tbuckley/cabot-search huggingface dataset:
Phase II trial of dasatinib in triple-negative breast cancer: results of study CA180059.
Authors: RS Finn, C Bengala, N Ibrahim, LC Strauss, J Fairchild, O Sy, H Roche, J Sparano, LJ Goldstein
Journal: Cancer Research (2009)

Abstract Abstract #3118 Background: Dasatinib (SprycelR; BMS-354825) is a potent orally-available inhibitor of Src-family kinases and other kinases with anti-proliferative, anti-osteoclastic and anti-metastatic activity demonstrated pre-clinically. Expression profiling suggested that basal-like cancers may be preferentially sensitive to dasatinib. Methods: A Phase II single-agent trial of dasatinib, using a continuous schedule, was performed in patients with advanced triple-negative (as proxy for basal-like) breast cancers. Subjects were required to have measurable locally-advanced or metastatic triple-negative (ER/PR-negative, Her2-normal) disease and prior anthracycline and/or taxane therapy. A 2-stage Gehan design was adopted, with RECIST-defined response as primary endpoint; subjects discontinued for toxicity were considered non-responders. The original dasatinib dose of 100 mg BID (n=21) was reduced to 70 mg BID (n=23) to improve tolerability. Biomarkers were analyzed in tumor and plasma samples obtained for PK analysis. Results: From 12/06 through 12/07, 44 subjects were treated at 14 institutions: median age 55 yrs, median time from diagnosis 30 mo, prior therapy for advanced disease in 29 (66%). Of 43 response-evaluable subjects, 7 discontinued for toxicity prior to on-study assessment. Of 36 subjects with radiographic assessment, there were 2 confirmed PR [1 continues &amp;gt;1 year + 1 discontinued for intolerance at week 16] plus 2 SD lasting &amp;gt;16 weeks. Four additional subjects had transient clinical benefit reflected by improvement in bone pain (anecdotal) or short-term tumor shrinkage (reductions of 11 - 29%). Tolerability was improved at a dose of 70 mg compared with 100 mg BID. In preliminary analysis, fewer subjects experienced any serious adverse event (13% at 70 mg BID vs 48% at 100 mg BID), fewer reported Grade 3 toxicity, including gastrointestinal (10% vs 26%), pleural effusion (4% vs 9%), generalized edema (0% vs 9%) or pericardial effusion (0% vs 9%), and fewer had dasatinib dose reduction (24% vs 61%). Fatigue, myalgia/arthralgia and headache were comparable at the two doses. No Grade 4 drug-related events occurred. Grade 3-4 abnormal laboratory values were uncommon. Biomarker and PK data will be presented. Conclusions: Modest but encouraging single-agent activity was observed with dasatinib in patients with advanced triple-negative breast cancers, with clinical benefit rate of 9.3% (4/43). Future studies are warranted to address optimal dose and schedule of dasatinib in combination with chemotherapy for this challenging tumor type. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3118.
The effects of cross-linked thermo-responsive PNIPAAm-based hydrogel injection on retinal function
Authors: Sanja B. Turturro, Micah J. Guthrie, Alyssa A. Appel, Pawel W. Drapala, Eric M. Brey, Victor H. Pérez-Luna, William F. Mieler, Jennifer J. Kang-Mieler
Journal: Biomaterials (2011)
Typhoid Fever in Camps During the War with Spain.
Authors: H. V. Boynton
Journal: JAMA (1900)

<h3>Sir:</h3> —I am directed by the commanding officer, Col. E. L. Huggins, Eighth Vol. Inf., to reply to your inquiry with reference to the sick report of the troops stationed at this post, and in compliance with these directions, I have the honor to state that the average number of troops from Oct. 9, 1898 (date of arrival), until Jan. 20, 1899, was 1150; and since the latter date, 950. During the 111 days of the present encampment, there were treated in the post hospital a total of 118 separate cases, of which 31 were measles, 7 gunshot wounds, 40 were due to the imprudence of the patients, and the remainder were nearly all due to grip. Since the first day of the organization of the first company of this regiment—June 1, 1898—there has not occurred a single death from disease in this regiment, nor among the troops attached to
Abstract 395: Farnesyl diphosphate farnesyltransferase induces metastasis via upregulating secreted phosphoprotein 1 in non-small cell lung cancer.
Authors: Yi-Fang Yang, Yi-Hua Jan, Michael Hsiao
Journal: Cancer Research (2013)

