tbuckley/cabot-search huggingface dataset:
Executive Function Predicting Longitudinal Change in Type 1 Diabetes Management During the Transition to Emerging Adulthood
Authors: Cynthia A. Berg, Deborah J. Wiebe, Yana Suchy, Sara L. Turner, Jonathan Butner, Ascher Munion, Amy Hughes Lansing, Perrin C. White, Mary Murray
Journal: Diabetes Care (2018)

OBJECTIVE The objective of this study was to examine 1) whether teens’ glycemic control and adherence to type 1 diabetes treatment regimen worsen during the transition from late adolescence to emerging adulthood, and 2) whether teens’ executive function (EF), as measured by performance and self-reported problems with EF, is predictive of these changes (after controlling for general intelligence). RESEARCH DESIGN AND METHODS High school seniors with type 1 diabetes (N = 236; mean age 17.74 years) were assessed at three yearly time points. At baseline, during the senior year of high school, participants completed a self-report measure of problems with EF and performance-based measures of EF and general intelligence (IQ). Glycemic control was determined on the basis of results collected from HbA1c assay kits, and teens reported their adherence at all three time points. RESULTS HbA1c increased significantly across the three time points and adherence declined. EF performance was not associated with adherence or HbA1c at baseline, nor with changes in adherence over time. However, better EF performance predicted slower increases in HbA1c over time (i.e., slope) while controlling for IQ. Teens’ self-reported problems with EF were associated with worse glycemic control and poorer adherence at baseline (i.e., intercept), but they did not predict changes in either HbA1c or adherence over time (i.e., slope). CONCLUSIONS Abilities involved in performance on EF tests may be one resource for maintaining better glycemic control during the transition to emerging adulthood. Assessment of such EF abilities may allow for the identification of individuals who are most at risk for deterioration of glycemic control during this transition.
Personalized treatment based on mini patient‐derived xenografts and WES/RNA sequencing in a patient with metastatic duodenal adenocarcinoma
Authors: Peng Zhao, Hui Chen, Danyi Wen, Shuo Mou, Feifei Zhang, Shusen Zheng
Journal: Cancer Communications (2018)

Abstract Background Treatment guidelines for a variety of cancers have been increasingly used in clinical practice, and have resulted in major improvement in patient outcomes. However, recommended regimens (even first‐line treatments) are clearly not ideal for every patients. In the present study, we used mini patient‐derived xenograft (mini‐PDX) and next‐generation sequencing to develop personalized treatment in a patient with metastatic duodenal adenocarcinoma. Methods Resected metachronous metastatic tumor tissues were implanted into SCID mice to determine the sensitivity to a variety of drug regimens. Mutation profiles were assessed using both DNA whole‐exome sequencing (DNA–WES) and RNA sequencing. The results of the analyses were used to select optimal treatment for the patient with metastatic duodenal adenocarcinoma. Results Assessment with mini‐PDX models took only 7 days. The results showed high sensitivity to S‐1 plus cisplatin, gemcitabine plus cisplatin and everolimus alone. The patient received gemcitabine plus cisplatin initially, but the treatment was terminated due to toxicity. The patient was then switched to treatment with S‐1 alone. The overall disease‐free survival was 34 months. DNA–WES and RNA sequencing identified KRAS mutation (A146T), TP53 (C229Yfs*10) and RICTOR amplification in the metastatic duodenal adenocarcinoma. These findings provided further support to the results of the mini‐PDX, and suggest mTOR inhibitors should be used if and when relapse eventually occurs in this patient. Conclusions Mini‐PDX model combined with WES/RNA sequencing can rapidly assess drug sensitivity in cancer patients and reveal key genetic alterations. Further research on this technology for personalized therapy in patients with refractory malignant tumors is warranted.
Abstract P020: High-sensitivity Cardiac Troponin T is an Independent Predictor for Coronary Artery Disease in Japanese Population: The Circulatory Risk in Communities Study
Authors: Hironori Imano, Kazumasa Yamagishi, Takeo Okada, Akihiko Kitamura, Hiroyasu Iso
Journal: Circulation (2016)

