tbuckley/cabot-search huggingface dataset:
Abstract 5665: Multiplexing markers of response to sorafenib/mapatumumab combination therapy in hepatocellular carcinoma circulating tumor cells
Authors: Nathan G. Dolloff, Lanlan Zhou, Kristi Peters, Arunasalam Navaraj, Joshua Allen, Avisnata Das, David Dicker, Wafik El-Deiry
Journal: Cancer Research (2012)

Abstract Hepatocellular carcinoma (HCC) accounts for approximately 600,000 deaths per year worldwide. Effective therapeutic strategies for advanced stage patients are lacking, and the median survival rate for patients who are not eligible for surgical resection is a mere 6 months. Circulating tumor cells (CTCs) are detectable in the peripheral blood of cancer patients, are accessible through a minimally invasive procedure, and may provide a source of tumor tissue for analyzing molecular markers of therapeutic response that may help guide treatment protocols. To demonstrate this potential, we developed a system for imaging and quantifying multiplexed molecular markers of response to sorafenib/mapatumumab combination therapy in an HCC CTC model. The sorafenib/mapatumumab combination regimen is currently in phase 2 clinical trials for the treatment of HCC, and molecular markers that mediate the synergistic anti-tumor activity of this combination have been identified. These markers include phospho-p42/44 MAPK (p-ERK), Mcl-1, c-IAP2, and apoptotic markers such as cleaved caspase-3. We developed a technical approach using MultiSpectral Imaging (MSI) to quantitatively measure multiplexed fluorescent signals from primary antibodies specific to phospho-ERK, Mcl-1, c-IAP-2, and cleaved caspase-3 that had been conjugated to quantum dots (Qdots) with distinct fluorescence emission spectra. We first confirmed the ability to modulate marker expression and uncouple multiplexed Qdot signals by MSI in cultured HCC cells that had been treated with sorafenib or sorafenib/mapatumumab combinations. We then applied this detection system to HCC cells that were spiked into human blood and recovered using FDA-approved CTC isolation technology (CellSearch CTC Test by Veridex). Our data demonstrate the potential for studying molecular markers of therapeutic response in CTCs. Information gained from this technology may be used to guide therapeutic decisions or serve as pharmacokinetic/pharmacodynamic endpoints in experimental clinical protocols. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5665. doi:1538-7445.AM2012-5665
Fatigue Crack Growth Under Pulsatile Pressure and Plaque Rupture
Authors: Xuan Pei, Baijian Wu, Tjun Y. Tang, Jonathan H. Gillard, Zhi-Yong Li
Journal: JACC. Cardiovascular imaging (2014)

Identification of vulnerable plaque pre-rupture is extremely important for patient risk stratification. The mechanism of plaque rupture is still not entirely clear, but it is thought to be a process involving multiple factors. From a biomechanical viewpoint, plaque rupture is usually seen as a
Contribution of regional specialty subcommittees to organising audit.
Authors: C D Collins
Journal: BMJ (1990)

underprescribing could be occurring as well as overprescribing.In due course the district health authorities will be able to produce the referral, admission, and investigation rates for individual general practitioners, which again will be indicators rather than targets.As already seen in prescribing analysis and cost data interpretation of these figures is reliable only at the practice level and may be unreliable for individual doctors because of recording errors and variations in workload and case mix.We do now have a defined target for cervical cytology (table II) as well as the long established target of 90% for childhood immunisation.These indicators and targets comprise a contractual audit.Unfortunately general practitioners may be so occupied meeting their obligations under this audit that they will not appreciate the difference between it and audit led by the profession, the most important part of which is considering the results and learning how to improve, and this is best done in an educational setting.Recording data should be part of routine care provision and gathering data for analysis delegated whenever possible, leaving interpretation to general practitioners.The dramatic increase in the use of computers for clinical recording makes this the most valuable tool for future audit.
CD33 target validation and sustained depletion of AML blasts in long-term cultures by the bispecific T-cell–engaging antibody AMG 330
Authors: Christina Krupka, Peter Kufer, Roman Kischel, Gerhard Zugmaier, Jan Bögeholz, Thomas Köhnke, Felix S. Lichtenegger, Stephanie Schneider, Klaus H. Metzeler, Michael Fiegl, Karsten Spiekermann, Patrick A. Baeuerle, Wolfgang Hiddemann, Gert Riethmüller, Marion Subklewe
Journal: Blood (2013)
Future medical applications of single-cell sequencing in cancer
Authors: Nicholas Navin, James Hicks
Journal: Genome Medicine (2011)

