tbuckley/cabot-search huggingface dataset:
The cysteinyl leukotriene 3 receptor regulates expansion of IL-25–producing airway brush cells leading to type 2 inflammation
Authors: Lora G. Bankova, Daniel F. Dwyer, Eri Yoshimoto, Saltanat Ualiyeva, John W. McGinty, Hannah Raff, Jakob von Moltke, Yoshihide Kanaoka, K. Frank Austen, Nora A. Barrett
Journal: Science Immunology (2018)

The leukotriene E 4 receptor, CysLT 3 R, regulates allergen-elicited expansion of airway brush cells and type 2 inflammation.
Abstract 18308: Cardiorespiratory Fitness and Incident Cerebrovascular Accidents: The FIT (Henry Ford ExercIse Testing) Project
Authors: Mouaz H Al-Mallah, Michael J Blaha, Amjad Ahmed, Fatimah Almasoudi, Sherif Sakr, Waqas Qureshi, Clinton A Brawner, Jonathan K Ehrman, Steven J Keteyian
Journal: Circulation (2017)

Background: Prior studies have shown that cardiorespiratory fitness (CRF) is a strong predictor of mortality. However, there is limited data investigating the association between CRF and incident c...
Abstract 17627: Is the Post-menopausal Rise in PCSK9 Levels Due to Loss of the Estrogen Responsive Anti-atherogenic Protein, Heat Shock Protein 27? Insights Into a Potential New PCSK9 Lowering Therapy
Authors: Jean-Claude Bakala N'Goma, Chunhua Shi, Vivek Krishna Pulakazhi Venu, Yong-Xiang Chen, Edward R O'Brien
Journal: Circulation (2015)

Introduction: Previously we reported that elevated serum levels of Heat Shock Protein 27 represent a predictive biomarker of reduced cardiovascular clinical events. Moreover, attenuation of experimental atherogenesis, characterized by reduced cholesterol levels in both the artery wall and serum, can be achieved by augmenting serum HSP27 levels (e.g., with recombinant HSP27). PCSK9 plays a central role in regulating the abundance of hepatic LDL-receptors, and hence serum and plaque cholesterol levels. Interestingly, PCSK9 levels rise with menopause (Dallas Heart Study) and we previously published that HSP27 levels are markedly attenuated post-ovariectomy. Hence, we hypothesize that HSP27 augments hepatic cholesterol uptake via reductions in PCSK9 levels. Methods / Results: 1. In vitro studies: HepG2 (liver) cells were maintained in culture for 24 hours with or without rHSP27. The hepatic levels of apoB100 did not change with rHSP27 treatment. ApoB100 containing lipoproteins were reduced in the cell culture media with rHSP27 treatment (Western Blot: p=0.008; ELISA: p=0.0025). rHSP27 treatment reduced hepatic PCSK9 protein levels (Western Blot: p=0.019), increased LDL receptor protein levels (Western Blot: p=0.001) and increased (fluorescent) LDL uptake (p=0.022). Levels of hepatic SREBP2 and HMG-CoA reductase proteins were unaltered with rHSP27 treatment. 2. In vivo studies: Female ApoE-/- mice fed high fat diet and injected weekly with rHSP27 or PBS for 8 weeks. Serum total cholesterol and plasma PCSK9 levels were ~20-40% lower in the rHSP27 treated vs. control mice. Mice treated with rHSP27 showed reductions in aortic lesion area of ~40% for en face and ~35% for cross-sectional sinus tissue sections. Conclusions: These findings suggest that HSP27, an endogenous estrogen responsive protein, can lower extracellular cholesterol levels by reducing PCSK9 expression. Hence there is promise for the development of HSP27 “replacement” therapy for the prevention and modification of atherosclerosis via reductions in PCSK9 expression. Current clinical studies examining the relationship between HSP27 and PCSK9 levels in women undergoing prophylactic ovariectomy for BRAC1/2 (i.e., the “Angelina Effect”) are ongoing.
Percutaneous Intramyocardial Septal Radiofrequency Ablation for Hypertrophic Obstructive Cardiomyopathy
Authors: Liwen Liu, Jing Li, Lei Zuo, Jinzhou Zhang, Mengyao Zhou, Bo Xu, Rebeccca T. Hahn, Martin B. Leon, David H. Hsi, Junbo Ge, Xiaodong Zhou, Jun Zhang, Shuping Ge, Lize Xiong
Journal: Journal of the American College of Cardiology (2018)
Cholestenoic acid is a prognostic biomarker in acute respiratory distress syndrome
Authors: Jennifer H. Madenspacher, Renee D. Stapleton, Benjamin T. Suratt, Anne E. Dixon, Fred B. Lih, Julie M. Lowe, Kara J. Mould, William J. Janssen, Eric D. Morrell, Mark M. Wurfel, Stavros Garantziotis, Kenneth B. Tomer, Michael B. Fessler
Journal: Journal of Allergy and Clinical Immunology (2018)
Abstract 19326: Ventricular Arrhythmia is Correlated to Novel Indices of Myocardial Viability in the Peri-Infarct Region Using Manganese Enhanced MRI
Authors: Atsushi Tachibana, Junaid Zaman, Evgenios Neofytou, Hiromi Sano, Jennifer Lyons, Ikeno Fumiaki, Yoshiaki Mitsutake, Joseph Gold, Sanjiv Narayan, Rajesh Dash, Joseph Wu, Phillip Yang
Journal: Circulation (2016)

