tbuckley/cabot-search huggingface dataset:
Expanding the insurance hypothesis of obesity with physiological cues
Authors: Aaron D Blackwell
Journal: Behavioral and Brain Sciences (2017)

Abstract Food insecurity relates to fat storage, but cannot explain fat storage in excess of levels optimal for buffering – that is, obesity. However, factors related to food unpredictability in the past, including stress, disease, micronutrient content of food, and physical activity, may cue physiological processes that change intake or fat deposition even in the absence of actual food unpredictability.
Randomized, controlled, multicenter, multinational phase 2 study of docetaxel (DCT) or AXL1717 treatment in patients with squamous cell carcinoma (SCC) or adenocarcinoma (AC) of non-small cell lung cancer (NSCLC).
Authors: Michael Bergqvist, Igor Bondarenko, Marcus Thuresson, Maria Klockare, Johan Harmenberg
Journal: Journal of Clinical Oncology (2014)

8091 Background: AXL1717 (picropodophyllin) is small molecule that inhibits the IGF-1R signaling pathway as well as suppresses tumor cell division by arresting cells in mitosis through a non-IGF-1R dependent mechanism. Preclinical data have shown extensive anti-tumor effects includingcomplete regressionsin xenograft studies against a range of tumors. Methods: A total of 101 patients (99 treated, ITT population) with locally advanced or metastatic NSCLC (Stage IIIB or IV, SCC or AD) with 1-2 lines of previous treatmentwere randomized. Patients had ECOG PS 0–2 and a life expectancy ≥ 3 months. The patients were randomized to either AXL1717 or DCT as monotherapy, in a 3:2 ratio for each NSCLC subtype. AXL1717 was administrated as an oral suspension given twice daily ata dose of 400 mg (later changed to 300 mg) and DCT was administered at 75 mg/m2 on Day 1 of every 21-day cycle. The treatmentduration was 12 weeks. Results: The primary objective was to compare the rate of progression-free survival (PFS) at 12 weeks between the treatment groups. The 12-week PFS rate for the ITT population was 25.9% in the AXL1717 and 39.0% in the DCT group (p=0.19). The median follow-up time was 27 weeks. Updated data will be presented at ASCO. The median OS was 38.7 weeks (w) for AXL1717 treated patients compared with 39.6 w for DCT patients (HR 1.063, p=0.813 [log rank test]). The median OS for the 49 patients with AC was 57.3 w for AXL1717 treated and 24.8 w for DCT patients(HR 0.932, p=0.846). The main side effects were hematological, mainly reduced neutrophil counts: 22.4% of the AXL1717 treated patients reported at least one event of CTCAE grade 3/4 neutropenia compared with 53.7% of the DCT treated patients. Some of the early neutropenic episodes in the AXL1717 group developed into serious events and some of these were fatal. The side effects were managed with a dose reduction of AXL1717 coupled with increased supervision of the patients. Conclusions: The phase 2 data in 99 patients did not show statistically confirmed difference between the two treatment groups for all patients or any of the histological subgroups for OS or PFS. Clinical trial information: NCT01561456.
Abstract 20484: National Trends and Outcomes in Dialysis-requiring Acute Kidney Injury in patients With Congestive Heart Failure: 2002-2013
Authors: Ashish Correa, Harshil Shah, Abhishek Mishra, Mihir Dave, Achint Patel, Tushar Mishra, Marwa Elnazeir, Naga Vijaya Lakshmi Divya Kallakuri, Kinsuk Chauhan, Suman Khicher, Dwight D Stapleton, Girish Nadkarni
Journal: Circulation (2016)

Background: Acute kidney injury requiring dialysis (AKI-D) is a serious and preventable complication in patients admitted with Congestive Heart Failure (CHF). However, data on national trends in AK...
This Is Why
Authors: None Cassandra
Journal: Annals of Internal Medicine (2017)