Abstract Identifying cancer progression associated genes that predicting patient outcome might provide opportunities for developing better therapeutic strategies for lung cancer patients. In the present study, we investigated whether farnesyl diphosphate farnesyltransferase (FDFT1), an enzyme of mevalonate pathway, is a potential biomarker of lung cancer metastasis. We further investigated its prognostic value and functional role in lung cancer invasion and metastasis. Our results by immunohistochemistry (IHC) analysis showed the expression of FDFT1 was significantly higher in tumors compared to normal lung tissues. Overexpression of FDFT1 was significantly associated with tumor size (P &amp;lt; 0.001), advanced tumor stage (P &amp;lt;0.001), lymph node metastasis (P = 0.02), distal metastasis (P = 0.043), and poor prognosis (P &amp;lt;0.001). Loss of FDFT1 expression significantly suppressed invasion and migration potential of lung cancer cell lines, whereas FDFT1 overexpression promoted invasion and migration in vitro and in vivo. Microarray analysis further identified secreted phosphoprotein 1 (SPP1) as an important mediator for FDFT1-induced invasion and migration. Furthermore, patients with high FDFT1 and high SPP1 expression showed dismal outcomes as compared to patients with low FDFT1 and low SPP1 expression with good prognosis. In conclusion, we identified the FDFT1 in this study as a new lung cancer progression biomarker that is associated poor prognosis and its overexpression resulted in enhanced tumor invasion and metastasis through upregulation of SPP1. Our findings may implicate the possibility of targeting FDFT1 as a novel therapeutic strategy to inhibit lung cancer metastasis. Citation Format: Yi-Fang Yang, Yi-Hua Jan, Michael Hsiao. Farnesyl diphosphate farnesyltransferase induces metastasis via upregulating secreted phosphoprotein 1 in non-small cell lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 395. doi:10.1158/1538-7445.AM2013-395 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
The Endoscopic Spectrum of Primary Non-Hodgkin's Lymphoma of the Stomach
Authors: B. G. Taal, F. C. A. den Hartog Jager, G. N. J. Tytgat
Journal: Endoscopy (1987)

Thirty-one consecutive patients with primary non-Hodgkin's lymphoma of the stomach were studied to outline the spectrum of endoscopic abnormalities. The 17 men and 14 women had a median age of 65 years. There were 22 patients in stage I and 9 in stage II. Three endoscopic patterns were recognized: diffuse infiltration (9), ulceration (9) and polypoid lesions (13). There was no apparent correlation between the endoscopic appearance and the grading or subtype of the malignancy. Local recurrence did not occur once complete remission was obtained. The disease-free 5-year survival rate was 45%. Recognition of these endoscopic patterns may lead to earlier detection and, hopefully, improved survival.
Alterations in intravascular volume affect the relation between right ventricular diastolic collapse and the hemodynamic severity of cardiac tamponade
Authors: H. Sidney Klopfenstein, Terrence L. Cogswell, Gregory A. Bernath, L. Samuel Wann, R. Keith Tipton, Raymond G. Hoffmann, Harold L. Brooks, Dennis J. Janzer, Donna M. Peterson
Journal: Journal of the American College of Cardiology (1985)
Abstract 2803: The role of the sarcosine pathway in prostate cancer progression
Authors: Amjad P. Khan, Thekkelnaycke M. Rajendiran, Bushra Ateeq, Irfan Asangani, Anastasia K. Yocum, Rohit Mehra, Arun Sreekumar, Arul M. Chinnaiyan
Journal: Cancer Research (2011)

