tbuckley/cabot-search huggingface dataset:
The role of trehalose in the global spread of epidemic<i>Clostridium difficile</i>
Authors: James Collins, Heather Danhof, Robert A. Britton
Journal: Gut Microbes (2018)

In a recent study, we reported on two distantly related, epidemic lineages of Clostridium difficile that have acquired independent mechanisms to metabolize low concentrations of trehalose. Here we provide further comment and evidence that a third epidemic lineage common in Asia and Europe, ribotype 017, has evolved this ability.
Exercise Stress Test Amplifies Genotype-Phenotype Correlation in the LQT1 and LQT2 Forms of the Long-QT Syndrome
Authors: KotoeTakenaka, TomohikoAi, WataruShimizu, AtsushiKobori, TomonoriNinomiya, HideoOtani, TomoyukiKubota, HiroshiTakaki, ShiroKamakura, MinoruHorie
Journal: Circulation (2003)

Background— Experimental studies suggest that the interval between peak and end of T wave (Tpe) in transmural ECGs reflects transmural dispersion of repolarization (TDR), which is amplified by β-adrenergic stimulation in the LQT1 model. In 82 patients with genetically identified long-QT syndrome (LQTS) and 33 control subjects, we examined T-wave morphology and various parameters for repolarization in 12-lead ECGs including corrected QT (QTc; QT/R-R1/2) and corrected Tpe (Tpec; Tpe/R-R1/2) before and during exercise stress tests. Methods and Results— Under baseline conditions, LQT1 (n=51) showed 3 cardinal T-wave patterns (broad-based, normal-appearing, late-onset) and LQT2 (n=31) 3 patterns (broad-based, bifid with a small or large notch). The QTc and Tpec were 510±68 ms and 143±53 ms in LQT1 and 520±61 ms and 195±69 ms in LQT2, respectively, which were both significantly larger than those in control subjects (402±36 ms and 99±36 ms). Both QTc and Tpec were significantly prolonged during exercise in LQT1 ...
Abstract P221: Plasma Triglyceride/High Density Lipoprotein Cholesterol Ratio and Subclinical Cardiovascular Disease Parameters in a South Asian Population
Authors: MohanThanikachalam, JahnaviSunderarajan, ShravantiShankar, VijaykumarHarivanzan, SadagopanThanikachalam
Journal: Circulation (2015)

Background: There is increasing focus on biomarkers for early detection of cardiovascular disease (CVD). Studies suggest that the ratio of triglyceride (TG)/high density lipoprotein (HDL) could be a simple marker for insulin resistant and increased cardiometabolic risk, but the association between TG/HDL ratio and CVD is not fully defined. In the current study we assess the relationship between TG/HDL ratio and subclinical CVD parameters in a South Asian population. Methods: In the cross-sectional analysis of 8080 South Indians, the assessments included left ventricular mass indexed (LVMI) to body surface area by echocardiograph, carotid intimal medial thickness (IMT), arterial stiffness by carotid-femoral pulse wave velocity (PWV) and endothelial function by brachial artery flow mediated dilatation (FMD). Generalized linear regression models were used to test the association of TG/HGL ratio with subclinical parameters. All models were adjusted for age, gender, BMI, physical activity, LDL, blood sugar, sm...
Questioning Prediction of Lumbar Spine Surgery Outcome—Why We Need to Pay Attention—Reply
Authors: Sara Khor, David R. Flum
Journal: JAMA Surgery (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Expression of Interleukin-18 in Human Atherosclerotic Plaques and Relation to Plaque Instability
Authors: ZiadMallat, AnneCorbaz, AlexandraScoazec, SandrineBesnard, GuyLesèche, YolandeChvatchko, AlainTedgui
Journal: Circulation (2001)

Background Interleukin (IL)-18 is a potent proinflammatory cytokine with potential atherogenic properties. Its expression and role in atherosclerosis, however, are unknown. Methods and Results In the present study, we examined stable and unstable human carotid atherosclerotic plaques retrieved by endarterectomy for the presence of IL-18 using reverse transcription-polymerase chain reaction (PCR), Western blot, and immunohistochemical techniques. IL-18 was highly expressed in the atherosclerotic plaques compared with control normal arteries and was localized mainly in plaque macrophages. IL-18 receptor was also upregulated in plaque macrophages and endothelial cells, suggesting potential biological effects. To examine the role of IL-18 in atherosclerosis, we determined the relation between IL-18 mRNA expression and signs of plaque instability using real-time quantitative PCR. Interestingly, significantly higher levels of IL-18 mRNA were found in symptomatic (unstable) plaques than asymptomatic (stable) pla...
Abstract 20080: Health Status Profiles in Patients Presenting for Specialty Care With New Versus Worsening Symptoms of Peripheral Arterial Disease: Insights From the PORTRAIT Study
Authors: Mohamed Omer, Mohammed Qintar, Fengming Tang, John Spertus, Kim Smolderen
Journal: Circulation (2016)

