tbuckley/cabot-search huggingface dataset:
Prospective genomic surveillance of methicillin-resistant Staphylococcus aureus (MRSA) associated with bloodstream infection, England, 1 October 2012 to 30 September 2013
Authors: Michelle S Toleman, Sandra Reuter, Dorota Jamrozy, Hayley J Wilson, Beth Blane, Ewan M Harrison, Francesc Coll, Russell J Hope, Angela Kearns, Julian Parkhill, Sharon J Peacock, M Estée Török
Journal: Eurosurveillance (2019)

Background Mandatory reporting of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) has occurred in England for over 15years. Epidemiological information is recorded, but routine collection of isolates for characterisation has not been routinely undertaken. Ongoing developments in whole-genome sequencing (WGS) have demonstrated its value in outbreak investigations and for determining the spread of antimicrobial resistance and bacterial population structure. Benefits of adding genomics to routine epidemiological MRSA surveillance are unknown. Aim To determine feasibility and potential utility of adding genomics to epidemiological surveillance of MRSA. Methods We conducted an epidemiological and genomic survey of MRSA BSI in England over a 1-year period (1 October 2012­–30 September 2013). Results During the study period, 903 cases of MRSA BSI were reported; 425 isolates were available for sequencing of which, 276 (65%) were clonal complex (CC) 22. Addition of 64 MRSA genomes from published outbreak investigations showed that the study genomes could provide context for outbreak isolates and supported cluster identification. Comparison to other MRSA genome collections demonstrated variation in clonal diversity achieved through different sampling strategies and identified potentially high-risk clones e.g. USA300 and local expansion of CC5 MRSA in South West England. Conclusions We demonstrate the potential utility of combined epidemiological and genomic MRSA BSI surveillance to determine the national population structure of MRSA, contextualise previous MRSA outbreaks, and detect potentially high-risk lineages. These findings support the integration of epidemiological and genomic surveillance for MRSA BSI as a step towards a comprehensive surveillance programme in England.
Results of a Phase 2 Trial of the Monocyte-Targeted Histone Deacetylase Inhibitor Tefinostat (CHR-2845) in Chronic Myelomonocytic Leukemia (CMML) — the UK Monocle Study
Authors: Steven Knapper, Michael Dennis, Mark W Drummond, Robert K. Hills, Richard James Dillon, Christopher Pocock, Dominic J. Culligan, Paresh Vyas, Daniel Wiseman, Joanna Zabkiewicz, Marie Hodges, Catherine Cargo, Jan Taylor, Laura Upton, Melissa Wright, David Bowen
Journal: Blood (2018)
Optimality is both elusive and necessary
Authors: Joachim Meyer
Journal: Behavioral and Brain Sciences (2018)

Abstract Optimality of any decision, including perceptual decisions, depends on the criteria used to evaluate outcomes and on the assumptions about available alternatives and information. In research settings, these are often difficult to define, and therefore, claims about optimality are equivocal. However, optimality is important in applied settings when evaluating, for example, the detection of abnormalities in medical images.
Abstract 21148: Stress-Induced Cardiac Repolarization Changes Are Associated With Mental Stress-Induced Mycoardial Ischemia
Authors: Amit J Shah, Pratik M Pimple, Zakaria Almuwaqqat, Matt Amin, Mhd Alaa Hammoud, Muhammad Hammadah, Mohamad M Gafeer, Ayman Alkhoder, Naser Abdelhadi, Kobina Wilmot, Oleksiy Levantsevych, Ibhar Al Mheid, Ernest Garcia, Michael Kutner, Paolo Raggi, Rachel Lampert, Nino Isakadze, Elsayed Z Soliman, Arshed A Quyyumi, Viola Vaccarino
Journal: Circulation (2017)