Background: Coronary heart disease (CHD) has become No.1 cause of death in the world. Therefore, it is important to seek new predicting indicators to capture high risk individuals of CHD. Cardiac Troponin T in healthy individuals may be a candidate of predictor. Hypothesis: High-sensitivity cardiac Troponin T (hs-cTnT) is an independent predictor for incident CHD in general population. Methods: We conducted a nested case-control study in four Japanese communities of the Circulatory Risk in Communities Study (CIRCS). We investigated 120 cases (81 men and 39 women, aged 38-86 years) of first incident CHDs between 2001 and 2011, and 240 controls matched with age, sex, communities and the year of examination. Serum hs-cTnT levels were measured by electrochemiluminescence immunoassay. We used the serum storing at –80°C. The median (range of) period until the incidence of CHD was 2.0 years (4 days to 9.5 years) among cases. The incidence of CHD was ascertained by systematic active surveillance. Odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of incident CHD were calculated with conditional logistic regression analyses. We calculated the ORs for each quartile of hs-cTnT against the lowest quartile as a reference. The adjustment variables included body mass index, systolic blood pressure, antihypertensive medication use, diabetes mellitus, serum total cholesterol, serum high-density lipoprotein cholesterol, and drinking status. Results: The distribution of hs-cTnT was from ≤0.003 ng/mL (measurement limit) to 0.155 ng/mL. The percentage of cases in each quartile of hs-cTnT was 24.7% (23/93) in the lowest quartile (≤0.004 ng/mL), 30.5% (29/95) in the second quartile (0.005 to 0.007 ng/mL), 38.4% (33/86) in the third quartile (0.008 to 0.011 ng/mL) and 40.7% (35/86) in the highest quartile (≥0.012 ng/mL). The ORs for incident CHD were 1.73 (95%CI: 0.83 to 3.58) for the second quartile, 2.63 (1.21 to 5.68) for the third quartile, and 2.90 (1.33 to 6.32) for the highest quartile against the lowest quartile. Each multivariable OR was 1.59 (0.74 to 3.45), 2.50 (1.08 to 5.77), and 2.61 (1.10 to 6.20), respectively. Conclusions: In conclusion, hs-cTnT was an independent predictor for CHD in Japanese general population.
Is Asymptomatic Esophageal Eosinophilia the Same Disease Entity as Eosinophilic Esophagitis?
Authors: Norihisa Ishimura, Shohei Sumi, Mayumi Okada, Hironobu Mikami, Eiko Okimoto, Nahoko Nagano, Asuka Araki, Yuji Tamagawa, Tsuyoshi Mishiro, Naoki Oshima, Shunji Ishihara, Riruke Maruyama, Yoshikazu Kinoshita
Journal: Clinical Gastroenterology and Hepatology (2018)
Clinical and echocardiographic predictors of embolism in infective endocarditis: systematic review and meta-analysis
Authors: A. Yang, C. Tan, N. Daneman, M.S. Hansen, G. Habib, E. Salaun, C. Lavoute, S. Hubert, N.K.J. Adhikari
Journal: Clinical Microbiology and Infection (2018)
An Afferent Neuropeptide System Transmits Mechanosensory Signals Triggering Sensitization and Arousal in C. elegans
Authors: Yee Lian Chew, Yoshinori Tanizawa, Yongmin Cho, Buyun Zhao, Alex J. Yu, Evan L. Ardiel, Ithai Rabinowitch, Jihong Bai, Catharine H. Rankin, Hang Lu, Isabel Beets, William R. Schafer
Journal: Neuron (2018)

