tbuckley/cabot-search huggingface dataset:
Cancer of the esophagus and esophagogastric junction—Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual
Authors: Thomas W. Rice, Donna M. Gress, Deepa T. Patil, Wayne L. Hofstetter, David P. Kelsen, Eugene H. Blackstone
Journal: CA A Cancer Journal for Clinicians (2017)

Answer questions and earn CME/CNE New to the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual for epithelial cancers of the esophagus and esophagogastric junction are separate, temporally related cancer classifications: 1) before treatment decision (clinical); 2) after esophagectomy alone (pathologic); and 3) after preresection therapy followed by esophagectomy (postneoadjuvant pathologic). The addition of clinical and postneoadjuvant pathologic stage groupings was driven by a lack of correspondence of survival, and thus prognosis, between both clinical and postneoadjuvant pathologic cancer categories (facts about the cancer) and pathologic categories. This was revealed by a machine-learning analysis of 6-continent data from the Worldwide Esophageal Cancer Collaboration, with consensus of the AJCC Upper GI Expert Panel. Survival is markedly affected by histopathologic cell type (squamous cell carcinoma and adenocarcinoma) in clinically and pathologically staged patients, requiring separate stage grouping for each cell type. However, postneoadjuvant pathologic stage groups are identical. For the future, more refined and granular data are needed. This requires: 1) more accurate clinical staging; 2) innovative solutions to pathologic staging challenges in endoscopically resected cancers; 3) integration of genomics into staging; and 4) precision cancer care with targeted therapy. It is the responsibility of the oncology team to accurately determine and record registry data, which requires eliminating both common errors and those related to incompleteness and inconsistency. Despite the new complexity of eighth edition staging of cancers of the esophagus and esophagogastric junction, these key concepts and new directions will facilitate precision cancer care. CA Cancer J Clin 2017;67:304-317. © 2017 American Cancer Society.
Intracranial Gadolinium Deposition Following Gadodiamide-Enhanced Magnetic Resonance Imaging in Pediatric Patients
Authors: Jennifer S. McDonald, Robert J. McDonald, Mark E. Jentoft, Michael A. Paolini, David L. Murray, David F. Kallmes, Laurence J. Eckel
Journal: JAMA Pediatrics (2017)

This study determines the extent of deposition in gadolinium-based contrast agent–exposed pediatric population and whether prior observations were related to age-dependent breakdown of the blood blood-brain barrier.
Merkel Cell Carcinoma Guidelines
Authors: Stanley J Miller, Murad Alam, James Andersen, Daniel Berg, Christopher K Bichakjian, Glen Bowen, Richard T Cheney, Frank Glass, Roy C Grekin, James M Grichnik, Timothy M Johnson, Anne Kessinger, Nancy Y Lee, Stuart Lessin, Daniel D Lydiatt, Lawrence W Margolis, Kishwer S Nehal, Paul Nghiem, Allan R Oseroff, E William Rosenberg, Ashok R Shaha, Ronald J Siegle
Journal: Journal of the National Comprehensive Cancer Network (2006)

Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous tumor that combines the local recurrence rates of infiltrative non-melanoma skin cancer with the regional and distant metastatic rates of thick melanoma. The mortality rate of MCC exceeds that of melanoma, and the 5-year disease-specific survival rate is 64%. These guidelines and most biomedical literature suggest that the workup of a patient with MCC should include chest radiograph and additional studies as clinically indicated. These guidelines, which the NCCN Non-Melanoma Skin Cancer Panel developed as a supplement to those for squamous cell and basal cell skin cancer, also outline treatment strategies. For the most recent version of the guidelines, please visit NCCN.org
MEDU-42. BCL-XL DISRUPTION AS A POTENTIAL THERAPEUTIC AVENUE FOR MEDULLOBLASTOMA TREATMENT
Authors: Katherine Veleta, Timothy Gershon
Journal: Neuro-Oncology (2017)