Abstract Differential metabolomic alterations occur during prostate cancer progression. Exploring the metabolome of prostate cancer progression, may lead to the identification of critical biomarkers for cancer invasion and disease aggressiveness. Recently, we have identified sarcosine, an N-methyl derivative of the amino acid glycine, as a key metabolite increased most robustly in metastatic prostate cancer and detectable in the urine of men with organ-confined disease (Sreekumar et al., Nature, 2009). Here, we examined if the proximal regulatory enzymes of sarcosine, glycine-N-methyl transferase (GNMT), sarcosine dehydrogenase (SARDH) and pipecolic acid oxidase (PIPOX), play a functional role in prostate cancer progression. By tissue microarray analysis, we observed that GNMT protein levels are strongly associated with prostate cancer aggressiveness. Here, we demonstrate that stable knockdown of GNMT inhibits cell proliferation, induces apoptosis, attenuates cell invasion in Matrigel coated transwells, and blocks the anchorage-independent growth of the cancerous DU145 cells. Overexpression of GNMT in benign RWPE cells showed significantly increased cell invasion and increased sarcosine level. Importantly, knockdown of GNMT in DU145 cells also inhibited intravasation using chick chorioallantoic membrane (CAM) assay and tumor growth in xenograft assays. In contrast, we also showed that while the knockdown of sarcosine degrading enzymes, SARDH and PIPOX, induced invasion and increased sarcosine level in RWPE cells, the overexpression of these enzymes attenuated invasion and decreased sarcosine level. Further, overexpression of SARDH inhibited cell proliferation, blocked the anchorage-independent growth and also inhibited intravasation using CAM assay. Taken together, this study shows that the components of the sarcosine pathway may have potential as biomarkers of prostate cancer progression and serve as new avenues for therapeutic intervention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2803. doi:10.1158/1538-7445.AM2011-2803
Rapid Detection of Tuberculosis and Drug-Resistant Tuberculosis
Authors: Michael D. Iseman, Leonid B. Heifets
Journal: New England Journal of Medicine (2006)

Tuberculosis remains one of the major unresolved global health problems, and the situation is worsening in many parts of the world, primarily because of the association between tuberculosis and the epidemic of human immunodeficiency virus (HIV) infection and AIDS and the growing prevalence of drug resistance. The highest prevalence of both tuberculosis and drug resistance is found in countries with limited resources, which cannot afford to implement modern methods of epidemic control of tuberculosis. The detection of new cases of tuberculosis in these areas is based on provisional diagnosis by means of direct acid-fast bacilli testing of sputum smears, a . . .
A genome-wide association meta-analysis identifies new childhood obesity loci
Authors: Jonathan P Bradfield, H Rob Taal, Nicholas J Timpson, André Scherag, Cecile Lecoeur, Nicole M Warrington, Elina Hypponen, Claus Holst, Beatriz Valcarcel, Elisabeth Thiering, Rany M Salem, Fredrick R Schumacher, Diana L Cousminer, Patrick M A Sleiman, Jianhua Zhao, Robert I Berkowitz, Karani S Vimaleswaran, Ivonne Jarick, Craig E Pennell, David M Evans, Beate St Pourcain, Diane J Berry, Dennis O Mook-Kanamori, Albert Hofman, Fernando Rivadeneira, André G Uitterlinden, Cornelia M van Duijn, Ralf J P van der Valk, Johan C de Jongste, Dirkje S Postma, Dorret I Boomsma, W James Gauderman, Mohamed T Hassanein, Cecilia M Lindgren, Reedik Mägi, Colin A G Boreham, Charlotte E Neville, Luis A Moreno, Paul Elliott, Anneli Pouta, Anna-Liisa Hartikainen, Mingyao Li, Olli Raitakari, Terho Lehtimäki, Johan G Eriksson, Aarno Palotie, Jean Dallongeville, Shikta Das, Panos Deloukas, George McMahon, Susan M Ring, John P Kemp, Jessica L Buxton, Alexandra I F Blakemore, Mariona Bustamante, Mònica Guxens, Joel N Hirschhorn, Matthew W Gillman, Eskil Kreiner-Møller, Hans Bisgaard, Frank D Gilliland, Joachim Heinrich, Eleanor Wheeler, Inês Barroso, Stephen O'Rahilly, Aline Meirhaeghe, Thorkild I A Sørensen, Chris Power, Lyle J Palmer, Anke Hinney, Elisabeth Widen, I Sadaf Farooqi, Mark I McCarthy, Philippe Froguel, David Meyre, Johannes Hebebrand, Marjo-Riitta Jarvelin, Vincent W V Jaddoe, George Davey Smith, Hakon Hakonarson, Struan F A Grant
Journal: Nature Genetics (2012)
Cutaneous fibroses induced by Borrelia burgdorferi
Authors: W. CH. MARSCH, A. MAYET, M. WOLTER
Journal: British Journal of Dermatology (1993)

Three cases of chronic intection with Borrelia burgdorferi are descrihed. The patients presented with nodular or discoid fibrosis, partly in conjunction with acrodermatitis chronica atrophicans (ACA). Juxta‐articular fihrotic nodules may develop within a few months of the onset of ACA. Nodular, discoid morphoea‐like, and widespread cutaneous fibroses in chronic Borrelia infection may be provoked by trauma, surgery or electromagnetic radiation. They respond well to antibiotic therapy. These lesions offer an in vivo model for studying the evolution of immunologically induced fibrosis.
Audit Commission calls for improvements to critical care
Authors: C. White
Journal: BMJ (1999)

Critical care services in England and Wales are often inefficiently managed and poorly researched, concludes a report from the Audit Commission.

