tbuckley/cabot-search huggingface dataset:
Abstract P195: High-density Lipoprotein Subfractions Are Associated With Low-grade Inflammation, Insulin Resistance and Metabolic Syndrome Components: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)
Authors: Giuliano Generoso, Isabela J Bensenor, Raul D Santos, Itamar S Santos, Alessandra C Goulart, Steven R Jones, Krishnaji R Kulkarni, Michael J Blaha, Peter P Toth, Paulo A Lotufo, Marcio S Bittencourt
Journal: Circulation (2018)

Background: HDL cholesterol (HDL-C) can be divided into subfractions, which may have variable association with atherogenic process. There are mixed results about the association between HDL-C subfractions and risk factors for cardiovascular disease. Hypothesis: HDL-C subfractions have different associations with metabolic syndrome, low-grade inflammation and insulin resistance. Methods: 4,532 individuals between 35 and 74 years without previous cardiovascular disease not in use of fibrates were enrolled. HDL-C subfractions were separated by vertical ultracentrifugation (Vertical Auto Profile - in mg/dl) in HDL 2 -C and HDL 3 -C. HDL 2 -C/HDL 3 -C ratio, insulin resistance (HOMA-IR) and high-sensitivity C-reactive protein (CRP) were also included in the analysis. Results: The mean age was 51 ± 9 years, and 54.8% were women. In univariate analysis, HDL-C, HDL 2 -C, and HDL 3 -C were all inversely associated with each of the MetS defining factors, HOMA-IR values, and serum CRP. It was also observed a negative association between HDL 2 -C/HDL 3 -C ratio with the variables mentioned above even after adjusting for smoking, alcohol use, physical activity, and HDL-C levels (p &lt;0.01). Conclusion: HDL-C and both subfractions are inversely associated with all the factors that define MetS, insulin resistance and low-grade inflammation. Additionally, the HDL 2 -C/HDL 3 -C subfractions ratio assessed by VAP is also significantly associated with the former factors even after further adjustment for total HDL-C and other confounding variables.
“NEW” SKIN DISEASES IN AFRICA
Authors: James Marshall
Journal: British Journal of Dermatology (1968)

Journal Article “NEW” SKIN DISEASES IN AFRICA Get access James Marshall James Marshall Department of Dermatology, Steilenbosch University, South Africa Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 80, Issue 2, 1 February 1968, Pages 118–119, https://doi.org/10.1111/j.1365-2133.1968.tb12271.x Published: 01 February 1968
Abstract 16383: Contemporary Costs of Care Stratified by INTERMACS Profiles Among Patients Undergoing Primary Left Ventricular Assist Device Implantation
Authors: Bryan T Lawlor, Kenneth Bilchick, Carole Ballew, LaVone Smith, Ken Scully, Timothy Welch, James D Bergin, Jamie L Kennedy, Mohammad Abuannadi, Sula Mazimba
Journal: Circulation (2016)

Introduction: Durable mechanical circulatory support (dMCS) is an integral part of advanced heart failure (AHF) management. Risk stratification for patients undergoing dMCS using the Interagency Re...
Safety and efficacy of the selective FGFR inhibitor debio 1347 in phase I study patients with FGFR genomically activated advanced biliary tract cancer (BTC).
Authors: James M. Cleary, Martin Henner Voss, Funda Meric-Bernstam, Cinta Hierro, Rebecca Suk Heist, Nobuya Ishii, Yulia Kirpicheva, Valerie Nicolas-Metral, Anna Pokorska-Bocci, Anne Vaslin, Werner Venetz, Claudio Zanna, Keith Flaherty, Josep Tabernero, Jose Baselga
Journal: Journal of Clinical Oncology (2018)