Introduction: Mental Stress-Induced Myocardial Ischemia (MSIMI) can occur in patients with coronary artery disease (CAD) during acute mental stress challenge and is associated with an increased risk of adverse cardiovascular events. Adverse dynamic changes in repolarization with stress may also be particularly important when assessing risk of MSIMI. Hypothesis: In subjects with CAD, dynamic ECG repolarization changes during stress and recovery are associated with MSIMI. Methods: We studied 419 individuals with CAD who underwent mental stress challenge via a standardized speech stressor. Digital 12-lead ECGs were collected at baseline during resting , 1 minute after speech started, immediately after speech, and during recovery (5 minutes after speech ended). Repolarization metrics, including QRS-T angle, T-axis, ST depression, and T wave area were quantified in all 12 leads. Heart rate was also included. Subjects with baseline artifact were excluded. Changes amongst baseline, stress, and recovery were analyzed. Forward selection with alpha=0.01 was used to help guide the final model. MSIMI was assessed via Tc99m myocardial perfusion imaging (read by experienced clinicians). Results: The mean (SD) age was 56 (10), 38% were women, and 17% had MSIMI. The most significant predictors of MSIMI, based on the multivariate model, are summarized in the table. The C-statistic was 0.73, but reduced to 0.71 after leave-one-out cross validation. Goodness of fit was adequate. No significant race or gender differences were noted. Conclusion: Baseline and dynamic ECG repolarization changes in recovery (but not peak stress) contribute to MSIMI classification, and may be useful for risk stratification of arrhythmia risk due to emotional triggers. While the mechanisms regarding the relationship of MSIMI and ECG metrics during recovery are unknown, they could be due to hysteresis phenomena and/or known autonomic changes during recovery from stress.
Drug Approved for Rare Muscle Weakening Syndrome
Authors: Rebecca Voelker
Journal: JAMA (2019)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Recombinant Human C1 Esterase Inhibitor as Short-Term Prophylaxis for Dental Procedures in Patients With Angioedema: A Case Series
Authors: Anna Valerieva, Maria T. Staevska, Milos Jesenak, Katarina Hrubiskova, Marta Sobotkova, Radana Zachova, Roman Hakl, Sladjana Andrejevic, Tobias M. Suiter, Vesna Grivcheva-Panovska, Ljerka Karadza-Lapic, Ralph Shapiro, Florence Ida Hsu, Andrea Zanichelli
Journal: Journal of Allergy and Clinical Immunology (2019)
Second-line chemotherapy in advanced biliary tract cancer: Who may benefit?
Authors: Massimiliano Salati, Francesco Caputo, Luigi Marcheselli, Margherita Rimini, Andrea Spallanzani, Fabio Gelsomino, Kalliopi Andrikou, Sandra Zironi, Katia Di Emidio, Vera Clo', Gabriele Luppi, Stefano Cascinu
Journal: Journal of Clinical Oncology (2019)

