tbuckley/cabot-search huggingface dataset:
Abstract 16682: No Increased Risk of Early or Late Adjudicated Cardiovascular Events With Dapagliflozin
Authors: James List, Christian Sonesson, Ingrid Gause-Nilsson, Agata Ptaszynska, Eva Johnsson, Peter A Johansson, Bob Frederich
Journal: Circulation (2014)

Dapagliflozin (DAPA), a sodium-glucose cotransporter 2 inhibitor, reduces plasma glucose in patients (pts) with type 2 diabetes by inhibiting renal glucose reuptake leading to glucosuria. DAPA has diuretic and longterm weight loss effects, and is associated with blood pressure (BP) reduction. Diuresis and BP reduction are evident soon after commencement of therapy, raising the question of whether there could be time dependent effects on cardiovascular safety. Data were pooled from 21 double blind phase 2b and phase 3 studies of DAPA with duration of treatment of up to 4 years and analyzed for prospectively adjudicated composite CV event end points, both for major adverse cardiac events ([MACE]; CV death, myocardial infarction, and stroke) and for the prespecified primary end point of MACE plus unstable angina (UA). The pt cohort (n=5936 for DAPA; n=3403 for controls) included 3214 pts with a history of CV disease. As previously reported, the overall hazard ratio for the primary end point between DAPA and control cohorts was 0.79 (95% CI 0.58-1.07). For MACE it was 0.77 (95% CI 0.54-1.10). Although the hazard rates (HR) per month demonstrated large variation, the HR for the primary end point and for MACE in the DAPA group in the first 30 days were similar to later time points, showing no evidence of an early increase in risk (Figure). Kaplan-Meier estimates of both end points showed no notable separation between DAPA and control in the first 30 days of treatment; however, a separation favoring DAPA started at approximately 250 days that was not statistically significant. Baseline characteristics for pts who had events in the first 30 days were similar to those of the general population and did not suggest a population with early risk for MACE events. Results were consistent across composite end points and pt subgroups with respect to history of a CV event. In conclusion, there was no increase in early CV events with DAPA, and no evidence for a population susceptible to early CV events with DAPA.
Medicine and multimedia: “Butchers and gropers”
Authors: Kamran Abbasi
Journal: BMJ (1998)

From dangerous to salacious, the medical profession’s indiscretions have been repeatedly laid bare in this Annus horribilis. Wisheart, Dhasmana, Ledward, Walmsley, and others have been named and shamed. They are probably only the tip of the iceberg. Horror stories of medical incompetence, arrogance, and libidinousness have filled newspapers; broadsheets and tabloids have been united in their condemnation of a profession unable to regulate itself except when it’s too late.
Abstract B45: Pancreatic cancers depend on a non-canonical glutamine metabolism pathway
Authors: Costas A. Lyssiotis, Jaekyoung Son, Joesph D. Mancias, Haoqiang Ying, Lewis C. Cantley, Alec C. Kimmelman
Journal: Cancer Research (2015)

Abstract Cancer cells exhibit metabolic dependencies that distinguish them from their normal counterparts. Among these addictions is an increased utilization of the amino acid glutamine (Gln) to fuel anabolic processes. Recently, we reported the identification of a non-canonical pathway of Gln utilization in human pancreatic cancer cells that is required for tumor growth. While most cells utilize glutamate dehydrogenase (GLUD1) to convert Gln-derived glutamate (Glu) into alpha-ketoglutarate (alpha-KG) in the mitochondria to fuel the tricarboxylic acid cycle, pancreatic cancer cells rely on a distinct pathway that integrates the mitochondrial and cytosolic aspartate aminotransferases GOT2 and GOT1. By generating alpha-KG from Glu (in conjunction with the conversion of oxaloacetate into aspartate), GOT2 fuels anaplerosis in place of GLUD1. The Asp created is released into the cytosol and acted on by GOT1. This is subsequently used through a series of reactions to yield cytosolic NADPH from malic enzyme. Importantly, we have demonstrated that pancreatic cancers are strongly dependent on this series of reactions to maintain redox homeostasis which enables proliferation. Herein, we detail the subcellular compartmentalization and consequences of the aforementioned reactions on pancreatic cancer metabolism. We have also investigated the essentiality of this pathway in other contexts and find that pancreatic cancers have a uniform and unique reliance on this pathway, which may provide novel therapeutic approaches to treat these refractory tumors. Citation Format: Costas A. Lyssiotis, Jaekyoung Son, Joesph D. Mancias, Haoqiang Ying, Lewis C. Cantley, Alec C. Kimmelman. Pancreatic cancers depend on a non-canonical glutamine metabolism pathway. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B45.
Identification of viral load signatures for HBV and HCV in human hepatocellular carcinoma
Authors: Hyun Goo Woo, Ing Jos van Pelt, Ju-Seog Lee, Chris Verslype, Louis Libbrecht, In-Sun Chu, Snorri Thorgeirsson
Journal: Cancer Research (2007)

