tbuckley/cabot-search huggingface dataset:
Use of an ingredient-based analysis to investigate a national outbreak of Escherichia coli O157, United Kingdom, July 2016
Authors: Daniel Gardiner, Maya Gobin, Neville Q Verlander, Isabel Oliver, Jeremy Hawker
Journal: Eurosurveillance (2018)

Public Health England was alerted to a national outbreak of Shiga toxin-producing Escherichia coli O157 PT34 in July 2016. Early investigations suggested that the likely source was a salad item consumed outside of the home. A number of cases reported consuming meals at a staff canteen (Venue A) and a garden café (Venue B). Both venues shared a common salad supplier. An investigation was undertaken to measure associations between salad items and illness using an 'ingredient-based analysis'. A retrospective case–control study was conducted using an online questionnaire to collect information on menu items consumed at each venue. Chefs at both venues were interviewed to identify ingredients contained within each menu item. Both venues were pooled together for multivariable analysis measuring associations at the ingredient level. Among 203 responses, 24 cases were identified (13 confirmed, two probable and nine possible). Case onsets ranged between 7 and 25 June 2016. Multivariable analysis identified strong evidence that only baby mixed-leaf salad from the common supplier was a vehicle of infection (adjusted odds ratio = 13.1; 95% confidence interval: 1.6–106.5). Identifying the specific salad ingredient associated with illness was made possible by using an ingredient-based analysis. We recommend the increased use of ingredient-based analyses.
Immune responses induced by nano-self-assembled lipid adjuvants based on a monomycoloyl glycerol analogue after vaccination with the Chlamydia trachomatis major outer membrane protein
Authors: Letícia Rodrigues, Konstantinos N. Raftopoulos, Signe Tandrup Schmidt, Fabian Schneider, Hendrik Dietz, Thomas Rades, Henrik Franzyk, Anders Elm Pedersen, Christine M. Papadakis, Dennis Christensen, Gerhard Winter, Camilla Foged, Madlen Hubert
Journal: Journal of Controlled Release (2018)
Multi-center evaluation of GenoType MTBDRsl line probe assay for rapid detection of pre-XDR and XDR Mycobacterium tuberculosis in China
Authors: Yazhou Gao, Zhengdong Zhang, Jianping Deng, Mikael Mansjö, Zhu Ning, Yang Li, Xuliang Li, Yi Hu, Sven Hoffner, Biao Xu
Journal: Journal of Infection (2018)
Stability or improvement in forced vital capacity with nintedanib in patients with idiopathic pulmonary fibrosis
Authors: Kevin R. Flaherty, Martin Kolb, Carlo Vancheri, Wenbo Tang, Craig S. Conoscenti, Luca Richeldi
Journal: European Respiratory Journal (2018)

In the Phase III INPULSIS® trials, nintedanib reduced the annual rate of decline in forced vital capacity (FVC) versus placebo in patients with idiopathic pulmonary fibrosis (IPF). We conducted post hoc analyses of the distribution of changes in FVC in the INPULSIS® trials and FVC changes in the open-label extension trial INPULSIS®-ON in subgroups of patients based on whether patients had shown an improvement or no decline in FVC in INPULSIS®. Analyses were descriptive. Based on the annual rate of change in FVC, 158 of 638 patients (24.8%) treated with nintedanib and 38 of 423 patients (9.0%) treated with placebo had an improvement/no decline in FVC in the INPULSIS® trials. In patients whose FVC improved/did not decline, median (interquartile range) improvements in FVC at week 52 were 76.5 (31–152) mL and 57.5 (31–103) mL in the nintedanib and placebo groups, respectively. Changes in FVC from baseline to week 48 of INPULSIS®-ON were similar in patients whose FVC improved or declined in the preceding INPULSIS® trial. In the INPULSIS® trials, treatment with nintedanib resulted in a greater proportion of patients with IPF showing an improvement/no decline in FVC compared to taking placebo. Mechanisms underlying improvement in FVC in patients with IPF are unknown.
Abstract 18317: Abnormal High Density Lipoprotein (HDL) from Patients with Chronic Kidney Disease (CKD) Increases Arterial Blood Pressure: Role of Toll-Like Receptor-2 (TLR-2)
Authors: Timo Speer, Lucia Rohrer, Przemyslaw Blyszczuk, Nicolle Kränkel, Kira Kuschnerus, Yi Shi, Alexander Akhmedov, Stephen Zewinger, Arnold von Eckardstein, Thomas Lúscher, Ferdinand Bahlmann, Danilo Fliser, Ulf Landmesser
Journal: Circulation (2012)