381 Background: No established second-line treatment (2L) is available for patients (pts) with advanced biliary tract cancer (ABC) failing gemcitabine/platinum first-line chemotherapy (CT). However, 20-40% of pts are offered 2L CT in daily practice. We evaluated the impact of clinical and biochemical parameters on survival of ABC in order to identify factors aiding in 2L treatment selection. Methods: Medical records of consecutive ABC pts treated with 2L CT between 2005 and 2018 at the Modena Cancer Centre were reviewed. Log-rank test and multiple Cox proportional hazard regression were performed to assess the prognostic significance of covariates on OS. A prognostic score was developed from the multivariate model. Results: A total of 98 pts were identified and included in the analysis. Median (m) age was 63 years, 52% of pts were female, 75% had ECOG PS of 1-2. 72% of pts received first-line gemcitabine/platinum combination. In the 2L setting, 70% of pts received a doublet and the most common regimen was FOLFIRI (26%), followed by FOLFOX (20%) and fluoropyrimidine monotherapy (19%). Disease control rate was 39%, with 7% of objective responses. mOS and mPFS were 7.2 months and 3.5 months, respectively. At both univariate and multivariate analysis ECOG PS &gt; 0 ( P= 0.002), peritoneum involvement ( P&lt; 0.001), LDH &gt; 430 UI/L ( P&lt; 0.001), albumin &lt; 3.5 g/dL ( P= 0.001), gamma-GT &gt; 100 UI/L ( P= 0.001), PFS to first-line &lt; 6 months ( P= 0.025), Na+ &lt; 140 mEq/L ( P= 0.010), absolute lymphocyte count &lt; 1000/uL ( P= 0.030) were significantly associated with shorter OS. By assigning to each of the 8 variables weight = 1, three different risk groups were identified: low-risk group (0-2 factors), intermediate-risk group (3-4 factors) and high-risk group (5-8 factors). mOS was 18, 9.4, and 2.9 months in the low-, intermediate-, and high-risk group, respectively ( P&lt; 0.001). Conclusions: Our 2L study confirms the prognostic value of ECOG PS, PFS to first-line and peritoneal carcinomatosis, identifies novel biochemical prognosticators and proposes a readily-available and inexpensive score to risk stratify patients both in daily practice and clinical trials.
Abstract 17697: Long-Term Dietary Nitrite and Nitrate Deficiency Causes Metabolic Syndrome, Endothelial Dysfunction, and Cardiovascular Death in Mice
Authors: Masato Tsutsui, Mika Kina-Tanada, Haruaki Kubota, Mayuko Sakanashi, Toshihiro Matsuzaki, Katsuhiko Noguchi, Junko Nakasone, Hiroaki Shimokawa, Yusuke Ohya, Akira Arasaki
Journal: Circulation (2017)

Background: Nitric oxide (NO) is synthesized not only from L-arginine by NO synthases (NOSs), but also from its inert metabolites, nitrite and nitrate (NOx). Green leafy vegetables are abundant in ...
Epigenetic Modifications of the Bone Marrow (BM) Niche in Multiple Myeloma (MM) - a Three-Dimensional (3D) in Vitro Approach
Authors: Stefan J. Müller, Dagmar Wider, Andreas R. Thomsen, Marie Follo, Johannes M. Waldschmidt, Gabriele Ihorst, Sandra M. Dold, Julia Felthaus, Johanna Senger, Julia Schüler, Justus Duyster, Abdel Kareem Azab, Martin J. Hug, Manfred Jung, Ralph Wäsch, Monika Engelhardt
Journal: Blood (2017)
Direct-acting antivirals response in hepatocellular carcinoma: Does the presence of hepatocellular carcinoma matter?
Authors: Chung-Feng Huang, Ming-Lung Yu
Journal: Clinical and Molecular Hepatology (2019)

During the clinical trial development of directly acting antivirals (DAAs), evidence regarding the treatment efficacy in chronic hepatitis C patients with hepatocellular carcinoma (HCC) was scarce because these patients have always been excluded. Apart from the clinical trials, more HCC patients are currently being treated in daily practice, given that these treatments are highly effective and involve well-tolerated regimens. Large scale, real-world studies have demonstrated potentially suboptimal antiviral treatment efficacy in HCC patients who received DAAs. It is postulated that the impairment of the bioavailability of DAAs may account for the inferior treatment response. However, the results could not be generalized across all studies. The differing results were attributed to diverse patient characteristics, suboptimal regimens or imprecise definitions of active cancer statuses at the time of treatment initiation. Additional large-scale studies that utilize the treatment of choice in clearly defined HCC patients with different disease severities are warranted to clarify the issue.
Agreement and Predictors of Discordance of 6 Visual Field Progression Algorithms
Authors: Osamah J. Saeedi, Tobias Elze, Loris D’Acunto, Ramya Swamy, Vikram Hegde, Surabhi Gupta, Amin Venjara, Joby Tsai, Jonathan S. Myers, Sarah R. Wellik, Carlos Gustavo De Moraes, Louis R. Pasquale, Lucy Q. Shen, Michael V. Boland
Journal: Ophthalmology (2019)
Genomic sequence of yellow fever virus from a Dutch traveller returning from the Gambia-Senegal region, the Netherlands, November 2018
Authors: My VT Phan, Sarwa Darwish Murad, Annemiek A van der Eijk, Herold J. Metselaar, Hermien Hartog, Femme Harinck, Corine H GeurtsvanKessel, Richard Molenkamp, Matthew Cotten, Marion PG Koopmans
Journal: Eurosurveillance (2019)

