tbuckley/cabot-search huggingface dataset:
Abstract 18160: Distinct Transcriptomic Signatures Across Postnatal Cardiomyocyte Development
Authors: Amy M Nicks, Sara R Holman, Andrea Chan, David T Humphreys, Nicola J Smith, Joshua W Ho, Nawazish Naqvi, Ahsan Husain, Robert M Graham, Siiri E Iismaa
Journal: Circulation (2016)

Background: The murine heart undergoes profound growth between postnatal day 10 (P10) and P18 due to both cardiomyocyte (CM) hypertrophy and hyperplasia. Objective: To determine the dynamic changes...
GW29-e0217 Study of Ghrelin Regulating Calcification in A7r5 Aortic Smooth Muscle Cells Mediated by Osteoprotegerin Signaling
Authors: Lili Zhang, Li Lihua, Yan Jinchuan, Bao Zhengyang, Sun Zhen, Jing Lele, Wang Zhongqun
Journal: Journal of the American College of Cardiology (2018)
Five-Year Risk of Cervical Precancer Following p16/Ki-67 Dual-Stain Triage of HPV-Positive Women
Authors: Megan A. Clarke, Li C. Cheung, Philip E. Castle, Mark Schiffman, Diane Tokugawa, Nancy Poitras, Thomas Lorey, Walter Kinney, Nicolas Wentzensen
Journal: JAMA Oncology (2018)

As cervical cancer screening transitions to primary human papillomavirus (HPV) testing, effective triage and management of HPV-positive women is critical to avoid unnecessary colposcopy referral and associated harms while maintaining high sensitivity for cervical precancer. Triage with p16/Ki-67 dual-stain (DS) testing has shown high sensitivity and specificity for detection of cervical precancers; however, longitudinal studies are needed to determine the long-term risk of precancer following a negative DS result.To evaluate the longitudinal performance of p16/Ki-67 DS triage for detection of cervical precancer in HPV-positive women over 5 years of follow-up in the context of clinical management thresholds.Prospective cohort study of HPV-positive women 30 years or older undergoing routine cervical cancer screening in 2012 with HPV and Papanicolaou (hereinafter "cytology") co-testing within the Kaiser Permanente Northern California health care system. Follow-up of medical records was conducted through 2017.All p16/Ki-67 DS testing was performed on residual SurePath material, and slides were evaluated for p16/Ki-67 positivity.Histological end points were ascertained from the clinical database through 2017. We estimated 5-year cumulative risks of cervical intraepithelial neoplasia grades of 2 or worse (≥CIN2) or grades 3 or worse (≥CIN3) by baseline DS and cytology at yearly intervals using Logistic Weibull models. Risks were compared with clinical management thresholds for colposcopy referral and a 1-year return interval.Among the 1549 HPV-positive women in this study, the mean age at enrollment was 42.2 years, and the median follow-up time was 3.7 years (range, 0.2-5.4 years). Positive DS results were associated with significantly higher cumulative 5-year risks of ≥CIN2 compared with abnormal cytology (31.0%; 95% CI, 27.2%-35.3% vs 25.0%; 95% CI, 21.7%-28.7%; P = .03). Women with DS-negative findings had significantly lower 5-year risks of ≥CIN2 compared with women with normal cytology (8.5%; 95% CI, 6.5%-11.1% vs 12.3%; 95% CI, 9.8%-15.4%; P = .04). In DS-negative women, the risks of both ≥CIN2 and ≥CIN3 remained below the colposcopy referral threshold for all 5 years, crossing the 1-year return threshold at 3 years.Triage with p16/Ki-67 DS provides better long-term risk stratification than cytology over 5 years. The low risk of cervical precancer in p16/Ki-67 DS-negative women permits safe extension of follow-up intervals for 3 years.
Abstract MP42: Dietary Linoleic Acid Intake Is Inversely Associated With Type 2 Diabetes Risk In Three Large Prospective Cohort Studies Of U.s. Men And Women.
Authors: Geng Zong, Gang Liu, Anne J Wanders, Marjan Alssema, Peter L Zock, Walter Willett, Frank B Hu, Qi Sun
Journal: Circulation (2018)

