tbuckley/cabot-search huggingface dataset:
<i>TCF7L2</i> Genetic Variation Augments Incretin Resistance and Influences Response to a Sulfonylurea and Metformin: The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH)
Authors: Shylaja Srinivasan, Varinderpal Kaur, Bindu Chamarthi, Katherine R. Littleton, Ling Chen, Alisa K. Manning, Jordi Merino, Melissa K. Thomas, Margo Hudson, Allison Goldfine, Jose C. Florez
Journal: Diabetes Care (2018)

OBJECTIVE The rs7903146 T allele in transcription factor 7 like 2 (TCF7L2) is strongly associated with type 2 diabetes (T2D), but the mechanisms for increased risk remain unclear. We evaluated the physiologic and hormonal effects of TCF7L2 genotype before and after interventions that influence glucose physiology. RESEARCH DESIGN AND METHODS We genotyped rs7903146 in 608 individuals without diabetes and recorded biochemical data before and after 1) one dose of glipizide (5 mg) on visit 1 and 2) a 75-g oral glucose tolerance test (OGTT) performed after administration of metformin 500 mg twice daily over 2 days. Incretin levels were measured in 150 of the 608 participants. RESULTS TT risk-allele homozygotes had 1.6 mg/dL higher baseline fasting glucose levels and 2.5 pg/mL lower glucagon levels per T allele than carriers of other genotypes at baseline. In a subset of participants, the T allele was associated with higher basal glucagon-like peptide 1 (GLP-1) levels at visit 1 (β = 1.52, P = 0.02 and β = 0.96, P = 0.002 for total and active GLP-1, respectively), and across all points of the OGTT after metformin administration. Regarding drug response, the T allele was associated with a shorter time (β = −7.00, P = 0.03) and a steeper slope (β = 0.23, P = 0.04) to trough glucose levels after glipizide administration, and lower visit 2 fasting glucose level adjusted for visit 1 fasting glucose level (β = −1.02, P = 0.04) and a greater decline in glucose level between visits (β = −1.61, P = 0.047) after metformin administration. CONCLUSIONS Our findings demonstrate that common variation at TCF7L2 influences acute responses to both glipizide and metformin in people without diabetes and highlight altered incretin signaling as a potential mechanism by which TCF7L2 variation increases T2D risk.
CHANGES IN METABONOMIC PROFILE DURING PEANUT-INDUCED ANAPHYLAXIS AND CORRELATION WITH SYMPTOM
Authors: Paul J. Turner, Monica Ruiz Garcia, Isabel J. Skypala, Stephen R. Durham, Robert J. Boyle, Gonçalo D.S. Correia, Jake T.M. Pearce, Elaine Holmes
Journal: Journal of Allergy and Clinical Immunology (2018)
Abstract 20518: Improved Adherence to Heart Failure Medications Correlates With Reduced Mortality
Authors: Anton M Vehovec, Emily Gathright, Mary A Dolansky, Richard Josephson, Joel Hughes
Journal: Circulation (2016)

Introduction: Adherence to heart failure (HF) medication regimens is associated with improved outcomes, such as reduced mortality. However, many studies define adequate adherence as 80% despite a l...
Changes in Hospital–Physician Affiliations in U.S. Hospitals
Authors: Kirstin W. Scott, E. John Orav, David M. Cutler, Ashish K. Jha
Journal: Annals of Internal Medicine (2018)

