tbuckley/cabot-search huggingface dataset:
Molecular and Cellular Mechanisms of Cardiovascular Disorders in Diabetes
Authors: Manasi S. Shah, Michael Brownlee
Journal: Circulation Research (2016)

The clinical correlations linking diabetes mellitus with accelerated atherosclerosis, cardiomyopathy, and increased post-myocardial infarction fatality rates are increasingly understood in mechanistic terms. The multiple mechanisms discussed in this review seem to share a common element: prolonged increases in reactive oxygen species (ROS) production in diabetic cardiovascular cells. Intracellular hyperglycemia causes excessive ROS production. This activates nuclear poly(ADP-ribose) polymerase, which inhibits GAPDH, shunting early glycolytic intermediates into pathogenic signaling pathways. ROS and poly(ADP-ribose) polymerase also reduce sirtuin, PGC-1α, and AMP-activated protein kinase activity. These changes cause decreased mitochondrial biogenesis, increased ROS production, and disturbed circadian clock synchronization of glucose and lipid metabolism. Excessive ROS production also facilitates nuclear transport of proatherogenic transcription factors, increases transcription of the neutrophil enzyme initiating NETosis, peptidylarginine deiminase 4, and activates the NOD-like receptor family, pyrin domain-containing 3 inflammasome. Insulin resistance causes excessive cardiomyocyte ROS production by increasing fatty acid flux and oxidation. This stimulates overexpression of the nuclear receptor PPARα and nuclear translocation of forkhead box O 1, which cause cardiomyopathy. ROS also shift the balance between mitochondrial fusion and fission in favor of increased fission, reducing the metabolic capacity and efficiency of the mitochondrial electron transport chain and ATP synthesis. Mitochondrial oxidative stress also plays a central role in angiotensin II–induced gap junction remodeling and arrhythmogenesis. ROS contribute to sudden death in diabetics after myocardial infarction by increasing post-translational protein modifications, which cause increased ryanodine receptor phosphorylation and downregulation of sarco-endoplasmic reticulum Ca ++ -ATPase transcription. Increased ROS also depress autonomic ganglion synaptic transmission by oxidizing the nAch receptor α3 subunit, potentially contributing to the increased risk of fatal cardiac arrhythmias associated with diabetic cardiac autonomic neuropathy.
Donor Attrition At The Confirmatory Typing Stage Results In Poorer Transplant Options For Patients Of All Ethnicities
Authors: Robert N Lown, Steven GE Marsh, Helen Blake, Irina Evseeva, Stephen Mackinnon, Antonio Pagliuca, Michael N Potter, Nigel H. Russell, Charles Craddock, J. Alejandro Madrigal, Bronwen E. Shaw
Journal: Blood (2013)
The AKT Inhibitor MK2206 In Combination With Rituximab and Bendamustine Is Tolerable and Active In Relapsed Or Refractory Chronic Lymphocytic Leukemia: Results From a Phase 1 Study (NCCTG N1087 Alliance)
Authors: Wei Ding, Tait D Shanafelt, Clive S. Zent, Jose F. Leis, Betsy R. LaPlant, Timothy G. Call, Curtis A Hanson, Charles Erlichman, Thomas M. Habermann, Craig Reeder, Daniel Nikcevich, Deborah Bowen, Michael J. Conte, Justin Boysen, Charla Secreto, Connie Lesnick, Renee C. Tschumper, Diane F. Jelinek, Neil E. Kay
Journal: Blood (2013)
Validation of the European Practice Guidelines for the Use of Recombinant Activated Factor VII In Patients with Massive Bleeding
Authors: Prasad Pillai, Raghuveer Ranganathan, Rodina Vatanparast, Ravindar Reddimallu, Sarah Lantz, Lohith Bachegowda, Kristine Ward, Michael Styler, David Topolsky, Pamela Ann Crilley
Journal: Blood (2010)
Controversies in Breast Cancer Screening Strategies
Authors: Therese Bevers, Kirsten Bibbins-Domingo, Kevin C. Oeffinger, Mary Lou Smith
Journal: Journal of the National Comprehensive Cancer Network (2016)

A panel discussion on controversies in breast cancer screening held recently at the NCCN 21st Annual Conference included only a few controversies. Representatives of the U.S. Preventive Services Task Force, American Cancer Society, and NCCN disagreed primarily on 2 main areas: when to start screening (ages 40, 45, or 50 years) and frequency of screening (annual vs biennial). Panelists from these organizations presented the rationales for their respective recommendations.
Commentary: Patient's experience
Authors: Denise Prior, James Heathcote
Journal: BMJ (2004)

It's not often that I'm ill and I had no intention of saying anything, but Bill brought it up for me because I wouldn't.1 Nineteen years ago I'd gone to my previous GP with bad stomach pains, and he just told me that it was an ulcer, so I always put it down to an ulcer. We sometimes had the odd glass of wine together in the evening, but not every evening, so it wasn't alcohol causing my pain. My Nan had skin problems, and I've dealt with cystitis before, so it didn't seem worth mentioning.