Introduction: While a significant correlation between the peri-infarct region (PIR) and ventricular arrhythmia has been well recognized, reliable non-invasive detection of this arrhythmogenic regio...
Who are Sierra Leone’s health security efforts for?
Authors: Mara Kardas-Nelson, Raphael Frankfurter
Journal: BMJ (2018)

After the west African Ebola outbreak of 2014-16, international agencies have helped to establish disease surveillance operations in the region, find <b>Mara Kardas-Nelson</b> and <b>Raphael Frankfurter</b>, but Sierra Leone’s health security efforts may not be improving outcomes for patients
Regulating 3D-printed medical products
Authors: Laura M. Ricles, James C. Coburn, Matthew Di Prima, Steven S. Oh
Journal: Science Translational Medicine (2018)

Additive manufacturing [also known as three-dimensional (3D) printing] is the layer-wise deposition of material to produce a 3D object. This rapidly emerging technology has the potential to produce new medical products with unprecedented structural and functional designs. Here, we describe the U.S. regulatory landscape of additive manufactured (3D-printed) medical devices and biologics and highlight key challenges and considerations.
Secreted IgD Amplifies Humoral T Helper 2 Cell Responses by Binding Basophils via Galectin-9 and CD44
Authors: Meimei Shan, Jorge Carrillo, Ada Yeste, Cindy Gutzeit, Daniel Segura-Garzón, A. Cooper Walland, Marc Pybus, Emilie K. Grasset, John R. Yeiser, Dean B. Matthews, Willem van de Veen, Laura Comerma, Bing He, Tadech Boonpiyathad, Haekyung Lee, Julià Blanco, Lisa C. Osborne, Mark C. Siracusa, Mübeccel Akdis, David Artis, Saurabh Mehandru, Hugh A. Sampson, M. Cecilia Berin, Kang Chen, Andrea Cerutti
Journal: Immunity (2018)
Publisher Correction: Clinical activity and molecular correlates of response to atezolizumab alone or in combination with bevacizumab versus sunitinib in renal cell carcinoma
Authors: David F. McDermott, Mahrukh A. Huseni, Michael B. Atkins, Robert J. Motzer, Brian I. Rini, Bernard Escudier, Lawrence Fong, Richard W. Joseph, Sumanta K. Pal, James A. Reeves, Mario Sznol, John Hainsworth, W. Kimryn Rathmell, Walter M. Stadler, Thomas Hutson, Martin E. Gore, Alain Ravaud, Sergio Bracarda, Cristina Suárez, Riccardo Danielli, Viktor Gruenwald, Toni K. Choueiri, Dorothee Nickles, Suchit Jhunjhunwala, Elisabeth Piault-Louis, Alpa Thobhani, Jiaheng Qiu, Daniel S. Chen, Priti S. Hegde, Christina Schiff, Gregg D. Fine, Thomas Powles
Journal: Nature Medicine (2018)
SERPINE1 IDENTIFIED AS POTENTIAL THERAPEUTIC TARGET THROUGH RNA-SEQ OF CLINICALLY RELEVANT INVASIVE GLIOBLASTOMA CELLS ISOLATED FROM PATIENTS BY 5-ALA BASED METHODOLOGY
Authors: Jonathan Rowlinson, Maria de los Angeles Estevez-Cebrero, Anbarasu Lourdusamy, Ruman Rahman, Stuart Smith
Journal: Neuro-Oncology (2018)