Sensitization is a simple form of behavioral plasticity by which an initial stimulus, often signaling danger, leads to increased responsiveness to subsequent stimuli. Cross-modal sensitization is an important feature of arousal in many organisms, yet its molecular and neural mechanisms are incompletely understood. Here we show that in C. elegans, aversive mechanical stimuli lead to both enhanced locomotor activity and sensitization of aversive chemosensory pathways. Both locomotor arousal and cross-modal sensitization depend on the release of FLP-20 neuropeptides from primary mechanosensory neurons and on their receptor FRPR-3. Surprisingly, the critical site of action of FRPR-3 for both sensory and locomotor arousal is RID, a single neuroendocrine cell specialized for the release of neuropeptides that responds to mechanical stimuli in a FLP-20-dependent manner. Thus, FLP-20 peptides function as an afferent arousal signal that conveys mechanosensory information to central neurons that modulate arousal and other behavioral states.
Abstract 10756: Detection of Increased Targeted H2S Delivery to the Myocardial Microvasculature Using Ultrasound and Intravenous Microbubbles
Authors: Juefei Wu, Feng Xie, Jia Liu, John Lof, Luke Drvol, Shelby L Kutty, Thomas R Porter
Journal: Circulation (2012)

Background: Studies have demonstrated that the gaseous signaling molecule hydrogen sulfide (H2S) may have clinical benefit in preventing myocardial ischemic-reperfusion injury. However, systemic de...
Evaluation of Macitentan in Patients With Eisenmenger Syndrome
Authors: Michael A. Gatzoulis, Michael Landzberg, Maurice Beghetti, Rolf M. Berger, Michela Efficace, Sophie Gesang, Jian’guo He, Kelly Papadakis, Tomás Pulido, Nazzareno Galiè
Journal: Circulation (2018)

Eisenmenger syndrome describes congenital heart disease-associated severe pulmonary hypertension accompanied by right-to-left shunting. The multicenter, double-blind, randomized, placebo-controlled, 16-week, phase III MAESTRO study (Macitentan in Eisenmenger Syndrome to Restore Exercise Capacity) evaluated the efficacy and safety of the endothelin receptor antagonist macitentan in patients with Eisenmenger syndrome.
In vitro placenta barrier model using primary human trophoblasts, underlying connective tissue and vascular endothelium
Authors: Akihiro Nishiguchi, Catherine Gilmore, Aman Sood, Michiya Matsusaki, Gavin Collett, Dionne Tannetta, Ian L. Sargent, Jennifer McGarvey, Nagaraj D. Halemani, Jon Hanley, Fiona Day, Simon Grant, Catherine Murdoch-Davis, Helena Kemp, Paul Verkade, John D. Aplin, Mitsuru Akashi, C Patrick Case
Journal: Biomaterials (2018)
Abstract 14812: Echolucency of the Carotid Artery is Associated With Short-term Plaque Progression and Positive Remodeling in Culprit Coronary Artery in AMI Survivors
Authors: Mika Futamata, Satoshi Matsuoka, Takuya Shimizu, Toru Yoshizaki, Jun-ei Obata, Takamitsu Nakamura, Daisuke Fujioka, Kiyotaka Kugiyama
Journal: Circulation (2016)

Background: Rapid plaque progression and positive remodeling are recognized as vulnerable coronary plaque phenotypes. Non-invasive technique capable of assessing these subclinical features of vulne...
Exploring the pre-immune landscape of antigen-specific T cells
Authors: Mikhail V. Pogorelyy, Alla D. Fedorova, James E. McLaren, Kristin Ladell, Dmitri V. Bagaev, Alexey V. Eliseev, Artem I. Mikelov, Anna E. Koneva, Ivan V. Zvyagin, David A. Price, Dmitry M. Chudakov, Mikhail Shugay
Journal: Genome Medicine (2018)

