tbuckley/cabot-search huggingface dataset:
The genomics of Young Lung Cancer Study.
Authors: Barbara J. Gitlitz, Deborah Morosini, Alicia L. Sable-Hunt, Bonnie J. Addario, Mark Byron Jennings, Stacy L. Mach, Geoffrey R. Oxnard
Journal: Journal of Clinical Oncology (2015)

TPS11110 Background: Primary lung cancer is increasingly understood as a heterogeneous disease made up of genomically defined subtypes requiring distinct treatment strategies. We hypothesize young age at diagnosis ( < 40 years) is a clinical characteristic associated with an increased chance for a targetable genomic alteration. This ALCMI study will prospectively characterize the somatic and germline genomics of young lung cancer. Our goals are to identify a genomically enriched subtype of lung cancer, facilitate delivery of targeted therapy and lay groundwork for further studies of heritable and environmental lung cancer risk factors. Methods: Accrual opened 07/2014. Patients are eligible if they were diagnosed with bronchogenic lung cancer less than age 40. A study specific website allows for virtual consenting so patients can participate remotely from anywhere in the country or the world; and use social media to share our trial. We have an integrated data and biorepository (Open Medicine Institute) that allows for seamless communication and completion of study activities like remote consenting, storage and routing of blood and tumor specimens. We have defined 7 genomic alterations of interest based on the Lung Cancer Mutational Consortium (LCMC) (EGFR, KRAS, HER2, BRAF, ALK, ROS1, RET). On study subjects without a known genotype will undergo comprehensive genomic profiling with the FoundationOne test to ensure that all of these genes have been tested. Subjects with advanced adenocarcinoma who are wild-type for all 7 genes will receive additional genomic profiling using the FoundationOne Heme test with the goal of identifying novel oncogenic drivers. Additional investigational genomics will include blood for germline analysis. All on study genomic analysis is at no cost to the participant. We aim to demonstrate that the prevalence of targetable genomic alterations will be greater in our population compared to the LCMC and have powered our study to show an increase from 35% to 50%; and an improvement in use of targeted therapy from 22% to 40%. The trial is currently accruing (NCT02273336) https://www.openmednet.org/site/alcmi-goyl. (Supported by grants from The Bonnie J. Addario Lung Cancer Foundation, Peter Barker Foundation, Genentech and Schmidt Legacy Foundation.) Clinical trial information: NCT02273336.
BMA Annual Representative Meeting, Belfast, 26 June to 29 June: BMA leaders accused of weak opposition to the government
Authors: Annabel Ferriman
Journal: BMJ (2006)

The BMA leadership was accused at its annual meeting this week of having failed patients, doctors, and the country by not actively opposing the current wave of organisational and financial reforms of the health service.

The representatives voted by 58% to 42% in support of a motion saying that the current policy of exposing defects in policy was not powerful enough and insisted that it be replaced by a policy of active opposition and proper scrutiny.

Fay Wilson, a GP and a member of the BMA council, said that doctors were frustrated and disappointed at the ineffectiveness of the BMA policy. “It is all very well having private meetings with the government and hoping they will see the light, but we need a higher profile. We need action as well as words.”

Dr Wilson said she would like to see the BMA put as much effort into defending the NHS as it had into fighting tobacco use and getting smoking banned in public enclosed spaces.

“If we had drawn a line in the sand a few years ago we might not be having to put up a breakwater now.”

Hamish Brown, a consultant surgeon and a member of the BMA's consultants' committee, said: “The unchallenging nature of the BMA response [to the government's policy] has painted us as supporting the reforms.

Mr Brown said members had been telling the BMA leadership for years what the consequence of the reforms was going to be. “These reforms will be bad for patients, bad for taxpayers, and bad for doctors.”

James Johnson, chairman of the BMA's council, replied that the BMA had no choice but to talk to the government. “We have spent the best part of the last two years telling the government in great detail what is wrong with their policies.”