Introduction: Peripheral arterial disease (PAD) symptoms are associated with impairment in ambulatory function and overall quality of life (QOL). However, no data exist on PAD-specific health statu...
Nanoemulsion aminolaevulinic acid photodynamic therapy for nonaggressive basal cell carcinoma: a comparison study
Authors: C. Morton, R. Dominicus, P. Radny, T. Dirschka, A. Hauschild, U. Reinhold, R. Aschoff, M. Ulrich, S. Keohane, S. Ekanayake-Bohlig, S. Ibbotson, R. Ostendorf, C. Berking, D. Grone, H. J. Schulze, H. M. Ockenfels, V. Jasnoch, H. Kurzen, M. Sebastian, R. M. Szeimies
Journal: British Journal of Dermatology (2017)
Electrocardiographic Changes in Head Injuries
Authors: Colinhersch
Journal: Circulation (1961)

Electrocardiograms of 164 Bantu patients with head trauma were recorded and studied with reference to two control groups, 100 Bantu patients with trauma to limbs and 164 healthy Bantu subjects. The electrocardiographic abnormalities that occurred more commonly in the head injury group than in either of the control groups were an increased Q-Tc interval and an increased voltage of the P wave. Both traumatic groups differed from the healthy controls in showing a higher incidence of increased QRS voltage and raised S-T segments in precordial leads, inverted T waves in precordial leads V4 to V6, U waves of more than 1 mm. in height, sinus arrhythmia with fixed pacemaker, and sinus arrhythmia with pacemaker wandering in the sinoatrial node. The number of electrocardiographic abnormalities increased as the level of consciousness deteriorated.
Abstract 17211: Edoxaban versus Warfarin in Patients With Atrial Fibrillation in the US FDA Approval Population: An Analysis From the ENGAGE AF-TIMI 48 Trial
Authors: Alon Eisen, Robert P Giugliano, Christian T Ruff, Francesco Nordio, Harinder S Gogia, Vivek R Awasty, David A Henderson, Michele Mercuri, Howard Rutman, Elliott M Antman, Eugene Braunwald
Journal: Circulation (2015)

Background: Edoxaban (edo), a QD oral direct factor Xa inhibitor, is non-inferior to warfarin for preventing stroke or systemic embolism (SE) in mod-high risk pts with AF. Due to reduced protection from ischemic stroke in pts with CrCl &gt;95 ml/min, the US FDA approved the higher dose edo regimen in pts with AF and a CrCl 15-95 ml/min (60mg QD if CrCl 50-95 ml/min; 30mg QD if CrCl 15-50 ml/min) without dose reduction for weight &lt; 60 kg or use of P-glycoprotein (P-gp) inhibitors. We report here for the first time the clinical characteristics, efficacy and safety of the FDA-approved population. Methods: From the ENGAGE AF-TIMI 48 trial population, we excluded pts who received the lower-dose edo regimen (30/15 mg), had CrCl &gt;95 ml/min, or were dose-reduced for weight≤ 60 kg or potent P-gp use. The 1° efficacy endpoint was stroke/SE and principal safety endpoint was major bleeding. Efficacy data are from the ITT cohort in the overall study period, unless otherwise specified. Results: There were 9387 pts with CrCl 15-95 ml/min randomized to either warfarin or edo 60/30 mg per the FDA label followed for 2.8 yrs (median). These pts were older (74 vs 64 yrs), more likely women (40 vs 33%), and had higher CHADS 2 and HAS-BLED scores compared to pts not included in the FDA label, but were balanced by randomization group. The annualized rate of stroke/SE on-treatment was 1.11% with edo vs. 1.72% with warfarin (HR vs. warfarin 0.64 [0.51-0.81], p&lt;0.001). Rates in the ITT cohort were 1.63% and 2.02% with edo and warfarin, respectively (HR 0.81 [0.67-0.97], p=0.023). Ischemic stroke rates were similar (1.31 vs 1.39%, HR 0.94, p=0.97). Edo significantly reduced hemorrhagic stroke, CV death, major and intracranial bleeding events (Fig). Conclusion: Among high risk pts in the ENGAGE AF-TIMI 48 trial who represent the FDA approval population and dosing regimen of edo, treatment with edo 60/30 mg is superior to warfarin in the prevention of stroke/SE and reduces major bleeding, intracranial hemorrhage, and CV death.
Local Delivery of Plasmid DNA Into Rat Carotid Artery Using Ultrasound
Authors: YoshiakiTaniyama, KatsuroTachibana, KazuyaHiraoka, TsunetatsuNamba, KeitaYamasaki, NaotakaHashiya, MotokuniAoki, ToshioOgihara, KanedaYasufumi, RyuichiMorishita
Journal: Circulation (2002)