Advances in whole genome amplification and next-generation sequencing methods have enabled genomic analyses of single cells, and these techniques are now beginning to be used to detect genomic lesions in individual cancer cells. Previous approaches have been unable to resolve genomic differences in complex mixtures of cells, such as heterogeneous tumors, despite the importance of characterizing such tumors for cancer treatment. Sequencing of single cells is likely to improve several aspects of medicine, including the early detection of rare tumor cells, monitoring of circulating tumor cells (CTCs), measuring intratumor heterogeneity, and guiding chemotherapy. In this review we discuss the challenges and technical aspects of single-cell sequencing, with a strong focus on genomic copy number, and discuss how this information can be used to diagnose and treat cancer patients.
Law and disorders
Authors: Des Spence
Journal: BMJ (2007)

We have no body armour, no air cover, no weapons—only our wits to protect us. General practice is door to door, street fighting medicine. Personality disorders are our stock in trade. The dependent, the paranoid, the histrionic, the borderline—we jolly them along, not responding to their ill placed health anxieties. Our job is to keep them away from the vortex of secondary care investigation that would only feed their introspection. 

One group of patients, however, is different: those with antisocial personality disorder, defined by …
Distinct Functional Lineages of Human Vα24 Natural Killer T Cells
Authors: Peter T. Lee, Kamel Benlagha, Luc Teyton, Albert Bendelac
Journal: The Journal of Experimental Medicine (2002)

CD1d-restricted autoreactive natural killer (NK)T cells have been reported to regulate a range of disease conditions, including type I diabetes and immune rejection of cancer, through the secretion of either T helper (Th)2 or Th1 cytokines. However, mechanisms underlying Th2 versus Th1 cytokine secretion by these cells are not well understood. Since most healthy subjects express &amp;lt;1 NKT cell per 1,000 peripheral blood lymphocytes (PBLs), we devised a new method based on the combined used of T cell receptor (TCR)-specific reagents α-galactosylceramide (αGalCer) loaded CD1d-tetramers and anti-Vα24 monoclonal antibody, to specifically identify and characterize these rare cells in fresh PBLs. We report here that CD4+ and CD4−CD8− (double negative [DN]) NKT cell subsets represent functionally distinct lineages with marked differences in their profile of cytokine secretion and pattern of expression of chemokine receptors, integrins, and NK receptors. CD4+ NKT cells were the exclusive producers of interleukin (IL)-4 and IL-13 upon primary stimulation, whereas DN NKT cells had a strict Th1 profile and prominently expressed several NK lineage receptors. These findings may explain how NKT cells could promote Th2 responses in some conditions and Th1 in others, and should be taken into consideration for intervention in relevant diseases.
Corticosteroids for prevention of tuberculosis mortality – Authors' reply
Authors: Julia A Critchley, Fiona Young, Lois Orton, Paul Garner
Journal: The Lancet Infectious Diseases (2013)

We thank Karan Madan and colleagues for their comments. Our aim was to summarise the trial evidence for adjunctive steroid therapy in tuberculosis across all organ systems to look for evidence of consistent effects, and open a debate as to whether there is a "class effect". Their letter is part of this debate.
Mesenchymal stem cell-based cell engineering with multifunctional mesoporous silica nanoparticles for tumor delivery
Authors: Xinglu Huang, Fan Zhang, Hui Wang, Gang Niu, Ki Young Choi, Magdalena Swierczewska, Guofeng Zhang, Haokao Gao, Zhe Wang, Lei Zhu, Hak Soo Choi, Seulki Lee, Xiaoyuan Chen
Journal: Biomaterials (2012)
OPTICAL COHERENCE TOMOGRAPHY-GUIDED ANTIPLATELET THERAPY IN PATIENTS WITH CORONARY ARTERY DISEASE AND CANCER: THE PROTECT-OCT REGISTRY
Authors: Cezar Iliescu, Jake Thomas LeBeau, Guilherme Silva, Simone Frusina, Muskan Agarwal, Gloria Iliescu, Gerryross Tomakin, George Manoukian, Jose Banchs, Peter Kim, Saamir Hassan, Jean-Bernard Durand
Journal: Journal of the American College of Cardiology (2013)
Acceptance of Some Acupuncture Applications
Authors: Charles Marwick
Journal: JAMA (1997)