Medulloblastoma is distinct among malignant brain tumors in being typically sensitive to radiation therapy. We have previously shown that the radiation sensitivity of medulloblastomas depends on the function of the intrinsic apoptosis pathway. We tested whether this pathway could be activated directly, without radiation, by disrupting the anti-apoptotic protein BCL-xL. Analysis of mice with conditional deletion of Bcl-xL in cerebellar progenitors showed that absence of BCL-xL caused progenitors to undergo apoptosis when exiting the cell cycle. Bcl-xL deletion in SHH-driven medulloblastomas in SmoM2 mice impaired tumor growth and caused focal regions of tumor necrosis. However, Bcl-xL-deleted medulloblastomas eventually progressed, so that ultimately Bcl-xL-deleted SmoM2 mice did not survive longer than SmoM2 mice with intact BCL-xL. Gene expression microarray analysis showed up-regulation of the cell cycle regulator Cdk2 in Bcl-xL-deleted tumors, consistent with the idea that tumor cells that remained in the cell cycle were protected from BCL-xL dependent apoptosis. To address this mechanism, in on-going work, we are combining Bcl-xL deletion with SHH inhibition, testing the hypothesis that forced cell cycle exit will sensitize medulloblastomas to Bcl-xL disruption. Combined targeting of proliferative program driven by SHH and the apoptosis program, may open a new avenue for medulloblastoma treatment.
Dipeptidyl Peptidase 4 Inhibition Stimulates Distal Tubular Natriuresis and Increases in Circulating SDF-1α1-67 in Patients With Type 2 Diabetes
Authors: Julie A. Lovshin, Harindra Rajasekeran, Yulyia Lytvyn, Leif E. Lovblom, Shajiha Khan, Robel Alemu, Amy Locke, Vesta Lai, Huaibing He, Lucinda Hittle, Weixun Wang, Daniel J. Drucker, David Z.I. Cherney
Journal: Diabetes Care (2017)

OBJECTIVE Antihyperglycemic agents, such as empagliflozin, stimulate proximal tubular natriuresis and improve cardiovascular and renal outcomes in patients with type 2 diabetes. Because dipeptidyl peptidase 4 (DPP-4) inhibitors are used in combination with sodium–glucose cotransporter 2 (SGLT2) inhibitors, we examined whether and how sitagliptin modulates fractional sodium excretion and renal and systemic hemodynamic function. RESEARCH DESIGN AND METHODS We studied 32 patients with type 2 diabetes in a prospective, double-blind, randomized, placebo-controlled trial. Measurements of renal tubular function and renal and systemic hemodynamics were obtained at baseline, then hourly after one dose of sitagliptin or placebo, and repeated at 1 month. Fractional excretion of sodium and lithium and renal hemodynamic function were measured during clamped euglycemia. Systemic hemodynamics were measured using noninvasive cardiac output monitoring, and plasma levels of intact versus cleaved stromal cell–derived factor (SDF)-1α were quantified using immunoaffinity and tandem mass spectrometry. RESULTS Sitagliptin did not change fractional lithium excretion but significantly increased total fractional sodium excretion (1.32 ± 0.5 to 1.80 ± 0.01% vs. 2.15 ± 0.6 vs. 2.02 ± 1.0%, P = 0.012) compared with placebo after 1 month of treatment. Moreover, sitagliptin robustly increased intact plasma SDF-1α1-67 and decreased truncated plasma SDF-1α3-67. Renal hemodynamic function, systemic blood pressure, cardiac output, stroke volume, and total peripheral resistance were not adversely affected by sitagliptin. CONCLUSIONS DPP-4 inhibition promotes a distal tubular natriuresis in conjunction with increased levels of intact SDF-1α1-67. Because of the distal location of the natriuretic effect, DPP-4 inhibition does not affect tubuloglomerular feedback or impair renal hemodynamic function, findings relevant to using DPP-4 inhibitors for treating type 2 diabetes.
Devenir à long terme de drainage d'abcès pelviens guidés par échoendoscopie: une série bi-centrique
Journal: Endoscopy (2017)

Certaines collections pelviennes sont difficiles à aborder par voie per-cutanée du fait d’interposition digestive ou vasculaire. Le drainage par voie écho-endoscopique des abcès pelviens peut s’affranchir de ces écueils. Deux équipes françaises rapportent le suivi rétrospectif à long terme de leur expérience sur 12 ans de 37 patients de cette technique décrite pour la première fois par Marc Giovannini cocorico.
The association between psoriasis and coeliac disease
Authors: A. Egeberg, C.E.M. Griffiths, L. Mallbris, G.H. Gislason, L. Skov
Journal: British Journal of Dermatology (2017)

Psoriasis is known to be associated with inflammatory comorbidities. Coeliac disease (CD) is an immune-mediated enteropathy caused by permanent intolerance to dietary gliadin, which is present in wheat, barley, and rye.1 The disease occurs in predisposed individuals, and is characterized clinically by malabsorption and histologically by villous atrophy and crypt hyperplasia, which improves when the causal antigen is removed through a gluten-free diet.1 We investigated the relationship between psoriasis and CD in Denmark.

