tbuckley/cabot-search huggingface dataset:
Identification of Prognosis-Relevant Subgroups in Patients with Chemoresistant Triple-Negative Breast Cancer
Authors: Ke-Da Yu, Rui Zhu, Ming Zhan, Angel A. Rodriguez, Wei Yang, Stephen Wong, Andreas Makris, Brian D. Lehmann, Xi Chen, Ingrid Mayer, Jennifer A. Pietenpol, Zhi-Ming Shao, W. Fraser Symmans, Jenny C. Chang
Journal: Clinical Cancer Research (2013)

Patients with triple-negative breast cancer (TNBC) and residual disease after neoadjuvant chemotherapy generally have worse outcome; however, some patients with residual tumor after neoadjuvant chemotherapy do not relapse. We hypothesize that there are subgroups of patients with chemoresistant TNBC with different prognosis.Forty-nine chemoresistant cases from 111 patients with TNBC treated with neoadjuvant chemotherapy (M.D. Anderson Cancer Center, Houston, TX) constituted the discovery cohort, and 25 chemoresistant samples from 47 neoadjuvant chemotherapy-treated TNBC (The Methodist Hospital, Houston, TX) were chosen for validation. Extended validation was carried out in 269 operable TNBC predicted to be chemoresistant by expression pattern from published datasets.We established a seven-gene prognostic signature using dChip and gene set enrichment analyses. In the independent validation cohort, the classifier predicted correctly with positive predictive value of 75.0% and negative predictive value (i.e., relapse-free survival; RFS) of 76.9% at 3 years. Those predicted to relapse had a HR of 4.67 [95% confidence interval (CI): 1.27-17.15] for relapse in 3 years. In extended validation, patients predicted not to relapse exhibited 3-year RFS of 78.9%, whereas the 3-year RFS was 48.5% for patients predicted to relapse, with HR of 2.61 (95% CI: 1.52-4.49). The TNBC subgroup that predicted to have relatively favorable prognosis was characterized by high expression of "luminal-like" genes [androgen-receptor (AR) and GATA3], whereas the subgroup with worse prognosis was characterized by expression of cancer stem-cell markers.We developed a clinically relevant signature for patients with chemoresistant TNBC. For these women, new therapeutic strategies like targeting AR activation or cancer stem cells may need to be developed.
The T Deflection of Isolated Mammalian Heart Muscle Electrogram
Authors: SOLOMON GARB, MAYNARD B. CHENOWETH
Journal: Circulation Research (1953)

Both bipolar and unipolar electrograms recorded from well-oxygenated isolated papillary muscle preparations consist of R and T deflections in the same direction. The T is inverted by anoxia, rapid late, and injury. When cut linear strips of ventricular muscle are observed for many hours, during which time they presumably recover from the initial injury, the T deflection becomes upright in most cases, and then can be depressed and inverted by anoxia or rapid rates of stimulation. Since, in the absence of modifying factors, the T is in the same direction as the R deflection in a simple linear strip, it probably cannot be adequately explained on the basis of membrane repolarization. Since the nerve after-potentials are believed to represent processes involving oxidative metabolism, the T deflection may also be produced by metabolic processes, although the possibility cannot be excluded that it represents a combination of membrane repolarization and other processes.
Administration of Recombinant Soluble Urokinase Receptor Per Se Is Not Sufficient to Induce Podocyte Alterations and Proteinuria in Mice
Authors: Dominique Cathelin, Sandrine Placier, Michael Ploug, Marie-Christine Verpont, Sophie Vandermeersch, Yosu Luque, Alexandre Hertig, Eric Rondeau, Laurent Mesnard
Journal: Journal of the American Society of Nephrology (2014)