The BMA would be putting its views to the government at next week's summit meeting with the health secretary, Patricia Hewitt.
Refining and expanding the proposal of an inherence heuristic in human understanding
Authors: Andrei Cimpian, Erika Salomon
Journal: Behavioral and Brain Sciences (2014)

Abstract The inherence heuristic is a cognitive process that supplies quick and effortless explanations for a wide variety of observations. Due in part to biases in memory retrieval, this heuristic tends to overproduce explanations that appeal to the inherent features of the entities in the observations being explained (hence the heuristic's name). In this response, we use the commentators' input to clarify, refine, and expand the inherence heuristic model. The end result is a piece that complements the target article, amplifying its theoretical contribution.
Substitution of blood coagulation factor X-binding to Ad5 by position-specific PEGylation: Preventing vector clearance and preserving infectivity
Authors: L. Krutzke, J.M. Prill, T. Engler, C.Q. Schmidt, Z. Xu, A.P. Byrnes, T. Simmet, F. Kreppel
Journal: Journal of Controlled Release (2016)

The biodistribution of adenovirus type 5 (Ad5) vector particles is heavily influenced by interaction of the particles with plasma proteins, including coagulation factor X (FX), which binds specifically to the major Ad5 capsid protein hexon. FX mediates hepatocyte transduction by intravenously-injected Ad5 vectors and shields vector particles from neutralization by natural antibodies and complement. In mice, mutant Ad5 vectors that are ablated for FX-binding become detargeted from hepatocytes, which is desirable for certain applications, but unfortunately such FX-nonbinding vectors also become sensitive to neutralization by mouse plasma proteins. To improve the properties of Ad5 vectors for systemic delivery, we developed a strategy to replace the natural FX shield by a site-specific chemical polyethylene glycol shield. Coupling of polyethylene glycol to a specific site in hexon hypervariable region 1 yielded vector particles that were protected from neutralization by natural antibodies and complement although they were unable to bind FX. These vector particles evaded macrophages in vitro and showed significantly improved pharmacokinetics and hepatocyte transduction in vivo. Thus, site-specific shielding of Ad5 vectors with polyethylene glycol rendered vectors FX-independent and greatly improved their properties for systemic gene therapy.
OC-061 Change in size of hepatic colorectal metastases after completion of chemotherapy is greater than during treatment, but doesn’t influence disease-free survival after resection
Authors: M Wiggans, E Lim, G Shahtahmassebi, S Aroori, M Bowles, C Briggs, D Stell
Journal: Gut (2015)

<h3>Introduction</h3> The aim of this study was to assess the change in size of colorectal liver metastases between post-chemotherapy imaging and liver resection and to measure potential associations of this change with disease-free survival. <h3>Method</h3> Analysis of a prospectively maintained database of patients undergoing liver resection for colorectal liver metastases between 2005 and 2012 was undertaken. Response to chemotherapy was assessed by RECIST criteria. Change in tumour size between completion of chemotherapy and liver resection was measured by comparing the maximum diameter of lesions determined by post-chemotherapy imaging and those determined by examination of the resected specimen. <h3>Results</h3> In 146 patients the median interval between post-chemotherapy imaging and liver resection was 10.4 weeks (7.1–17.6 weeks). During this period tumour diameter increased in 102 patients (69.9%) and decreased in 37 (25.3%) with a median change of +2.3% per week (–19.4 to +1624%). Tumour behaviour after completion of treatment was not associated with disease-free survival in patients who initially responded to chemotherapy (P = 0.591) or those with stable disease (P = 0.436). Among patients with progressive disease after completion of chemotherapy the median disease-free survival of patients who initially responded (26 months) was longer than in those with stable disease (7 months) (P = 0.002), but there was no association between the rate of increase in size and disease-free survival (P = 0.406). <h3>Conclusion</h3> Change in tumour size after completion of chemotherapy is variable and can be rapid, especially in patients who initially responded to treatment. It does not however appear to affect outcome and should not be considered an adverse factor when counselling patients. <h3>Disclosure of interest</h3> None Declared.
Comprehensive drug programs: the Dade County example
Authors: R S Weppner, D C McBride
Journal: American Journal of Psychiatry (1975)

The authors present data from a survey of four methadone maintenance programs, five outpatient clinics, six nonresidential facilities, and nine therapeutic communities affiliated with the Dade County Comprehensive Drug Program. The treatment population included more blacks but fewer Latins than the general county population. Primary drugs of abuse were narcotics in methadone clinics and "softer" drugs in outpatient and nonresidential facilities. Most patients were either self- or court referrals. Direct per patient costs, which were lowest in the outpatient clinics, averaged $1,041. The authors suggest that their data may aid other comprehensive drug treatment programs in establishing guidelines.
IKBKE Is a Substrate of EGFR and a Therapeutic Target in Non–Small Cell Lung Cancer with Activating Mutations of EGFR
Authors: Sridevi Challa, Jian-Ping Guo, Xiaowen Ding, Cheng-Xiong Xu, Yajuan Li, Donghwa Kim, Matthew A. Smith, Douglas W. Cress, Domenico Coppola, Eric B. Haura, Jin Q. Cheng
Journal: Cancer Research (2016)