Background Patients with chronic kidney disease (CKD) exhibit a high cardiovascular morbidity and mortality, even in the early stages, and frequently develop hypertension. , Patients with advanced CKD have an uremic dyslipidemia, characterized by low levels of total cholesterol, low density lipoprotein and HDL cholesterol and elevated levels of triglycerides. In addition to its role in reverse cholesterol transport, HDL from healthy subjects (HS) exerts several potential vasoprotective effects. Thus, we compared endothelial effects of HDL from CKD patients and HS and potential consequences for blood pressure responses. Methods HDL was isolated from patients with CKD (K/DOQI stadium II, IV, V, each n=15) and healthy subjects (n=15) by sequential ultracentrifugation. The effect of HDL on endothelial nitric oxide production (NO) was assessed by electron spin resonance (ESR) spectroscopy. To evaluate the effects of HDL on systolic blood pressure (SBP) in vivo, HDL was injected into wild type and eNOS-deficient mice. Expression of VCAM-1 and endothelial mononuclear cell (MNC) adhesion was assessed. Moreover, endothelial repair capacity of HDL was assessed in vitro and vivo, using a gap closure assay and carotid injury model in nude mice . Results HDL from HS stimulated endothelial NO production; whereas HDL from CKD patients markedly inhibited the endothelial NO production (-80 % by HDL of these patients; P&lt;0.05), even in incipient CKD. TLR2, but not TLR4 inhibition, prevented the inhibitory effects of HDLCKD on endothelial NO production. In vivo, CKD-HDL induced an increase of SBP (+10.7±1.1 mmHg; P&lt;0.05), while healthy HDL reduced SBP (-11.3±1.7, P&lt;0.05). Notably, HDL from patients with CKD induced endothelial VCAM-1 expression and promoted endothelial MNC adhesion, while HDL from healthy subjects did not. In vitro gap closure and in vivo reendothelialization after carotid injury were suppressed by HDL of CKD patients. Conclusion Our data demonstrate for the first time that endothelial-protective effects of HDL are considerably impaired in patients with CKD independently of the severity of CKD. Furthermore, HDL may be involved in initiation and aggravation of hypertension in these patients.
Management of Ventricular Arrhythmias and Sudden Cardiac Death Risk Associated With Cardiac Channelopathies
Authors: Sana M. Al-Khatib, William G. Stevenson
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
Coexpression profile of leukemic stem cell markers for combinatorial targeted therapy in AML
Authors: S. Haubner, F. Perna, T. Köhnke, C. Schmidt, S. Berman, C. Augsberger, F. M. Schnorfeil, C. Krupka, F. S. Lichtenegger, X. Liu, P. Kerbs, S. Schneider, K. H. Metzeler, K. Spiekermann, W. Hiddemann, P. A. Greif, T. Herold, M. Sadelain, M. Subklewe
Journal: Leukemia (2018)

Targeted immunotherapy in acute myeloid leukemia (AML) is challenged by the lack of AML-specific target antigens and clonal heterogeneity, leading to unwanted on-target off-leukemia toxicity and risk of relapse from minor clones. We hypothesize that combinatorial targeting of AML cells can enhance therapeutic efficacy without increasing toxicity. To identify target antigen combinations specific for AML and leukemic stem cells, we generated a detailed protein expression profile based on flow cytometry of primary AML (n = 356) and normal bone marrow samples (n = 34), and a recently reported integrated normal tissue proteomic data set. We analyzed antigen expression levels of CD33, CD123, CLL1, TIM3, CD244 and CD7 on AML bulk and leukemic stem cells at initial diagnosis (n = 302) and relapse (n = 54). CD33, CD123, CLL1, TIM3 and CD244 were ubiquitously expressed on AML bulk cells at initial diagnosis and relapse, irrespective of genetic characteristics. For each analyzed target, we found additional expression in different populations of normal hematopoiesis. Analyzing the coexpression of our six targets in all dual combinations (n = 15), we found CD33/TIM3 and CLL1/TIM3 to be highly positive in AML compared with normal hematopoiesis and non-hematopoietic tissues. Our findings indicate that combinatorial targeting of CD33/TIM3 or CLL1/TIM3 may enhance therapeutic efficacy without aggravating toxicity in immunotherapy of AML.
Strengthening the Case for the Role of Thrombophilia in Calciphylaxis
Authors: Allison S. Dobry, Daniela Kroshinsky
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Differential incidence trends of colon and rectal cancers in Hong Kong: an age‐period‐cohort analysis
Authors: Bo Zhang, Shao‐Hua Xie, Ignatius Tak‐sun Yu
Journal: Cancer Communications (2018)