Circulating levels of soluble forms of urokinase-type plasminogen activator receptor (suPAR) are generally elevated in sera from children and adults with FSGS compared with levels in healthy persons or those with other types of kidney disease. In mice lacking the gene encoding uPAR, forced increases in suPAR concentration result in FSGS-like glomerular lesions and proteinuria. However, whether overexpression of suPAR, per se, contributes to the pathogenesis of FSGS in humans remains controversial. We conducted an independent set of animal experiments in which two different and well characterized forms of recombinant suPAR produced by eukaryotic cells were administered over the short or long term to wild-type (WT) mice. In accordance with the previous study, the delivered suPARs are deposited in the glomeruli. However, such deposition of either form of suPAR in the kidney did not result in increased glomerular proteinuria or altered podocyte architecture. Our findings suggest that glomerular deposits of suPAR caused by elevated plasma levels are not sufficient to engender albuminuria.
Defining prognosis for women with breast cancer and CNS metastases by HER2 status
Authors: S. Dawood, K. Broglio, F.J. Esteva, N.K. Ibrahim, S.-W. Kau, R. Islam, K.D. Aldape, T.-K. Yu, G.N. Hortobagyi, A.M. Gonzalez-Angulo
Journal: Annals of Oncology (2008)
Politicians set out their stall at health election debate
Authors: R. Coombes
Journal: BMJ (2015)

Politicians from two major UK political parties have refused to rule out yet more reorganisation—even of a “radical” nature—of the NHS in England after May’s general election.

Speaking on 19 March at a debate about the future of the NHS at the Royal College of Surgeons in London, Andy Burnham, Labour’s shadow health secretary, said that he wanted to “reset” the NHS into a “national health and care service,” including social care. England “will need to embrace radical change in the way it delivers services,” he said, so that hospitals were no longer the “default setting for care.” He floated the idea of local integrated care organisations that would employ GPs directly and an annual care payment to elderly people that would act as …
T cell immune response during HBeAG seroconversion? Evidence of T cell activation, cytotoxicity and proliferation during treatment with interferon/thymosin in patients with chronic hepatitis B
Authors: S. Lim, L. Zhou, L. Li, T. Tan, F. Peter, E. Ren, D.S. Selamat, C. Wai, Y. Lee, L. Lim, S. Chan
Journal: Journal of Hepatology (2001)
Cisplatin and Fluorouracil Alone or with Docetaxel in Head and Neck Cancer
Authors: Marshall R. Posner, Diane M. Hershock, Cesar R. Blajman, Elizabeth Mickiewicz, Eric Winquist, Vera Gorbounova, Sergei Tjulandin, Dong M. Shin, Kevin Cullen, Thomas J. Ervin, Barbara A. Murphy, Luis E. Raez, Roger B. Cohen, Monica Spaulding, Roy B. Tishler, Berta Roth, Rosana del Carmen Viroglio, Varagur Venkatesan, Ilya Romanov, Sanjiv Agarwala, K. William Harter, Matthew Dugan, Anthony Cmelak, Arnold M. Markoe, Paul W. Read, Lynn Steinbrenner, A. Dimitrios Colevas, Charles M. Norris, Robert I. Haddad
Journal: New England Journal of Medicine (2007)

A randomized phase 3 trial of the treatment of squamous-cell carcinoma of the head and neck compared induction chemotherapy with docetaxel plus cisplatin and fluorouracil (TPF) with cisplatin and fluorouracil (PF), followed by chemoradiotherapy.
Antiscience and ethical concerns associated with advocacy of Lyme disease
Authors: Paul G Auwaerter, Johan S Bakken, Raymond J Dattwyler, J Stephen Dumler, John J Halperin, Edward McSweegan, Robert B Nadelman, Susan O'Connell, Eugene D Shapiro, Sunil K Sood, Allen C Steere, Arthur Weinstein, Gary P Wormser
Journal: The Lancet Infectious Diseases (2011)
Relative contribution of mucosal injury and Helicobacter pylori in the development of gastroduodenal lesions in patients taking non-steroidal anti-inflammatory drugs
Authors: C J Hawkey
Journal: Gut (2002)