4428   Chronic infections with hepatitis B virus (HBV) or hepatitis C virus (HCV) have been established as the major risk factors for human hepatocellular carcinoma (HCC). It is also known that viral load is an independent predictor of HCC risk (Chen et al, 2006). However, the underlying mechanism(s) by which the viral load exerts this effect remains unclear.  In the present study, we examined gene expression profiles in HepG2 cells that were transfected with HBsAg or HCV core-encoding genes. Using the genome-scale microarray analysis, we found that cell proliferation and immune related genes were overexpressed in HCV core transfected cells, while splicing related genes were overexpressed in HBsAg-transfected cells. To identify the lead genes in the HCV core-induced signature, we constructed an interaction network from the HCV core-induced genes. The metallothionein 1G (MT1G) was identified as the hub gene that had the most frequent interacting partners among the HCV core-induced genes. Other MT genes ( i.e. , MT1F, MT1H) were also dysregulated. These results suggest that the MT genes may have key regulatory roles in the HCV core signature. Furthermore, we compared the viral load signatures with the expression profile of human HCC, and observed that both HBsAg and HCV core signatures reflect the prognostic features of human HCC in HBV- and HCV-infected subjects, respectively. In conclusion, these data identify the putative target genes associated with the effects of viral load on HCC prognosis which may be useful as prognostic predictors for human HCC.
Minister expects call for extra beds for Ireland
Authors: Doug Payne
Journal: BMJ (2001)

The Irish minister of health, Micheal Martin, has said he expects that within days a review body will recommend a “quite significant” increase in the number of hospital beds.

Mr Martin was speaking at the recent annual general meeting of the Irish Medical Organisation, which represents 5000 Irish doctors. He said that he expects a recommendation that some of the beds should be specifically designated for emergency care, …
Abstract 14111: Polycystin 2 is Required for Stress-induced Activation of Autophagy in Heart
Authors: Alfredo Criollo, Zully Pedrozo, Nan Jiang, Xiang Luo, Thomas G Gillette, Sergio Lavandero, Joseph A Hill
Journal: Circulation (2013)

Background: Autophagy is a ubiquitous process of intracellular protein and organelle recycling, critical to numerous forms of stress responsiveness. Polycystins are integral membrane proteins local...
Evidence based palliative care
Authors: G. McLaren, C. Preston, B. Grant, T. Lovel
Journal: BMJ (1999)

Cancer survival in Britain Cancer chemotherapy costs moneyEditor-I strongly endorse Sikora's claim that poor rates of survival from cancer in the United Kingdom reflect a lack of NHS resources. 1Increasing the number of specialist oncologists will not, however, make up for the massive shortfall in funds required to provide these oncologists with the essential tools of their trade.Recent review of the budgetary allocation to Addenbrooke's Oncology Centre identified that, on average, £1700 a year is available to spend on drugs for any individual patient with cancer.Since a single course of chemotherapy may cost between £50 and £1500, oncologists cannot be expected to deliver the quality of care the public expects to receive.There are no other untapped sources of funding.Our clinical practice is already heavily subsidised: about one in six of all new patients with cancer referred to Addenbrooke's receives his or her standard chemotherapy courtesy of funds raised from industry sponsored research.The government cannot claim commitment to improving cancer care while patients are being denied effective treatments on the grounds of lack of affordability.
Cortactin is required for lamellipodia retraction in MTLn3 Breast Cancer Cells
Authors: Amanda S. Gatesman Ammer, Laura C. Kelley, Scott A. Weed
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