Background— Although viral vector systems are efficient to transfect foreign genes into blood vessels, safety issues remain in relation to human gene therapy. In this study, we examined the feasibility of a novel nonviral vector system by using high-frequency, low-intensity ultrasound irradiation for transfection into blood vessels. Methods and Results— Luciferase plasmid mixed with or without echo contrast microbubble (Optison) was transfected into cultured human vascular smooth muscle cells (VSMC) and endothelial cells (EC) with the use of ultrasound. Interestingly, luciferase activity was markedly increased in both cell types treated with Optison. We then transfected luciferase plasmid mixed with Optison by means of therapeutic ultrasound into rat artery. Two days after transfection, luciferase activity was significantly higher in carotid artery transfected with luciferase gene with Optison and ultrasound than with plasmid alone. In addition, we transfected an anti-oncogene (p53) plasmid into carotid a...
Serum Elastase Activity, Serum Elastase Inhibitors, and Occurrence of Carotid Atherosclerotic Plaques
Authors: MahmoudZureik, LadislasRobert, DominiqueCourbon, Pierre-JeanTouboul, LatifaBizbiz, PierreDucimetière
Journal: Circulation (2002)

Background— In the last decades, interest has increased in the potential deleterious atherogenic effects of some cellular elastase activities. The results of experimental and clinical investigations were inconsistent. In this report, we assessed the associations of serum elastase activity and serum elastase inhibitors with carotid plaque occurrence during the 4-year follow-up in a population of 859 subjects free of coronary heart disease and stroke (age, 59 to 71 years). Methods and Results— Serum elastase activity and serum elastase inhibitors were measured at baseline examination. Carotid B-mode ultrasound examination was performed at baseline and 2 years and 4 years later. The occurrence of carotid plaques in subjects with the lowest serum elastase activity values (quartile 1), in those with the intermediate values (quartiles 2 to 3), and in those with the highest values (quartile 4) was, respectively, 24.6%, 18.9%, and 12.2% (P<0.001 for trend). The multivariate odds ratios of carotid plaque occurrenc...
Abstract 4386: Regulation of FIP200 by Her2 and its role in Her2-driven mammary tumors
Authors: Mingang Hao, Jun-Lin Guan
Journal: Cancer Research (2018)

Abstract Autophagy has been shown to play both tumor promoting and suppressive roles in various cancers, although the underlying mechanisms are not well understood. Compared to other subtypes of breast cancer (BCa), Her2+ BCa displays a lower autophagy gene signature, suggesting a potentially tumor suppressive function of autophagy in this subtype of BCa. FIP200 is a component of the ULK1/ATG13/FIP200/Atg101 complex essential for autophagy induction in mammalian cells, and our previous studies showed that Fip200 deletion suppressed BCa in MMTV-PyMT mouse model. Indeed, analysis of TCGA database showed that higher FIP200 expression correlated with decreased survival of BCa patients including all subtypes. In contrast, in Her2+ BCa population specifically, higher expression of FIP200 correlated with better patient survival, suggesting a differential function of FIP200. To uncover the role of FIP200 and autophagy in Her2+ BCa, we studied Fip200 in MMTV-Neu mouse tumor cells that model Her2+ BCa. We found that inhibiting autophagy by deletion of Fip200 or Atg13 using Crispr-Cas9 led to increased migration and partial EMT for MMTV-Neu cells. Further, deletion of Fip200 or Atg13 as well as autophagy inhibition by Spautin1 significantly enhanced β-catenin/LEF1/TCF reporter activity, which may promote cell migration and EMT. These changes in Fip200-null tumor cells could be rescued by re-expression of ectopic FIP200, excluding any potential off-target effects of gene knockout. We also found that Her2 knockdown or lapatinib treatment of MMTV-Neu cells increased Fip200 expression and autophagy. Together, these results raised the interesting possibility that Her2 may promote tumor development and/or progression at least in part by reducing FIP200 expression to inhibit autophagy, which might play a tumor suppressive role in Her2-driven BCa. Citation Format: Mingang Hao, Jun-Lin Guan. Regulation of FIP200 by Her2 and its role in Her2-driven mammary tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4386.
Abstract 2759: Rational combinations for immune checkpoint blockade using β-catenin RNAi therapy
Authors: Shanthi Ganesh, Serena Shui, Kevin Craig, Weimin Wang, Bob D. Brown, Marc Abrams
Journal: Cancer Research (2018)