Colorectal cancer has been the second most common cancer among men and women in Hong Kong since 2012, but the underlying reasons for this increase remain unclear. We describe the incidence trend for colorectal cancer in Hong Kong to explore its etiology within this population.The temporal trends in colorectal cancer incidence between 1983 and 2012 were analyzed with joinpoint regressions by sex, age groups, and anatomic sites among adults using data from the Hong Kong Cancer Registry. An age-period-cohort analysis was used to evaluate the effects of age, calendar periods, and birth cohorts on the observed temporal trends.The incidence of colon cancer among those aged 50 years and older in both sexes increased steadily from 1983 until the mid-1990s and was followed by a slight decrease thereafter, whereas the incidence among those aged 20-49 years decreased steadily from 1983 to 2012. In contrast, the incidence of rectal cancer steadily increased in men and remained stable in women throughout the study period. Significant period and birth cohort effects were observed for colon cancer, whereas period effects on the temporal trends were observed for male rectal cancer.The incidences of colon and rectal cancers have exhibited divergent patterns between 1983 and 2012 in Hong Kong, indicating heterogeneous etiologies between these two types of cancers. Surveillance of the risk factors related to colon and rectal cancers in the Hong Kong population should be performed, and the increased rectal cancer incidence in males is worthy of extra attention.
Abstract 15358: Improving Visualization and Interaction During Transcatheter Ablation Using an Augmented Reality System: First-in-Human Experience
Authors: Jennifer N Silva, Michael K Southworth, Aarti Dalal, George F Van Hare, Jonathan R Silva
Journal: Circulation (2017)

Introduction: A novel augmented reality (AR) based system that displays a real time intraprocedural hologram of cardiac geometry, electroanatomic maps, catheter localization with a controllable via...
TET2 controls chemoresistant slow-cycling cancer cell survival and tumor recurrence
Authors: Isabel Puig, Stephan P. Tenbaum, Irene Chicote, Oriol Arqués, Jordi Martínez-Quintanilla, Estefania Cuesta-Borrás, Lorena Ramírez, Pilar Gonzalo, Atenea Soto, Susana Aguilar, Cristina Eguizabal, Ginevra Caratù, Aleix Prat, Guillem Argilés, Stefania Landolfi, Oriol Casanovas, Violeta Serra, Alberto Villanueva, Alicia G. Arroyo, Luigi Terracciano, Paolo Nuciforo, Joan Seoane, Juan A. Recio, Ana Vivancos, Rodrigo Dienstmann, Josep Tabernero, Héctor G. Palmer
Journal: Journal of Clinical Investigation (2018)

Dormant or slow-cycling tumor cells can form a residual chemoresistant reservoir responsible for relapse in patients, years after curative surgery and adjuvant therapy. We have adapted the pulse-chase expression of H2BeGFP for labeling and isolating slow-cycling cancer cells (SCCCs). SCCCs showed cancer initiation potential and enhanced chemoresistance. Cells at this slow-cycling status presented a distinctive nongenetic and cell-autonomous gene expression profile shared across different tumor types. We identified TET2 epigenetic enzyme as a key factor controlling SCCC numbers, survival, and tumor recurrence. 5-Hydroxymethylcytosine (5hmC), generated by TET2 enzymatic activity, labeled the SCCC genome in carcinomas and was a predictive biomarker of relapse and survival in cancer patients. We have shown the enhanced chemoresistance of SCCCs and revealed 5hmC as a biomarker for their clinical identification and TET2 as a potential drug target for SCCC elimination that could extend patients' survival.
Genome-wide prediction of childhood asthma and related phenotypes in a longitudinal birth cohort
Authors: Ben D. Spycher, John Henderson, Raquel Granell, David M. Evans, George Davey Smith, Nicholas J. Timpson, Jonathan A.C. Sterne
Journal: European Respiratory Journal (2012)