In November 2018, yellow fever was diagnosed in a Dutch traveller returning from a bicycle tour in the Gambia-Senegal region. A complete genome sequence of yellow fever virus (YFV) from the case was generated and clustered phylogenetically with YFV from the Gambia and Senegal, ruling out importation into the Netherlands from recent outbreaks in Brazil or Angola. We emphasise the need for increased public awareness of YFV vaccination before travelling to endemic countries.
Altered NFE2 activity predisposes to leukemic transformation and myelosarcoma with AML-specific aberrations
Authors: Jonas Samuel Jutzi, Titiksha Basu, Maximilian Pellmann, Sandra Kaiser, Doris Steinemann, Mathijs A. Sanders, Adil S. A. Hinai, Annelieke Zeilemaker, Sarolta Bojtine Kovacs, Christoph Koellerer, Jenny Ostendorp, Konrad Aumann, Wei Wang, Emmanuel Raffoux, Bruno Cassinat, Lars Bullinger, Brigitte Schlegelberger, Peter J. M. Valk, Heike Luise Pahl
Journal: Blood (2019)
Patient's T Cell Functionality Determines Blinatumomab-Mediated Killing of B-ALL Leukemia Cells
Authors: Hong Yin, Xian Jia, Xiaojie Guo, Yong Zhou, Manman Deng, Jian Li, Yan Qiu, Limin Lu, En-Tzu Tang, Xiaolei Chen, Guo Fu, Mingqiang Zhang, Bing Xu, Ruibao Ren, Zhiqiang Du
Journal: Blood (2018)
Abstract P276: Activity Tracker Increases Daily Step Count Post-Cardiac Rehabilitation Compared to Placebo Device
Authors: Erica Schorr, Hilton Dahl, Alicia Sarkinen, Rebecca Brown
Journal: Circulation (2018)

