tbuckley/cabot-search huggingface dataset:
Arginine methylation controls the strength of γc-family cytokine signaling in T cell maintenance
Authors: Maia Inoue, Kazuo Okamoto, Asuka Terashima, Takeshi Nitta, Ryunosuke Muro, Takako Negishi-Koga, Toshio Kitamura, Tomoki Nakashima, Hiroshi Takayanagi
Journal: Nature Immunology (2018)
Underdiagnosis and Overdiagnosis of Asthma
Authors: Shawn D. Aaron, Louis Philippe Boulet, Helen K. Reddel, Andrea S. Gershon
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Asthma is diagnosed on the basis of respiratory symptoms of wheeze, cough, chest tightness, and/or dyspnea together with physiologic evidence of variable expiratory airflow limitation. The prevalence of asthma varies widely around the world, ranging from 0.2% to 21.0% in adults and from 2.8% to 37.6% in 6- to 7-year-old children. Population-based studies in children, adults, and the elderly suggest that from 20% to 70% of people with asthma in the community remain undiagnosed and hence untreated. Underdiagnosis of asthma has been found to be associated with underreporting of respiratory symptoms by patients to physicians as well as poor socioeconomic status. On the opposite side of the spectrum, studies of patients with physician-diagnosed asthma suggest that 30-35% of adults and children diagnosed with asthma do not have current asthma, suggesting that asthma is also overdiagnosed in the community. Overdiagnosis of current asthma can occur because of physicians' failure to confirm variable airflow limitation at the time of diagnosis or when sustained clinical remission of disease goes unrecognized. In this review, we define under- and overdiagnosis and explore the prevalence and burden of under- and overdiagnosis of asthma both in patients and within healthcare systems. We further describe potential solutions to prevent under- and overdiagnosis of asthma.
GW29-e0363 Aortic Constriction Induces Cardiac Hypertrophy Via The (Pro)Renin Receptor And Plc-Β3 Signaling Pathway
Authors: Yanling Zhang, Chuanjun Liu, Aihuan Zhang, Jingjun Zhang, Junyan Wu, Li An, Yuzhuang Jiao
Journal: Journal of the American College of Cardiology (2018)
Association of Frequency of Organic Food Consumption With Cancer Risk
Authors: Julia Baudry, Karen E. Assmann, Mathilde Touvier, Benjamin Allès, Louise Seconda, Paule Latino-Martel, Khaled Ezzedine, Pilar Galan, Serge Hercberg, Denis Lairon, Emmanuelle Kesse-Guyot
Journal: JAMA Internal Medicine (2018)

<h3>Importance</h3> Although organic foods are less likely to contain pesticide residues than conventional foods, few studies have examined the association of organic food consumption with cancer risk. <h3>Objective</h3> To prospectively investigate the association between organic food consumption and the risk of cancer in a large cohort of French adults. <h3>Design, Setting, and Participants</h3> In this population-based prospective cohort study among French adult volunteers, data were included from participants with available information on organic food consumption frequency and dietary intake. For 16 products, participants reported their consumption frequency of labeled organic foods (never, occasionally, or most of the time). An organic food score was then computed (range, 0-32 points). The follow-up dates were May 10, 2009, to November 30, 2016. <h3>Main Outcomes and Measures</h3> This study estimated the risk of cancer in association with the organic food score (modeled as quartiles) using Cox proportional hazards regression models adjusted for potential cancer risk factors. <h3>Results</h3> Among 68 946 participants (78.0% female; mean [SD] age at baseline, 44.2 [14.5] years), 1340 first incident cancer cases were identified during follow-up, with the most prevalent being 459 breast cancers, 180 prostate cancers, 135 skin cancers, 99 colorectal cancers, 47 non-Hodgkin lymphomas, and 15 other lymphomas. High organic food scores were inversely associated with the overall risk of cancer (hazard ratio for quartile 4 vs quartile 1, 0.75; 95% CI, 0.63-0.88;<i>P</i>for trend = .001; absolute risk reduction, 0.6%; hazard ratio for a 5-point increase, 0.92; 95% CI, 0.88-0.96). <h3>Conclusions and Relevance</h3> A higher frequency of organic food consumption was associated with a reduced risk of cancer. If these findings are confirmed, further research is necessary to determine the underlying factors involved in this association.
Bile Acid G Protein-Coupled Membrane Receptor TGR5 Modulates Aquaporin 2–Mediated Water Homeostasis
Authors: Suchun Li, Miaojuan Qiu, Yonglun Kong, Xiaoduo Zhao, Hyo-Jung Choi, Maria Reich, Brady H. Bunkelman, Qiaojuan Liu, Shan Hu, Mengke Han, Haixia Xie, Avi Z. Rosenberg, Verena Keitel, Tae-Hwan Kwon, Moshe Levi, Chunling Li, Weidong Wang
Journal: Journal of the American Society of Nephrology (2018)