<b>Background and aims:</b> A past history of peptic ulceration increases the risk of an ulcer developing during non-steroidal anti-inflammatory drug (NSAID) use. Whether this is due to <i>Helicobacter pylori</i> infection or to reactivation of the original lesion is unclear. <b>Methods:</b> We used multivariate regression analyses of three large similar trials to identify factors that placed patients at high risk of ulcer development or relapse. We compared the efficacy of omeprazole 20 mg daily, misoprostol 200 μg twice daily, and ranitidine 150 mg twice daily in preventing ulcers and erosions at different sites and in patients who were <i>H pylori</i> positive and negative. <b>Results:</b> Patients with endoscopic lesions (which healed) initially were significantly more likely than those without to develop further erosions or ulcers during treatment (rate ratio 2.12, 1.07–4.17). Risk mounted further with ulcers versus erosions, particularly those that had been slow to heal. There was a highly significant tendency for the relapse lesion to replicate the site and type of the original lesion (mean odds ratios ranging from 3 to 14). Treatment failure was significantly less likely with omeprazole than with placebo, misoprostol, or ranitidine. This advantage was especially evident in <i>H pylori</i> positive patients receiving acid suppression (5.7% <i>v</i> 16.6% for gastric ulcer with omeprazole). <b>Conclusions:</b> Relapse of lesions in patients taking NSAIDs was highly site and type specific and not adversely affected by <i>H pylori</i> status. This strongly implies that local mucosal factors predispose to ulcer development in patients taking NSAIDs. Identification of the responsible mucosal changes would aid understanding and could promote better treatment.
Pharmacokinetic study of patients with follicular or mantle cell lymphoma treated with rituximab as ‘in vivo purge’ and consolidative immunotherapy following autologous stem cell transplantation
Authors: J. Mangel, R. Buckstein, K. Imrie, D. Spaner, E. Franssen, P. Pavlin, A. Boudreau, N. Pennell, D. Combs, N.L. Berinstein
Journal: Annals of Oncology (2003)
Care at first-level facilities for children with severe pneumonia in Bangladesh: a cohort study
Authors: Enayet K Chowdhury, Shams El Arifeen, Muntasirur Rahman, DM Emdadul Hoque, M Altaf Hossain, Khadija Begum, Ashraf Siddik, Nazma Begum, Qazi Sadeq-ur Rahman, Tasnima Akter, Twaha M Haque, ZA Motin Al-Helal, Abdullah H Baqui, Jennifer Bryce, Robert E Black
Journal: The Lancet (2008)
Effects of extracellular fluid volume and plasma bicarbonate concentration on proximal acidification in the rat.
Authors: R J Alpern, M G Cogan, F C Rector
Journal: Journal of Clinical Investigation (1983)