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Use of arterial transfer functions for the derivation of central aortic waveform characteristics in subjects with type 2 diabetes and cardiovascular disease [6] (multiple letter)
Authors: Ian B. Wilkinson, Carmel McEniery, Alberto P. Avolio, John R. Cockcroft, Michael F. O'Rourke, Sarah A. Hope, David B. Tay, Ian T. Meredith, James D. Cameron, Kieren Mather, Richard Lewanczuk
Journal: Diabetes Care (2004)
Abstract P263: Mechanism for Reductive Stress in Mutant Protein Aggregation Cardiomyopathy
Authors: Rajasekaran Namakkal Soorappan, Gayatri D Khanderao, Saradhadevi Varadharaj, Corey J Miller, Sankarnarayanan Kannan, Kalavathy Ramachandran, Curtis Olson, Christopher J Davidson, Jay L Zweier, Sheldon E Litwin, Ivor J Benjamin
Journal: Circulation Research (2011)

Background: We recently demonstrated that the hR120GCryAB associated with protein aggregation cardiomyopathy (PAC) causes reductive stress (RS) linked to dysregulation of G6PD in mice (Rajasekaran et.al Cell, 2007). Nrf2 (nuclear erythroid related factor -2) is the master transcription factor that regulates induction of genes encoding antioxidant responsive element (ARE) dependent pathways. However, the temporal effects of reductive stress on the molecular mechanisms of transcriptional regulation of Nrf2 - Keap1 pathway are unknown. Methods: Age-matched control and mutant TG mice at 3 and 6 months with RS were used to assess activation and nuclear translocation of Nrf2 and ARE-dependent transcriptional mechanisms. Electron paramagnetic resonance (EPR) analysis was used to measure the ROS and RNS in heart tissues. Results: Nuclear translocation of Nrf2 was significantly increased in compensated hR120GCryAB transgenic mice at 3 months compared with controls. EPR analysis revealed significantly increased ROS (superoxide, hydrogen peroxide and nitroxide) in 3-month old hR120GCryAB TG compared with controls. In contrast, hR120GCryAB-TG mice at 6-months exhibiting cardiac hypertrophy and RS (i.e., increased GSH/GSSG ratio) had attenuated ROS/RNS levels that were indistinguishable from age-matched controls. Conclusions: Oxidative stress triggers the activation of redox sensitive Nrf2-Keap1 pathway, which might be targeted therapeutically to prevent pathogenic transition and reductive stress-induced hR120GCryAB cardiomyopathy and heart failure.
Ability of children aged 5-16 years to perform scat3 and child-scat3 testing in the emergency department
Authors: Franz E Babl, Diana V Dionisio, Lucy Davenport, Amy Baylis, Stephen Hearps, Silvia Bressan, Vicki Anderson, Ed Oakley, Gavin A Davis
Journal: British Journal of Sports Medicine (2017)

Objective To evaluate children’s ability to perform the child-SCAT3 and SCAT3 Sports Concussion Assessment Tool. Design Prospective observational study. Setting Tertiary children’s hospital emergency department. Participants 264 children presenting to ED with concussion (CONC, n=90) and two control groups (i) upper limb injury (ULI, n=90) and (ii) well children (WELL, n=84) with equal sized subgroups in three age bands of 5–8, 9–12, and 13–16 years. Assessment and outcome Ability to complete SCAT subtests administered by trained research assistants, stratified by age band and participant group. Child-SCAT3 was used for 5–12 years, SCAT3 for 13–16 years. Results Inability to complete at least one sub-test of child-SCAT3 occurred in 29 (32.2%) of the 5-8 year age band and 5 (5.5%) in the 9–12 year age band. The 5 and 6 year olds had the lowest completion rates. In the 13–16 year age band 11 (13.3%) participants were unable to complete at least one sub-test of SCAT3. The most frequent reasons for inability to complete any sub-test (n=116) were ‘did not understand’ (n=45), and ‘refusal to continue’ (n=26). Fewer were due to ‘feeling too unwell to continue’ (n=13).The subtests with the highest rates of inability to complete were child-SCAT3 and SCAT symptoms scale (n=17), BESS (n=9), coordination (n=9), digits backwards (n=8) and concentration (n=8). Conclusions Child-SCAT3 should be applied with caution in young children due to an inability to understand certain test items and may need to be modified. SCAT3 can be reliably applied in teenagers 13–16 years of age. Competing interests GAD is an honorary member of the Australian Football League Concussion Working Group, and has attended meetings organised by sporting organisations including the National Football League (USA), National Rugby League (Australia) and FIFA (Switzerland); however has not received any payment, research funding, or other monies from these groups other than for travel costs. GAD is a member of the International Concussion in Sport group that developed the SCAT3 and ChildSCAT3.
Effects of the Informed Health Choices podcast on the ability of parents of primary school children in Uganda to assess claims about treatment effects: a randomised controlled trial
Authors: Daniel Semakula, Allen Nsangi, Andrew D Oxman, Matt Oxman, Astrid Austvoll-Dahlgren, Sarah Rosenbaum, Angela Morelli, Claire Glenton, Simon Lewin, Margaret Kaseje, Iain Chalmers, Atle Fretheim, Doris Tove Kristoffersen, Nelson K Sewankambo
Journal: The Lancet (2017)
TTF1 status as a better predictor of benefit to erlotinib (E) in metastatic non-small cell lung cancer (NSCLC) than sex, histology, and smoking status.
Authors: Charalambos Haris Charalambous, Charis Charalambous, Dimitrios Vomvas, Nikos Katodritis, Marios P. Decatris
Journal: Journal of Clinical Oncology (2013)