I never really thought I was ill, but the palms of my hands and the soles of my feet were driving me round the twist. I could have used a wire brush on them. It was so deep down I was making myself bleed, but I was scared: “What if something happened to me—what would happen to Bill and the kids?” He wouldn't have coped.

When my GP phoned and asked me to have more blood tests done, I thought, “Why?” and Bill asked, “Why?” It's very unusual for a doctor to call, so you think, “Hang on, what's happening? It can't be much. I don't feel ill.” All sorts of things go round in your mind, but I didn't think cancer until I turned yellow. My son noticed it first in my eyes, but Bill was too scared to say anything. “Once you turn yellow,” he thought, “it's cancer, and once you're opened up, the cancer takes over your whole body.”

I wanted to be told the truth. Every doctor except my GP said, “It's very serious,” but they wouldn't say, “You're not going to die” or “It's an everyday operation.” I kept being told, “You've got the best surgeon” but they couldn't tell me, “You'll be alright.” Why couldn't they tell us before the operation that gall bladders are removed every day? It was very scary. It was out of our control—something that had to be done. Bill said, “I can always do something to make things right, but not this one.” One doctor spoke to both of us but looked between us and said, “This is a life threatening operation.” When Bill asked, “How life threatening is life threatening?” he said, “You're just a partner. You'll have to ask the surgeon.”

If I could have gone into hospital, had the operation, and come home afterwards it would have been OK. But because I had to stay there it destroyed me. It destroyed Bill. He couldn't handle it. He thought as soon as I went into hospital I would die, because before I met him he'd lost two premature babies. He said, “I'm not going to be the same after this. Something inside me has changed.” He scratched “HELP ME” across his tummy with a knife—that's how stressed he was.

Two weeks after I came home, Bill woke up feeling very tired and complained of heartburn. I called an ambulance, but before it arrived he had died from a heart attack. He was 38.
Mobility and Site of Production of Homograft Resistance Factor
Authors: Prehn, Richmond T., Main, Joan M.
Journal: JNCI Journal of the National Cancer Institute (1954)

Journal Article Mobility and Site of Production of Homograft Resistance Factor Get access Richmond T. Prehn, Richmond T. Prehn National Cancer Institute,3Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar Joan M. Main Joan M. Main National Cancer Institute,3Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 14, Issue 6, June 1954, Pages 1277–1280, https://doi.org/10.1093/jnci/14.6.1277 Published: 01 June 1954 Article history Received: 18 January 1954 Published: 01 June 1954
2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America
Authors: Clyde W. Yancy, Mariell Jessup, Biykem Bozkurt, Javed Butler, Donald E. Casey, Monica M. Colvin, Mark H. Drazner, Gerasimos Filippatos, Gregg C. Fonarow, Michael M. Givertz, Steven M. Hollenberg, JoAnn Lindenfeld, Frederick A. Masoudi, Patrick E. McBride, Pamela N. Peterson, Lynne Warner Stevenson, Cheryl Westlake
Journal: Circulation (2016)

◼ angioedema ◼ angiotensin-converting enzyme inhibitors ◼ angiotensin receptor blockers ◼ angiotensin receptor
Old problems, new models
Authors: Fiona Godlee
Journal: BMJ (2016)

With the NHS registering ever worse financial figures (doi:10.1136/bmj.i2904) and GPs seeking a ballot on industrial action (doi:10.1136/bmj.i2900), few could argue that things are going well with England’s health service. In such dire times we need people willing to speak truth to power (doi:10.1136/bmj.i2822), but we also need innovators with the energy and optimism to try new ways to do things.