Non-small cell lung cancers (NSCLC) marked by EGFR mutations tend to develop resistance to therapeutic EGFR inhibitors, often due to secondary mutation EGFR(T790M) but also other mechanisms. Here we report support for a rationale to target IKBKE, an IκB kinase family member that activates the AKT and NF-κB pathways, as one strategy to address NSCLC resistant to EGFR inhibitors. While wild-type and mutant EGFR directly interacted with IKBKE, only mutant EGFR phosphorylated IKBKE on residues Y153 and Y179. The unphosphorylatable mutant IKBKE-Y153F/Y179-F that lost kinase activity failed to activate AKT and inhibited EGFR signaling. In clinical specimens of NSCLC with activating mutations of EGFR, we observed elevated levels of phospho-Y153 IKBKE. IKBKE ablation with shRNA or small-molecule inhibitor amlexanox selectively inhibited the viability of NSCLC cells with EGFR mutations in vitro In parallel, we found that these treatments activated the MAPK pathway due to attenuation of an IKBKE feedback mechanism. In vivo studies revealed that combining amlexanox with MEK inhibitor AZD6244 significantly inhibited the xenograft tumor growth of NSCLC cells harboring activating EGFR mutations, including EGFR(T790M) Overall, our findings define IKBKE as a direct effector target of EGFR and provide a therapeutic rationale to target IKBKE as a strategy to eradicate EGFR-TKI-resistant NSCLC cells. Cancer Res; 76(15); 4418-29. ©2016 AACR.
Case 36-1972
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, H. Richard Tyler, Peter C. Johnson
Journal: New England Journal of Medicine (1972)

Presentation of CaseA 64-year-old man was admitted to the hospital because of unresponsiveness.He had been well until 18 months previously, when several episodes of chest pain occurred, and cardiac enlargement was found. Nine months later epistaxes developed; a physician found hypertension and prescribed hydrochlorothiazide and reserpine. Five months before entry his gait became short-stepped and shuffling, and he occasionally fell. Thereafter, gradual intellectual deterioration was noticed by his family. His sentences were poorly articulated and rambling. There was occasional urinary incontinence, and he had difficulty using the left hand. On the day of admission he awoke feeling unwell . . .
Implementing endoscopic optical diagnosis into practice: a green light at the horizon
Authors: Roy Soetikno, Doreen Koay, Tonya Kaltenbach
Journal: Endoscopy (2015)

Endoscopic optical diagnosis (EOD), which is a major aim of image-enhanced endoscopy, refers to endoscopic interpretation to make histologic diagnosis – using objective and validated criteria [1]. The use of objective and validated criteria is important, as it will allow EOD to be practiced at the same level as pathologic diagnosis. The thresholds that must be met in order for EOD to be considered on a par with pathology have been defined a priori by the American and European endoscopy societies [2] [3].
Suppressive Effects of Insulin on Tumor Necrosis Factor–Dependent Early Osteoarthritic Changes Associated With Obesity and Type 2 Diabetes Mellitus
Authors: Daisuke Hamada, Robert Maynard, Eric Schott, Christopher J. Drinkwater, John P. Ketz, Stephen L. Kates, Jennifer H. Jonason, Matthew J. Hilton, Michael J. Zuscik, Robert A. Mooney
Journal: Arthritis & Rheumatology (2015)