Aim : Childhood asthma varies greatly in clinical presentation and time course and underlying disease pathways are assumed to be heterogenous. We assessed the extent to which single nucleotide polymorphisms (SNPs) associated with childhood asthma in a genome-wide association study (GWAS) are predictive of asthma-related phenotypes.   Method : In 8365 children from a population based birth cohort, the Avon Longitudinal Study of Parents and Children, allelic scores were derived based on between 10 and 215443 SNPs ranked according to inverse of the p-value for association with physician diagnosed asthma in an independent GWAS (6176 cases and 7111 controls). We assessed the predictive value of allelic scores for asthma-related outcomes at age 7-9 years (physician9s diagnosis, early wheezing phenotypes, pulmonary function, bronchial hyper-responsiveness (BHR) and atopy).   Results : Scores based on the 46 highest-ranked SNPs were associated with persistent (P -11 , area under ROC curve (AUC)=0.59) and intermediate onset (P -3 , AUC=0.58) wheeze. Among lower-ranked SNPs (ranks 21545-46416), there was evidence for associations with diagnosed asthma (P -4 , AUC=0.54) and atopy (P -5 , AUC=0.55). We found little evidence of associations with transient early wheezing, reduced pulmonary function or non-asthma phenotypes.   Conclusion : The genetic origins of asthma are diverse: some pathways are specific to wheezing syndromes while others are shared with atopy and BHR. Our study also provides evidence of aetiological differences among wheezing syndromes.   Funding : BDS is recipient of a ERS/Marie Curie Joint Research Fellowship (MC 1614 - 2010); RG was supported by the UK Medical Research Council (0401540).
Neuronal integrity and complement control synaptic material clearance by microglia after CNS injury
Authors: Geoffrey T. Norris, Igor Smirnov, Anthony J. Filiano, Hannah M. Shadowen, Kris R. Cody, Jeremy A. Thompson, Tajie H. Harris, Alban Gaultier, Christopher C. Overall, Jonathan Kipnis
Journal: The Journal of Experimental Medicine (2018)

Phagocytosis of synaptic material by microglia is critical for central nervous system development. Less well understood is this microglial function in the injured adult brain. Assay of microglial phagocytosis is challenging, because peripheral myeloid cells engraft the site of injury, which could obscure interpretation of microglial roles. The model used here, optic nerve crush injury, results in degeneration of synapses in the dorsal lateral geniculate nucleus (dLGN), which stimulates rapid activation and engulfment of synaptic material by resident microglia without myeloid cell engraftment. Pharmacological depletion of microglia causes postinjury accumulation of synaptic debris, suggesting that microglia are the dominant postinjury phagocytes. Genetic or pharmacological manipulations revealed that neuronal activity does not trigger microglia phagocytosis after injury. RNA sequencing reveals C1q and CD11b/CR3 involvement in clearance of debris by dLGN-resident microglia. Indeed, C1qa−/− and Itgam−/− mice exhibit impaired postinjury debris clearance. Our results show how neurodegenerative debris is cleared by microglia and offers a model for studying its mechanisms and physiological roles.
Abstract 16172: Association of Genetic Variation in the α2A-adrenergic Receptor Gene With Risk of Gestational Diabetes
Authors: Vivian K Kawai, Abiodun Adefurin, Rebecca T Levinson, Daniel Kurnik, Sarah Collier, Douglas Conway, C. M Stein
Journal: Circulation (2016)