CAUTIOUS approval of some applications of acupuncture has been handed down by a National Institutes of Health (NIH) consensus development meeting. The 12-member panel, asked to evaluate current evidence for the efficacy of acupuncture, concluded that there is "clear evidence" of efficacy in the control of the nausea and vomiting that occurs in some patients postoperatively and in association with chemotherapy, and for relief of postoperative dental pain. The panel said that acupuncture is "probably" also effective in the control of nausea in early pregnancy. The panelists added that there were "reasonable" studies showing that the use of acupuncture, by itself or as an adjunct to other therapies, resulted in satisfactory treatment of a number of other conditions, even though there was not "firm evidence of efficacy at this time." These conditions include addiction to illicit drugs and alcohol (but not to tobacco), stroke rehabilitation, headache, menstrual cramps, tennis elbow
Technology and Health Care: Official Journal of the European Society for Engineering and Medicine
Authors: Carol R. Glatt
Journal: JAMA (1995)

<b>JAMIA: Journal of the American Medical Informatics Association</b>, William W. Stead, editor-in-chief, bimonthly, $92 (individuals), $167 (institutions), Philadelphia, Pa, Hanley &amp; Belfus, Jan/Feb 1994-. With the dramatic growth of a new field like medical informatics, one naturally expects the emergence of new journals concerned with the subject. Similarly, one would expect that two new journals, one focused on medical informatics and the other on technology and health care, would cover comparable territory. Yet, striking differences can be found between these two new journals. The European Society of Engineering in Medicine established<i>Technology and Health Care</i>in 1993 as its official journal. The editors and editorial board are drawn from respected biomedical engineers and medical informatics researchers throughout Europe, many of whom are known here in the United States. An editorial in the inaugural issue describes the journal's mission as seeking to cover the "overlapping areas between Physics, Engineering, Informatics and
Suppression of Erythropoiesis by Alcohol
Authors: D. OB. Hourihane, D. G. Weir
Journal: BMJ (1970)

Serial measurements in alcoholic subjects showed a profound fall of serum iron for three days after withdrawal of alcohol and a reversion of abnormal accumulation of erythroblastic haemosiderin to normal. These findings suggest an interference in normal haem synthesis, most probably by a direct effect.
Cimetidine for Prevention and Treatment of Gastroduodenal Mucosal Lesions in Patients in an Intensive Care Unit
Authors: DAVID A. PEURA
Journal: Annals of Internal Medicine (1985)

The efficacy of Cimetidine in the prevention and treatment of stress-induced gastroduodenal lesions was evaluated in a randomized, double-blind, placebo-controlled study in which serial endoscopy was used to examine patients without clinical evidence of bleeding who were admitted to a medical intensive care unit. Endoscopy showed that 14 of 21 patients treated with Cimetidine, compared with 5 of 18 patients treated with placebo, had normal or improved gastroduodenal mucosa (p < 0.05). Endoscopic signs of bleeding cleared or did not develop in 20 patients treated with Cimetidine and in 11 patients treated with placebo (p < 0.01). Significantly fewer blood transfusions were given to patients with endoscopic signs of bleeding in the cimetidine-treated group (0.5 ±0.3 [SE] units) than in placebo-treated patients (4.5 ±1.5 units; p < 0.05). The mortality rate was not statistically different between treatment groups. By preventing established gastroduodenal stress lesions from progressing in severity, Cimetidine diminished both bleeding and the need for transfusions.
Interleukin 10 and transforming growth factor beta cooperate to induce anti-CD40-activated naive human B cells to secrete immunoglobulin A.
Authors: T Defrance, B Vanbervliet, F Brière, I Durand, F Rousset, J Banchereau
Journal: The Journal of Experimental Medicine (1992)