Letters16 January 2018Changes in Hospital–Physician Affiliations in U.S. HospitalsKirstin W. Scott, MPhil, PhD, E. John Orav, PhD, David M. Cutler, PhD, and Ashish K. Jha, MD, MPHKirstin W. Scott, MPhil, PhDHarvard Medical School, Boston, Massachusetts (K.W.S.)Search for more papers by this author, E. John Orav, PhDBrigham and Women's Hospital, Boston, Massachusetts (E.J.O.)Search for more papers by this author, David M. Cutler, PhDHarvard University, Cambridge, Massachusetts (D.M.C.)Search for more papers by this author, and Ashish K. Jha, MD, MPHHarvard T.H. Chan School of Public Health, Boston, Massachusetts (A.K.J.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L17-0686 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We agree with Dr. Bedsole that, as others have found, financial motivations often underlie the real reasons that hospitals acquire physician practices (1). We also agree that there are substantial and growing challenges to the private practice of medicine and that whether this form of practice will be sustainable in the long run is uncertain.Dr. Ertle notes the important nuance that an employment model does not mean that physicians are not compensated based on financial productivity. Our point in the statement that he quotes is that hospitals can use these arrangements to drive quality, but the evidence ...Reference1. Baker LC, Bundorf MK, Kessler DP. Vertical integration: hospital ownership of physician practices is associated with higher prices and spending. Health Aff (Millwood). 2014;33:756-63. [PMID: 24799571] doi:10.1377/hlthaff.2013.1279 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Harvard Medical School, Boston, Massachusetts (K.W.S.)Brigham and Women's Hospital, Boston, Massachusetts (E.J.O.)Harvard University, Cambridge, Massachusetts (D.M.C.)Harvard T.H. Chan School of Public Health, Boston, Massachusetts (A.K.J.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M16-0125. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoChanges in Hospital–Physician Affiliations in U.S. Hospitals and Their Effect on Quality of Care Kirstin W. Scott , E. John Orav , David M. Cutler , and Ashish K. Jha Changes in Hospital–Physician Affiliations in U.S. Hospitals Alan R. Ertle Changes in Hospital–Physician Affiliations in U.S. Hospitals Russell L. Bedsole Changes in Hospital–Physician Affiliations in U.S. Hospitals Edward Ringel Metrics 16 January 2018Volume 168, Issue 2Page: 156-157KeywordsDisclosureMotivation ePublished: 16 January 2018 Issue Published: 16 January 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Major Allergens Sensitized by Thai Patients with Wheat Anaphylaxis
Authors: Nuntanut Rutrakool, Surapon Piboonpocanun, Witchaya Srisuwatchari, Orathai Jirapongsananuruk, Nualanong Visitsunthorn, Torpong Thongngarm, Pakit Vichyanond, Punchama Pacharn
Journal: Journal of Allergy and Clinical Immunology (2018)
Subcutaneous immunotherapy with purified Der p1 and 2 suppresses type 2 immunity in a murine asthma model
Authors: L. Hesse, N. van Ieperen, C. Habraken, A. H. Petersen, S. Korn, T. Smilda, B. Goedewaagen, M. H. Ruiters, A. C. van der Graaf, M. C. Nawijn
Journal: Allergy (2018)

Abstract Background Allergen‐specific immunotherapy can induce long‐term suppression of allergic symptoms, reduce medication use, and prevent exacerbations of allergic rhinitis and asthma. Current treatment is based on crude allergen extracts, which contain immunostimulatory components such as β‐glucans, chitins, and endotoxin. Use of purified or recombinant allergens might therefore increase efficacy of treatment. Aims Here, we test application of purified natural group 1 and 2 allergens from Dermatophagoides pteronyssinus (Der p) for subcutaneous immunotherapy ( SCIT ) treatment in a house dust mite ( HDM )‐driven mouse model of allergic asthma. Materials and methods HDM ‐sensitized mice received SCIT with crude HDM extract, a mixture of purified Der p1 and 2 (DerP1/2), or placebo. Upon challenges, we measured specific immunoglobulin responses, allergen‐induced ear swelling response ( ESR ), airway hyperresponsiveness ( AHR ), and inflammation in bronchoalveolar lavage fluid ( BAL ) and lung tissue. Results ESR measurement shows suppression of early allergic response in HDM ‐SCIT– and DerP1/2‐ SCIT –treated mice. Both HDM ‐ SCIT and DerP1/2‐ SCIT are able to suppress AHR and eosinophilic inflammation. In contrast, only DerP1/2‐ SCIT is able to significantly suppress type 2 cytokines in lung tissue and BAL fluid. Moreover, DerP1/2‐ SCIT treatment is uniquely able suppress CCL 20 and showed a trend toward suppression of IL ‐33, CCL 17 and eotaxin levels in lung tissue. Discussion Taken together, these data show that purified DerP1/2‐ SCIT is able to not only suppress AHR and inflammation, but also has superior activity toward suppression of Th2 cells and HDM ‐induced activation of lung structural cells including airway epithelium. Conclusions We postulate that treatment with purified natural major allergens derived from HDM will likely increase clinical efficacy of SCIT .
Effects of Reslizumab on Nasal Polyp Inflammation in Aspirin Exacerbated Respiratory Disease
Authors: Whitney W. Stevens, Anna G. Staudacher, Anju T. Peters, Lydia A. Suh, Roderick G. Carter, Stephanie R. Fischer, Kathryn E. Hulse, Julie A. Poposki, James E. Norton, Atsushi Kato, Leslie C. Grammer, David B. Conley, Robert C. Kern, Stephanie Shintani-Smith, Bruce K. Tan, Kevin C. Welch, Robert P. Schleimer
Journal: Journal of Allergy and Clinical Immunology (2018)
Oncogenic KRAS Regulates Amino Acid Homeostasis and Asparagine Biosynthesis via ATF4 and Alters Sensitivity to L-Asparaginase
Authors: Dana M. Gwinn, Alex G. Lee, Marcela Briones-Martin-del-Campo, Crystal S. Conn, David R. Simpson, Anna I. Scott, Anthony Le, Tina M. Cowan, Davide Ruggero, E. Alejandro Sweet-Cordero
Journal: Cancer Cell (2018)
Circulating tumor cells and evaluation of targeted therapy effect in EGFR mutation/ALK translocation metastatic non-small cell lung cancer.
Authors: ChunXia Su, Xuefei Li, Shengxiang Ren, Guanghui Gao, Wei Li, Jing Zhao, Xiaoxia Chen, Chao Zhao, Caicun Zhou
Journal: Journal of Clinical Oncology (2015)