Introduction: Recent studies reported inverse associations between circulating levels of n-6 polyunsaturated fatty acids (PUFAs) and type 2 diabetes (T2D) risk, although whether intake of these fatty acids is associated T2D risk remains to be elucidated. Hypothesis: We examined the hypothesis that long-term intake of n-6 PUFAs, especially linoleic acid (LA), is associated with lower T2D risk. Methods: Diet was assessed using validated food-frequency questionnaires every 4 years in women participating in Nurses' Health Study (NHS, n=83,648) and NHSII (n=88,610), and men participating in the Health Professionals Follow-Up Study (n=41,771). Incident T2D was identified by self-report and confirmed by a supplemental questionnaire. Results: N-6 PUFAs accounted for 4.7-6.8% total energy on average, and 98% of n-6 PUFA intake was from LA. We identified 18,442 T2D cases during 4.93 million person-years of follow-up. In multivariate-adjusted models, HRs (95%CIs) of T2D comparing extreme quintiles (high vs low) were 0.92 (0.88, 0.97; P trend =0.01) for LA intake, and 1.14 (1.08, 1.20; P trend &lt;0.001) for arachidonic acid (AA) intake. It was further estimated that T2D risk were 6% lower when SFAs (2% of total energy) were iso-calorically replaced by LA intake ( table below). For each 2% energy from LA intake, T2D risk was 17% lower for iso-calorically replacing trans fats, and 4% lower for iso-calorically replacing total carbohydrates, and refined carbohydrates (All P values &lt;0.05). These findings remained after adjusting for baseline BMI instead updated BMI, further adjusting for incident hypertension and hypercholesterolemia, or placing a 4-year lag between dietary assessments and disease incidence. Conclusion: Higher LA consumption is associated with a lower T2D risk, especially when substituting for SFAs, trans fats, or refined carbohydrates. AA mainly comes from poultry and meats, and is associated with higher T2D risk.
Pre-treatment CD4 senescent T cells accurately predicts lack of response to PD-L1/PD-1 immune checkpoint blockade in non-small cell lung cancer and correlates with risk of hyperprogression
Authors: M. Zuazo, H. Arasanz, M. Gato-Cañas, G. Fernández-Hinojal, B. Hernández-Marín, M. Martínez-Aguillo, M. Ibáñez-Vea, M.J. Lecumberri Biurrun, Á Fernández de Lascoiti, R. Vera, G. Kochan, D. Escors
Journal: Annals of Oncology (2018)
The identification of the AXL/Gas6 signalling axis as a key player of myelodysplastic syndrome (MDS) and the potential of the oral selective AXL inhibitor bemcentinib in the treatment of MDS
Authors: H. Medyouf, I. Tirado-Gonzalez, A. Mies, A. Nevmerzhitskaya, A.-S. Kubasch, U. Platzbecker
Journal: Annals of Oncology (2018)
Commonly prescribed drugs associate with cognitive function: a cross-sectional study in UK Biobank
Authors: Alejo J Nevado-Holgado, Chi-Hun Kim, Laura Winchester, John Gallacher, Simon Lovestone
Journal: BMJ (2016)