We previously described a method to separate residual tumour cells from normal brain using fluorescent activated cell sorting (FACS). Using RNA-Seq on these cells we have identified new potential targets including SERPINE1, whose expression remains high in tumour cells as they invade into normal tissue. 5-aminolevulinic acid (5-ALA) is a clinically used drug that facilitates fluorescence guided resection of glioblastoma (GBM). 11 tumour samples were dissociated and FACS used to separate residual fluorescent cancer cells (1%) from within normal brain. FACS sorted and unsorted mixed samples from tumour core, rim and invasive margin were compared. Gene expression was analysed by RNA-Seq and validated by qPCR, IHC and in vivo xenografts. Differential expression analysis identified 2567 genes with differences between core and invasive margin, and 78 genes with differences between 5-ALA FACS positive and FACS negative. Interestingly SERPINE1 expression is reduced in the unsorted invasive margin but expression remains high within sorted invasive tumour cells. Pathway analysis identified a predominance of immune system pathway changes between core and invasive margin. The differential expression of SERPINE1, VEGF, CHI3L1 and RTN1 in qPCR and IHC validated the same changes observed from the RNA-Seq data. The invasive and tumorigenic capacity of 5-ALA positive sorted tumour cells was confirmed by enhanced engraftment in a mouse flank model compared to unsorted cells, whereas non 5-ALA sorted cells failed to engraft. This study has demonstrated that 5-ALA fluorescent sorting of tumour cells from the invasive margin can identify new targets such as SERPINE1, whose high expression in invasive tumour cells would otherwise be overlooked. Our approach gives hope that we can interrogate the true residual disease, and for the first time gain insight into the source of tumour recurrence.
Post‐traumatic stress disorder in Stevens–Johnson syndrome and toxic epidermal necrolysis: prevalence and risk factors. A prospective study of 31 patients
Authors: L. Hefez, K. Zaghbib, E. Sbidian, L. Valeyrie‐Allanore, M. Allain, T.A. Duong, A. Colin, F. Bellivier, H. Romano, N. de Prost, K. Chazelas, O. Chosidow, P. Wolkenstein, S. Ingen‐Housz‐Oro
Journal: British Journal of Dermatology (2018)

Epidermal necrolysis is a rare and severe cutaneous adverse reaction to drugs with long-term somatic consequences and potentially underrecognized psychological complications.To assess the prevalence and risk factors of post-traumatic stress disorder (PTSD) in Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in a population of adults undergoing psychiatric evaluation.In this prospective study, we included adult patients admitted at the acute phase of SJS/TEN to our dermatology department from June 2009 to February 2013. The main objective was to assess the prevalence of PTSD at 6 months after the acute disease phase, defined by a PTSD Checklist score > 44. Secondary objectives were to investigate risk factors of PTSD in the medical history of patients and characteristics of the disease at the acute phase by the Peritraumatic Dissociative Experience Questionnaire (PDEQ) and Peritraumatic Distress Inventory (PDI) and the degree of impairment on the Sheehan Disability Scale.We initially included 32 of 80 patients admitted during the study period. At 6 months, seven of 30 still followed up had a PTSD Checklist score > 44, suggesting a PTSD prevalence of 23%; 23 (77%) patients had a hydroxyzine prescription at the acute phase. The main risk factors associated with PTSD at 6 months were psychological results at the acute phase.Despite frequent prescription of hydroxyzine at the acute phase, almost one-quarter of patients with SJS/TEN had PTSD at 6 months. A systematic psychiatric evaluation should be offered regularly for at least 1 year after the acute disease phase.
Evolutionary and developmental dynamics of sex-biased gene expression in common frogs with proto-Y chromosomes
Authors: Wen-Juan Ma, Paris Veltsos, Roberto Sermier, Darren J Parker, Nicolas Perrin
Journal: Genome biology (2018)

The patterns of gene expression on highly differentiated sex chromosomes differ drastically from those on autosomes, due to sex-specific patterns of selection and inheritance. As a result, X chromosomes are often enriched in female-biased genes (feminization) and Z chromosomes in male-biased genes (masculinization). However, it is not known how quickly sexualization of gene expression and transcriptional degeneration evolve after sex-chromosome formation. Furthermore, little is known about how sex-biased gene expression varies throughout development.We sample a population of common frogs (Rana temporaria) with limited sex-chromosome differentiation (proto-sex chromosome), leaky genetic sex determination evidenced by the occurrence of XX males, and delayed gonadal development, meaning that XY individuals may first develop ovaries before switching to testes. Using high-throughput RNA sequencing, we investigate the dynamics of gene expression throughout development, spanning from early embryo to froglet stages. Our results show that sex-biased expression affects different genes at different developmental stages and increases during development, reaching highest levels in XX female froglets. Additionally, sex-biased gene expression depends on phenotypic, rather than genotypic sex, with similar expression in XX and XY males; correlates with gene evolutionary rates; and is not localized to the proto-sex chromosome nor near the candidate sex-determining gene Dmrt1.The proto-sex chromosome of common frogs does not show evidence of sexualization of gene expression, nor evidence for a faster rate of evolution. This challenges the notion that sexually antagonistic genes play a central role in the initial stages of sex-chromosome evolution.
THE ACCURACY OF BRAIN METASTASES CONTOURING FOR STEREOTACTIC RADIOSURGERY (SRS) BY NEURO-ONCOLOGISTS; WHAT DO THE NEURO-RADIOLOGIST AND NEURO-SURGEON ADD?
Authors: Claire Hobbs, Pieter Pretorius, Robin Joseph, Sanjeeva Jeyaretna, Nicola Warner, Sriram Padmanaban, Clare Tunstall, Rhona Watson
Journal: Neuro-Oncology (2018)