The effects of systemic bicarbonate concentration and extracellular fluid volume status on proximal tubular bicarbonate absorption, independent of changes in luminal composition and flow rate, were examined with in vivo luminal microperfusion of rat superficial proximal convoluted tubules. Net bicarbonate absorption and bicarbonate permeability were measured using microcalorimetry. From these data, net bicarbonate absorption was divided into two parallel components: proton secretion and passive bicarbonate diffusion. The rate of net bicarbonate absorption was similar in hydropenic and volume-expanded rats when tubules were perfused with 24 mM bicarbonate, but was inhibited in volume-expanded rats when tubules were perfused with 5 mM bicarbonate. Volume expansion caused a 50% increase in bicarbonate permeability, which totally accounted for the above inhibition. The rate of proton secretion was unaffected by volume expansion in both studies. The rate of net bicarbonate absorption was markedly inhibited in alkalotic expansion as compared with isohydric expansion. Bicarbonate permeabilities were not different in these two conditions, and the calculated rates of proton secretion were decreased by greater than 50% in alkalosis. Net bicarbonate absorption was stimulated in acidotic rats compared to hydropenic rats. This stimulation was attributable to a 25% increase in the rate of proton secretion. We conclude that (a) proton secretion is stimulated in acidosis, inhibited in alkalosis, and is not altered by volume status; (b) bicarbonate permeability is increased by volume expansion but is not altered by increases in plasma bicarbonate concentration; (c) when luminal bicarbonate concentrations are similar to those of plasma, net bicarbonate absorption is dominated by proton secretion and is thus sensitive to peritubular bicarbonate concentrations, and insensitive to extracellular fluid volume; (d) when luminal bicarbonate concentrations are low and proton secretion is slowed, bicarbonate permeability and thus extracellular fluid volume have a greater influence on net bicarbonate absorption.
Modulation of Soluble Receptor for Advanced Glycation End Products by Angiotensin-Converting Enzyme-1 Inhibition in Diabetic Nephropathy
Authors: Josephine M. Forbes, Suzanne R. Thorpe, Vicki Thallas-Bonke, Josefa Pete, Merlin C. Thomas, Elizabeth R. Deemer, Sahar Bassal, Assam El-Osta, David M. Long, Sianna Panagiotopoulos, George Jerums, Tanya M. Osicka, Mark E. Cooper
Journal: Journal of the American Society of Nephrology (2005)

Recent studies have identified that first-line renoprotective agents that interrupt the renin-angiotensin system not only reduce BP but also can attenuate advanced glycation end product (AGE) accumulation. This study used in vitro, preclinical, and human approaches to explore the potential effects of these agents on the modulation of the receptor for AGE (RAGE). Bovine aortic endothelial cells that were exposed to the angiotensin-converting enzyme inhibitor (ACEi) ramiprilat in the presence of high glucose demonstrated a significant increase in soluble RAGE (sRAGE) secreted into the medium. In streptozotocin-induced diabetic rats, ramipril treatment (ACEi) at 3 mg/L for 24 wk reduced the accumulation of skin collagen-linked carboxymethyllysine and pentosidine, as well as circulating and renal AGE. Renal gene upregulation of total RAGE (all three splice variants) was observed in ACEi-treated animals. There was a specific increase in the gene expression of the splice variant C-truncated RAGE (sRAGE). There were also increases in sRAGE protein identified within renal cells with ACEi treatment, which showed AGE-binding ability. This was associated with decreases in renal full-length RAGE protein from ACEi-treated rats. Decreases in plasma soluble RAGE that were significantly increased by ACEi treatment were also identified in diabetic rats. Similarly, there was a significant increase in plasma sRAGE in patients who had type 1 diabetes and were treated with the ACEi perindopril. Complexes between sRAGE and carboxymethyllysine were identified in human and rodent diabetic plasma. It is postulated that ACE inhibition reduces the accumulation of AGE in diabetes partly by increasing the production and secretion of sRAGE into plasma.
Development and Cancer: At the Crossroads of Nodal and Notch Signaling
Authors: Luigi Strizzi, Katharine M. Hardy, Elisabeth A. Seftor, Fabricio F. Costa, Dawn A. Kirschmann, Richard E.B. Seftor, Lynne-Marie Postovit, Mary J.C. Hendrix
Journal: Cancer Research (2009)

Aggressive tumor cells express a plastic, multipotent phenotype similar to embryonic stem cells. However, the absence of major regulatory checkpoints in these tumor cells allows aberrant activation of embryonic signaling pathways, which seems to contribute to their plastic phenotype. Emerging evidence showing the molecular cross-talk between two major stem cell signaling pathways Nodal and Notch suggests a promising therapeutic strategy that could target aggressive tumor cells on the basis of their unique plasticity, and provide new insights into the mechanisms underlying the re-emergence of developmental signaling pathways during tumor progression.
I<scp>G</scp>E AND I<scp>G</scp>GA ANTIBODY-MEDIATED RELEASE OF HISTAMINE FROM RAT PERITONEAL CELLS
Authors: Michael K. Bach, Kurt J. Bloch, K. Frank Austen
Journal: The Journal of Experimental Medicine (1971)