Objective  To investigate medications associated with cognitive function.  Design  Population-based cross-sectional cohort study.  Setting  UK Biobank.  Participants  UK Biobank participants aged 37–73 years who completed cognitive tests at the baseline visit in 2006–2010.  Main outcome measures  Cognitive test outcomes on verbal–numerical reasoning test (n=165 493), memory test (n=482 766) and reaction time test (n=496 813).  Results  Most drugs (262 of 368) were not associated with any cognitive tests after adjusting for age, gender, education, household income, smoking, alcohol status, psychostimulant/nootropic medication use, assessment centre, and concurrent diagnoses and medications. Drugs used for nervous system disorders were associated with poorer cognitive performance (antiepileptics, eg, topiramate breasoning(score) −0.65 (95% CI −1.05 to −0.24), bmemory(score) −1.41 (−1.79 to −1.04); antipsychotics, eg, risperidone breaction time(ms) −33 (−46 to −20), negative values indicate poor cognitive performance and vice versa). Drugs used for non-nervous system conditions also showed significant negative association with cognitive score, including those where such an association might have been predicted (antihypertensives, eg, amlodipine breasoning −0.1 (−0.15 to −0.06), bmemory −0.08 (−0.13 to −0.03), breaction time −3 (−5 to −2); antidiabetics, eg, insulin breaction time −13 (−17 to −10)) and others where such an association was a surprising observation (proton pump inhibitors, eg, omeprazole breasoning −0.11 (−0.15 to −0.06), bmemory −0.08 (−0.12 to −0.04), breaction time −5 (−6 to −3); laxatives, eg, contact laxatives breaction time −13 (−19 to −8)). Finally, only a few medications and health supplements showed association towards a positive effect on cognitive function (anti-inflammatory agents, eg, ibuprofen breasoning 0.05 (0.02 to 0.08), breaction time 4 (3, 5); glucosamine breasoning 0.09 (0.03 to 0.14), breaction time 5 (3 to 6)).  Conclusions  In this large volunteer study, some commonly prescribed medications were associated with poor cognitive performance. Some associations may reflect underlying diseases for which the medications were prescribed, although the analysis controlled for the possible effect of diagnosis. Other drugs, whose association cannot be linked to the effect of any disease, may need vigilance for their implications in clinical practice.
A phase II clinical trial of veliparib and topotecan in patients with platinum resistant ovarian cancer
Authors: A.E. Wahner Hendrickson, B. Costello, A. Jewell, V. Kennedy, G. Fleming, B. Corr, S.E. Taylor, J. Lea, J. Reid, E. Swisher, D. Satele, J. Allred, J. Lensing, S.P. Ivy, C. Erlichman, A.A. Adjei, S. Kaufmann
Journal: Annals of Oncology (2018)
Meta-analysis of Icelandic and UK data sets identifies missense variants in SMO, IL11, COL11A1 and 13 more new loci associated with osteoarthritis
Authors: Unnur Styrkarsdottir, Sigrun H. Lund, Gudmar Thorleifsson, Florian Zink, Olafur A. Stefansson, Jon K. Sigurdsson, Kristinn Juliusson, Kristbjörg Bjarnadottir, Sara Sigurbjornsdottir, Stefan Jonsson, Kristjan Norland, Lilja Stefansdottir, Asgeir Sigurdsson, Gardar Sveinbjornsson, Asmundur Oddsson, Gyda Bjornsdottir, Reynir L. Gudmundsson, Gisli H. Halldorsson, Thorunn Rafnar, Ingileif Jonsdottir, Eirikur Steingrimsson, Gudmundur L. Norddahl, Gisli Masson, Patrick Sulem, Helgi Jonsson, Thorvaldur Ingvarsson, Daniel F. Gudbjartsson, Unnur Thorsteinsdottir, Kari Stefansson
Journal: Nature Genetics (2018)
Brain Mechanisms of Attention Orienting Following Frustration: Associations With Irritability and Age in Youths
Authors: Wan-Ling Tseng, Christen M. Deveney, Joel Stoddard, Katharina Kircanski, Anna E. Frackman, Jennifer Y. Yi, Derek Hsu, Elizabeth Moroney, Laura Machlin, Laura Donahue, Alexandra Roule, Gretchen Perhamus, Richard C. Reynolds, Roxann Roberson-Nay, John M. Hettema, Kenneth E. Towbin, Argyris Stringaris, Daniel S. Pine, Melissa A. Brotman, Ellen Leibenluft
Journal: American Journal of Psychiatry (2018)