Abstract Recent research has shown that Wnt/β-catenin signaling drives resistance to cancer immunotherapy by promoting the exclusion of T-cells from the tumor microenvironment. DCR-BCAT is an RNAi-based experimental medicine targeting β-catenin, formulated in a tumor-selective nanoparticle. We had previously reported that systemic administration of DCR-BCAT increased tumor-associated cytotoxic T-cells and dramatically improved responses to immunotherapy agents, in murine syngeneic models and GEM models. In this new work, we explore the mechanisms by which Wnt/β-catenin signaling promotes resistance to immune checkpoint blockade, and propose context-specific therapeutic combinations using RNAi therapy. We will present novel in vivo experimentation demonstrating that DCR-BCAT significantly enhances sensitivity to immunotherapy using different drug regimens in multiple tumor types. Citation Format: Shanthi Ganesh, Serena Shui, Kevin Craig, Weimin Wang, Bob D. Brown, Marc Abrams. Rational combinations for immune checkpoint blockade using β-catenin RNAi therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2759.
Abstract 3124: Cytotoxic effects of tumor-specific T lymphocytes on autologous cancer initiator stem-like glioblastoma cells
Authors: Yin-Cheng Huang, Kuo-Chen Wei, Chen-Nen Chang, Wen K. Yang
Journal: Cancer Research (2018)