You will have heard about the vanguards launched last year to develop new models of care as part of NHS …
EUTOS Score Predicts Optimal Response To Imatinib According To The Revised ELN Recommendations Better Than Sokal Score: A Study From The “Gruppo Triveneto LMC”
Authors: Mario Tiribelli, Massimiliano Bonifacio, Gianni Binotto, Elisabetta Calistri, Elena Maino, Roberta Zanotti, Antonio Branca, Marta Medeot, Gianpietro Semenzato, Giovanni Pizzolo, Renato Fanin
Journal: Blood (2013)
Immunity to Methylcholanthrene-Induced Sarcomas
Authors: Prehn, Richmond T., Main, Joan M.
Journal: JNCI Journal of the National Cancer Institute (1957)

Journal Article Immunity to Methylcholanthrene-Induced Sarcomas Get access Richmond T. Prehn, Richmond T. Prehn National Cancer Institute,4Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Joan M. Main Joan M. Main National Cancer Institute,4Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 18, Issue 6, June 1957, Pages 769–778, https://doi.org/10.1093/jnci/18.6.769 Published: 01 June 1957 Article history Received: 28 January 1957 Published: 01 June 1957
PTU-008 Is cranial to caudal approach a feasible technique for complete mesocolic excision (cme) in laparoscopic transverse colectomy?
Authors: T Shimada, M Tsuruta, H Hasegawa, K Okabayashi, T Kondo, M Matsuda, M Yahagi, Y Yoshikawa, Y Kitagawa
Journal: Gut (2015)

<h3>Introduction</h3> Laparoscopic transverse colectomy (LTC) is one of the most challenging techniques because the region of its mesentery and lymph node (LN) dissection is controversial. In addition, anatomical anomalies are often observed in the root of middle colic artery (MCA), which is surrounded by critical vessels such as superior mesenteric vein (SMV), splenic vein (SPV) and inferior mesenteric vein (IMV). We believe that cranial to caudal approach is one of the answers against how to overcome the hurdle of CME and LN dissection in LTC because it’s relatively easy to discern the border of transverse colon mesentery from pancreas. Another is to clarify the dominantly feeding vessel and establish the interest region of lymphandectomy by using CT colonography and angiography preoperatively. <h3>Method</h3> First, we open the bursa omentalis widely through the gastrocolic ligament, and subsequently mobilise and take down the hepatic and splenic flexure. The anterior lobe of transverse mesocolon is then dissected at the inferior border of the pancreas with the so-called cranial to caudal approach. Right gastroepiploic vein (RGEV) is a landmark to reach SMV. Exposing pancreatic head and second potion of duodenum and blunt dissection are also important to take down hepatic flexure of transverse colon and detach mesentery of transverse colon. In the process, we transect one or two accessory right colonic vein (ARCV). With skeletonizing SMV to proximal side, merging of SMV, SPV and IMV are uncovered. We think it’s critical to harvest the lymph nodes completely in the region enclosed by SMV, SPV and IMV where there should be generally the root of MCA. CT angiography is a robust support to comprehensively recognise the vessel anatomical anomalies and dissected region of colon mesentery. Continuously, it’s possible to dissect the root of ileocolic and right colic vessels with skeletonizing ventral surface of SMA and SMV in this approach. <h3>Results</h3> We herein present our practical laparoscopic transverse colectomy with LN dissection in video as attatched to demonstrate our concept and strategy in this field. <h3>Conclusion</h3> We think that cranial to caudal approach is a feasible technique for complete mesocolic excision in laparoscopic transverse colectomy. <h3>Disclosure of interest</h3> None Declared.
Lecithin in the treatment of mania: double-blind, placebo-controlled trials
Authors: B M Cohen, J F Lipinski, R I Altesman
Journal: American Journal of Psychiatry (1982)

The authors report double-blind, placebo-controlled trials of pure lecithin in the treatment of mania. As in preliminary trials, lecithin appeared to be nontoxic and effective. Improvement with lecithin was significantly greater than improvement with placebo in five of the six patients studied. The concurrent use of anticholinergic agents did not prevent the antimanic effect of lecithin. The authors discuss the possible mechanism of action of lecithin, including cholinergic and membrane-altering effects.
A Randomized Trial of Factor VIII and Neutralizing Antibodies in Hemophilia A
Authors: Flora Peyvandi, Pier M. Mannucci, Isabella Garagiola, Amal El-Beshlawy, Mohsen Elalfy, Vijay Ramanan, Peyman Eshghi, Suresh Hanagavadi, Ramabadran Varadarajan, Mehran Karimi, Mamta V. Manglani, Cecil Ross, Guy Young, Tulika Seth, Shashikant Apte, Dinesh M. Nayak, Elena Santagostino, Maria Elisa Mancuso, Adriana C. Sandoval Gonzalez, Johnny N. Mahlangu, Santiago Bonanad Boix, Monica Cerqueira, Nadia P. Ewing, Christoph Male, Tarek Owaidah, Veronica Soto Arellano, Nathan L. Kobrinsky, Suvankar Majumdar, Rosario Perez Garrido, Anupam Sachdeva, Mindy Simpson, Mathew Thomas, Ezio Zanon, Bulent Antmen, Kaan Kavakli, Marilyn J. Manco-Johnson, Monica Martinez, Esperanza Marzouka, Maria G. Mazzucconi, Daniela Neme, Angeles Palomo Bravo, Rogelio Paredes Aguilera, Alessandra Prezotti, Klaus Schmitt, Brian M. Wicklund, Bulent Zulfikar, Frits R. Rosendaal
Journal: New England Journal of Medicine (2016)