Objective: Childhood irritability is a common, impairing problem with changing age-related manifestations that predict long-term adverse outcomes. However, more investigation of overall and age-specific neural correlates is needed. Because youths with irritability exhibit exaggerated responses to frustrating stimuli, the authors used a frustration functional MRI (fMRI) paradigm to examine associations between irritability and neural activation and tested the moderating effect of age. Method: The authors studied a transdiagnostic sample of 195 youths with varying levels of irritability (disruptive mood dysregulation disorder, N=52; anxiety disorder, N=42; attention deficit hyperactivity disorder, N=40; and healthy volunteers, N=61). Irritability was measured by parent and child reports on the Affective Reactivity Index. The fMRI paradigm was a cued-attention task differentiating neural activity in response to frustration (rigged feedback) from activity during attention orienting in the trial following frustration. Results: Whole-brain activation analyses revealed associations with irritability during attention orienting following frustration. Irritability was positively associated with frontal-striatal activation, specifically in the dorsolateral prefrontal cortex, inferior frontal gyrus, and caudate. Age moderated the association between irritability and activation in some frontal and posterior regions (the anterior cingulate cortex, medial frontal gyrus, cuneus, precuneus, and superior parietal lobule [F=19.04–28.51, df=1, 189, partial eta squared=0.09–0.13]). Specifically, higher irritability was more strongly related to increased activation in younger youths compared with older youths. Conclusions: Following frustration, levels of irritability correlated with activity in neural systems mediating attention orienting, top-down regulation of emotions, and motor execution. Although most associations were independent of age, dysfunction in the anterior cingulate cortex and posterior regions was more pronounced in young children with irritability.
GW29-e1460 S-Nitrosylation of NF-kappaB p65 Inhibits H2O2-Induced endothelial senescence
Authors: Dinghui Liu, Shujie Yu, Bin Zhou, Lin Wu, Xianguan Yu, Shiye Ke, Guangyao Shi, Xiaoxian Qian
Journal: Journal of the American College of Cardiology (2018)
Identification and characterization of a novel interaction between peroxisome-proliferator activated receptor gamma (PPARγ) and human mesoderm induction-early response 1 and potential implications for adipogenesis
Authors: Amanda Parsons, Laura Gillespie, Gary Paterno
Journal: Cancer Research (2008)

1222   PPARγ is a nuclear hormone receptor and master regulator of lipid metabolism and adipogenesis. It is also the target for the thiazolidinediones, a class of drugs used in the treatment of type 2 diabetes. PPARγ regulates these processes through the recruitment of a diverse set of transcriptional coregulators (both coactivators and corepressors) in a tissue and time specific manner. This study focused on characterizing the interaction between PPARγ and human mesoderm induction early response 1 (hMI-ER1), a transcription factor that has been shown to interact with other nuclear hormone receptors and regulate target gene expression. Glutathione-S-transferase pull-down assays have revealed that PPARγ interacts with both the α and β forms of hMI-ER1, specifically through the SANT domain located near the C-termini of both protein isoforms. Coimmunoprecipitations in HEK-293 (human embryonic kidney cells) confirmed that this interaction occurs  in vivo . Treatment with ligand (troglitazone) had no effect on the ability of PPAR to bind hMI-ER1 indicating that the interaction is ligand-independent. A reporter assay using luciferase regulated by the PPAR response element (PPRE) demonstrated that hMI-ER1α and β cause a 2-fold activation of PPAR-driven transcriptional activity and this was similar to the 3-fold activation observed with a known PPARγ coactivator (PPARγ coactivator 1-alpha, PGC1-α). This activation was also ligand-independent. Thus, hMI-ER1 interacts with PPAR in a ligand independent manner through its SANT domain, and causes activation of PPARγ-mediated transcriptional activity. We have recently discovered that hMI-ER1 expression is regulated in 3T3-L1 preadipocytes during their differentiation into adipocytes. Future work will determine the role of hMI-ER1 in adipogenesis using the well-established 3T3-L1 differentiation system.
Abstract 18266: The Impact of Text Message Reminders on Adherence to Exercise and Medications Stratified by Education
Authors: Avinash K Pandey, Tejal Patel, Neville Suskin, Niteesh Choudhry
Journal: Circulation (2016)