Objective Obesity is a state of chronic inflammation that is associated with insulin resistance and type 2 diabetes mellitus (DM), as well as an increased risk of osteoarthritis (OA). This study was undertaken to define the links between obesity‐associated inflammation, insulin resistance, and OA, by testing the hypotheses that 1) tumor necrosis factor (TNF) is critical in mediating these pathologic changes in OA, and 2) insulin has direct effects on the synovial joint that are compromised by insulin resistance. Methods The effects of TNF and insulin on catabolic gene expression were determined in fibroblast‐like synoviocytes (FLS) isolated from human OA synovium. Synovial TNF expression and OA progression were examined in 2 mouse models, high‐fat (HF) diet–fed obese mice with type 2 DM and TNF‐knockout mice. Insulin resistance was investigated in synovium from patients with type 2 DM. Results Insulin receptors (IRs) were abundant in both mouse and human synovial membranes. Human OA FLS were insulin responsive, as indicated by the dose‐dependent phosphorylation of IRs and Akt. In cultures of human OA FLS with exogenous TNF, the expression and release of MMP1 , MMP13, and ADAMTS4 by FLS were markedly increased, whereas after treatment with insulin, these effects were selectively inhibited by &gt;50%. The expression of TNF and its abundance in the synovium were elevated in samples from obese mice with type 2 DM. In TNF‐knockout mice, increases in osteophyte formation and synovial hyperplasia associated with the HF diet were blunted. The synovium from OA patients with type 2 DM contained markedly more macrophages and showed elevated TNF levels as compared to the synovium from OA patients without diabetes. Moreover, insulin‐dependent phosphorylation of IRs and Akt was blunted in cultures of OA FLS from patients with type 2 DM. Conclusion TNF appears to be involved in mediating the advanced progression of OA seen in type 2 DM. While insulin plays a protective, antiinflammatory role in the synovium, insulin resistance in patients with type 2 DM may impair this protective effect and promote the progression of OA.
Conduct disorder and its synonyms: diagnoses of dubious validity and usefulness
Authors: D O Lewis, M Lewis, L Unger, C Goldman
Journal: American Journal of Psychiatry (1984)

Psychiatrically hospitalized adolescents from city and voluntary services who had been diagnosed as having conduct disorder were compared with psychiatrically hospitalized adolescents who had never been so diagnosed. There were no significant symptomatic differences. The major factor distinguishing adolescents ever diagnosed as having conduct disorder was violence, regardless of other symptoms. The most common discharge diagnosis of those who had formerly been diagnosed as having conduct disorder was schizophrenia. However, even violence did not distinguish those discharged with a diagnosis of conduct disorder from those whose diagnoses were subsequently changed. With its focus on manifest behaviors and its lack of clear exclusionary criteria, the conduct disorder diagnosis obfuscates other potentially treatable neuropsychiatric disorders.
Virus of Avian Erythromyeloblastic Leukosis. IX. Antigenic Constitution and Immunologic Characterization&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: Edward A. Eckert, D. G. Sharp, Dorothy Beard, Irving Green, J. W. Beard
Journal: JNCI Journal of the National Cancer Institute (1955)

Virus of Avian Erythromyeloblastic Leukosis. IX. Antigenic Constitution and Immunologic Characterization Get access Edward A. Eckert, Edward A. Eckert Department of Surgery, Duke University School of Medicine, Durham, N. C. Search for other works by this author on: Oxford Academic PubMed Google Scholar D. G. Sharp, D. G. Sharp Department of Surgery, Duke University School of Medicine, Durham, N. C. Search for other works by this author on: Oxford Academic PubMed Google Scholar Dorothy Beard, Dorothy Beard Department of Surgery, Duke University School of Medicine, Durham, N. C. Search for other works by this author on: Oxford Academic PubMed Google Scholar Irving Green, Irving Green Department of Surgery, Duke University School of Medicine, Durham, N. C. Search for other works by this author on: Oxford Academic PubMed Google Scholar J. W. Beard J. W. Beard Department of Surgery, Duke University School of Medicine, Durham, N. C. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 16, Issue 3, December 1955, Pages 593–643, https://doi.org/10.1093/jnci/16.3.593 Published: 01 December 1955 Article history Received: 09 May 1955 Published: 01 December 1955
What would the NHS look like if the UK left the EU?
Authors: Anne Gulland
Journal: BMJ (2016)

Anne Gulland asks whether a post-Brexit NHS would look any different

The Conservative MP Boris Johnson has been touring the United Kingdom with his fellow Vote Leavers in a battle bus emblazoned with the words, “We send the EU £350m a week. Let’s fund our NHS instead.” Technically, that figure is correct, says the Institute for Fiscal Studies, but it does not take into account the rebate the UK receives from the European Union or money that doesn’t go through government departments, such as EU grants to universities. The UK’s net contribution to the EU will average £8bn a year over the next five years, the institute has calculated.1

Brexit campaigners have also pointed to the potential drain on NHS resources presented by the large numbers of European migrants who may come to the UK in coming years, from Turkey, Macedonia, Albania, Serbia, and Montenegro, all of which want to join the EU.