Adaptive immune responses to newly encountered pathogens depend on the mobilization of antigen-specific clonotypes from a vastly diverse pool of naive T cells. Using recent advances in immune repertoire sequencing technologies, models of the immune receptor rearrangement process, and a database of annotated T cell receptor (TCR) sequences with known specificities, we explored the baseline frequencies of T cells specific for defined human leukocyte antigen (HLA) class I-restricted epitopes in healthy individuals. We used a database of TCR sequences with known antigen specificities and a probabilistic TCR rearrangement model to estimate the baseline frequencies of TCRs specific to distinct antigens epitopespecificT-cells. We verified our estimates using a publicly available collection of TCR repertoires from healthy individuals. We also interrogated a database of immunogenic and non-immunogenic peptides is used to link baseline T-cell frequencies with epitope immunogenicity. Our findings revealed a high degree of variability in the prevalence of T cells specific for different antigens that could be explained by the physicochemical properties of the corresponding HLA class I-bound peptides. The occurrence of certain rearrangements was influenced by ancestry and HLA class I restriction, and umbilical cord blood samples contained higher frequencies of common pathogen-specific TCRs. We also identified a quantitative link between specific T cell frequencies and the immunogenicity of cognate epitopes presented by defined HLA class I molecules. Our results suggest that the population frequencies of specific T cells are strikingly non-uniform across epitopes that are known to elicit immune responses. This inference leads to a new definition of epitope immunogenicity based on specific TCR frequencies, which can be estimated with a high degree of accuracy in silico, thereby providing a novel framework to integrate computational and experimental genomics with basic and translational research efforts in the field of T cell immunology.
Clinically relevant differences in COPD health status: systematic review and triangulation
Authors: Harma Alma, Corina de Jong, Ioanna Tsiligianni, Robbert Sanderman, Janwillem Kocks, Thys van der Molen
Journal: European Respiratory Journal (2018)

The minimal clinically important difference (MCID) quantifies when measured differences can be considered clinically relevant. This study aims to review and triangulate MCIDs of chronic obstructive pulmonary disease (COPD) health status tools. A systematic search in PubMed, EMBASE and Cochrane Library was conducted (Prospero #CRD42015023221). Study details, patient characteristics, MCID methodology and estimates were assessed and extracted by two authors. A triangulated mean was obtained for each tool's MCID, with two-thirds weighting for anchor-based and one-third for distribution-based results. This was then multiplied by a weighted factor based upon the study size and quality rating. Overall, 785 records were reviewed of which 21 studies were included for analysis. MCIDs of 12 tools were presented. General quality and risk of bias were average to good. Triangulated MCIDs for the COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ) and St. George's Respiratory Questionnaire (SGRQ) were −2.54, −0.43 and −7.43 for improvement. Too few and/or too diverse studies were present to triangulate MCIDs of other tools. Evidence for the MCID of the CAT and CCQ was strong and triangulation was valid. Currently used MCIDs in clinical practice for the SGRQ (4) and Chronic Respiratory Questionnaire (0.5) did not match the reviewed content, for which the MCIDs were much higher. Using too low MCIDs may lead to an overestimation of the interpretation of treatment effects. MCIDs for deterioration were scarce, which highlights the need for more research.
Deciduous autologous tooth stem cells regenerate dental pulp after implantation into injured teeth
Authors: Kun Xuan, Bei Li, Hao Guo, Wei Sun, Xiaoxing Kou, Xiaoning He, Yongjie Zhang, Jin Sun, Anqi Liu, Li Liao, Shiyu Liu, Wenjia Liu, Chenghu Hu, Songtao Shi, Yan Jin
Journal: Science Translational Medicine (2018)

Dental pulp regeneration by tooth stem cells promotes recovery of damaged teeth in animal models and human patients.
Abstract 16297: Effect of Low-Dose Aspirin on Incidence of Dementia in Patients With Type 2 Diabetes Mellitus: Insights From JPAD2 Study
Authors: Chisa Matsumoto, Yoshihiko Saito Saito, Hisao Ogawa, Sadanori Okada, Hirofumi Soejima, Mio Sakuma, Izuru Masuda, Masafumi Nakayama, Hideakai Jinnouchi, Masako Waki, Takeshi Morimoto
Journal: Circulation (2017)