e19110 Background: Erlotinib (E) is currently indicated as first line therapy in patients with EGFR mutations, and as second and third line treatment for patients with advanced metastatic NSCLC. In Cyprus comprehensive EGFR testing started in January 2011. In this study we reviewed all the patients that received E between 2007-2010, without having undergone EGFR mutation testing, looking at predictive factors for benefit. Methods: 100 consecutive patients are included. 3 patients received this as 1st line, 49 patiens as 2nd line and 48 patients as 3rd line and beyond. Previous treatments gemcitabine platinum doublet as first line, and either pemetrexed or docetaxel as 2nd line therapy. Patients had regular Chest x-rays (every 2-3 months) and CT scans (every 4-6 months). Results: 40 female and 60 male, with 9 patients still alive and on treatment. Median age is 66 years (range 32-79). 45 patients were WHO performance status (PS) 0-1, 47 PS 2-3, 8 patients PS not recorded. Median progression-free survival (PFS) for all patients was 95 days( 95% CI 68-118). Median overall survival (OS) from starting E was 144 days (95% CI 103-185). Ten (10) patients had a partial response and 34 stable disease. Subset analyses were undertaken based on smoking status, sex, histology type and TTF1. Univariate analysis for PFS using KM plots showed a statistically significant difference for sex, smoking and TTF1. On Cox regression only gender and TTF1 were statistically significant (0.007 and 0.006). There was a striking difference in both median PFS and median OS between patients with TTF1-ve tumours (33 days) and TTF1 +ve tumours (149 days). Conclusions: TTF1 is a better predictor of benefit to E than histology, sex and smoking status. The very low median PFS and OS for patients with TTF1 –ve tumors would suggest that such patients derive little or no benefit from E. [Table: see text]
β-Blockers and Mortality After Acute Myocardial Infarction in Patients Without Heart Failure or Ventricular Dysfunction
Authors: Tatendashe B. Dondo, Marlous Hall, Robert M. West, Tomas Jernberg, Bertil Lindahl, Hector Bueno, Nicolas Danchin, John E. Deanfield, Harry Hemingway, Keith A.A. Fox, Adam D. Timmis, Chris P. Gale
Journal: Journal of the American College of Cardiology (2017)