But NHS England’s chief executive, Simon Stevens, has sounded the alarm over the potential of …
Dose-Response Relations in Experimental Transmission of Avian Erythromyeloblastic Leukosis. II. Host-Response to Whole Blood and to Washed Primitive Cells&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: Edward A. Eckert, Dorothy Beard, J. W. Beard, B. R. Burmester
Journal: JNCI Journal of the National Cancer Institute (1953)

Dose-Response Relations in Experimental Transmission of Avian Erythromyeloblastic Leukosis. II. Host-Response to Whole Blood and to Washed Primitive Cells Edward A. Eckert, Edward A. Eckert Search for other works by this author on: Oxford Academic PubMed Google Scholar Dorothy Beard, Dorothy Beard Search for other works by this author on: Oxford Academic PubMed Google Scholar J. W. Beard, J. W. Beard Department of Surgery, Duke University School of Medicine, Durham, N. C. Search for other works by this author on: Oxford Academic PubMed Google Scholar B. R. Burmester B. R. Burmester Regional Poultry Research Laboratory, East Lansing, Mich. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 13, Issue 5, April 1953, Pages 1167–1184, https://doi.org/10.1093/jnci/13.5.1167 Published: 01 April 1953 Article history Received: 15 October 1952 Published: 01 April 1953
Tumor necrosis factor-alpha (TNF-alpha) potently enhances in vitro macrophage production from primitive murine hematopoietic progenitor cells in combination with stem cell factor and interleukin-7: novel stimulatory role of p55 TNF receptors
Authors: C Fahlman, FW Jacobsen, OP Veiby, IK McNiece, HK Blomhoff, SE Jacobsen
Journal: Blood (1994)
SP0049 Evaluating the Work of a Patient Organisation: Results of a Member and Non-Member Survey of the Deutsche Rheuma-Liga
Authors: J. Clausen
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Introduction</h3> The Deutsche Rheuma-Liga (DRL) is a patient organisation with about 280 000 members. Its aim is the improvement of the living situation of the approximately 20 million people in Germany that suffer from rheumatic diseases. <h3>Objective</h3> In order to evaluate strengths and weaknesses of the DRL, a survey amongst members and non-members suffering from rheumatic diseases was conducted. <h3>Methods</h3> Members of the DRL were sent questionnaires by mail between November 2013 and January 2014. Non-members were recruited by an external institute via advertisements and/or questionnaires placed in medical practices during the same time period. <h3>Results</h3> 325 (members [M]; 76% female, 24% male) and 200 (non-members [NM]; 70% female, 30% male) questionnaires were evaluated. The most frequent diagnosis was osteoarthritis (M: 62%, NM: 76%), followed by rheumatoid arthritis (M: 39%, NM: 22%), fibromyalgia (M: 23%, NM: 11%) and osteoporosis (M: 19%, NM: 27%). A significantly higher percentage of non-members (18%) compared to members (6%) rated the severity of their disease as mild. The main source of disease-related information for non-members is the general practitioner (65%), followed by orthopaedic specialists (61%), whereas for members, the Deutsche Rheuma-Liga is just as important (64%) as the general practitioner (66%). The main reason that patients apply for membership is the availability of special training programs offered by the DRL (76%). In total, 74% of the members assessed the services of the DRL as good or very good (20% neutral). The main reasons that patients do not become a member of the DRL are the self-assessed mildness of the disease (40%) and a lack of knowledge about the existence of the DRL (22%). <h3>Conclusion</h3> The DRL is perceived very well by its members. The main future goal of the DRL must be to intensify collaboration with general practitioners and orthopaedic specialists in order to raise its profile and, by this, to guarantee best possible, up-to-date treatment for patients. In line with this, the DRL must disseminate information among non-members that prophylactic training programs are particularly important at a mild stage of symptom severity, in order to prevent aggravation of their disease. <h3>Disclosure of Interest</h3> None declared
A 3D-printed local drug delivery patch for pancreatic cancer growth suppression
Authors: Hee-Gyeong Yi, Yeong-Jin Choi, Kyung Shin Kang, Jung Min Hong, Ruby Gupta Pati, Moon Nyeo Park, In Kyong Shim, Chan Mi Lee, Song Cheol Kim, Dong-Woo Cho
Journal: Journal of Controlled Release (2016)