e19084 Background: Targeted therapies have considerably improved the prognosis of patients with non-small cell lung cancer (NSCLC) ,RESIST criteria was the most often used response assessment method to reflecting the clinical benefits. We propose a non-invasive, folate receptor (FR)–based circulating tumor cell (CTC) detection approach to interpret treatment response of targeted therapy between baseline and follow-up CTC values in EGFR mutation/ALK translocation advanced NSCLC. Methods: CTCs were collected from 4 ml of blood based on negative enrichment by immunomagnetic beads in blood from 51 advanced NSCLC patients before the start of targeted therapy and after one month, three months of therapy. The change of CTCs value, radiological response and patient reported outcome(PRO) were compared. Sequential analyses were conducted to monitor CTC signals during therapy and correlate radiological effects with treatment outcome. Results: CTCs were detected in pretreatment and protreatment blood samples from all 47 EGFR-mutant and 4 ALK translocation lung cancer patients. Of 51 eligible and evaluable patients, 35 (68.6%) of CTC values correlated well with radiological response (P = 0.065) and 38 (74.5%) of CTC values correlated well with patient reported outcome after one month treatment of EGFR-TKI or crizotinib (P = 0.034). The change of CTCs values increased correlation with radiological response (75%, P = 0.049) and patient reported outcome (79.2%,P = 0.032) after three month treatment of targeted therapy. Conclusions: This study confirms the predictive significance of CTCs in patients with EGFR mutation/ALK translocation NSCLC receiving targeted therapy. The change of CTCs value correlated significantly with radiological response and PRO with the interview time increased. This strategy may enable non-invasive, specific biomarker diagnostics and monitoring in patients undergoing targeted cancer therapies.
Mast cell activation test in the diagnosis of allergic disease and anaphylaxis
Authors: Rajia Bahri, Adnan Custovic, Peter Korosec, Marina Tsoumani, Martin Barron, Jiakai Wu, Rebekah Sayers, Alf Weimann, Monica Ruiz-Garcia, Nandinee Patel, Abigail Robb, Mohamed H. Shamji, Sara Fontanella, Mira Silar, E.N.Clare Mills, Angela Simpson, Paul J. Turner, Silvia Bulfone-Paus
Journal: Journal of Allergy and Clinical Immunology (2018)
The Relevance of CD20 Targeting of Oncolytic Measles Virus in the Treatment of Adult Acute Lymphoblastic Leukemia
Authors: Katharine E Bailey, Sarah Aref, Aditi Dey, Rachel J Mitchell, Richard J Burt, Naughton J Thomas, Dina Ahmed Said Aly Okasha, Krisztina Zuborne Alapi, Adele K Fielding
Journal: Blood (2017)
Baked Egg Oral Immunotherapy (OIT) Induces Significant Immune Modulation in Baked Egg Reactive Subjects and Induces Tolerance to Lightly Cooked Egg
Authors: Hannah White, April Clark, Irene Dougherty, L. Steven Brown, Amy Arneson, Maria Crain, Christopher P. Parrish, J. Andrew Bird
Journal: Journal of Allergy and Clinical Immunology (2018)
Abstract 20151: Supplementation of Carnosine Improves Wound Healing Responses
Authors: Adjoa Boakye, Luping Guo, Jaron Thomas, Daniel conklin, Aruni Bhatnagar, Shahid P Baba
Journal: Circulation (2016)