1810 

Changes in the actin cytoskeleton are mediated by a variety of actin-binding proteins and are essential for many cellular processes, including migration, invasion, and adhesion. Cortactin is an F-actin binding protein and Src family kinase substrate that is enriched in lamellipodia and is required for tumor cell motility and invasion. Cortactin functions to stimulate Arp2/3-mediated actin polymerization necessary for lamellipodia formation and extension, and serves to stabilize Arp2/3-F-actin networks. In this study we have investigated the role of cortactin in lamellipodia dynamics using MTLn3 breast adenocarcinoma cells, a model system for studying lamellipodia. Lamellipodia formation in MTLn3 cells stimulated with EGF was monitored using time-lapse video microscopy. MTLn3 cells expressing control siRNA displayed normal lamellipodial dynamics, with maximal extension at about 3-4 minutes, and retraction by 10 minutes. In contrast, MTLn3 cells transfected with cortactin siRNA exhibited normal lamellipodia extension, but were dramatically impaired in their ability to retract, resulting in increased lamellipod persistence. Rescue of cortactin-silenced cells by expression of GFP-tagged human cortactin partially restored the ability of these cells to retract the lamellae. Our data suggest that cortactin serves to regulate lamellipodia retraction, an essential requirement for productive cell motility. The role of cortactin tyrosine phosphorylation on lamellipodia dynamics and the impact of cortactin on the architecture of the lamellipodia actin cytoskeleton are currently under investigation.
Abstract 16938: Serial Phase-Contrast MRI for Prediction of Pulmonary Haemodynamic Changes in Patients with Pulmonary Arterial Hypertension
Authors: Santo Dellegrottaglie, Pasquale Perrone-Filardi, Leticia Fernandez-Friera, Ajith Nair, Valentin Fuster, Javier Sanz
Journal: Circulation (2010)
Outcome following ECT for primary unipolar depression: a test of newly proposed response predictors
Authors: W Coryell, M Zimmerman
Journal: American Journal of Psychiatry (1984)

This study considered dexamethasone suppression test (DST) results, Winokur 's familial subtyping, and the presence or absence of melancholia according to DSM-III criteria as potential predictors of response to ECT. Familial subtype and DST results independently predicted outcome after ECT, but melancholia did not. Relationships between outcome and several other traditional items tested for comparison generally agreed with those in earlier studies. The pattern of significant predictors varied considerably depending on outcome measure--Hamilton depression score at discharge, global rating at discharge, or symptom score during a 6-month follow-up--which may explain some of the discrepancies between results of earlier predictor studies.
Abstract 1878: Beneficial Electrophysiological Effects of bi-Ventricular Pacing for Cardiac Resynchronization Therapy in a Canine Model of Dyssynchronous Heart Failure
Authors: Takeshi Aiba, Andreas S Barth, Ting Liu, Khalid Chakir, Geoffrey G Hesketh, Veronica L Dimaano, Theodore P Abraham, Brian O’Rourke, Fadi G Akar, David A Kass, Gordon F Tomaselli
Journal: Circulation (2008)

Background : Cardiac resynchronization therapy (CRT) using bi-ventricular (bi-V) pacing improves cardiac function and mortality in patients with heart failure and dyssynchronous contraction (DHF). However, the mechanisms by which bi-V pacing restores DHF-induced electrophysiological remodeling remain controversial. We test the hypothesis that bi-V pacing has enhanced beneficial effects on DHF beyond resynchronization of contraction. Methods and Results : Adult dogs underwent RV pacing (190–200 bpm) for 6 weeks (DHF: n = 6), or 3-week DHF followed by 3 weeks of resynchronization by either bi-V pacing (n = 6) or RA pacing (A-pace: n = 5) at the same pacing rate. Myocytes were isolated from LV anterior (ANT) and lateral (LTR) walls in non-failing (NF), DHF, bi-V and A-pace dogs. Whole cell patch clamp was performed to measure action potential (AP), transient outward (I to ), inward rectifier (I K1 ) and delayed rectifier K + currents (I K ). L-type Ca 2+ current (I Ca,L ) and [Ca 2+ ] i transients (CaT) were measured in the absence (baseline) and presence of isoproterenol (ISO) (35°C). The QRS duration was wider in bi-V than in A-pace, the other ECG and hemodynamic parameters were not statistically different between Bi-V and A-pace dogs. Bi-V abbreviated DHF-induced prolongation of APD in the LTR but not ANT cells and diminished the regional gradient of APD, whereas A-pace less abbreviated APD in the LTR cells and still remained the gradient. Bi-V partially restored the DHF-induced down regulation of I K1 and I K but not I to , whereas A-pace restored only I K1 but not I K and I to . Furthermore, bi-V fully restored the DHF-induced reduction of I Ca,L at baseline and its ISO response, whereas A-pace did not restore I Ca,L at baseline but restored its ISO responsiveness. The CaT amplitude at baseline and in ISO were partially restored by both bi-V and A-pace but the restoration was more complete with bi-V compared to A-pace. Conclusion : Although both bi-V and A-pace resynchronize the LV contraction, DHF-induced downregulation of K + currents, Ca 2+ current and handling were less completely restored by A-pace compared with bi-V pace, suggesting bi-V pacing not only resynchronizes LV contraction but improves regional heterogeneity of repolarization and Ca 2+ homeostasis in DHF.
Abstract 16674: Using Novel Emergency Medical Services Data-Linkage to Evaluate the Timing and Quality of Pre-Hospital ST-Elevation Myocardial Infarction Care
Authors: Emil L Fosbol, Chris Granger, Li Lin, Barbara L Lytle, Greg Mears, James G Jollis, Eric D Peterson, Seth Glickman
Journal: Circulation (2011)