The development of neutralizing anti–factor VIII alloantibodies (inhibitors) in patients with severe hemophilia A may depend on the concentrate used for replacement therapy.
Abstract A21: The role of SOX4 in epithelial to mesenchymal transition in prostate cancer
Authors: Nitya V. Sharma, Soma Sannigrahi, YuHeng Lai, Carlos Moreno
Journal: Cancer Research (2016)

Abstract Prostate cancer remains the most commonly diagnosed cancer in U.S. males, and ranks second in mortality with over 28,000 deaths per year. Prostate cancer mortality is typically due to metastases, necessitating the understanding of how metastatic disease develops. One major step for cancer cells to metastasize and acquire migratory and invasive capabilities is the epithelial to mesenchymal transition (EMT). EMT encompasses vast molecular changes in gene expression, mediated by aberrant developmental signaling pathway activation, leading to the loss of cell-cell junctions and planar and apical-basal polarity, increased motility, and resistance to apoptosis and anoikis (cell death due to the detachment from the extracellular matrix). The sex determining region Y-box 4 (SOX4) gene is a developmental transcription factor that is over expressed in prostate cancer and plays a critical role in many developmental pathways inappropriately activated during EMT, such as the transforming growth factor (TGF-beta) and epidermal growth factor receptor (EGFR) signaling pathways. Our data suggest that concomitant treatment of TGF-beta and EGF induces SOX4, and initiates the EMT program in prostate epithelial cell lines. We also demonstrate that SOX4 over expression is sufficient to induce EMT in prostate epithelial cell lines. Currently, the molecular mechanisms that govern how SOX4 initiates EMT via transcriptional activation of target genes are poorly understood. We identified candidate SOX4 targets using the Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNE) on 9755 Pan Cancer samples from The Cancer Genome Atlas (TCGA). Gene ontology analysis of the top 1000 candidate SOX4 targets revealed genes that were enriched for epigenetic processes such as chromatin modification and DNA methylation. One putative target gene, PCAF, is a subunit of a large histone acetyltransferase (HAT) complex. Interestingly, our preliminary data also suggest that SOX4 interacts not only with PCAF, but also with TRRAP, another subunit of the PCAF HAT complex. These data suggest that SOX4 may induce and recruit the PCAF/TRRAP HAT complex in order to transcriptionally activate downstream targets to initiate the EMT program. Citation Format: Nitya V. Sharma, Soma Sannigrahi, YuHeng Lai, Carlos Moreno. The role of SOX4 in epithelial to mesenchymal transition in prostate cancer. [abstract]. In: Proceedings of the AACR Special Conference on Chromatin and Epigenetics in Cancer; Sep 24-27, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2016;76(2 Suppl):Abstract nr A21.
Ethics and Nonsense
Authors: Daniel S. Greenberg
Journal: New England Journal of Medicine (1974)

Ethics and NonsenseAt the risk of appearing both dense and perverse, I timorously suggest that perhaps the most inflated nonissue currently absorbing time and energy in the health community and its governmental command posts is that loose amalgamation of anxieties and passions that comes under the banner of medical ethics.It is purposeless to say, "Don't get me wrong," for to question concern with medical ethics today is akin to being unenthusiastic about mother's milk, solar energy, and election finance reform. I'm for all of them, and I'm for evolving and enforcing the highest standards of medical ethics. But . . .
Abstract P3-01-08: Sentinel lymph node biopsy alone after neoadjuvant chemotherapy in patients with cytologically proven node-positive breast cancer
Authors: S Park, JM Ryu, H-J Paik, HW Yi, SY Bae, SK Lee, WH Kil, SW Kim, JE Lee, SJ Nam
Journal: Cancer Research (2016)