Introduction:  Critical Limb ischemia (CLI) is a serious manifestation of peripheral artery disease. Advanced CLI patients are poor candidates for vascular surgeries. Numerous studies have shown that Hypoxia inducible factor 1α plays an important role in recovery. HIF1-α is regulated by oxygen dependent prolyl hydroxylases (PHDs). Previous studies had shown that inhibition of PHDs by metal quenchers and viral delivery of HIF1-α iimproves blood flow to the ischemic limb. However clinical trials with these therapies were largely negative.   Hypothesis:  Based on recent observations that endogenous histidyl dipeptides such as carnosine a food constituent can quench metals we hypothesize that supplementation of carnosine can inhibit PHDs, stabilize HIF1-α and attenuate ischemic injury.   Methods:  C57BL/6J mice were subjected to hindlimb ischemia (HLI) surgery by ligating the femoral artery and vein and supplemented with carnosine (1g/L) for 21 days.   Results:  Laser Doppler analysis showed that blood flow in the carnosine treated was significantly increased (31±2%) compared with the non-treated (20±2%) after 14 and 21 days (carnosine 50±6%  vs  non-treated 28±4%;  p  + /Sca + ) in the blood and VEGF expression in the ischemic limb was significantly increased by carnosine supplementation. Levels of carnosine in the ischemic muscle were increased 2 fold compared with non-treated HLI mice. Pre-treatment of C2C12 cells with carnosine and its analogue methyl carcinine that lacks the ability to quench metals showed increased HIF1-α nuclear translocation and VEGF secretion in hypoxic carnosine treated cells compared with carcinine treated hypoxic cells.   Conclusions:  Collectively our results demonstrate that carnosine treatment improves blood flow by increasing HIF1-α stabilization and EPC mobilization and thus can be used as a safe therapeutic intervention for CLI patients
Circular RNA VMA21 protects against intervertebral disc degeneration through targeting miR-200c and X linked inhibitor-of-apoptosis protein
Authors: Xiaofei Cheng, Liang Zhang, Kai Zhang, Guoying Zhang, Ying Hu, Xiaojiang Sun, Changqing Zhao, Hua Li, Yan Michael Li, Jie Zhao
Journal: Annals of the Rheumatic Diseases (2018)

Objectives Circular RNAs (circRNAs) have been proven to function as competing endogenous RNAs to interact with microRNAs (miRNAs) and influence the expression of miRNA target mRNAs. In this study, we investigated whether circRNAs could act as competing endogenous RNAs to regulate the pathological process of intervertebral disc degeneration (IVDD). Methods The role and mechanism of a circRNA, circVMA21, in IVDD were explored in nucleus pulposus (NP) cells and degenerative NP tissues from patients and rat models. The interaction between circVMA21 and miR-200c as well as the target mRNA, X linked inhibitor-of-apoptosis protein (XIAP), was examined. Results The decreased expression of XIAP in the inflammatory cytokines-treated NP cells and the degenerative NP tissues was directly associated with excessive apoptosis and imbalance between anabolic and catabolic factors of extracellular matrix. miR-200c regulated NP cell viability and functions through inhibiting XIAP. circVMA21 acted as a sponge of miR-200c and functioned in NP cells through targeting miR-200c and XIAP. Intradiscal injection of circVMA21 alleviated IVDD in the rat model. Conclusions CircVMA21 could alleviate inflammatory cytokines-induced NP cell apoptosis and imbalance between anabolism and catabolism of extracellular matrix through miR-200c-XIAP pathway. It provides a potentially effective therapeutic strategy for IVDD.
Abstract 16311: Resistance Training Improves Cardiac Output, Exercise Capacity and Tolerance to Positive Airway Pressure in Fontan Physiology
Authors: Rachael L Cordina, Shamus O’Meagher, Caroline L Rae, Carsten Leiss, Graham J Kemp, Raj Puranik, Nalin Singh, David S Celermajer
Journal: Circulation (2012)

Rachael L Cordina, 2012 Finalist and Presenting Author
Efficacy and Safety of Deep Brain Stimulation in Tourette Syndrome
Authors: Daniel Martinez-Ramirez, Joohi Jimenez-Shahed, James Frederick Leckman, Mauro Porta, Domenico Servello, Fan-Gang Meng, Jens Kuhn, Daniel Huys, Juan Carlos Baldermann, Thomas Foltynie, Marwan I. Hariz, Eileen M. Joyce, Ludvic Zrinzo, Zinovia Kefalopoulou, Peter Silburn, Terry Coyne, Alon Y. Mogilner, Michael H. Pourfar, Suketu M. Khandhar, Man Auyeung, Jill Louise Ostrem, Veerle Visser-Vandewalle, Marie-Laure Welter, Luc Mallet, Carine Karachi, Jean Luc Houeto, Bryan Timothy Klassen, Linda Ackermans, Takanobu Kaido, Yasin Temel, Robert E. Gross, Harrison C. Walker, Andres M. Lozano, Benjamin L. Walter, Zoltan Mari, William S. Anderson, Barbara Kelly Changizi, Elena Moro, Sarah Elizabeth Zauber, Lauren E. Schrock, Jian-Guo Zhang, Wei Hu, Kyle Rizer, Erin H. Monari, Kelly D. Foote, Irene A. Malaty, Wissam Deeb, Aysegul Gunduz, Michael S. Okun
Journal: JAMA Neurology (2018)