Background: Studies have demonstrated the role of socioeconomic factors on adherence to evidenced-based therapies. It has been postulated that those with less education may exhibit higher rates of ...
Association of PD-L1 expression with prognosis among patients with 10 select cancers
Authors: T. Steiniche, M. Ladekarl, J. Bæhr Georgsen, S. Andreasen, M. Busch-Sørensen, W. Zhou, S.K. Pruitt, A.K. Joe, K.-L. Liaw
Journal: Annals of Oncology (2018)
Efficacy and Safety of Sarilumab for the Treatment of Posterior Segment Noninfectious Uveitis (SARIL-NIU):
Authors: Jarmila Heissigerová, David Callanan, Marc D. de Smet, Sunil K. Srivastava, Michala Karkanová, Olga Garcia-Garcia, Sibel Kadayifcilar, Yilmaz Ozyazgan, Robert Vitti, Kristine Erickson, Aditya Athanikar, Karen Chu, Namrata Saroj, Preethi A. Sundaram, Rafael Varona, Valerie Corp-dit-Genti, Ronald Buggage, Yenchieh Cheng, Yuhwen Soo, Quan Dong Nguyen
Journal: Ophthalmology (2018)
Recent developments and highlights in mechanisms of allergic diseases: Microbiome
Authors: Nonhlanhla Lunjani, Pattraporn Satitsuksanoa, Zuzanna Lukasik, Milena Sokolowska, Thomas Eiwegger, Liam O'Mahony
Journal: Allergy (2018)

All body surfaces are exposed to a wide variety of microbes, which significantly influence immune reactivity within the host. This review provides an update on some of the critical novel findings that have been published on the influence of the microbiome on atopic dermatitis, food allergy and asthma. Microbial dysbiosis has consistently been observed in the skin, gut and lungs of patients with atopic dermatitis, food allergy and asthma, respectively, and the role of specific microbes in allergic disorders is being intensively investigated. However, many of these discoveries have yet to be translated into routine clinical practice.
Intermediate prognosis in metastatic germ cell tumors (IPGCT): Outcome and prognostic stratification
Authors: C. Seidel, K.G. Daugaard, A. Tryakin, A. Necchi, G. Cohn Cedermark, O. Ståhl, M. Hentrich, M. Brito, C. Albany, F. Taza, A. Gerl, K. Oechsle, C. Oing, C. Bokemeyer
Journal: Annals of Oncology (2018)
Advances in Acoustic Signal Processing Techniques for Enhanced Bowel Sound Analysis
Authors: Gary Allwood, Xuhao Du, K. Mary Webberley, Adam Osseiran, Barry James Marshall
Journal: IEEE Reviews in Biomedical Engineering (2018)

With the invention of the electronic stethoscope and other similar recording and data logging devices, acoustic signal processing concepts and methods can now be applied to bowel sounds. In this paper, the literature pertaining to acoustic signal processing for bowel sound analysis is reviewed and discussed. The paper outlines some of the fundamental approaches and machine learning principles that may be used in bowel sound analysis. The advances in signal processing techniques that have allowed useful information to be obtained from bowel sounds from a historical perspective are provided. The document specifically address the progress in bowel sound analysis, such as improved noise reduction, segmentation, signal enhancement, feature extraction, localization of sounds, and machine learning techniques. We have found that advanced acoustic signal processing incorporating novel machine learning methods and artificial intelligence can lead to better interpretation of acoustic information emanating from the bowel.
Effect of Genetic Diagnosis on Patients with Previously Undiagnosed Disease
Authors: Kimberly Splinter, David R. Adams, Carlos A. Bacino, Hugo J. Bellen, Jonathan A. Bernstein, Alys M. Cheatle-Jarvela, Christine M. Eng, Cecilia Esteves, William A. Gahl, Rizwan Hamid, Howard J. Jacob, Bijal Kikani, David M. Koeller, Isaac S. Kohane, Brendan H. Lee, Joseph Loscalzo, Xi Luo, Alexa T. McCray, Thomas O. Metz, John J. Mulvihill, Stanley F. Nelson, Christina G.S. Palmer, John A. Phillips, Leslie Pick, John H. Postlethwait, Chloe Reuter, Vandana Shashi, David A. Sweetser, Cynthia J. Tifft, Nicole M. Walley, Michael F. Wangler, Monte Westerfield, Matthew T. Wheeler, Anastasia L. Wise, Elizabeth A. Worthey, Shinya Yamamoto, Euan A. Ashley
Journal: New England Journal of Medicine (2018)

