the first 5 years following the approval of the first EGFR companion diagnostic, plateauing at approximately 33-35% testing rate. In addition to the low rates seen in the frequency of diagnostic testing, first-line therapy for stage III/IV NSCLC patients with EGFR mutations is divided between EGFR TKI (48-66%) and chemotherapy (21-34%). Year of NSCLC Diagnosis Stage III/IV Patients (N) EGFR Testing Prior to 1L Therapy EGFR+ Mutation EGFR+ and TKI as 1L Therapy EGFR+ and Chemo as 1L Therapy 2009 1223 94 (8%) 29 (31%) 14 (48%) 10 (34%) 2010 1281 160 (12%) 40 (25%) 21 (53%) 13 (33%) 2011 1378 323 (23%) 64 (20%) 33 (52%) 17 (27%) 2012 1523 401 (26%) 74 (18%) 42 (57%) 16 (22%) 2013 1547 439 (28%) 91 (21%) 43 (47%) 25 (27%) 2014 1601 524 (33%) 93 (18%) 61 (66%) 16 (17%) 2015 1679 557 (33%) 96 (17%) 56 (58%) 20 (21%) 2016 1423 496 (35%) 101 (20%) 60 (59%) 24 (24%)
A Consensus Statement on acromegaly therapeutic outcomes
Authors: Shlomo Melmed, Marcello D. Bronstein, Philippe Chanson, Anne Klibanski, Felipe F. Casanueva, John A. H. Wass, Christian J. Strasburger, Anton Luger, David R. Clemmons, Andrea Giustina
Journal: Nature Reviews Endocrinology (2018)

The 11th Acromegaly Consensus Conference in April 2017 was convened to update recommendations on therapeutic outcomes for patients with acromegaly. Consensus guidelines on the medical management of acromegaly were last published in 2014; since then, new pharmacological agents have been developed and new approaches to treatment sequencing have been considered. Thirty-seven experts in the management of patients with acromegaly reviewed the current literature and assessed changes in drug approvals, clinical practice standards and clinical opinion. They considered current treatment outcome goals with a focus on the impact of current and emerging somatostatin receptor ligands, growth hormone receptor antagonists and dopamine agonists on biochemical, clinical, tumour mass and surgical outcomes. The participants discussed factors that would determine pharmacological choices as well as the proposed place of each agent in the guidelines. We present consensus recommendations highlighting how acromegaly management could be optimized in clinical practice. Acromegaly is usually caused by a pituitary adenoma that secretes growth hormone; treatment of acromegaly and its comorbidities is often complex. In this Consensus Statement, Shlomo Melmed and colleagues provide updated recommendations for the treatment of patients with acromegaly.
Epithelial damage and tissue γδ T cells promote a unique tumor-protective IgE response
Authors: Greg Crawford, Mark David Hayes, Rocio Castro Seoane, Sophie Ward, Tim Dalessandri, Chester Lai, Eugene Healy, David Kipling, Charlotte Proby, Colin Moyes, Kile Green, Katie Best, Muzlifah Haniffa, Marina Botto, Deborah Dunn-Walters, Jessica Strid
Journal: Nature Immunology (2018)