On Being a Doctor16 May 2017This Is WhyCassandraCassandraSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M16-1745 Audio Reading - “This Is Why” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "This Is Why," by Anonymous. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail I write this because I am afraid to write this.I write this because I am a fourth-year medical student typing on a small laptop in my closet in the dark. Because I am sitting on the floor with my back against the wall. Because to my left lies a pile of unsorted clothes and underneath a silver knife. Because in my senior year of college, I sat on the corner of my bed—on my bed, because back then my closet was overfull of skeletons and nightmares seeped in under door cracks and through the walls and there was nowhere ...References1. Schwenk TL, Davis L, Wimsatt LA. Depression, stigma, and suicidal ideation in medical students. JAMA. 2010;304:1181-90. [PMID: 20841531] doi:10.1001/jama.2010.1300 CrossrefMedlineGoogle Scholar2. Givens JL, Tjia J. Depressed medical students' use of mental health services and barriers to use. Acad Med. 2002;77:918-21. [PMID: 12228091] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement Audio Reading - “This Is Why” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "This Is Why," by Anonymous. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetailsSee AlsoForbidden Topics Michael A. LaCombe Metrics Cited byHidden Curricula, Ethics, and Professionalism: Optimizing Clinical Learning Environments in Becoming and Being a Physician: A Position Paper of the American College of PhysiciansLisa Soleymani Lehmann, MD, PhD, Lois Snyder Sulmasy, JD, and Sanjay Desai, MD, for the ACP Ethics, Professionalism and Human Rights Committee*Forbidden TopicsMichael A. LaCombe, MD 16 May 2017Volume 166, Issue 10Page: 755-756KeywordsDeceptionForecastingHealth careOxycodonePersonality disordersPsychologyTouchVeinsVital signsWalking ePublished: 16 May 2017 Issue Published: 16 May 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 174: The Origin Of Cardiac Fibroblasts During Normal Development And After Injury
Authors: Sara Ranjbarvaziri, Shah R Ali, Mahmood Talkhabi, Ali Subat, Peng Zhao, Katharina S Volz, Kristy Red-Horse, Reza Ardehali
Journal: Circulation Research (2013)

Fibroblasts are the most abundant cells in the heart. They play a critical role in maintaining normal myocardial function as well as mediating fibrosis that occurs upon pathological injury. However, the source of cardiac fibroblasts during development and after the injury in the adult heart remains poorly characterized. The lack of cardiac fibroblast-specific markers has limited our ability to isolate or track them during normal development and in response to cardiac injury. Here, we define cardiac fibroblasts as mesenchymal cells with a surface-marker profile of CD45-/CD31-/Ter119-/CD11b-/Thy1.1+ /Thy1.2+. We used lineage tracing, transplantation studies, and parabiosis surgeries to identify the cellular origins of cardiac fibroblasts and their contribution to fibrosis during pathological injury induced by pressure overload. We show that fibrosis is associated with proliferation of fibroblasts within 7 days after pressure overload injury with no evidence of bone marrow or hematopoietic stem cells contributing to the cardiac fibroblast population. We then used the transgenic mouse models Tie2cre;mTmG, Tbx18cre;mTmG, and Pax3cre;mTmG to lineage trace the origin of fibroblasts from the epicardium, endothelial and the neural crest, respectively. By using fluorescent activated cell sorting (FACS) and immunostaining, we demonstrate that the majority of cardiac fibroblasts are derived from the epicardium, a minority arises from endothelial cells, and a small fraction from the neural crest. Although we observed an increase in the total number of fibroblasts after pressure overload injury, this response was not restricted to any single developmental subset. In summary, our findings show that the majority of the cardiac fibroblasts, during normal development as well as in response to pathological injury, are derived from the epicardium via epithelial-to-mesenchymal transformation. Endothelial to mesenchymal transition and neural crest sources also contribute to fibroblast generation and the progression of pressure overload-induced cardiac fibrosis.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Marilyn Sue Kozak, Helmut H. Hahn, William J. Lennarz, W. Barry Wood
Journal: The Journal of Experimental Medicine (1968)

Small quantities of highly purified granulocytic pyrogen have been separated from contaminating proteins by disc electrophoresis in polyacrylamide gel. The biologically active material thus isolated was shown to be electrophoretically homogeneous at pH 9 and pH 3.8. Earlier work on the chemical properties of the pyrogen molecule has been extended to include: (a) estimation of its molecular weight by gel filtration; (b) demonstration of free sulfhydryl groups essential for its biological activity; and (c) evidence that it is not inactivated by exhaustive extraction with ethanolether or n-heptane.
The case against
Authors: J Coast
Journal: BMJ (1997)

This paper must begin with some definitions. Implicit rationing of health care occurs when care is limited and where neither decisions about which forms of care are provided or the bases for those decisions are clearly expressed.1 Hence it is the unacknowledged limitation of care. Explicit rationing is, unsurprisingly, the opposite: decisions about the provision of health care are clear, as are the reasons for those decisions. Nevertheless, the term explicit has been used in various ways, from Klein's version of explicit rationing as rationing by exclusion2, to a more general concern with honesty and openness surrounding the context of healthcare rationing.3

Both types of rationing decision can be made at different levels. Various taxonomies have been used, but this paper will assume four distinct levels of priority setting: across whole services; within services but across treatments; within treatments; and between individual patients.1 It is at the last level, particularly, that explicit rationing may be most troublesome.