Abstract Background The purpose of this study was to identify the feasibility and accuracy of sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) in patients with axillary lymph node (ALN) metastasis at diagnosis. Methods This is a retrospective study of 332 patients who were diagnosed with invasive breast cancer and ALN metastasis and treated with NAC followed by curative surgery at Samsung Medical Center between January 2007 and December 2013. Patients were classified into five groups according to surgical procedure for the ALNs and pathologic results; group 1, patients with negative SLN status and no further dissection was performed; group 2, patients with negative SLN status undergoing further axillary lymph node dissection (ALND); group 3, patients with positive or undetected SLNs undergoing further ALND; group 4, patients without residual axillary metastasis undergoing complete ALND; and group 5, patients with pathologic nodal positive disease undergoing ALND. Results Sentinel lymph nodes identification rate after NAC was 99.1% and false negative rate was 24.1%. The median number of retrieved SLNs was 4 (range, 1–10). There was no difference in the overall survival among the groups (p=0.06). There was no significant difference in the disease-free survival rate between the SLNB only and complete ALN dissection groups who revealed a pathologic complete node response (79.6% versus 80.5%) and the rate of axillary recurrence demonstrated no significant differences among the groups. (p=0.225) There was a statistical difference of recurrence between group 1 versus 2, and group 1 versus 4 in hormone receptor-negative patients. (p=0.027) Conclusion SLNB after NAC in breast cancer patients with initial ALN metastasis may help identify downstaging to negative nodal status and thereby reduce the surgical morbidity by avoiding standard ALN dissection. Citation Format: Park S, Ryu JM, Paik H-J, Yi HW, Bae SY, Lee SK, Kil WH, Kim SW, Lee JE, Nam SJ. Sentinel lymph node biopsy alone after neoadjuvant chemotherapy in patients with cytologically proven node-positive breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-01-08.
A Novel Therapy Of HLA-Mismatched Sibling Donor Combined With Third-Party Single Cord Blood Cell Transplantation In Patients With Hematologic MalignanciesÂFimproved Outcome Compared To Conventional Transplantation
Authors: Aining Sun, Shuo Yang, Jun Wang, Xiao Ma, Weiyang Li, Xiaohui Hu, Huiying Qiu, Wu Depei
Journal: Blood (2013)
Asthma
Authors: Robert A. Goldstein
Journal: Annals of Internal Medicine (1994)

Asthma is characterized by inflammation, reversible airway obstruction, and increased airway responsiveness to various stimuli.It has received wide public attention in recent years because of increasing morbidity and deaths particularly among black persons. The important role of inflammation in the immunopathogenesis of asthma has led to a newer therapeutic approach directed at interrupting this inflammatory process. Among immune regulatory pathways involved in asthma pathogenesis, two lymphokines appear to be particularly important in controlling IgE production. Interleukin-4 is required for IgE production; without it, IgE production is inhibited. Interferon-γ can diminish cell priming for interleukin-4 production. Thus, the interplay of these two cytokines will determine whether cells that can make interleukin-4 will be produced and, therefore, whether IgE will be produced in response to allergic stimuli. Further, in response to appropriate stimuli, mast cells and eosinophils are attracted to airways and release cytokines, lipid mediators, and preformed substances that cause inflammation. Modern asthma treatment is directed at interrupting this inflammatory process and places a much greater emphasis on use of anti-inflammatory agents, such as aerosolized or parenteral corticosteroids, and on nonsteroidal anti-inflammatory agents, such as cromolyn sodium and nedocromil sodium. Research advances without therapeutic application, however, limit success. Projects such as the National Institute of Allergy and Infectious Diseases' National Cooperative Inner-City Asthma Study, which is directed toward underserved populations, are intended to identify more clearly the factors responsible for increasing morbidity and to develop appropriate therapeutic interventions.
Institutional Enrollment and Survival Among NSCLC Patients Receiving Chemoradiation: NRG Oncology Radiation Therapy Oncology Group (RTOG) 0617
Authors: Bree R Eaton, Stephanie L Pugh, Jeffrey D Bradley, Greg Masters, Vivek S Kavadi, Samir Narayan, Lucien Nedzi, Cliff Robinson, Raymond B Wynn, Christopher Koprowski, Douglas W Johnson, Joanne Meng, Walter J Curran
Journal: JNCI Journal of the National Cancer Institute (2016)

Background: The purpose of this analysis is to evaluate the effect of institutional accrual volume on clinical outcomes among patients receiving chemoradiation for locally advanced non–small cell lung cancer (LA-NSCLC) on a phase III trial.