Introduction:  Normal pregnancy is characterized by both increased sympathetic activity and an increased in insulin secretion due to insulin resistance. Sympathetic activation suppresses insulin secretion via the pancreatic α2A-adrenergic receptor; gain-of-function variants in its gene ( ADRA2A ) are associated with decreased insulin secretion and increased risk of type 2 diabetes (T2DM).   Hypothesis:  We hypothesized that because of the increase in sympathetic tone and insulin requirements during pregnancy, effects of  ADRA2A  genetic variation on glucose homeostasis may be particularly pronounced and would be associated with risk of gestational diabetes (GDM).   Methods:  We conducted a case-control study using BioVU, a DNA biobank linked to de-identified electronic medical records at Vanderbilt Medical Center. Using bioinformatic algorithms and manual review, we identified 458 cases of GDM and 1537 controls among pregnant women of European ancestry without preexisting diabetes. Cases of GDM had a positive 100g oral glucose tolerance test during pregnancy using Carpenter and Coustan criteria, or a physician’s diagnosis, or an ICD9 billing code for glucose intolerance in pregnancy with an intervention for GDM (nutritional or antidiabetic drug); controls were pregnant women with a normal 50g glucose challenge test. We genotyped 9  ADRA2A  SNPs and performed a logistic regression adjusting for maternal age, parity, maternal body mass index (BMI) and a single-count genetic risk score (GRS) that included 33 non-adrenergic SNPs previously associated with T2DM.   Results:  Two  ADRA2A  SNPs, rs1800038 (OR=2.47, P=0.014) and rs3750625 (OR=1.56, P=0.010), were associated with increased risk of GDM, and one (rs11195418) with decreased risk (OR=0.62, P=0.024). The associations remained significant after adjustment for age, parity, BMI, and the T2DM GRS (see Figure).   Conclusions:  ADRA2A  genetic variation contributes independently to the risk of GDM in Caucasian women.
MEK inhibition induces MYOG and remodels super-enhancers in RAS-driven rhabdomyosarcoma
Authors: Marielle E. Yohe, Berkley E. Gryder, Jack F. Shern, Young K. Song, Hsien-Chao Chou, Sivasish Sindiri, Arnulfo Mendoza, Rajesh Patidar, Xiaohu Zhang, Rajarashi Guha, Donna Butcher, Kristine A. Isanogle, Christina M. Robinson, Xiaoling Luo, Jin-Qiu Chen, Ashley Walton, Parirokh Awasthi, Elijah F. Edmondson, Simone Difilippantonio, Jun S. Wei, Keji Zhao, Marc Ferrer, Craig J. Thomas, Javed Khan
Journal: Science Translational Medicine (2018)

MEK inhibition decreases cell viability and induces differentiation in RAS-driven rhabdomyosarcoma via an epigenetic mechanism.
Methadone in Primary Care — One Small Step for Congress, One Giant Leap for Addiction Treatment
Authors: Jeffrey H. Samet, Michael Botticelli, Monica Bharel
Journal: New England Journal of Medicine (2018)

Methadone in Primary Care Methadone clinics serve the needs of some patients well, but for others, the need to obtain medication daily at one fixed site can be too burdensome. Increasing the availability of methadone in primary care could extend the benefits of a proven, effective medication.
Is it time to reframe how we care for people with non-traumatic musculoskeletal pain?
Authors: Jeremy Lewis, Peter O’Sullivan
Journal: British Journal of Sports Medicine (2018)

The majority of persistent non-traumatic musculoskeletal pain disorders do not have a pathoanatomical diagnosis that adequately explains the individual’s pain experience and disability. We contend this has resulted in two concerning developments in the management of people with such disorders. First, structural changes observed on imaging that are highly prevalent in pain free populations, such as rotator cuff tears, intervertebral disc degeneration, labral tears and cartilage changes, are ascribed to individuals as a diagnosis for their condition. In this context, this information may result in the individual believing that their body is damaged, fragile and in need of protection, resulting in a cascade of movement and activity avoidance behaviours and seeking interventions to correct the structural deficits.1 This trend has led to exponential increases in elective surgery rates and associated costs, while the efficacy of repairing (eg, rotator cuff and medical meniscal tears), reshaping (eg, subacromial decompression) or replacing (eg, lumbar intervertebral discs) the structures considered to be at fault has been substantially challenged.2–10Second, it is arguable that musculoskeletal clinicians have invented treatments for conditions that may not exist or be readily detected (such as trigger points, sacral torsions), and they have developed and perpetuated treatment paradigms (such as ‘correcting’ upper body posture and muscle imbalances) that do not conform to current …