Variability exists between clinical oncologists when contouring gross tumour volume (GTV) and normal tissue organs at risk (OAR) volumes. This variability is the ‘weakest link’ in the context of the highly conformal and highly accurate treatment delivery used for SRS. In 2016-17NHS England commissioned 17 SRS centres. The service specification mandates “treatment protocols will ensure that target definition is performed by either a sub-specialised neuro-surgeon and / or neuro-oncologist (clinical oncologist) with input from a neuro-radiologist before a treatment plan is created.”. To evaluate the additional contribution by the neuro radiologist we analysed contouring conformality for all 47 patients treated in our centre between June 2017 and February 2018. GTV margins were contoured first by the clinical oncologist, and then copied and amended with input from the neuroradiologist and sometimes neurosurgeon. 1 mm margin was added to the GTV for the planning target volume (PTV). 47 patients, each with 1–4 metastases/resection cavities, resulted in treatment plans for 67 metastases/cavities. Doses used were: 15-24Gy in 1 fraction, 24Gy in 3 fractions or 25-30Gy in 5 fractions (if close to critical optic structures or brainstem). We used Eclipse TPS (v13.7) for Varian (Palo Alto, CA) Clinac iX with millennium MLC (5 mm) and Exactrac imaging system (Brainlab, Munich DE). All plans were created either using dynamic conformal arc (DCA) or VMAT RapidArc (RA) techniques with 6 MV photons and calculated using AAA (v10) on a 1 mm dose grid. Values for the final treated GTV and PTV (A) were compared with the GTV and PTV that were generated by the Clinical oncologist alone (B) will be compared using the Conformity analysis consisted of Jaccard coefficient, Dice coefficient, Geographical Miss and Discordance index as defined below. Results will be presented.
Acupuncture for Women Undergoing In Vitro Fertilization
Authors: Sherman Gu
Journal: JAMA (2018)

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Indian government dissolves Medical Council of India
Authors: Sanjeet Bagcchi
Journal: BMJ (2018)

India’s government has discontinued the Medical Council of India—the top regulatory body for medical education in the country—with immediate effect.

The government issued an ordinance on 26 September 2018 to supersede the council and divest its functions to an appointed seven member board of governors.

This board will perform the council’s functions for one year until a new regulatory body—the National Medical Commission—is formed in accordance with the provisions of the National Medical Commission Bill 2017, which is pending clearance in the Indian parliament.

The decision was taken after an oversight committee, formed by the government …
Long-Term Survival in Patients Responding to Anti–PD-1/PD-L1 Therapy and Disease Outcome upon Treatment Discontinuation
Authors: Marie-Léa Gauci, Emilie Lanoy, Stéphane Champiat, Caroline Caramella, Samy Ammari, Sandrine Aspeslagh, Andrea Varga, Capucine Baldini, Rastilav Bahleda, Anas Gazzah, Jean-Marie Michot, Sophie Postel-Vinay, Eric Angevin, Vincent Ribrag, Antoine Hollebecque, Jean-Charles Soria, Caroline Robert, Christophe Massard, Aurélien Marabelle
Journal: Clinical Cancer Research (2018)