The optimum conditions for antigen-induced release of histamine in the rat IgE and IgGa antibody-mediated systems were studied in vitro. The IgE antibody-mediated reaction could be separated into two steps: preparation of target cells with antibody and challenge with antigen. The optimal conditions for these two steps were distinctly different. Release of histamine by IgGa antibody and antigen could not be separated into two steps, and the optimal conditions for the total reaction were identical to those of the antigen challenge step of the IgE antibody-mediated system.
Structural and functional implications of the alternative complement pathway C3 convertase stabilized by a staphylococcal inhibitor
Authors: Suzan H M Rooijakkers, Jin Wu, Maartje Ruyken, Robert van Domselaar, Karel L Planken, Apostolia Tzekou, Daniel Ricklin, John D Lambris, Bert J C Janssen, Jos A G van Strijp, Piet Gros
Journal: Nature Immunology (2009)
Polyamines stimulate the phosphorylation of phosphatidylinositol in rat mast cell granules
Authors: M. Kurosawa, D. Uno, K. Hanawa, S. Kobayashi
Journal: Allergy (1990)

Rat mast cell granules were obtained by homogenization of highly purified rat mast cells and isolated in a Percoll gradient. Diphosphoinositide (DPI) synthesis in rat mast cell granules was assayed by measuring the incorporation of 32 P from [y 32 P] ATP into DPI in the absence of exogenous phosphatidylinositol (PI). Lipids were isolated with methanol/ chloroform/HCl and were separated by thin‐layer chromatography on oxalic acid impregnated silica gel plates. DPI areas were identified by staining with iodine, scraped and measured for 32 P radioactivity. The addition of polyamines, spermine and spermidine, to the granules caused an increase of DPI synthesis, which can be catalyzed by PI kinase. This effect of polyamines in the DPI synthesis was in a dose‐dependent manner and maximal effects were observed at 1 mM spermine and 10 mM spermidine, respectively.
Migration Inhibition Factor Activity in Sera of Patients With Chronic Lymphatic Leukemia
Authors: D Benjamin, D Aderka, E Livni, H Joshua, M Shaklai, J Pinkhas
Journal: JNCI Journal of the National Cancer Institute (1979)

Migration inhibition factor (MIF) activity, expressed as a migration Index, was studied in the sera of 48 chronic lymphatic leukemia (CLL) patients and 48 healthy controls. MIF activity was detected In the sera of 50% of the CLL patients. The medical condition of patients in advanced clinical stages (III and IV) and with detectable MIF activity was more stable (after 18-mo follow-up) than was that of the patients In advanced stages but without detectable MIF activity. No relationship was found between the clinical stage of the disease, absolute lymphocyte count, and MIF activity.
Treatment for the Economy
Authors: S. C. Lewsen
Journal: BMJ (1966)