447 Background: BTC are aggressive tumors with limited treatment options and poor overall survival. Aberrant FGFR signaling has been implicated in BTC carcinogenesis. Debio 1347 is an orally available selective FGFRi with potent antitumor effect in preclinical model bearing FGFR alterations. Debio 1347 showed encouraging preliminary clinical activity and manageable treatment-emergent adverse events (TEAE) in its first-in-human (FIH) ph1 study (NCT1948297) dose-escalating part. Here we report only results from the BTC pts of this study. Methods: This FIH study enrolled pts with advanced solid malignancies harboring defined activating alterations of FGFR 1, 2, or 3: amplifications (amp), mutations (mut) and translocations (trans). Pharmacokinetics (PK) and pharmacodynamics were serially evaluated in blood, skin and/or tumor tissue. A confirmatory post-hoc analysis was performed centrally for all available biopsies. Results: Eight pts, six with intrahepatic cholangiocarcinoma (iCCA) and two with gallbladder cancer (GBC), were treated with Debio 1347 at doses between 60 and 150 mg orally daily in 28-day cycles. Among the iCCA pts, one had an FGFR2mut, one had an FGFR2 activating deletion (del), and one had an FGFR3mut; the other three had FGFR2trans. One of the two GBC pts had an FGFR3trans, the other one an FGFR2mut. All pts had prior systemic therapy (mostly 2 or 3 lines). The most common TEAEs were hyperphosphatemia (8/8), nail changes (5/8), nausea (5/8), dry mouth (4/8) and stomatitis (3/8). No grade ≥ 3 related TEAE were reported except grade 3 hyperphosphatemia (4/8). PK was comparable to that in pts with other solid malignancies.A partial response lasting up to 48 weeks was observed in an iCCA pt (FGFR2 del exon 5); three additional iCCA pts (FGFR2trans: ROCK1; KIAA1217; DDX21) and one GBC pt (FGFR3-TACC3 trans) had target lesions regression &lt; 30% and stayed on trial between 24 – 37 weeks. Overall disease control was 62.5%. Conclusions: These results suggest that BTC pts with genomic events leading to activation of FGFR2/3 may benefit from treatment with Debio 1347. Further study is ongoing in the expansion cohort of this trial. Clinical trial information: NCT1948297.
Randomised controlled trials may have many unrecognised potential biases
Authors: Nigel Hawkes
Journal: BMJ (2018)

Randomised controlled trials (RCTs) may be the gold standard, but all that glisters is not gold, warns a research fellow at the London School of Economics.1

Alexander Krauss has analysed the 10 most commonly cited RCTs in the medical literature—all with 6500 or more citations—and found that they have potential biases that are frequently unrecognised or unacknowledged by the trials’ originators. The claim that randomisation eliminates bias is simply not true, he says in Annals of Medicine .1

To take the simplest example, suppose that, after randomisation, the treatment group is different in significant ways from the control group. This was the case in a 1995 trial showing that a clot busting drug was effective for ischaemic stroke.2 The treatment group were 3% …
Abstract MP12: Cardiovascular Health Promoting Behaviors in Older Patients With Chronic Kidney Disease
Authors: Sarah Schrauben, Jesse Y Hsu, Ana C Ricardo, James P Lash, Harold I Feldman, Amanda H Anderson
Journal: Circulation (2018)