Introduction: Despite optimal levels of physical activity (PA) among patients immediately post-cardiac rehabilitation, little is known about PA levels long-term. Further, interventions to maintain recommended PA levels and functional capacity achieved during cardiac rehabilitation are lacking. Objective: To test the effect of wearing a Garmin vÍvofit for 3 months post-cardiac rehabilitation on PA levels and functional capacity compared to a placebo device. Methods: Change in daily step count and 6-minute walk test (6MWT) were assessed over 3 months using the vÍvofit activity tracker in 35 patients (mean age 62±8 years; 83% male; 94% Caucasian) post-cardiac rehabilitation. Goal was 10,000 steps for all participants. Patients were randomized into the control or intervention group with control devices displaying a digital clock. VÍvofit step data were recorded continuously; the 6MWT was conducted at 0, 9, 12, and 15 weeks. Comparisons between the 2 groups were made using test of proportions, t-test, and logistic and linear regression. Results: Control and intervention groups were balanced with respect to age, gender, education, baseline step count, and body composition. Although all participants exhibited above average daily step counts (&gt;8,000 steps at 3, 9, and 15 weeks); step counts for intervention group participants were higher at 3, 9, and 15 weeks (by 2,537 steps, 2,022 steps, and 1,545 steps, respectively). Intervention group participants (N=17) increased the distance covered during the 6MWT by 138 feet (sd=28), compared to a 48 foot (sd=18) improvement among control group participants (p=0.500); although not statistically significant, but perhaps clinically relevant. Conclusion: These data provide preliminary support for using wrist-worn activity tracking devices to continuously monitor and maintain PA levels post-cardiac rehabilitation. There is a need for larger trials testing the effectiveness of these devices with a more diverse sample over a longer period of time. Wrist worn activity tracking devices should be coupled with other components known to support long-term behavior change (e.g., social support and text messaging) to develop effective interventions for secondary cardiovascular disease prevention.
Global burden of postoperative death
Authors: Dmitri Nepogodiev, Janet Martin, Bruce Biccard, Alex Makupe, Aneel Bhangu, Dmitri Nepogodiev, Janet Martin, Bruce Biccard, Alex Makupe, Adesoji Ademuyiwa, Adewale Oluseye Adisa, Maria-Lorena Aguilera, Sohini Chakrabortee, J. Edward Fitzgerald, Dhruva Ghosh, James C. Glasbey, Ewen M. Harrison, J.C. Allen Ingabire, Hosni Salem, Marie Carmela Lapitan, Ismail Lawani, David Lissauer, Laura Magill, Rachel Moore, Daniel C. Osei-Bordom, Thomas D. Pinkney, Ahmad Uzair Qureshi, Antonio Ramos-De la Medina, Sarah Rayne, Sudha Sundar, Stephen Tabiri, Azmina Verjee, Raul Yepez, O. James Garden, Richard Lilford, Peter Brocklehurst, Dion G. Morton, Aneel Bhangu
Journal: The Lancet (2019)
Lipid Transfer Protein allergy in the United Kingdom: Characterization and comparison with a matched Italian cohort
Authors: Isabel J. Skypala, Lorenzo Cecchi, Mohamed H. Shamji, Enrico Scala, Stephen Till
Journal: Allergy (2019)

Although pollen-related food allergy occurs in all European populations, lipid transfer protein (LTP) allergy is considered to manifest mainly in Mediterranean countries. We aimed to characterize adults presenting with LTP allergy in a northern European country.The clinical history and sensitization patterns of subjects born and residing in the United Kingdom (UK), with a prior diagnosis of LTP allergy and sensitization to the peach LTP allergen Pru p 3, were compared to UK subjects with pollen food syndrome (PFS). The sensitization patterns were also evaluated against a matched cohort of Italian subjects diagnosed with LTP allergy.None of the 15 UK PFS subjects had a positive SPT to LTP-enriched peach reagent, compared to 91% of the 35 UK LTP subjects. The UK LTP cohort were also more likely to have positive skin prick tests to cabbage, lettuce and mustard and sensitization to the LTP allergens in peach, walnut, mugwort and plane tree These sensitization patterns to individual allergens were not significantly different to those obtained from the Italian LTP subjects, with significant correlations between Pru p 3 and the LTP allergens in peanuts, walnuts, plane tree and mugwort in both groups.Native UK subjects with LTP allergy are not dissimilar to those with LTP allergy in southern Europe. Testing to LTP-enriched peach SPT reagent and/or LTP allergens in peach, walnut, mugwort and plane tree may enhance diagnostic accuracy.
Overexpression of LTA4H in colon cancer of humans and animal models.
Authors: Su Wang, Jihyeung Ju, Peng Wang, Darren Seril, Guangyu Yang, Sandeep Sood, Chung S. Yang, Xiaoxin Chen
Journal: Cancer Research (2004)