The annual cost of critical care in England and Wales is around £700m ($1120m) and rising by up to 10% each year. The number of beds in intensive care units has increased by 50% over the past six …
Biological Rhythms in Psychiatry and Medicine
Authors: Marjorie C. Meehan
Journal: JAMA (1971)

Every doctor scanning temperature charts, or nurse observing depressed patients, as well as every east-west jet traveler or menstruating woman, recognizes the importance of rhythms in physiology and mood. Until recently, little scientific investigation was made of these rhythms, but now more and more workers in different fields are studying the effects of rhythms, called circadian if they have 24-hour cycles, ultradian if they have shorter, and infradian if they have longer cycles. The National Institute of Mental Health has supported some of this research and has gathered much of the material into this report. Apparently many workers collaborated in its preparation and no author's name is given on the title page. There is a small notation that it was written by Gay Gaer Luce for the Program Analysis and Evaluation Branch. Miss Luce must be congratulated for writing a smooth, readable, interesting, and easily understandable summary of much diverse
Arterial Flow Conditions Downregulate Thrombomodulin on Saphenous Vein Endothelium
Authors: Martin Gosling, Jonathan Golledge, Robert J. Turner, Janet T. Powell
Journal: Circulation (1999)

Background —The antithrombogenic properties of venous endothelium may be attenuated when vein is implanted in the arterial circulation. Such changes may facilitate thrombosis, which is the final common pathway for saphenous vein arterial bypass graft occlusion. Methods and Results —Using human saphenous vein in a validated ex vivo flow circuit, we investigated (1) the possibility that arterial flow conditions (mean pressure, 100 mm Hg, 90 cpm, ≈200 mL/min) alter the concentration of proteins involved in regulating thrombosis at the vessel wall and (2) the influence of ion channel blockade on such effects. Concentrations of thrombomodulin and tissue factor were quantified by Western blotting (ratio of von Willebrand factor staining) and immunohistochemistry (as a percentage of CD31-staining area). Thrombomodulin concentrations after 90 minutes of venous and arterial flow conditions were quantified by immunostaining (68.9±4.8% and 41.0±3.0% CD31, respectively; P &lt;0.01) and by Western blotting (1.35±0.20 and 0.15±0.03 ratio of von Willebrand factor, respectively; P &lt;0.01). The ability of endothelial cells to generate activated protein C also decreased from 62±14 to 19±10 ng · min −1 · 1000 cells −1 ( P =0.01). The significant reduction in thrombomodulin was attenuated if calcium was removed from the perfusate but not by external vein stenting. Inclusion in the vein perfusate of drugs that reduce calcium entry (including Gd 3+ , to block stretch-activated ion channels, and nifedipine) abolished the reduction in thrombomodulin concentration observed after arterial flow conditions. In freshly excised vein, negligible concentrations of tissue factor were detected on the endothelium and concentrations did not increase after 90 minutes of arterial flow conditions, although the inclusion of nifedipine caused the immunostaining to increase from 3.0±0.4% to 8.5±0.7% CD31 ( P &lt;0.02). Conclusions —In saphenous vein endothelium exposed to arterial flow conditions, there is rapid downregulation of thrombomodulin, sufficient to limit protein C activation, by a calcium-dependent mechanism.
Are Veterans Really Different? The Feasibility of Smoke-Free VA Hospitals
Authors: Anne Joseph, Jane Korn
Journal: JAMA (1988)