Background: Current national guidelines state that STEMI patients should receive primary percutaneous coronary intervention (PCI) within 90 minutes of “first medical contact” (FMC). Lacking access to emergency medical services (EMS) data, many hospitals are unprepared to implement this goal. Our objective was to utilize a novel statewide hospital/EMS data linkage to describe pre-hospital delays in care and to examine adherence to the 90 min rule. Methods: To assess pre-hospital patterns of care in North Carolina (NC), we linked data from the ACTION-GWTG registry and the statewide EMS Pre-hospital Medical Information System (PreMIS) from 06/2008 to 09/2010. We calculated the discrete elements of pre-hospital delay from the time of 911-activation to the time of hospital arrival using PreMIS data and in turn compared time from FMC to hospital arrival as recorded in PreMIS versus ACTION. Results: Analyses included 21 ACTION hospitals and 178 EMS agencies across NC. Of 6010 linked STEMI patients, 3077 (51%) arrived directly to a PCI capable hospital by EMS. Median age was 60 (IQR 52-71) and 69% were men. Calculated pre-hospital times are shown in the Table. Median total pre-hospital time interval was 42 min (IQR 33-53). Comparing PreMIS to ACTION data, time from FMC to hospital arrival was 30 min (IQR 23-40) vs. 34 min (IQR 26-45) with median difference of 3 minutes (IQR 0-7, p &lt;.0001 by signed rank test). Among patients with available data in both data sources (n= 2201), only 53% achieved the metric of PCI within 90 min of FMC by PreMIS and 49% by the ACTION data with 12% discordance between ACTION and PreMIS (p &lt;.0001 by McNemar's test). Conclusions: This work demonstrates that it is possible to link nationally representative hospital and EMS data for assessing the quality of pre-hospital STEMI care and further shortening treatment times. Pre-hospital data may also permit more accurate determination of first medical contact time than hospital data sources.
Improving doctor-patient communication
Authors: S. Meryn
Journal: BMJ (1998)

In most Western countries healthcare systems are changing; political and economic forces are behind the growth of profit driven medicine, managed care, and an increasingly technological focus. Paradoxically, at a time of global communication and the “Net generation,” we are faced with a breakdown in communication between patients and doctors, increasing patient dissatisfaction, rising numbers of complaints and claims for malpractice, and abandonment of conventional medicine for alternatives that are often unproved.1

What do patients want? Most complaints by patients and the public about doctors deal with problems of communication not with clinical competency.2 The commonest complaint is that doctors do not listen to them. Patients want more and better information about their problem and the outcome, more openness about the side effects of treatment, relief of pain and emotional distress, and advice on what they can …
Abstract 4346: CRT In Mild Heart Failure: Left Ventricular Remodeling In Relation To Heart Failure Etiology. Results From The Resynchronization Reverses Remodeling In Systolic Left Ventricular Dysfunctie (reverse) Study
Authors: Stefano Ghio, Martin St. John Sutton, Luigi Tavazzi, Ted Plappert, Jean Claude Daubert, William T Abraham, Michael R Gold, Cecilia Linde
Journal: Circulation (2008)
Abstract 16193: Impaired Cardiac and Skeletal Muscle Lipid Metabolism and Reduced Cardiac Fatty Acid and Triglyceride Levels in Patients With Advanced Heart Failure
Authors: Ruiping Ji, Tuba Khawaja, Hongfeng Jiang, Shuiqing Yu, Donna Mancini, Ira Goldberg, P. Christian Schulze
Journal: Circulation (2011)