Background The bile acid-activated receptors, including the membrane G protein–coupled receptor TGR5 and nuclear farnesoid X receptor (FXR), have roles in kidney diseases. In this study, we investigated the role of TGR5 in renal water handling and the underlying molecular mechanisms. Methods We used tubule suspensions of inner medullary collecting duct (IMCD) cells from rat kidneys to investigate the effect of TGR5 signaling on aquaporin-2 (AQP2) expression, and examined the in vivo effects of TGR5 in mice with lithium-induced nephrogenic diabetes insipidus (NDI) and Tgr5 knockout ( Tgr5 −/− ) mice. Results Activation of TGR5 by lithocholic acid (LCA), an endogenous TGR5 ligand, or INT-777, a synthetic TGR5-specific agonist, induced AQP2 expression and intracellular trafficking in rat IMCD cells via a cAMP-protein kinase A signaling pathway. In mice with NDI, dietary supplementation with LCA markedly decreased urine output and increased urine osmolality, which was associated with significantly upregulated AQP2 expression in the kidney inner medulla. Supplementation with endogenous FXR agonist had no effect. In primary IMCD suspensions from lithium-treated rats, treatment with INT-767 (FXR and TGR5 dual agonist) or INT-777, but not INT-747 (FXR agonist), increased AQP2 expression. Tgr5 −/− mice exhibited an attenuated ability to concentrate urine in response to dehydration, which was associated with decreased AQP2 expression in the kidney inner medulla. In lithium-treated Tgr5 −/− mice, LCA treatment failed to prevent reduction of AQP2 expression. Conclusions TGR5 stimulation increases renal AQP2 expression and improves impaired urinary concentration in lithium-induced NDI. TGR5 is thus involved in regulating water metabolism in the kidney.
Brain metastases response to nivolumab in patients with renal cell carcinoma (RCC): Prospective analysis from the GETUG-AFU 26 (NIVOREN) trial
Authors: R. Flippot, C. Dalban, B. Laguerre, D. Borchiellini, G. Gravis, S. Negrier, C.M. Chevreau, F. Joly, L. Geoffrois, S. Ladoire, H. Mahammedi, F. Tantot, B. Escudier, L. Albiges
Journal: Annals of Oncology (2018)
Localization of Secretory Mucins MUC5AC and MUC5B in Normal/Healthy Human Airways
Authors: Kenichi Okuda, Gang Chen, Durai B. Subramani, Monroe Wolf, Rodney C. Gilmore, Takafumi Kato, Giorgia Radicioni, Mehmet Kesimer, Michael Chua, Hong Dang, Alessandra Livraghi-Butrico, Camille Ehre, Claire M. Doerschuk, Scott H. Randell, Hirotoshi Matsui, Takahide Nagase, Wanda K. O’Neal, Richard C. Boucher
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

MUC5AC and MUC5B are the predominant gel-forming mucins in the mucus layer of human airways. Each mucin has distinct functions and site-specific expression. However, the regional distribution of expression and cell types that secrete each mucin in normal/healthy human airways are not fully understood.
Abstract 16940: Decreased Left Atrial Function in Kawasaki Disease Patients
Authors: Marco A Pinder, Michal Schafer, Bruce Landeck, Pei-Ni Jone
Journal: Circulation (2017)

Background: Left atrial (LA) strain analysis using two-dimensional speckle tracking echocardiography is a diagnostic tool showing promise in identifying early ventricular dysfunction. Kawasaki Dise...
Abstract 18718: Trends, Predictors, and Regional Variation in Use of Catheter Ablation Among 184,443 Hospitalizations for Ventricular Tachycardia
Authors: Wendy S Tzou, David F Katz, Ryan G Aleong, William H Sauer, David P Kao
Journal: Circulation (2015)