In the present report, we have investigated the in vitro differentiation of surface(s) sIgD+ and sIgD- human B cells into Ig-secreting cells in response to various stimuli. sIgD+ B cells homogeneously expressed some of the antigens identifying mantle zone B cells, but lacked expression of germinal center markers, thus confirming that the B cell populations positively selected on the basis of sIgD expression were highly enriched for naive B lymphocytes. Conversely, sIgD- B cells expressed some of the antigens specifically associated with germinal center B cells. T cell-independent differentiation of sIgD+ and sIgD- B cells could be achieved by simultaneous crosslinking of sIgs and CD40 in the presence of a mouse Ltk- cell line stably expressing human CDw32/Fc gamma RII (CDw32 L cells). In this experimental system, sIgD+ B cells were exclusively proned for IgM synthesis, whereas sIgD- B cells produced IgG, IgM, and IgA. Both the human and viral forms of interleukin 10 (IL-10) strongly increased the Ig secretion by sIgD+ and sIgD- B cells simultaneously activated through sIgs and CD40. IgM and IgG constituted the predominant Ig isotype produced by sIgD+ and sIgD- B cells, respectively, in response to IL-10. sIgD+ B cells could be induced for IgA synthesis upon co-culturing with transforming growth factor beta (TGF-beta) and IL-10, in the presence of an anti-CD40 monoclonal antibody presented by the CDw32 L cells. In contrast, TGF-beta suppressed the IL-10-mediated IgG, IgM, and IgA secretions by sIgD- B cells. sIgD+ B cells could not be induced for IgA synthesis by TGF-beta and IL-10 after crosslinking of their sIgs, suggesting that ligation of CD40 was one of the obligatory signals required for commitment of naive B cells to IgA secretion. Limiting dilution experiments indicated that the IgA-potentiating effect of TGF-beta was due to its capacity to increase the frequency of IgA-producing cells, most likely as a consequence of class switching. Taken together, our data strongly suggest that TGF-beta is involved in the regulation of IgA isotype selection in humans.
Access controls on bmj.com
Authors: Gunther Eysenbach
Journal: BMJ (2005)

Secondary prevention of heart disease with statins Groups were as different as chalk and cheeseEditor-Wei et al say that the results of their observational study of treatment with statins in routine clinical practice in Tayside are consistent with, and similar to, those reported in clinical trials. 1 This conclusion is hardly justified.A cohort of patients, defined by a discharge diagnosis of myocardial infarction between January 1993 and December 2001, was studied to compare the outcomes in those treated with statins and those not receiving these drugs.The data clearly show that the two groups differed substantially in terms of age, sex, comorbidity, and other cardiovascular drug treatment-all of these factors were biased in favour of a poorer outcome in patients not given statins.Furthermore, the two groups belonged to different time periods, most of the untreated patients to the earlier part and most of those given statins to the later part of the study.Given the changes between 1993 and 2001-including, for example, those related to the management of acute myocardial infarction and the criteria for diagnosis-it is only to be expected that the untreated group would have a higher risk of subsequent cardiovascular events.Multivariate analysis was reported as showing that statins reduced all cause mortality by 31% and the composite end point of myocardial infarction plus cardiovascular mortality by 18%.These results should be greeted with scepticism.Firstly, many trials of statins have failed to show any reduction whatsoever in all cause mortality. [2]][4][5] Secondly, as observed in other studies, any reduction in all cause mortality would be expected to be much less than that for composite cardiovascular end points. 2 4 5 The two groups in this study were as different as chalk and cheese.It should come as no surprise, therefore, that the results were anomalous.In such circumstances, no amount of statistical trickery could be expected to furnish anything of value.
Maximizing Survival Benefit With Primary Prevention Implantable Cardioverter-Defibrillator Therapy in a Heart Failure Population
Authors: Wayne C. Levy, Kerry L. Lee, Anne S. Hellkamp, Jeanne E. Poole, Dariush Mozaffarian, David T. Linker, Aldo P. Maggioni, Inder Anand, Philip A. Poole-Wilson, Daniel P. Fishbein, George Johnson, Jill Anderson, Daniel B. Mark, Gust H. Bardy
Journal: Circulation (2009)