Currently, rationing in the United Kingdom at all levels is predominantly implicit.4 5 It is carried out by doctors who are aware of the resources available and who ration by telling patients that they cannot help them, rather than explicitly stating that resources are not available.4 6 7 8 9 The denial of care is instead made to seem optimal or routine.4 10 Hence there is little sense among the public that healthcare rationing takes place on a daily basis. Indeed, on those occasions when explicit rationing is perceived (particularly at the level of the individual patient)–for example, in the case of child B11 12–there tends to be public outcry about the introduction of rationing.

The proposition put forward, that rationing should be made explicit at all levels of NHS decision making is …
Metformin ameliorates core deficits in a mouse model of fragile X syndrome
Authors: Ilse Gantois, Arkady Khoutorsky, Jelena Popic, Argel Aguilar-Valles, Erika Freemantle, Ruifeng Cao, Vijendra Sharma, Tine Pooters, Anmol Nagpal, Agnieszka Skalecka, Vinh T Truong, Shane Wiebe, Isabelle A Groves, Seyed Mehdi Jafarnejad, Clément Chapat, Elizabeth A McCullagh, Karine Gamache, Karim Nader, Jean-Claude Lacaille, Christos G Gkogkas, Nahum Sonenberg
Journal: Nature Medicine (2017)
Radiation Safety in Children With Congenital and Acquired Heart Disease
Authors: Kevin D. Hill, Donald P. Frush, B. Kelly Han, Brian G. Abbott, Aimee K. Armstrong, Robert A. DeKemp, Andrew C. Glatz, S. Bruce Greenberg, Alexander Sheldon Herbert, Henri Justino, Douglas Mah, Mahadevappa Mahesh, Cynthia K. Rigsby, Timothy C. Slesnick, Keith J. Strauss, Sigal Trattner, Mohan N. Viswanathan, Andrew J. Einstein
Journal: JACC. Cardiovascular imaging (2017)

There is a need for consensus recommendations for ionizing radiation dose optimization during multimodality medical imaging in children with congenital and acquired heart disease (CAHD). These children often have complex diseases and may be exposed to a relatively high cumulative burden of ionizing radiation from medical imaging procedures, including cardiac computed tomography, nuclear cardiology studies, and fluoroscopically guided diagnostic and interventional catheterization and electrophysiology procedures. Although these imaging procedures are all essential to the care of children with CAHD and have contributed to meaningfully improved outcomes in these patients, exposure to ionizing radiation is associated with potential risks, including an increased lifetime attributable risk of cancer. The goal of these recommendations is to encourage informed imaging to achieve appropriate study quality at the lowest achievable dose. Other strategies to improve care include a patient-centered approach to imaging, emphasizing education and informed decision making and programmatic approaches to ensure appropriate dose monitoring. Looking ahead, there is a need for standardization of dose metrics across imaging modalities, so as to encourage comparative effectiveness studies across the spectrum of CAHD in children.
The search for orally active medications through combinatorial chemistry
Authors: Robert A. Fecik, Kristine E. Frank, Elmer J. Gentry, Sanjay R. Menon, Lester A. Mitscher, Hanumaiah Telikepalli
Journal: Medicinal Research Reviews (1998)

The literature of combinatorial chemistry is reviewed with particular attention paid to considerations of absorption, distribution, metabolism and excretion in the design and evaluation of libraries containing drug-like molecules. Published libraries are evaluated in particular for the likelihood that the products would possess oral bioavailability. © 1998 John Wiley & Sons, Inc. Med. Res. Rev., 18, No. 3, 149–185, 1998.
Automated Quantification of Coronary Plaque Volume From CT Angiography Improves CV Risk Prediction at Long-Term Follow-Up
Authors: Simon Deseive, Ramona Straub, Maximilian Kupke, Jonathan Nadjiri, Alexander Broersen, Pieter H. Kitslaar, Steffen Massberg, Martin Hadamitzky, Jörg Hausleiter
Journal: JACC. Cardiovascular imaging (2017)
The functional movement test 9+ is a poor screening test for lower extremity injuries in professional male football players: a 2-year prospective cohort study
Authors: Arnhild Bakken, Stephen Targett, Tone Bere, Cristiano Eirale, Abdulaziz Farooq, Johannes L Tol, Rod Whiteley, Karim M Khan, Roald Bahr
Journal: British Journal of Sports Medicine (2017)