Introduction: Catheter radiofrequency ablation (RFA) is used increasingly for treatment of ventricular tachycardia (VT), but little is known about utilization patterns. Hypothesis: Regional trends in VT hospitalization and RFA,and patient characteristics associated with VT RFA vary. Methods: Hospital discharge data was obtained from state agencies in California, New York, New Jersey, Vermont, New Hampshire, West Virginia, Colorado, and Texas from 1994-2012. All records with primary diagnosis of VT (ICD9-CM 427.1) were analyzed. Population-adjusted hospitalization rates were estimated using US Census Bureau data. In hospitals performing VT RFA, patient characteristics associated with RFA were identified using multivariate logistic regression. Results: In total, 184,443 hospitalizations for VT were reported; 11,941/136,437 (8.8%) admitted to VT ablation hospitals underwent RFA. Annual VT hospitalization rates varied from 10-17/100,000 in California (CA) and Texas (TX) to 20-30 in New York and New Jersey (NJ). VT ablation/hospitalization frequency varied from 9% in NJ to 18% in CA and TX. Positive predictors of undergoing VT RFA were female gender, non-white race, admission from home, and atrial flutter. Negative predictors included advancing age, non-private insurance, atrial fibrillation, anemia, coronary artery disease, heart failure, hypertension, and shock on admission (Figure, A). Higher RFA rates for women were driven by more patients without structural heart disease compared to men (Figure, B). Non-white patients were more likely to undergo RFA irrespective of structural heart disease. Conclusion: Significant regional variations exist in VT hospitalization and ablation rates. Also of note, women and non-white patients were more likely to undergo ablation, which may have reflected important differences in cardiac disease substrate.
GMC investigators get training to include system issues in fitness to practise decisions
Authors: Clare Dyer
Journal: BMJ (2018)

General Medical Council (GMC) staff and clinical experts who investigate doctors’ fitness to practise will receive “human factors” training so that the context in which doctors have to work is taken into account when the regulator takes decisions.

The move follows the case of the junior doctor Hadiza Bawa-Garba, which sparked a widespread loss of confidence among doctors regarding the GMC. After she was convicted by a jury of gross negligence manslaughter in the death from sepsis of 6 year old Jack Adcock,1 a medical practitioners tribunal decided to suspend her from the medical register rather than strike her off.2

The tribunal had taken account of substantial system failures …
Type 2 deiodinase polymorphism causes ER stress and hypothyroidism in the brain
Authors: Sungro Jo, Tatiana L. Fonseca, Barbara M. L. C. Bocco, Gustavo W. Fernandes, Elizabeth A. McAninch, Anaysa P. Bolin, Rodrigo R. Da Conceição, Joao Pedro Werneck-de-Castro, Daniele L. Ignacio, Péter Egri, Dorottya Németh, Csaba Fekete, Maria Martha Bernardi, Victoria D. Leitch, Naila S. Mannan, Katharine F. Curry, Natalie C. Butterfield, J.H. Duncan Bassett, Graham R. Williams, Balázs Gereben, Miriam O. Ribeiro, Antonio C. Bianco
Journal: Journal of Clinical Investigation (2018)

Levothyroxine (LT4) is a form of thyroid hormone used to treat hypothyroidism. In the brain, T4 is converted to the active form T3 by type 2 deiodinase (D2). Thus, it is intriguing that carriers of the Thr92Ala polymorphism in the D2 gene (DIO2) exhibit clinical improvement when liothyronine (LT3) is added to LT4 therapy. Here, we report that D2 is a cargo protein in ER Golgi intermediary compartment (ERGIC) vesicles, recycling between ER and Golgi. The Thr92-to-Ala substitution (Ala92-D2) caused ER stress and activated the unfolded protein response (UPR). Ala92-D2 accumulated in the trans-Golgi and generated less T3, which was restored by eliminating ER stress with the chemical chaperone 4-phenyl butyric acid (4-PBA). An Ala92-Dio2 polymorphism–carrying mouse exhibited UPR and hypothyroidism in distinct brain areas. The mouse refrained from physical activity, slept more, and required additional time to memorize objects. Enhancing T3 signaling in the brain with LT3 improved cognition, whereas restoring proteostasis with 4-PBA eliminated the Ala92-Dio2 phenotype. In contrast, primary hypothyroidism intensified the Ala92-Dio2 phenotype, with only partial response to LT4 therapy. Disruption of cellular proteostasis and reduced Ala92-D2 activity may explain the failure of LT4 therapy in carriers of Thr92Ala-DIO2.
Harnessing autophagy to overcome mitogen‐activated protein kinase kinase inhibitor‐induced resistance in metastatic melanoma
Authors: S. Verykiou, M. Alexander, N. Edwards, R. Plummer, B. Chaudhry, P.E. Lovat, D.S. Hill
Journal: British Journal of Dermatology (2018)