Collective evidence has strongly suggested that deep brain stimulation (DBS) is a promising therapy for Tourette syndrome.To assess the efficacy and safety of DBS in a multinational cohort of patients with Tourette syndrome.The prospective International Deep Brain Stimulation Database and Registry included 185 patients with medically refractory Tourette syndrome who underwent DBS implantation from January 1, 2012, to December 31, 2016, at 31 institutions in 10 countries worldwide.Patients with medically refractory symptoms received DBS implantation in the centromedian thalamic region (93 of 163 [57.1%]), the anterior globus pallidus internus (41 of 163 [25.2%]), the posterior globus pallidus internus (25 of 163 [15.3%]), and the anterior limb of the internal capsule (4 of 163 [2.5%]).Scores on the Yale Global Tic Severity Scale and adverse events.The International Deep Brain Stimulation Database and Registry enrolled 185 patients (of 171 with available data, 37 females and 134 males; mean [SD] age at surgery, 29.1 [10.8] years [range, 13-58 years]). Symptoms of obsessive-compulsive disorder were present in 97 of 151 patients (64.2%) and 32 of 148 (21.6%) had a history of self-injurious behavior. The mean (SD) total Yale Global Tic Severity Scale score improved from 75.01 (18.36) at baseline to 41.19 (20.00) at 1 year after DBS implantation (P < .001). The mean (SD) motor tic subscore improved from 21.00 (3.72) at baseline to 12.91 (5.78) after 1 year (P < .001), and the mean (SD) phonic tic subscore improved from 16.82 (6.56) at baseline to 9.63 (6.99) at 1 year (P < .001). The overall adverse event rate was 35.4% (56 of 158 patients), with intracranial hemorrhage occurring in 2 patients (1.3%), infection in 4 patients with 5 events (3.2%), and lead explantation in 1 patient (0.6%). The most common stimulation-induced adverse effects were dysarthria (10 [6.3%]) and paresthesia (13 [8.2%]).Deep brain stimulation was associated with symptomatic improvement in patients with Tourette syndrome but also with important adverse events. A publicly available website on outcomes of DBS in patients with Tourette syndrome has been provided.
NHS weight management programme makes clinical difference in patients with type 2 diabetes
Authors: Jacqui Wise
Journal: BMJ (2018)

An inexpensive weight management programme delivered in the NHS has helped patients with type 2 diabetes achieve long term weight loss and improved glycaemic control, leading to a reduction in their diabetes medicine.

The study, published in Diabetes Obesity and Metabolism ,1 examined records from an NHS 16 week lifestyle programme. It found that patients who successfully completed the programme had no increase in their oral diabetes medicine and were only half as likely to progress to insulin as those who did not complete the programme and those who did not lose weight.

A renewed focus on weight loss programmes for treating type 2 diabetes includes a …
Frequent Exertion and Frequent Standing at Work, by Industry and Occupation Group — United States, 2015
Authors: Taylor M. Shockey, Sara E. Luckhaupt, Matthew R. Groenewold, Ming-Lun Lu
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

Repeated exposure to occupational ergonomic hazards, such as frequent exertion (repetitive bending or twisting) and frequent standing, can lead to injuries, most commonly musculoskeletal disorders (1). Work-related musculoskeletal disorders have been estimated to cost the United States approximately $2.6 billion in annual direct and indirect costs (2). A recent literature review provided evidence that prolonged standing at work also leads to adverse health outcomes, such as back pain, physical fatigue, and muscle pain (3). To determine which industry and occupation groups currently have the highest prevalence rates of frequent exertion at work and frequent standing at work, CDC analyzed data from the 2015 National Health Interview Survey (NHIS) Occupational Health Supplement (OHS) regarding currently employed adults in the United States. By industry, the highest prevalence of both frequent exertion and frequent standing at work was among those in the agriculture, forestry, fishing, and hunting industry group (70.9%); by occupation, the highest prevalence was among those in the construction and extraction occupation group (76.9%). Large differences among industry and occupation groups were found with regard to these ergonomic hazards, suggesting a need for targeted interventions designed to reduce workplace exposure.
Palliative Care Assessment in the Surgical and Trauma Intensive Care Unit
Authors: Emily B. Rivet, Egidio Del Fabbro, Paula Ferrada
Journal: JAMA Surgery (2018)

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