Background: The chronic kidney disease (CKD) epidemic continues to grow, and cardiovascular disease (CVD) is the leading cause of death. To modify CVD risk, CKD patients are asked to engage in health promoting behaviors. However, older patients with CKD likely face challenges to engage in healthy behaviors due to social and health factors. This study examined the relationship of social and health factors to health promoting behaviors among younger and older CKD patients and the association of these behaviors with CVD events, death, and CKD progression. Methods: Data from the Chronic Renal Insufficiency Cohort (CRIC) Study were analyzed using latent class analysis (LCA) to identify health promoting behavior clusters, stratified by &lt;65 and ≥65 years of age. LCA was based on: BMI of &gt;20 and ≤25kg/m 2 vs. other, healthy diet vs. not, physical activity ≥150min/week vs. not, blood pressure ≤140/90mmHg vs. greater, never/past smoker vs. current, and &lt;7.0% hemoglobin A1c vs. greater. Social factors (self-efficacy, social support, education, income, insurance) and health factors (depressive symptoms, cognition, co-morbidities) were measured by validated surveys and self-report. Logistic regression assessed the association of social and health factors to the behavior clusters. Cox proportional hazards models estimated risk of clusters to CVD events (myocardial infarction/revascularization, peripheral arterial disease, or stroke), CKD progression (incident end-stage renal disease or 50% decline in eGFR), and death from any cause. Results: All social and health factors significantly differed between age groups. Three clusters with varying levels of engagement in health promoting behaviors were identified separately among &lt;65 and ≥65 years of age. Among &lt;65 years, the cluster with the highest level of engagement in healthy behaviors was associated with more self-efficacy and lower depressive symptoms. In this age group, in multivariable adjusted models, the clusters with less healthy behavior engagement had a statistically significant increased risk of CVD events (32-81%), death (29-78%), and CKD progression (32-38%). Among ≥65 years, the cluster with the highest level of engagement in healthy behaviors was associated with higher self-efficacy, social support, cognition, and less depressive symptoms. In this age group, in multivariable adjusted models, the clusters with less healthy behaviors had a statistically significant 49% increased risk of death. Conclusion: This study demonstrated three clusters of health promoting behaviors that distinguish risk for CVD and other outcomes among older and younger CKD patients. These clusters could identify high-risk groups and be targeted for aggressive management. Clusters with less health promoting behaviors were associated with self-efficacy and depressive symptoms, which could serve as potential targets for intervention.
ALT-803, an IL-15 superagonist, in combination with nivolumab in patients with metastatic non-small cell lung cancer: a non-randomised, open-label, phase 1b trial
Authors: John M Wrangle, Vamsidhar Velcheti, Manish R Patel, Elizabeth Garrett-Mayer, Elizabeth G Hill, James G Ravenel, Jeffrey S Miller, Mohammad Farhad, Kate Anderton, Kathryn Lindsey, Michele Taffaro-Neskey, Carol Sherman, Samantha Suriano, Marzena Swiderska-Syn, Amy Sion, Joni Harris, Andie R Edwards, Julie A Rytlewski, Catherine M Sanders, Erik C Yusko, Mark D Robinson, Carsten Krieg, William L Redmond, Jack O Egan, Peter R Rhode, Emily K Jeng, Amy D Rock, Hing C Wong, Mark P Rubinstein
Journal: The Lancet Oncology (2018)
ESMO Consensus Conference on malignant lymphoma: general perspectives and recommendations for the clinical management of the elderly patient with malignant lymphoma
Authors: C. Buske, M. Hutchings, M. Ladetto, V. Goede, U. Mey, P. Soubeyran, M. Spina, R. Stauder, M. Trněný, U. Wedding, P. Fields, Christian Buske, Martin Dreyling, Andrés J M Ferreri, Paul Fields, Gianluca Gaidano, Valentin Goede, Martin Hutchings, Marco Ladetto, Steven Le Gouill, Stefano Luminari, Ulrich Mey, Peter de Nully Brown, Michael Pfreundschuh, Christiane Pott, Norbert Schmitz, Pierre Soubeyran, Michele Spina, Reinhard Stauder, Anna Sureda Balari, Marek Trněný, Gustaaf van Imhoff, Jan Walewski, Ulrich Wedding, Alberto Zamò, Emanuele Zucca
Journal: Annals of Oncology (2017)
Assessing Pharmaceutical Research and Development Costs
Authors: Joseph A. DiMasi
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Long-Term Outcomes Following Surgical Aortic Bioprosthesis Implantation
Authors: Tania Rodriguez-Gabella, Pierre Voisine, François Dagenais, Siamak Mohammadi, Jean Perron, Eric Dumont, Rishi Puri, Lluis Asmarats, Mélanie Côté, Sebastien Bergeron, Philippe Pibarot, Josep Rodés-Cabau
Journal: Journal of the American College of Cardiology (2018)
Cell-Free DNA Modification Dynamics in Abiraterone Acetate-Treated Prostate Cancer Patients
Authors: Juozas Gordevičius, Algimantas Kriščiūnas, Daniel E. Groot, Steven M. Yip, Miki Susic, Andrew Kwan, Rafal Kustra, Anthony M. Joshua, Kim N. Chi, Art Petronis, Gabriel Oh
Journal: Clinical Cancer Research (2018)

Purpose: Primary resistance to abiraterone acetate (AA), a key medication for the treatment of metastatic castration-resistant prostate cancer, occurs in 20% to 40% of patients. We aim to identify predictive biomarkers for AA-treatment response and understand the mechanisms related to treatment resistance.Experimental Design: We used the Infinium Human Methylation 450K BeadChip to monitor modification profiles of cell-free circulating DNA (cfDNA) in 108 plasma samples collected from 33 AA-treated patients.Results: Thirty cytosines showed significant modification differences (FDR Q < 0.05) between AA-sensitive and AA-resistant patients during the treatment, of which 21 cytosines were differentially modified prior to treatment. In addition, AA-sensitive patients, but not AA-resistant patients, lost interindividual variation of cfDNA modification shortly after starting AA treatment, but such variation returned to initial levels in the later phases of treatment.Conclusions: Our findings provide a list of potential biomarkers for predicting AA-treatment response, highlight the prognostic value of using cytosine modification variance as biomarkers, and shed new insights into the mechanisms of prostate cancer relapse in AA-sensitive patients. Clin Cancer Res; 24(14); 3317-24. ©2018 AACR.
SALL1 functions as a tumor suppressor in breast cancer by regulating cancer cell senescence and metastasis through the NuRD complex
Authors: Chunling Ma, Fang Wang, Bing Han, Xiaoli Zhong, Fusheng Si, Jian Ye, Eddy C. Hsueh, Lynn Robbins, Susan M. Kiefer, Yanping Zhang, Pamela Hunborg, Mark A. Varvares, Michael Rauchman, Guangyong Peng
Journal: Molecular Cancer (2018)