The 9+ screening battery test consists of 11 tests to assess limitations in functional movement.To examine the association of the 9+ with lower extremity injuries and to identify a cut-off point to predict injury risk.Professional male football players in Qatar from 14 teams completed the 9+ at the beginning of the 2013/2014 and 2014/2015 seasons. Time-loss injuries and exposure in training and matches were registered prospectively by club medical staff during these seasons. Univariate and multivariate Cox regression analyses were used to calculate HR and 95% CI. Receiver operating characteristic (ROC) curves were calculated to determine sensitivity and specificity and identify the optimal cut-off point for risk assessment.362 players completed the 9+ and had injury and exposure registration. There were 526 injuries among 203 players (56.1%) during the two seasons; injuries to the thigh were the most frequent. There was no association between 9+ total score and the risk of lower extremity injuries (HR 1.02, 95% CI 0.99 to 1.05, p=0.13), even after adjusting for other risk factors in a multivariate analysis (HR 1.01, 95% CI 0.98 to 1.04, p=0.37). ROC curve analysis revealed an area under the curve of 0.48, and there was no cut-off point that distinguished injured from non-injured players.The 9+ was not associated with lower extremity injury, and it was no better than chance for distinguishing between injured and uninjured players. Therefore, the 9+ test cannot be recommended as an injury prediction tool in this population.
BMPR-II DYSFUNCTION LEADS TO ABNORMAL GROWTH RESPONSES TO TRANSFORMING GROWTH FACTOR BETA IN PULMONARY ARTERY SMOOTH MUSCLE CELLS: ROLE OF UPREGULATION OF NUCLEAR FACTOR KAPPA B SIGNALLING
Authors: R. J. Davies, P. D. Upton, L. Long, Richard Trembath, N. W. Morrell
Journal: Thorax (2008)
Oncolytic viral therapy for malignant gliomas using myxoma virus deleted for antiapoptotic M11L gene.
Authors: Peter A. J. Forsyth, Brienne McKenzie, Alexandra Pisklakova, Rajappa Kenchappa, Grant McFadden
Journal: Journal of Clinical Oncology (2014)

3105 Background: Malignant gliomas (MGs) remain largely incurable with a poor prognosis and an average survival of approximately 1 year. They are resistant to radiotherapy (RT) and temozolomide (TMZ). Clearly more effective treatments for MGs are needed. Oncolytic viruses are promising new agents used against experimental models of MGs and are now in several clinical trials. Myxoma virus is an excellent oncolytic virus because it is safe, selectively infecting and killing only cancer cells. We have shown that myxoma virus is efficacious in MGs and brain tumor initiating cells (BTICs) in vitro and in vivo, but the effect on survival in BTICs is not striking and only seen when combined with rapamycin. We think that manipulating myxoma virus will improve its therapeutic efficacy in MG, and hypothesize that genetic deletion of the anti-apoptotic gene M11L in Myxoma virus will enhance cell killing in MGs/BTICs and may be synergistic with TMZ and RT. Methods: We created the myxoma M11L knockout virus (M11L-KO) and tested its ability to kill MG cells and BTICs isolated from fresh human malignant gliomas. We have also examined the efficacy of M11L-KO virus on killing of BTICs when combined with TMZ and RT. Results: We found that M11L-KO is superior to WT-myxoma, produces a productive infection, and kills glioma cells and BTICs via apoptosis as shown by cleavage of PARP and caspase-3. As expected, the M11L protein in the WT virus does associate with the mitochondria, which is consistent with its role in inhibiting apoptosis. We have also found an additive effect of TMZ and RT with the M11L-KO virus compared to WT-myxoma. Finally, a microarray screen in BTICs showed several promising candidates in the intrinsic and extrinsic apoptosis pathways that are down- or up-regulated by M11L in WT-myxoma. Interestingly, our microarray data showed that TNFSF10 is up-regulated in BTICs infected with M11L-KO myxoma compared to cells infected with WT-myxoma, indicating its possible role in Myxv-M11L-KO-mediated killing of BTICs. Conclusions: These results will have clinical significance in the development of an experimental treatment in MGs patients.
Moderated Poster Session - Heart245The involvement of TWEAK and FN14 in murine autoimmune myocarditis246Sympathetic neurons that innervate the heart locally modulate cardiomyocyte trophic and electrophysiological properties247W4R variant of CSRP3 leads to the expression of a novel alternate reading frame protein due to alternative splicing248Glucocorticoid intervention prenatally: effects on fetal heart maturation249Uncoupling of myofilament Ca2+-sensitivity from troponin I phosphorylation by …
Authors: A Fischer, N Pianca, V Azzimato, E J Batchen, A E Messer, R Ben Jehuda, A-M Mueller, A Bangert, M Bockstahler, R Oettl, HA Katus, Z Kaya, V Prando, M Franzoso, A Di Bona, M Campione, M Sandri, T Zaglia, M Mongillo, AM Tabish, B Buyandelger, KN Enesa, J Hunt, R Milner, JW Wiseman, J Wahlgren, M Bohlooly, R Knoell, R V Richardson, A J W Thomson, C M Moran, G A Gray, K E Chapman, M Papadaki, PG Vikhorev, A Sheehan, SB Marston, T Hallas, T Haykain, B Eisen, R Schick, M Gherghiceanu, H Mandel, M Arad, O Binah
Journal: Cardiovascular Research (2016)
THE MEDIATOR OF CELLULAR IMMUNITY
Authors: D. D. McGregor, Pamela S. Logie
Journal: The Journal of Experimental Medicine (1973)