Introduction: Type 2 diabetes mellitus (T2DM) was reported one of the risk factors for dementia. Several observational studies and randomized controlled trials (RCT) evaluated the association betwe...
Abstract 13087: Are All Patients Equal in Response to Intra-Aortic Balloon Counterpulsation?
Authors: David A Baran, Marc Cohen, Gautam K Visveswaran, Michael DiVita, Ahmed Seliem, Amar Dave, Najam Wasty, Jonathan E Swinden
Journal: Circulation (2015)

Background: Intra-Aortic Balloon Counterpulsation (IABC) with a 50 cc (MEGA 50™) balloon catheter is associated with an average increase of 0.5- 0.7 liters/min in cardiac output. However, some patients (pts) have a much more dramatic response. We retrospectively analyzed our single center tertiary care experience with 150 consecutive pts undergoing IABC. Methods: Chart review for demographic, procedural, and hemodynamic data was collected for 150 pts of whom 64 had both pre and 4 hour post IABC hemodynamic measurements. The responder (R) group was defined by any positive change in cardiac output (CO) and cardiac index (CI) between baseline prior to IABC and 4 hours post initiation. Non-responders (NR) were defined as those with a decline in CO or no change. Results: IABC with a 50 cc balloon was associated with a significant improvement in CO of 0.7 L/min for the overall cohort (Pre-IABC mean CO 3.9±1.4 vs post 4.6 ±1.6 L/Min, paired t-test p=.0004). There were 38 pts in the R group (60 %) and 26 in the NR group. The CO / CI post-IABC improved significantly: CO 3.5±1.3 to 5.0±1.7 L/Min and CI 1.8±0.6 vs 2.6±0.7 L/min/M 2 ) (p&lt;0.0001). For NR pts, CO dropped from 4.5±1.3 to 3.9±1.2 L/Min (p&lt;0.0001) and CI from 2.2±0.6 to 2.1±0.5 L/min/M 2 (p=0.1). Interestingly, systemic vascular resistance varied significantly between groups (R: 1568±657 vs NR 1218±461 (dyne*sec)/cm 5 (p=0.02). Nominal logistic regression identified pre-IABC CO as a significant predictor of response. Conclusion: Among a cohort of pts receiving IABC, there appears to be a binary response with “responders” augmenting CO by 1.5 L/min which is close to that provided by percutaneous ventricular assist catheters such as Impella. Patients with lower pre-IABC CO and higher SVR appear to have the most favorable response to IABC. This binary response may have influenced prior neutral clinical outcome trials of IABC.
Multidrug-resistance conferred by RalBP1/RLIP76
Authors: Kenneth J. Drake, Sharad S. Singhal, Jyotsana Singhal, Sushma Yadav, Yogesh C. Awasthi, Sanjay Awasthi
Journal: Cancer Research (2005)