Abstract Background SALL1 is a multi-zinc finger transcription factor that regulates organogenesis and stem cell development, but the role of SALL1 in tumor biology and tumorigenesis remains largely unknown. Methods We analyzed SALL1 expression levels in human and murine breast cancer cells as well as cancer tissues from different types of breast cancer patients. Using both in vitro co-culture system and in vivo breast tumor models, we investigated how SALL1 expression in breast cancer cells affects tumor cell growth and proliferation, metastasis, and cell fate. Using the gain-of function and loss-of-function strategies, we dissected the molecular mechanism responsible for SALL1 tumor suppressor functions. Results We demonstrated that SALL1 functions as a tumor suppressor in breast cancer, which is significantly down-regulated in the basal like breast cancer and in estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2) triple negative breast cancer patients. SALL1 expression in human and murine breast cancer cells inhibited cancer cell growth and proliferation, metastasis, and promoted cell cycle arrest. Knockdown of SALL1 in breast cancer cells promoted cancer cell growth, proliferation, and colony formation. Our studies revealed that tumor suppression was mediated by recruitment of the Nucleosome Remodeling and Deacetylase (NuRD) complex by SALL1, which promoted cancer cell senescence. We further demonstrated that the mechanism of inhibition of breast cancer cell growth and invasion by SALL1-NuRD depends on the p38 MAPK, ERK1/2, and mTOR signaling pathways. Conclusion Our studies indicate that the developmental control gene SALL1 plays a critical role in tumor suppression by recruiting the NuRD complex and thereby inducing cell senescence in breast cancer cells.
The Quantified Relationship
Authors: John Danaher, Sven Nyholm, Brian D. Earp
Journal: The American Journal of Bioethics (2018)

The growth of self-tracking and personal surveillance has given rise to the Quantified Self movement. Members of this movement seek to enhance their personal well-being, productivity, and self-actualization through the tracking and gamification of personal data. The technologies that make this possible can also track and gamify aspects of our interpersonal, romantic relationships. Several authors have begun to challenge the ethical and normative implications of this development. In this article, we build upon this work to provide a detailed ethical analysis of the Quantified Relationship (QR). We identify eight core objections to the QR and subject them to critical scrutiny. We argue that although critics raise legitimate concerns, there are ways in which tracking technologies can be used to support and facilitate good relationships. We thus adopt a stance of cautious openness toward this technology and advocate the development of a research agenda for the positive use of QR technologies.
Folic acid and vitamin B <sub>12</sub> fortification of food for preventing neural tube defects in Europe
Authors: Michael Turner
Journal: BMJ (2018)

Both sides in the debate on mandatory folate food fortification agree that it would reduce the incidence of neural tube defects and improve population rates of folate deficiency.1

Reynolds, however, argues that it should be accompanied by mandatory vitamin B12 fortification to protect elderly people from neurological dysfunction. National audits in the Republic of Ireland during 2009-11 and 2012-15 found no improvement in rates of neural tube defects with a …
Abstract 18012: Variability in the Utilization of Mechanical Circulatory Support in Cardiogenic Shock Complicating STEMI: Impact of Hospital PCI Volumes
Authors: Shikhar Agarwal, Karan Sud, Joseph M Martin, Venu Menon
Journal: Circulation (2015)