<h3>To the Editor.—</h3> The Veterans Administration (VA) health care system is the largest in the nation, serving approximately 3.4 million patients per year. Many patients have medical conditions related to smoking, such as lung cancer, head and neck cancers, chronic obstructive pulmonary disease, and atherosclerotic heart disease. In spite of this, the VA has been reluctant to impose restrictions on smoking in its medical facilities.<sup>1</sup>In the past, VA hospitals have distributed free cigarettes to patients, and many still provide tobacco products in the canteen service. Why hasn't the VA taken a more active role in discouraging smoking? Many have the impression that the majority of veterans are smokers, who would vehemently object to restrictive smoking policies. Others question the fairness of smoking limitations to patients who smoke as a result of the military's past practice of distributing free cigarettes. Reluctance to deprive those veterans with chronic disabling illnesses
Researcher cleared of misconduct charges
Authors: Jeanne Lenzer
Journal: BMJ (2005)

A US researcher who was charged with scientific misconduct after she reported that doctors and psychologists may be overdiagnosing attention deficit hyperactivity disorder (ADHD) in schoolchildren has been cleared of all charges.

Gretchen LeFever, a clinical psychologist and associate professor in the department of paediatrics at the Eastern Virginia Medical School, was told earlier this year that her federally funded research was terminated and that her employment would also be terminated by the medical school after anonymous charges of scientific misconduct were filed against her ( BMJ 2005;330:691).

The school seized her computers, saying that Dr LeFever had held a research trial without getting informed consent from …
Avascular necrosis of a single vertebral body, an atypical site of disease in a patient with SLE and secondary APLS
Authors: M. Y. MOK
Journal: Annals of the Rheumatic Diseases (2000)

How should we manage fibromyalgia?We read with interest your leader, "How should we manage fibromyalgia?". 1 We were puzzled by Paul Reilly's statement that a comprehensive pain management programme...has the best chances of success, although even rheumatologists can practise amateur cognitive behavioural therapy in the clinic".Is Dr Reilly really suggesting that a rheumatologist's amateur eVorts oVer the best outcome for people with fibromyalgia?Dr Reilly oVers no evidence to support this statement.He does, however, find evidence to raise questions as to the value of patient self help groups.Dr Reilly cites a 1992 paper that reports an association between membership of such a group and worse prognosis in chronic fatigue syndrome. 2As the authors emphasised the caution with which the results should be interpreted, it is surprising that Dr Reilly has used this evidence to inform his clinical practice.Firstly, this is ancient research.Things have moved on.Although we would agree that some so called self help groups can end up as a circular review of symptoms, self management courses, which we at Arthritis Care espouse, are a very diVerent matter.Challenging Arthritis is a self management programme-and that title was chosen very deliberately.It is run by people with arthritis for people with arthritis.It gives people the skills to take control of their lives and their arthritis.It is practical and positive, and it works.The eVectiveness of similar programmes in the USA is well recorded. 3 Experience in the United Kingdom shows similar results, including better understanding of symptoms, improved communication with medical staV, and increased use of exercise and relaxation techniques.Probably most importantly of all, self management programmes significantly decrease pain, fatigue, and anxiety. 4 So it is extremely important to diVerentiate between navel gazing self help systems and courses such as ours, which encourage people to take control for themselves-and which work.Similar courses run on the Challenging Arthritis model are now available to people with other chronic conditions.Given Dr Reilly's desire to disabuse patients of the notion that their fibromyalgia is his problem alone, shouldn't eVective courses which encourage people to take control for themselves be a welcome adjunct to his treatment, even if it is run by a patient self management group?ROBINA
Mapping rehabilitation resources for head injury
Authors: J D Pickard, H M Seeley, S Kirker, C Maimaris, K McGlashan, E Roels, R Greenwood, C Steward, P J Hutchinson, G Carroll
Journal: Journal of the Royal Society of Medicine (2004)

Several reports have pointed to the unevenness in the UK of services for rehabilitation after head injury. A study was conducted in the Eastern Region of England to define the key stages in recovery and rehabilitation, by an iterative process of questionnaire, interview and consensus conference. Findings were translated into a draft set of maps showing current availability of services which were revised after feedback. Working groups then developed a set of definitions and classification codes for each stage of rehabilitation which were likewise disseminated for feedback. The maps were then redrafted to correspond with the definitions together with a flowchart of potential head injury rehabilitation services. The definitions were piloted at a regional neurosurgery unit and a rehabilitation hospital. Core services for neurorehabilitation region-wide were found to be variable and uncoordinated with fragmented and inequitable allocation of resources. The definitions and mapping system that emerged from this study should facilitate the design of care pathways for patients and identify gaps in the services.