For acute myocardial infarction (AMI) without heart failure (HF), it is unclear if β-blockers are associated with reduced mortality. The goal of this study was to determine the association between β-blocker use and mortality in patients with AMI without HF or left ventricular systolic dysfunction (LVSD). This cohort study used national English and Welsh registry data from the Myocardial Ischaemia National Audit Project. A total of 179,810 survivors of hospitalization with AMI without HF or LVSD, between January 1, 2007, and June 30, 2013 (final follow-up: December 31, 2013), were assessed. Survival-time inverse probability weighting propensity scores and instrumental variable analyses were used to investigate the association between the use of β-blockers and 1-year mortality. Of 91,895 patients with ST-segment elevation myocardial infarction and 87,915 patients with non–ST-segment elevation myocardial infarction, 88,542 (96.4%) and 81,933 (93.2%) received β-blockers, respectively. For the entire cohort, with >163,772 person-years of observation, there were 9,373 deaths (5.2%). Unadjusted 1-year mortality was lower for patients who received β-blockers compared with those who did not (4.9% vs. 11.2%; p < 0.001). However, after weighting and adjustment, there was no significant difference in mortality between those with and without β-blocker use (average treatment effect [ATE] coefficient: 0.07; 95% confidence interval [CI]: −0.60 to 0.75; p = 0.827). Findings were similar for ST-segment elevation myocardial infarction (ATE coefficient: 0.30; 95% CI: −0.98 to 1.58; p = 0.637) and non–ST-segment elevation myocardial infarction (ATE coefficient: −0.07; 95% CI: −0.68 to 0.54; p = 0.819). Among survivors of hospitalization with AMI who did not have HF or LVSD as recorded in the hospital, the use of β-blockers was not associated with a lower risk of death at any time point up to 1 year. (β-Blocker Use and Mortality in Hospital Survivors of Acute Myocardial Infarction Without Heart Failure; NCT02786654)
LGG-06. FUNCTIONAL AND THERAPEUTIC RELEVANCE OF MYB-QKI-INDUCED TRANSCRIPTIONAL EVENTS TO GLIOMAGENESIS
Authors: Cecile Rouleau, Pratiti Bandopadhayay, Lori Ramkissoon, Rameen Beroukhim
Journal: Neuro-Oncology (2017)

INTRODUCTION: The large-scale genomic analysis of pediatric low-grade gliomas recently conducted in our laboratories identified the MYB-QKI fusion as a genetic driver of angiocentric glioma. MYB-QKI retains the MYB HTH DNA-binding domain and functions as a transcription factor. These findings present the opportunity to design the first targeted therapy for this tumor. METHODS: We investigated the functional significance of MYB-QKI-driven transcriptional events using the Connectivity Map, a catalog of transcriptional signatures from disease states and genetic and pharmacological perturbation experiments. To identify potential dependencies in the MYB-QKI phenotype, we focused on genetic perturbagens, such as knockdown or overexpression of single genes, with transcriptional signatures similar to that of MYB-QKI. To identify drugs with potential activity against MYB-QKI-driven glioma, we focused on pharmacological perturbagens with transcriptional signatures that oppose that of MYB-QKI. Findings were validated empirically in functional assays. RESULTS: Expression analysis identified CDK6 and the tyrosine kinase receptor c-KIT as two of the genes most highly upregulated by MYB-QKI compared to control. Connectivity Map analysis showed that overexpression of CDK6 as a single gene produced a transcription signature highly similar to that of MYB-QKI, suggesting that CDK6 may be a key mediator of the MYB-QKI phenotype. The Connectivity Map also suggested that pharmacological inhibition of signaling pathways downstream of tyrosine kinase receptors produced an opposing signature to that of MYB-QKI. Since expression of the tyrosine kinase receptor c-KIT is highly induced by MYB-QKI, this result suggested that c-KIT inhibition may be therapeutically effective in MYB-QKI-driven glioma. Functional assays confirmed that the c-KIT inhibitor dasatinib could inhibit the growth of MYB-QKI-expressing neural stem cells but not that of control cells. CONCLUSIONS: Exploration of the MYB-QKI transcriptional signature with the Connectivity Map suggests that CDK6 and c-KIT inhibition warrant further investigation as potential therapies for MYB-QKI tumors. *Co-First Authors: Dr. Cecile Rouleau and Dr. Pratiti Bandopadayay. Co-Last Authors: Dr. Keith Ligon and Dr. Rameen Beroukhim
Influenza Activity—United States, 1989-1990
Journal: JAMA (1990)

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The physiognomic unity of sign, word, and gesture
Authors: Carlos Cornejo, Roberto Musa
Journal: Behavioral and Brain Sciences (2017)

Abstract Goldin-Meadow &amp; Brentari (G-M&amp;B) are implicitly going against the dominant paradigm in language research, namely, the “speech as written language” metaphor that portrays vocal sounds and bodily signs as means of delivering stable word meanings. We argue that Heinz Werner's classical research on the physiognomic properties of language supports and complements their view of sign and gesture as a unified system.
What fixations reveal about oculomotor scanning behavior in visual search
Authors: Zhuanghua Shi, Xuelian Zang, Thomas Geyer
Journal: Behavioral and Brain Sciences (2017)

Abstract Hulleman &amp; Olivers' (H&amp;O's) conceptual framework does not consider variation of fixation duration and its interaction with the size of the functional viewing field (FVF). Here we provide empirical evidence of a dynamic interaction between the two parameters, suggesting that fixations, as the central unit in H&amp;O's framework, should be studied on both the spatial and temporal dimensions.