Anti-PD-(L)1 can provide overall survival (OS) benefits over conventional treatments for patients with many different cancer types. However, the long-term outcome of cancer patients responding to these therapies remains unknown. This study is an exploratory study that aimed to describe the long-term survival of patients responding to anti-PD-(L)1 monotherapy across multiple cancer types.Patients and Methods: Data from patients treated with an anti-PD-(L)1 monotherapy in a phase I trial at Gustave Roussy were retrospectively analyzed over a period of 5 years. All cancer types (n = 19) were included. Clinical and biological factors associated with response, long-term survival, and secondary refractory disease were studied.Among 262 eligible patients, the overall objective response rate was 29%. The median progression-free survival of responder patients (RP) at 3 months was 30 months, and the median OS of RP was not reached after a median follow-up of 34 months. In RPs, 3- and 5-year OS percentages were 84% and 64%, respectively. No death occurred in the 21 complete responders (CR) during the overall follow-up. However, many partial responders (PR) showed subsequent tumor relapses to treatment. Long responders (response ≥2 years) represented 11.8% of the overall population. These findings should be validated in further prospective studies.There are currently no differences in therapeutic strategies between CRs and PRs to anti-PD-(L)1. We found a striking difference in OS between these two types of responses. Our results are in favor of evaluating patient stratification strategies and intensification of treatments when tumor lesions of a partial responder to immunotherapy stop improving.See related commentary by Cohen and Flaherty, p. 910.
Abstract 13090: Increased U Vector Magnitude is Associated With Increased Risk of Sudden Cardiac Death - The Atherosclerosis Risk in Communities Study
Authors: Jonathan W Waks, Muammar Kabir, Golriz Sedaghat, Jason Thomas, Tor Biering-Sørensen, Nona Sotoodehnia, Colleen M Sitlani, Mary L Biggs, Charles A Henrikson, Elsayed Z Soliman, Scott D Solomon,, Wendy S Post, David S Siscovick, Alfred E Buxton, Mark E Josephson, Larisa G Tereshchenko
Journal: Circulation (2016)

Introduction: The U wave is a poorly understood electrocardiographic (ECG) manifestation of late ventricular repolarization. The association between U waves and sudden cardiac death (SCD) in the general population is unclear. Hypothesis: Large U vector magnitude is associated with increased SCD risk. Methods: Data from the Atherosclerosis Risk in Communities study (n=13,705; mean age 54.1±5.8 y; 73% male; 55% white; median follow-up 14 y) were analyzed. U wave onset and offset were identified using a semi-automated approach on XYZ transformed ECG leads. The 3-dimensional U wave loop was reconstructed and smoothed to reduce noise. U loop origin was defined as the point halfway between U-onset and U-offset in 3-dimensional space. Maximum U vector magnitude (UVMmax) was measured as the 3-dimensional distance between U loop origin and the point on the smoothed U loop farthest from the origin (Figure A). Participants with UVMmax &gt;100 μV were excluded due to difficulty differentiating the T wave and U wave on these ECGs. Adjusted Cox proportional hazards models were used to investigate the association between UVMmax and adjudicated SCD. Results: Median UVMmax was 9.4 μV. After adjustment for multiple demographic and clinical characteristics, electrolytes, and ECG parameters associated with SCD, UVMmax remained associated with SCD. Each 1 standard deviation increase in UVMmax was associated with an increase in the hazard of SCD (HR 1.53, 95% CI 1.29-1.81, p&lt;0.0001). Using cubic splines, the HR for SCD increased as UVMmax increased (Figure B). A minority of participants with the highest UVMmax values had SCD risk that was 4-5 times that of participants with UVMmax of ~10 μV. Conclusions: Larger U-waves as assessed vectorcardiographically by higher UVMmax are independently associated with SCD in a large community based cohort. VCG analysis of the U wave is useful, and further study of the association between U waves and ventricular arrhythmias/SCD is warranted.
A cross-species approach to disorders affecting brain and behaviour
Authors: Orrin Devinsky, Jordyn M. Boesch, Sofia Cerda-Gonzalez, Barbara Coffey, Kathryn Davis, Daniel Friedman, Brian Hainline, Katherine Houpt, Daniel Lieberman, Pamela Perry, Harald Prüss, Martin A. Samuels, Gary W. Small, Holger Volk, Artur Summerfield, Charles Vite, Thomas Wisniewski, Barbara Natterson-Horowitz
Journal: Nature Reviews Neurology (2018)
Genomic Differences Between “Primary” and “Secondary” Muscle-invasive Bladder Cancer as a Basis for Disparate Outcomes to Cisplatin-based Neoadjuvant Chemotherapy
Authors: Eugene J. Pietzak, Emily C. Zabor, Aditya Bagrodia, Joshua Armenia, Wenhuo Hu, Ahmet Zehir, Samuel Funt, Francois Audenet, David Barron, Noelia Maamouri, Qiang Li, Min Yuen Teo, Maria E. Arcila, Michael F. Berger, Nikolaus Schultz, Guido Dalbagni, Harry W. Herr, Dean F. Bajorin, Jonathan E. Rosenberg, Hikmat Al-Ahmadie, Bernard H. Bochner, David B. Solit, Gopa Iyer
Journal: European Urology (2018)