<h3>Background</h3> The incidence of oral cancer is increasing. Guidance for oral cancer from the National Institute for Health and Care Excellence (NICE) is unique in recommending cross-primary care referral from GPs to dentists. <h3>Aim</h3> This review investigates knowledge about delays in the diagnosis of symptomatic oral squamous cell carcinoma (OSCC) in primary care. <h3>Design and setting</h3> An independent multi-investigator literature search strategy and an analysis of study methodologies using a modified data extraction tool based on Aarhus checklist criteria relevant to primary care. <h3>Method</h3> The authors conducted a focused systematic review involving document retrieval from five databases up to March 2018. Included were studies looking at OSCC diagnosis from when patients first accessed primary care up to referral, including length of delay and stage of disease at time of definitive diagnosis. <h3>Results</h3> From 538 records, 16 articles were eligible for full-text review. In the UK, more than 55% of patients with OSCC were referred by their GP, and 44% by their dentist. Rates of prescribing between dentists and GPs were similar, and both had similar delays in referral, though one study found greater delays attributed to dentists as they had undertaken dental procedures. On average, patients had two to three consultations before referral. Less than 50% of studies described the primary care aspect of referral in detail. There was no information on inter-GP–dentist referrals. <h3>Conclusion</h3> There is a need for primary care studies on OSCC diagnosis. There was no evidence that GPs performed less well than dentists, which calls into question the NICE cancer option to refer to dentists, particularly in the absence of robust auditable pathways.
The Trp64Arg mutation of the beta3 adrenergic receptor gene has no effect on obesity phenotypes in the Québec Family Study and Swedish Obese Subjects cohorts.
Authors: J Gagnon, P Mauriège, S Roy, D Sjöström, Y C Chagnon, F T Dionne, J M Oppert, L Pérusse, L Sjöström, C Bouchard
Journal: Journal of Clinical Investigation (1996)

The beta adrenergic system plays a key role in regulating energy balance through the stimulation of both thermogenesis and lipid mobilization in brown and white adipose tissues in human and various animal models. Recent studies have suggested that a missense Trp64Arg mutation in the beta3 adrenergic receptor (ADRB3) gene was involved in obesity and insulin resistance. We have investigated the effect of this mutation on obesity-related phenotypes in two cohorts: the Québec Family Study (QFS) and the Swedish Obese Subjects (SOS). In QFS, no association was found between this mutation and body mass index (BMI), body fat including abdominal visceral fat, resting metabolic rate, various diabetes and cardiovascular risk factors, and changes in body weight and body fat over a 12-yr period. With the exception of RMR (P = 0.04), no evidence of linkage was detected between the mutation and phenotypes of QFS based on sib-pair data. In SOS, the frequency of the Trp64Arg allele was not significantly different between nonobese and obese female subjects and no association was found between the mutation and body weight gain over time. These findings do not support the view that there is an association between the Trp64Arg mutation in the ADRB3 gene and obesity.
Plasma Leptin and the Risk of Cardiovascular Disease in the West of Scotland Coronary Prevention Study (WOSCOPS)
Authors: A. Michael Wallace, Alex D. McMahon, Chris J. Packard, Anne Kelly, James Shepherd, Allan Gaw, Naveed Sattar
Journal: Circulation (2001)

Leptin plays a role in fat metabolism and correlates with insulin resistance and other markers of the metabolic syndrome, independent of total adiposity. Therefore, we hypothesized that raised leptin levels may identify men at increased risk of a coronary event in the West of Scotland Coronary Prevention Study (WOSCOPS). Methods and Results- Plasma leptin levels were measured at baseline in 377 men (cases) who subsequently experienced a coronary event and in 783 men (controls) who remained free of an event during the 5-year follow-up period of the study. Controls were matched to cases on the basis of age and smoking history and were representative of the entire WOSCOPS cohort. Leptin levels were significantly higher in cases than controls (5.87+/-2.04 ng/mL versus 5.04+/-2.09 ng/mL, P<0.001). In univariate analysis, for each 1 SD increase in leptin, the relative risk (RR) of an event increased by 1.25 (95% confidence interval [CI], 1.10 to 1.43; P<0.001). There was minimal change in this RR with correction for body mass index (RR, 1.24; 95% CI, 1.06 to 1.45; P=0.006) or with further correction for classic risk factors, including age, lipids, and systolic blood pressure (RR, 1.20; 95% CI, 1.02 to 1.42; P=0.03). Leptin correlated with C-reactive protein (r=0.24, P<0.001) and, even with this variable added to the model, leptin retained significance as a predictor of coronary events (RR, 1.18; 95% CI, 1.00 to 1.39; P=0.05) at the expense of C-reactive protein.We show, for the first time, in a large prospective study that leptin is a novel, independent risk factor for coronary heart disease.