Despite controversy about efficacy, mechanical circulatory support (MCS) is often utilized in patients with cardiogenic shock after ST elevation myocardial infarction (STEMI). We aimed to characterize the variability in MCS utilization in cardiogenic shock patients across hospitals in the US, according to annual volume of primary percutaneous interventions (PPCI). Methods: We used the 2003-2011 Nationwide Inpatient Sample for the study. All admissions with principal diagnosis of STEMI, with an additional diagnosis of cardiogenic shock, were identified using ICD 9 diagnosis codes. MCS devices were identified using ICD-9 procedure codes. All hospitals were divided into quartiles based on annual PPCI volume. Results: Of 372984 admissions with STEMI, we identified 32482 (8.5%) cases with cardiogenic shock during admission. Of these, MCS was utilized in 17415 (53.6%) patients. All hospitals treating cardiogenic shock patients were divided into quartiles such that quartiles 1-4 corresponded to hospitals performing &lt; 36, 37-68, 69-118 and ≥119 PPCIs annually. The number of cardiogenic shock patients treated in quartile 1, quartile 2, quartile 3 and quartile 4 hospitals were 1875, 4712, 8061 and 15853 patients respectively. There was progressive increase in MCS utilization across hospital quartiles with increasing PPCI volume (Figure). MCS utilization in quartiles 1-4 hospitals was 44.9%, 55.2%, 57.6% and 58.5% respectively (p-trend&lt;0.001). After adjustment for baseline, clinical and hospital characteristics (geographic location, teaching status, bed size), we still observed progressive increase in MCS utilization across the hospital quartiles (Figure). Conclusion: There was significant variability in MCS utilization among STEMI patients with cardiogenic shock, based on annual PPCI volume of the treating hospital. Increase in annual PPCI volume was correlated with an increase in MCS utilization in STEMI patients complicated by cardiogenic shock.
Conduct of clinical ADME study for vosaroxin in oncology patients via real-time adaptive manufacture of intravenous drug product.
Authors: Lisa Clarke-Lens, Ian Nisbet, Nick Johnson, Nicholas McEntee, Gene Jamieson, Wendy Hill
Journal: Journal of Clinical Oncology (2015)

e18058 Background: Vosaroxin is in Phase III development for treatment of acute myeloid leukaemia. Conduct of clinical ADME study was required to evaluate mass balance, determine routes/rates of elimination and gain understanding of metabolic fate. As a cytotoxic drug, dosing in oncology patients rather than healthy volunteers was required. Subject recruitment is unpredictable and prolonged demanding long shelf-life for the 14C drug substance (DS) and 14C drug product (DP) which can be inherently unstable due to radiolysis risk. A new approach for conduct of these studies is described via on-demand manufacture of the DP on a per-patient basis. Rapid manufacturing, testing QP release and delivery methods were developed and validated to satisfy the on demand need. Methods: A small scale GMP manufacturing process for 14C IV vosaroxin injection was established via a processing trial and an aseptic validation. Short-term stability data were generated to support 7 day shelf-life based on chemical and microbiological evaluation. Following regulatory approval from local authorities, patients were recruited and the 14C DP manufactured on a per-patient basis and sent QP released to clinic for dosing. Six patients with advanced solid tumors are recruited and dosed with maximum 100 µCi radioactivity at 60 mg/m2 vosaroxin. The pharmacokinetics and total radioactivity (TRA) in plasma and urine are analysed over 7 days post dose and the blood:plasma ratio measured. Faeces are collected over 7 days post dose and analysed for TRA to confirm mass balance recovery. Results: The DP manufacturing process was successfully established and regulatory submission accepted. 14C DP was manufactured and supplied internationally within 14 days of notification of patient availability at the clinical site. Patients were dosed within 7 days of manufacture. Conclusions: Real-time adaptive manufacture and supply of IV 14C DP provides an innovative, quicker, cost-effective approach for the conduct of clinical ADME studies in oncology patients. Manufacture on per-patient basis ensures product shelf-life can be minimized and stability assured. The 14C DS can also be used efficiently in line with subject recruitment.
Circulating tumor DNA detection in hepatocellular carcinoma
Authors: L. Cabel, C. Proudhon, B. Buecher, J.-Y. Pierga, F.-C. Bidard
Journal: Annals of Oncology (2018)

Circulating tumor DNA (ctDNA) analysis has demonstrated excellent specificity and satisfactory sensitivity to detect somatic mutations across many tumor types and particularly in patients with metastatic disease [1, 2]. ctDNA detection rate and level primarily depend on tumor burden, proliferation and tumor type [3]. Its clinical use as a theragnostic biomarker for detecting EGFR mutation has been approved in stage IV non-small-cell lung cancer patients, in whom invasive tumor biopsy may be perilous because of limited accessibility and/or pre-existing organ dysfunction (e.g.
Shamanism and psychosis: Shared mechanisms?
Authors: Albert R. Powers, Philip R. Corlett
Journal: Behavioral and Brain Sciences (2018)

Individual-specific predispositions may precede the cultural evolution of shamanism and may be linked to it via principles of predictive coding. We have used these principles to identify commonalities between clinical and shaman-like non-clinical voice-hearers. The author may find this approach helpful in relating the experiences of shamans to those of their clients.