Patients with malignant melanoma often relapse after treatment with BRAF and/or mitogen‐activated protein kinase kinase (MEK) inhibitors (MEKi) owing to development of drug resistance. To establish the temporal pattern of CD271 regulation during development of resistance by melanoma to trametinib, and determine the association between development of resistance to trametinib and induction of prosurvival autophagy. Immunohistochemistry for CD271 and p62 was performed on human naevi and primary malignant melanoma tumours. Western blotting was used to analyse expression of CD271, p62 and LC3 in melanoma subpopulations. Flow cytometry and immunofluorescence microscopy was used to evaluate trametinib‐induced cell death and CD271 expression. MTS viability assays and zebrafish xenografts were used to evaluate the effect of CD271 and autophagy modulation on trametinib‐resistant melanoma cell survival and invasion, respectively. CD271 and autophagic signalling are increased in stage III primary melanomas vs. benign naevi. In vitro studies demonstrate MEKi of BRAF‐mutant melanoma induced cytotoxic autophagy, followed by the emergence of CD271‐expressing subpopulations. Trametinib‐induced CD271 reduced autophagic flux, leading to activation of prosurvival autophagy and development of MEKi resistance. Treatment of CD271‐expressing melanoma subpopulations with RNA interference and small‐molecule inhibitors to CD271 reduced the development of MEKi resistance, while clinically applicable autophagy modulatory agents – including Δ9‐tetrahydrocannabinol and Vps34 – reduced survival of MEKi‐resistant melanoma cells. Combined MEK/autophagy inhibition also reduced the invasive and metastatic potential of MEKi‐resistant cells in an in vivo zebrafish xenograft. These results highlight a novel mechanism of MEKi‐induced drug resistance and suggest that targeting autophagy may be a translatable approach to resensitize drug‐resistant melanoma cells to the cytotoxic effects of MEKi.
Neurogenetic contributions to amyloid beta and tau spreading in the human cortex
Authors: Jorge Sepulcre, Michel J. Grothe, Federico d’Oleire Uquillas, Laura Ortiz-Terán, Ibai Diez, Hyun-Sik Yang, Heidi I. L. Jacobs, Bernard J. Hanseeuw, Quanzheng Li, Georges El-Fakhri, Reisa A. Sperling, Keith A. Johnson
Journal: Nature Medicine (2018)
Determinants of oncologist’s choice in offering drug holidays during first line therapy for patients with metastatic colorectal cancer
Authors: S.K.K. Garattini, M. Bonotto, L. Porcu, E. Ongaro, D. Basile, F. Cortiula, G. Pelizzari, M. Cattaneo, A. Parnofiello, V.J. Andreotti, C. Corvaja, G.G. Cardellino, P. Ermacora, M. Casagrande, D. Iacono, N. Pella, A. Buonadonna, A.M. Minisini, F. Puglisi, G. Fasola
Journal: Annals of Oncology (2018)
Complete response (CR) to anthracycline-based chemotherapy using magnetic resonance imaging (MRI) predicts high rates of pathologic complete response (pCR) for triple negative breast cancer (TNBC) patients treated preoperatively with anthracycline and taxane-based regimens
Authors: M. Marin Alcala, G. Llort Pursals, J.H. Del Riego Ferrari, J. Giner, F.X. Andreu Navarro, S. Medina, O. Aparicio, E. Dalmau Portulas, P. Ribera Fernandez, H. Oliveres, C. Martinez Vila, J.M. Cabrera Romero, M.A. Segui Palmer, L.A. Fernandez Morales
Journal: Annals of Oncology (2018)
Prenatal exercise (including but not limited to pelvic floor muscle training) and urinary incontinence during and following pregnancy: a systematic review and meta-analysis
Authors: Margie H Davenport, Taniya S Nagpal, Michelle F Mottola, Rachel J Skow, Laurel Riske, Veronica J Poitras, Alejandra Jaramillo Garcia, Casey E Gray, Nick Barrowman, Victoria L Meah, Frances Sobierajski, Marina James, Megan Nuspl, Ashley Weeks, Andree-Anne Marchand, Linda G Slater, Kristi B Adamo, Gregory A Davies, Ruben Barakat, Stephanie-May Ruchat
Journal: British Journal of Sports Medicine (2018)