5953  RLIP76 (RALBP1) is a Ral-effector and Rho/Rac GAP protein that functions as a multispecific transporter for cellular metabolites and amphiphilic xenobiotic compounds. Its physiological function appears to be present in a variety of membrane movement functions, most prominently, chemotaxis and clathrin-coated pit mediated receptor endocytosis that regulates activity of extracellular signals including insulin, TGF and EGF. One of its physiological substrates is the glutathione-conjugate such as leukotriene C4, a key determinant of chemotaxis, and another is 4-hydroxynonenal-S-glutathione, the metabolite of a potent apoptosis inducing lipid-peroxidation product. Because it is a very broad specificity transporter, it can utilize many un-metabolized amphiphilic xenobiotics as substrates, which compete for transport with its physiological substrates. In lung cancer cells, RLIP76 has been shown to confer resistance to alkylating agents, (which are metabolized to glutathione-conjugates), as well as un-metabolized xenobiotic toxins including chemotherapy drugs such as doxorubicin, daunorubicin, vincristine, vinblastine and vinorelbine. In lung cancer cells, inhibition of RLIP76 in the absence of chemotherapy drug induced apoptosis through increased cellular accumulation of 4-hydroxynonenal, whereas its inhibition in the presence of toxic chemotherapy agents synergistically increased cytotoxicity. The role of RLIP76 in multidrug-resistance in other cell types was not known. Present studies in K562 human myelogenous leukemia cell line showed that RLIP76 over-expression in these cells results in resistance to cisplatin, melphalan, doxorubicin, daunorubicin, vincristine, vinblastine, vinorelbine, and mitomycin-C. Conversely, inhibition of RLIP76 by specific antibodies targeted for the cell-surface domains causes increased drug-accumulation along with synergistically increasing cytotoxicity in multiple relatively resistant cell types including melanoma, colon, and prostate cancer. Taken together with our previous studies in lung cancer, these results show that RLIP76 confers multidrug-resistance in epithelial as well as hematological neoplasia, and demonstrate the potential utility of targeting RLIP76 in treatment of other resistant cancers.
Noncommunicable Respiratory Disease and Air Pollution Exposure in Malawi (CAPS). A Cross-Sectional Study
Authors: Rebecca Nightingale, Maia Lesosky, Graham Flitz, Sarah J. Rylance, Jamilah Meghji, Peter Burney, John Balmes, Kevin Mortimer
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: Noncommunicable respiratory diseases and exposure to air pollution are thought to be important contributors to morbidity and mortality in sub-Saharan African adults.Objectives: We set out to explore the prevalence and determinants of noncommunicable respiratory disease among adults living in Chikhwawa District, Malawi.Methods: We performed a cross-sectional study among adults in communities participating in a randomized controlled trial of a cleaner-burning biomass-fueled cookstove intervention (CAPS [Cooking and Pneumonia Study]) in rural Malawi. We assessed chronic respiratory symptoms, spirometric abnormalities, and personal exposure to air pollution (particulate matter <2.5 μm in aerodynamic diameter [PM2.5] and carbon monoxide [CO]). Weighted prevalence estimates were calculated; multivariable and intention-to-treat analyses were done.Measurements and Main Results: One thousand four hundred eighty-one participants (mean [SD] age, 43.8 [17.8] yr; 57% female) were recruited. The prevalence of chronic respiratory symptoms, spirometric obstruction, and restriction were 13.6% (95% confidence interval [CI], 11.9–15.4), 8.7% (95% CI, 7.0–10.7), and 34.8% (95% CI, 31.7–38.0), respectively. Median 48-hour personal PM2.5 and CO exposures were 71.0 μg/m3 (interquartile range [IQR], 44.6–119.2) and 1.23 ppm (IQR, 0.79–1.93), respectively. Chronic respiratory symptoms were associated with current/ex-smoking (odds ratio [OR], 1.59; 95% CI, 1.05–2.39), previous tuberculosis (OR, 2.50; 95% CI, 1.04–15.58), and CO exposure (OR, 1.46; 95% CI, 1.04–2.05). Exposure to PM2.5 was not associated with any demographic, clinical, or spirometric characteristics. There was no effect of the CAPS intervention on any of the secondary trial outcomes.Conclusions: The burden of chronic respiratory symptoms, abnormal spirometry, and air pollution exposures in adults in rural Malawi is of considerable potential public health importance. We found little evidence that air pollution exposures were associated with chronic respiratory symptoms or spirometric abnormalities and no evidence that the CAPS intervention had effects on the secondary trial outcomes. More effective prevention and control strategies for noncommunicable respiratory disease in sub-Saharan Africa are needed.Clinical trial registered with www.isrctn.com (ISRCTN 59448623).