BACKGROUND: Impaired lipid metabolism contributes to cardiac dysfunction and progression of heart failure (HF). Aim of this study was to evaluate pathways of lipid metabolism and changes in free fa...
Abstract A38: Adiponectin receptor agonists cause inhibition of pancreatic cancer proliferation
Authors: Alisha Mendonsa, Lee Gorden, Michael Nathan VanSaun
Journal: Cancer Research (2015)

Abstract Adiponectin is an anti-atherogenic hormone which is typically decreased in the setting of obesity, diabetes, and pancreatitis. Adiponectin and/or its receptor levels have been inversely correlated with risk for pancreatic cancer. The purpose of this study was to determine the effect of adiponectin on pancreatic cancer cells and to investigate the primary molecular pathways that it regulates. We have previously shown that pancreatic cancer cells primarily produce adiponectin receptor 1. In our current studies, recombinant adiponectin and a novel small molecular adiponectin agonist, AdipoRon, were used to stimulate human and murine pancreatic cancer cell lines in vitro. Proliferation was assessed through an EdU incorporation assay, metabolism was measured through MTT, and apoptosis was assessed through Annexin V staining. Results demonstrate that adiponectin stimulation leads to a decrease in proliferation of pancreatic cancer cells. Further, AdipoRon elicits a more potent suppression of proliferation and an additional increase in apoptosis. To better understand the molecular mechanisms activated by adiponectin stimulation, we performed western blot analysis of treated cells. We were able to confirm that AMPK was a direct target of both adiponectin and AdipoRon. Further, we were able to show that FBS stimulated phosphorylation of Akt was diminished in the presence of AdipoRon. Our data demonstrate that adiponectin and adiponectin receptor agonists act in a suppressive manner against pancreatic cancer cell proliferation. Current studies will determine whether adiponectin agonists can additionally decrease proliferation in vivo. Citation Format: Alisha Mendonsa, Lee Gorden, Michael Nathan VanSaun. Adiponectin receptor agonists cause inhibition of pancreatic cancer proliferation. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A38.
英格兰的国家痴呆干预策略——包括证据、经济和责任
Authors: 沈航, 高晶
Journal: BMJ (2009)

现在公众对痴呆的知晓有了较大提高，这主要是由于人们接触到不同患病个体以亲身感受所做的记述，例如作家特里普拉切特爵士。在英国，痴呆影响到大约70万人，估计每年耗费170亿英镑（190亿欧元；240亿美元）。在英格兰，2009年2月启动国家痴呆策略，这是一个广泛咨询的产物，估值1．5亿英镑。该策略内容提出了17项建议，
Associations between dynamics of the blood glucose level after hypoglycemia and intensive care unit mortality: a retrospective multicenter study
Authors: Roosmarijn T. M. van Hooijdonk, Jan M. Binnekade, Ameen Abu–Hanna, Floris van Braam Houckgeest, Lieuwe S. Hofstra, Janneke Horn, Michael A. Kuiper, Nicole P. Juffermans, Huub L. A. van den Oever, Johannes P. van der Sluijs, Peter E. Spronk, Marcus J. Schultz
Journal: Intensive Care Medicine (2015)
An in vivo screen identifies ependymoma oncogenes and tumor-suppressor genes
Authors: Kumarasamypet M Mohankumar, David S Currle, Elsie White, Nidal Boulos, Jason Dapper, Christopher Eden, Birgit Nimmervoll, Radhika Thiruvenkatam, Michele Connelly, Tanya A Kranenburg, Geoffrey Neale, Scott Olsen, Yong-Dong Wang, David Finkelstein, Karen Wright, Kirti Gupta, David W Ellison, Arzu Onar Thomas, Richard J Gilbertson
Journal: Nature Genetics (2015)