Background— Although implantable cardioverter-defibrillator (ICD) therapy reduces mortality in moderately symptomatic heart failure patients with an ejection fraction ≤35%, many such patients do not require ICD shocks over long-term follow-up. Methods and Results— Using a modification of a previously validated risk prediction model based on routine clinical variables, we examined the relationship between baseline predicted mortality risk and the relative and absolute survival benefits of ICD treatment in the primary prevention Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). In the placebo arm, predicted 4-year mortality grouped into 5 equal-sized risk groups varied from 12% to 50% (c statistic=0.71), whereas the proportion of SCD in those same risk groups decreased from 52% to 24% of all deaths. ICD treatment decreased relative risk of SCD by 88% in the lowest-risk group versus 24% in the highest-risk group ( P =0.009 for interaction) and decreased relative risk of total mortality by 54% in the lowest-risk group versus no benefit (2%) in the highest-risk group ( P =0.014 for interaction). Absolute 4-year mortality reductions were 6.6%, 8.8%, 10.6%, 14.0%, and −4.9% across risk quintiles. In highest-risk patients (predicted annual mortality &gt;20%), no benefit of ICD treatment was seen. Projected over each patient’s predicted lifespan, ICD treatment added 6.3, 4.1, 3.0, 1.9, and 0.2 additional years of life in the lowest- to highest-risk groups, respectively. Conclusions— A clinical risk prediction model identified subsets of moderately symptomatic heart failure patients in SCD-HeFT in whom single-lead ICD therapy was of no benefit and other subsets in which benefit was substantial.
Subintimal Ki-67 as a synovial tissue biomarker for inflammatory arthropathies
Authors: F Pessler, A Ogdie, C Diaz-Torne, L Dai, X Yu, E Einhorn, S Gay, H R Schumacher
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objectives:</h3> Ki-67 is expressed in the nuclei of dividing cells and can be used to assess proliferation of synovial inflammatory and stromal cells. We evaluated subintimal Ki-67+ cell density as a tissue biomarker for inflammatory arthropathies and compared it to subintimal CD68, a synovial biomarker of RA. <h3>Methods:</h3> Subintimal Ki-67+ and CD68+ cell densities were measured immunohistochemically in synovial specimens obtained from patients with rheumatoid arthritis (RA; n = 19), osteoarthritis (OA; n = 18), "non-inflammatory" orthopaedic arthropathies (avascular necrosis, meniscus injury, femur fracture; n = 16), chronic septic arthritis (n = 9), and histologically normal synovium (n = 10). Results were correlated with a histological synovitis score. Utilising the areas under receiver operating characteristic curves (AUCs), we compared the abilities of Ki-67 and CD68 to differentiate among these arthropathies. <h3>Results:</h3> Ki-67 was expressed widely in the subintima of inflamed specimens and in RA pannus invading hard tissues. Compared to normal controls, it was highly overexpressed in RA (26.6-fold) and chronic septic arthritis (55-fold), and mildly elevated in OA (3.9-fold) and orthopaedic arthropathies (2.1-fold). Ki-67 and CD68 differentiated similarly well between RA and OA (AUC: Ki-67 = 0.91, CD68 = 0.94), Ki-67 better between chronic septic arthritis and RA, and CD68 better between OA and normal controls. Ki-67 (<i>r</i> = 0.80) and CD68 (<i>r</i> = 0.79) correlated positively with the synovitis score. <h3>Conclusions:</h3> Subintimal Ki-67 was overexpressed in inflammatory arthropathies, distinguished among differentially inflamed arthropathies, and correlated positively with the histological severity of synovitis. It may prove useful in synovial tissue classification and as a synovial marker of disease activity in clinical trials when biopsies are available.
Endothelin B Receptor Blockade Accelerates Disease Progression in a Murine Model of Autosomal Dominant Polycystic Kidney Disease
Authors: Ming-Yang Chang, Emma Parker, Meguid El Nahas, John L. Haylor, Albert C.M. Ong
Journal: Journal of the American Society of Nephrology (2007)

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disease that causes kidney failure and accounts for 10% of all patients who are on renal replacement therapy. However, the marked phenotypic variation between patients who carry the same PKD1 or PKD2 mutation suggests that nonallelic factors may have a greater influence on the cystic phenotype. Endothelin-1 (ET-1) transgenic mice have been reported to develop profound renal cystic disease and interstitial fibrosis without hypertension. The hypothesis that ET-1 acts as a modifying factor for cystic disease progression was tested in an orthologous mouse model of ADPKD (Pkd2(WS25/-)). Four experimental groups (n = 8 to 11) were treated from 5 to 16 wk of age with the highly selective orally active receptor antagonists ABT-627 (ETA) and A-192621 (ETB) singly or in combination. Unexpected, ETB blockade led to accelerated cystic kidney disease. Of significance, this was associated with a reduction in urine volume and sodium excretion and increases in urine osmolarity and renal cAMP and ET-1 concentrations. The deleterious effect of chronic ETB blockade was neutralized by simultaneous ETA blockade. ETA blockade alone resulted in a significant increase in tubular cell proliferation but did not alter the cystic phenotype. It is concluded that the balance between ETA and ETB signaling is critical for maintaining tubular structure and function in the cystic kidney. These results implicate ET, acting via vasopressin-dependent and independent pathways, as a major modifying factor for cystic disease progression in human ADPKD.