2221   Leukotriene A4 hydrolase (LTA4H) is a bifunctional zinc enzyme with the activities of epoxide hydrolase and aminopeptidase. As an epoxide hydrolase, LTA4H catalyzes the hydrolysis of the epoxide LTA4 to the diol, leukotriene B4 (LTB4), which mainly functions as a chemoattractant and an activator of inflammatory cells. As an aminopeptidase, LTA4H processes peptides that may be related to inflammation and host defense. Previously we have demonstrated overexpression of LTA4H in esophageal adenocarcinoma of humans and a surgical rat model. Bestatin, an LTA4H inhibitor, suppressed esophageal adenocarcinogenesis in the rat model. In this study, we found the expression level of LTA4H was significantly increased by 1.8 folds in the epithelial cells of human colon cancer (67 cases) as compared with paired normal samples (P Apc Min   mice (10 cases) and sodium disulfide-induced mucinous colon adenocarcinoma (10 cases), LTA4H was also significantly increased by 2.2 folds (P= ???) and 3.7 folds (P=???), as compared with adjacent normal epithelium, respectively. With Western blotting and enzyme immunoassay, we found overexpression of LTA4H and overproduction of LTB4 in the intestinal tumors of the  Apc Min   mice, as compared with non-tumorous intestinal tissues of  Apc Min   mice and normal intestinal tissues of wild-type mice. Our results suggest that LTA4H/LTB4 may play an important role in the development of color cancer. A chemoprevention study using an LTA4H inhibitor, bestatin, is still ongoing to investigate whether bestatin can inhibit intestinal tumorigenesis in the  Apc Min   mouse model. (Supported by NIH grants CA101235 and CA75683)
Landscape of circulating tumor DNA and tissue-based profiling in advanced cholangiocarcinoma.
Authors: Kabir Mody, Pashtoon Murtaza Kasi, Phani Keerthi Surapaneni, Tanios S. Bekaii-Saab, Ramesh K. Ramanathan, Daniel H. Ahn, Amit Mahipal, Jason Scott Starr, Ashton Ritter, Jessica McMillan, Natasha Wylie, Ali Roberts, Rebecca J Nagy, Mitesh J. Borad
Journal: Journal of Clinical Oncology (2019)

291 Background: Cholangiocarcinoma (CCA) has limited treatment options. Genomic analyses have led to development of targeted therapies now in clinical trials, and may enable discovery of new treatment options. However, biopsy often yields limited tissue, thus hampering tissue-based profiling opportunities. Comparative data regarding circulating tumor DNA (ctDNA) analysis and tissue based profiling in CCA are limited. Methods: We performed ctDNA NGS analysis along with tissue based profiling in pts with advanced CCA (January 2015- February 2018). ctDNA analysis was performed using Guardant 360 (Guardant Health, CA) which detects single nucleotide variants, amplifications, fusions, and specific insertion/deletion mutations in up to 73 different genes and the majority of tissue based profiling using Foundation One. The mutant allele fraction (MAF) for detected alterations was calculated relative to wild type in ctDNA. Therapeutic relevance was defined as alterations within OncoKB levels 1-3B and R1. The study was conducted in accordance with Mayo Clinic IRB requirements. Results: Among 124 pts and 139 total samples, ctDNA NGS revealed at least one genomic alteration (excluding variants of uncertain significance and synonymous mutations) in 89% of pts. Median number of alterations per pt was 3 [range, 1-15], with a median MAF of 0.42% (range, 0.1% - 94.2%). The total number of unique alterations was 321. The most commonly altered genes: TP53 (31%), KRAS (11%), FGFR2 (7%), APC and PIK3CA (each 5%) and ARID1A (3%). Amplifications were noted in 14 genes: BRAF, CCND1, CCND2, CCNE1, CDK4, CDK6, EGFR, ERBB2, FGFR1, FGFR2, MET, MYC, PDGFRA, and PIK3CA. Tissue-based profiling was available in 57 (46%) pts, with a median of 63 days between liquid and tissue biopsy. IDH1, FGFR2, TP53 and KRAS were most common gene mutations found in pts who had both liquid and tissue biopsy done. (Comparative results to be shown). Conclusions: ctDNA plasma profiling of pts with advanced CCA is a feasible alternative method to gather comprehensive genomic data. Further larger cohort studies comparing landscape of alterations seen on ctDNA versus tissue-based assays are needed.