To examine the relationships between prenatal physical activity and prenatal and postnatal urinary incontinence (UI).Systematic review with random effects meta-analysis and meta-regression.Online databases were searched up to 6 January 2017.Studies of all designs were included (except case studies) if they were published in English, Spanish or French and contained information on the Population (pregnant women without contraindication to exercise), Intervention (subjective or objective measures of frequency, intensity, duration, volume or type of exercise, alone ["exercise-only"] or in combination with other intervention components [e.g., dietary; "exercise + co-intervention"]), Comparator (no exercise or different frequency, intensity, duration, volume and type of exercise) and Outcome (prenatal or postnatal UI).24 studies (n=15 982 women) were included. 'Low' to 'moderate' quality evidence revealed prenatal pelvic floor muscle training (PFMT) with or without aerobic exercise decreased the odds of UI in pregnancy (15 randomised controlled trials (RCTs), n=2764 women; OR 0.50, 95% CI 0.37 to 0.68, I2=60%) and in the postpartum period (10 RCTs, n=1682 women; OR 0.63, 95% CI 0.51, 0.79, I2=0%). When we analysed the data by whether women were continent or incontinent prior to the intervention, exercise was beneficial at preventing the development of UI in women with continence, but not effective in treating UI in women with incontinence. There was 'low' quality evidence that prenatal exercise had a moderate effect in the reduction of UI symptom severity during (five RCTs, standard mean difference (SMD) -0.54, 95% CI -0.88 to -0.20, I2=64%) and following pregnancy (three RCTs, 'moderate' quality evidence; SMD -0.54, 95% CI -0.87 to -0.22, I2=24%).Prenatal exercise including PFMT reduced the odds and symptom severity of prenatal and postnatal UI. This was the case for women who were continent before the intervention. Among women who were incontinent during pregnancy, exercise training was not therapeutic.
Misclassification of cricket in the American College of Cardiology (ACC) Task Force classification of sports
Authors: Jessica J Orchard, John W Orchard, Andre La Gerche, Hariharan Raju, Christopher Semsarian
Journal: British Journal of Sports Medicine (2018)

‘The Mitchell classification’1 is a widely known system published by the American College of Cardiology (ACC) to catalogue sports based on peak static and dynamic components achieved during competition.1 2 Used in the Bethesda guidelines3 and more recent scientific statement from the American Heart Association (AHA) and ACC,2 this helpful framework is widely used for assisting with clinical decisions regarding participation in specific sports by athletes with known cardiovascular disease. These guidelines have twice1 2 classified cricket as a sport with low static and low dynamic cardiovascular demands (category IA) and where impact is not expected. Other sports in this category include bowling, golf and yoga. The guidelines only provide minimal objective thresholds for each category, and do not provide any data for individual sports.

Like all professional sports, in cricket the risk of sudden cardiac death must be considered. The level of risk is relevant for both players with known cardiovascular disease and also …
Altered brain microstructure in association with repetitive subconcussive head impacts and the potential protective effect of jugular vein compression: a longitudinal study of female soccer athletes
Authors: Gregory D Myer, Kim Barber Foss, Staci Thomas, Ryan Galloway, Christopher A DiCesare, Jonathan Dudley, Brooke Gadd, James Leach, David Smith, Paul Gubanich, William P Meehan III, Mekibib Altaye, Philip Lavin, Weihong Yuan
Journal: British Journal of Sports Medicine (2018)

Purpose To (1) quantify white matter (WM) alterations in female high school athletes during a soccer season and characterise the potential for normalisation during the off-season rest period, (2) determine the association between WM alterations and exposure to repetitive subconcussive head impacts, and (3) evaluate the efficacy of a jugular vein compression collar to prevent WM alterations associated with head impact exposure. Methods Diffusion tensor imaging (DTI) data were prospectively collected from high school female soccer participants (14–18 years) at up to three time points over 9 months. Head impacts were monitored using accelerometers during all practices and games. Participants were assigned to a collar (n=24) or non-collar group (n=22). The Tract-Based Spatial Statistics approach was used in the analysis of within-group longitudinal change and between-group comparisons. Results DTI analyses revealed significant pre-season to post-season WM changes in the non-collar group in mean diffusivity (2.83%±2.46%), axial diffusivity (2.58%±2.34%) and radial diffusivity (3.52%±2.60%), but there was no significant change in the collar group despite similar head impact exposure. Significant correlation was found between head impact exposure and pre-season to post-season DTI changes in the non-collar group. WM changes in the non-collar group partially resolved at 3 months off-season follow-up. Discussion Microstructural changes in WM occurred during a season of female high school soccer among athletes who did not wear the collar device. In comparison, there were no changes in players who wore the collar, suggesting a potential prophylactic effect of the collar device in preventing changes associated with repetitive head impacts. In those without collar use, the microstructural changes showed a reversal towards normal over time in the off-season follow-up period.