Many patients remain without a diagnosis despite extensive medical evaluation. The Undiagnosed Diseases Network (UDN) was established to apply a multidisciplinary model in the evaluation of the most challenging cases and to identify the biologic characteristics of newly discovered diseases. The UDN, which is funded by the National Institutes of Health, was formed in 2014 as a network of seven clinical sites, two sequencing cores, and a coordinating center. Later, a central biorepository, a metabolomics core, and a model organisms screening center were added.
Association of Chronic Kidney Disease With Allopurinol Use in Gout Treatment
Authors: Ana Beatriz Vargas-Santos, Christine E. Peloquin, Yuqing Zhang, Tuhina Neogi
Journal: JAMA Internal Medicine (2018)

<h3>Importance</h3> Clinicians are often cautious about use of allopurinol in patients with gout when renal function declines. <h3>Objective</h3> To assess the association of allopurinol use in gout with the risk of developing chronic kidney disease stage 3 or higher. <h3>Design, Setting, and Participants</h3> A time-stratified propensity score–matched, population-based, prospective cohort study of individuals with newly diagnosed gout who initiated allopurinol (≥300 mg/d) compared with those who did not initiate allopurinol, using the Health Improvement Network (THIN), a United Kingdom general practitioner electronic health records database, was carried out. The data were analyzed using Cox proportional hazards regression. Among adults aged 18 to 89 years with newly diagnosed gout, we propensity score matched 4760 initiators of allopurinol (≥300 mg/d) to the same number of noninitiators of allopurinol, excluding those with chronic kidney disease stage 3 or higher or urate-lowering therapy use before their gout diagnosis. <h3>Exposures</h3> Allopurinol initiation at a dose of 300 mg or more per day. <h3>Main Outcomes and Measures</h3> Development of chronic kidney disease stage 3 or higher. <h3>Results</h3> Of the 4760 allopurinol initiators (3975 men, 785 women) and same number of noninitiators (3971 men, 789 women), 579 and 623, respectively, developed chronic kidney disease stage 3 or higher, with a mean follow-up time of 5 and 4 years, mean age of 57 years, and mean body mass index (calculated as weight in kilograms divided by height in meters squared) of 30 for both groups. Use of allopurinol of at least 300 mg/d was associated with lower risk of developing chronic kidney disease stage 3 or higher compared with nonusers, with a hazard ratio (HR) of 0.87 (95% CI, 0.77-0.97). Allopurinol initiation at less than 300 mg/d was not associated with renal function decline (HR, 1.00; 95% CI, 0.91-1.09). <h3>Conclusions and Relevance</h3> In this large cohort, allopurinol initiation of at least 300 mg/d was associated with a lower risk of renal function deterioration. Because allopurinol does not appear to be associated with renal function decline, clinicians should consider evaluating other potential causes when patients with gout experience renal function decline.
Time to Implement Immediate Personalized Feedback and Individualized Action Planning for Hand Hygiene
Authors: Sheldon Paul Stone
Journal: JAMA Network Open (2018)

Daniel J. Livorsi, MD, MSc; Cassie Cunningham Goedken, MPH; Michael Sauder, PhD; Mark W. Vander Weg, PhD; Eli N. Perencevich, MD, MS; Heather Schacht Reisinger, PhD