Abstract [Purpose] In clinical trial of autologous dendritic cell/autologous tumor cell antigens (ADCTA) adjuvant immunotherapy of glioblastoma multiforme (GBM), we studied if and how GBM CD133(+) stem-like initiator cells are susceptible to immune cytotoxic eradication [Methods] Tumor-infiltrating T lymphocytes (TILs) were isolated from GBM patients after the ADCTA vaccination and tested for their effects on CD133(+) and CD133(-) glioma cells separated from the same patients. [Results] TILs isolated from GBM patients after ADCTA vaccination were cytotoxic to both CD133(+) and CD133(-) autologous glioma cells. However, the cell lysis was detectable in CD133(-) in 4 hours but did not occur until more than 18 hours later in the CD133(+) cancer stem-like initiator cells. Surprisingly, we found that, upon exposure to the TILs, the GBM tumor cells showed phenotype shift from CD133(+) to CD133 (-). Similar CD133(+) to CD133(-) phenotype shift was also observed by exposure to culture condition medium of the TILs. The responsible factors secreted by the TILs that caused the phenotype shift was determined to be INFγ and TNFα. [Conclusion] ADCTA vaccination in GBM patients would generate TILs that are not only specifically cytotoxic to autologous CD133(-) glioma cells but also secret INFγ and TNFα etc to induce phenotypic shift of the resistant CD133(+) stem-like GBM to susceptible CD133(-) glioma cells. Citation Format: Yin-Cheng Huang, Kuo-Chen Wei, Chen-Nen Chang, Wen K. Yang. Cytotoxic effects of tumor-specific T lymphocytes on autologous cancer initiator stem-like glioblastoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3124.
Early Plasma Matrix Metalloproteinase Profiles. A Novel Pathway in Pediatric Acute Respiratory Distress Syndrome
Authors: Matt S. Zinter, Kevin L. Delucchi, Michele Y. Kong, Benjamin E. Orwoll, Aaron S. Spicer, Michelle J. Lim, Mustafa F. Alkhouli, Anna E. Ratiu, Anne V. McKenzie, Patrick S. McQuillen, Christopher C. Dvorak, Carolyn S. Calfee, Michael A. Matthay, Anil Sapru
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: MMPs (Matrix metalloproteinases) and their endogenous tissue inhibitors may contribute to lung injury through extracellular matrix degradation and modulation of inflammation and fibrosis.Objectives: To test for an association between MMP pathway proteins and inflammation, endothelial dysfunction, and clinical outcomes.Methods: We measured MMPs in plasma collected on acute respiratory distress syndrome (ARDS) Day 1 from 235 children at five hospitals between 2008 and 2017. We used latent class analysis to identify patients with distinct MMP profiles and then associated those profiles with markers of inflammation (IL-1RA, -6, -8, -10, and -18; macrophage inflammatory protein-1α and -1β; tumor necrosis factor-α and -R2), endothelial injury (angiopoietin-2, von Willebrand factor, soluble thrombomodulin), impaired oxygenation (PaO2/FiO2 [P/F] ratio, oxygenation index), morbidity, and mortality.Measurements and Main Results: In geographically distinct derivation and validation cohorts, approximately one-third of patients demonstrated an MMP profile characterized by elevated MMP-1, -2, -3, -7, and -8 and tissue inhibitor of metalloproteinase-1 and -2; and depressed active and total MMP-9. This MMP profile was associated with multiple markers of inflammation, endothelial injury, and impaired oxygenation on Day 1 of ARDS, and conferred fourfold increased odds of mortality or severe morbidity independent of the P/F ratio and other confounders (95% confidence interval, 2.1–7.6; P < 0.001). Logistic regression using both the P/F ratio and MMP profiles was superior to the P/F ratio alone in prognosticating mortality or severe morbidity (area under the receiver operating characteristic curve, 0.75; 95% confidence interval, 0.68–0.82 vs. area under the receiver operating characteristic curve, 0.66; 95% confidence interval, 0.58–0.73; P = 0.009).Conclusions: Pediatric patients with ARDS have specific plasma MMP profiles associated with inflammation, endothelial injury, morbidity, and mortality. MMPs may play a role in the pathobiology of children with ARDS.
Risk Profile and Prediction of Long-Term Ischemic Stroke Mortality
Authors: DavidTanne, ShlomitYaari, UriGoldbourt
Journal: Circulation (1998)

Background—Multinational comparisons demonstrate marked ethnic and regional variation in stroke mortality and risk-factor distribution. We assessed the role of ethnicity and estimated the cumulative effect of multiple risk factors on long-term ischemic stroke mortality. Methods and Results—Civil servants and municipal employees in Israel (n=9734 men; age, ≥42 years), chosen by stratified sampling in 6 prespecified areas of birth (those born in Israel and those who were immigrants from 5 other regional-ethnic strata), were included in the Israeli Ischemic Heart Disease (IIHD) Project. Over a 21-year follow-up period, age-adjusted mortality rates per 10 000 person-years attributed to ischemic stroke (n=282; International Classification of Diseases [ICD]-9 codes 433 to 438) were higher among immigrants to Israel from northern Africa and the Mideast (17.1 to 19.0), than from 3 parts of Europe (11.3 to 12.4). Crude rates per 1000 subjects observed in those born in Asia or Africa (29.4 to 31.2) exceeded rates p...
Mitochondrial metabolism in pulmonary hypertension: beyond mountains there are mountains
Authors: Miranda K. Culley, Stephen Y. Chan
Journal: Journal of Clinical Investigation (2018)

Pulmonary hypertension (PH) is a heterogeneous and fatal disease of the lung vasculature, where metabolic and mitochondrial dysfunction may drive pathogenesis. Similar to the Warburg effect in cancer, a shift from mitochondrial oxidation to glycolysis occurs in diseased pulmonary vessels and the right ventricle. However, appreciation of metabolic events in PH beyond the Warburg effect is only just emerging. This Review discusses molecular, translational, and clinical concepts centered on the mitochondria and highlights promising, controversial, and challenging areas of investigation. If we can move beyond the "mountains" of obstacles in this field and elucidate these fundamental tenets of pulmonary vascular metabolism, such work has the potential to usher in much-needed diagnostic and therapeutic approaches for the mitochondrial and metabolic management of PH.