The antimitotic drug vinblastine (Vbl) has a profound impact upon the specifically sensitized lymphocytes that transfer cellular resistance to Listeria monocytogenes. A 12-h pulse of the drug given to prospective donors during the first week of an immunizing Listeria infection inhibits the delivery of protective lymphocytes to the thoracic duct and their subsequent movement into an inflammatory exudate induced in the peritoneal cavity. The effect of Vbl is clearly related to its antimitotic activity, not to an effect on lymphocytes regardless of their position in the division cycle. This conclusion was drawn from an autoradiographic analysis of cells in the lymph of Vbl-treated rats and from failure of the drug to abrogate a known function of small lymphocytes, namely, their ability to initiate a graft-vs.-host reaction. The results imply that large lymphocytes, the rapidly proliferating cells in central lymph, are the principal effector cells responsible for transmitting resistance to L. monocytogenes and provide a plausible explanation for their rapid turnover and short circulating life-span.
A phase I dose escalation and pharmacokinetic study of BIBF 1120 in combination with paclitaxel and carboplatin in patients with advanced gynecological malignancies
Authors: P. Harter, J. Huober, J. Pfisterer, P. Wimberger, S. Loibl, P. Stopfer, R. Kaiser, V. Reichardt, A. du Bois
Journal: Journal of Clinical Oncology (2007)

3561 Background: BIBF 1120 is an oral triple angiokinase inhibitor targeting VEGFR, PDGFR, FGFR kinases which might be interesting targets for gynecologic tumor therapy. Therefore, we performed a phase I study to evaluate maximal tolerated dose (MTD), safety, and pharmacokinetics (PK) of twice daily BIBF 1120 in combination with carboplatin AUC 5 and paclitaxel 175 mg/m 2 q21 (CP) in patients with advanced or recurrent gynecological malignancies. Methods: 6 courses of CP and escalating bid doses of BIBF 1120 (2x100 mg to 2x250 mg) on the days without i.v. chemotherapy were administered. A 3 + 3 dose escalation design was followed. An additional cohort of 6 pts was treated on the MTD level. Results: Twenty-three pts were enrolled and 21 pts were treated with at least one cycle of CP and BIBF 1120. At 2x250 mg of BIBF 1120, two pts developed reversible CTCAE °3 and °4 elevations of AST and ALT in the first treatment course. MTD was determined as 200 mg BIBF 1120 bid for the combination with CP. Within the other dose cohorts (2x100 mg, n= 3, 2x150 mg, n= 4, 2x200 mg, n= 13) no dose limiting toxicities were observed. There was no increase in hematological toxicity with the addition of BIBF 1120 compared to standard CP. Further non-hematological °3 toxicities were: diarrhea (n=4), ascites (n=1), dyspnoe (n=1), nausea (n=3).Thus far, the PK profiles of carboplatin, paclitaxel, and BIBF 1120 have been evaluated in seven pts (2x100 mg, n=3 and 2x150 mg, n=4). There was no significant change of the individual and geometric mean plasma concentrations of C and P before and after 3 weeks of continuous daily bid dosing with BIBF 1120. Conclusions: BIBF 1120 can be given safely at a dose of 200 mg bid together with standard doses of CP in pts with advanced gynecological malignancies. Preliminary PK analyses did not reveal any interaction of CP and BIBF 1120. [Table: see text]