tbuckley/cabot-search huggingface dataset:
Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial
Authors: James Chih-Hsin Yang, Jin-Yuan Shih, Wu-Chou Su, Te-Chun Hsia, Chun-Ming Tsai, Sai-Hong Ignatius Ou, Chung-Jen Yu, Gee-Chen Chang, Ching-Liang Ho, Lecia V Sequist, Arkadiusz Z Dudek, Mehdi Shahidi, Xiuyu Julie Cong, Robert M Lorence, Pan-Chyr Yang, Vincent A Miller
Journal: The Lancet Oncology (2012)
Analysis of Prognostic Factors of Comprehensive Geriatric Assessment and Development of a Clinical Scoring System in Elderly Asian Patients With Cancer
Authors: Ravindran Kanesvaran, Huihua Li, Khai-Nee Koo, Donald Poon
Journal: Journal of Clinical Oncology (2011)

To determine the impact of each comprehensive geriatric assessment (CGA) domain on overall survival (OS) and develop a prognostic scoring system for elderly patients with cancer.A retrospective analysis of CGA data collected from 249 consecutive patients with cancer who attended the outpatient geriatric oncology clinic at the National Cancer Center Singapore age 70 years or older was performed. Univariate and multivariate analyses were performed using Cox proportional hazards method to identify significant prognostic factors within the CGA. A simple nomogram to predict OS was developed using regression coefficients from the multivariate model. Concordance between predicted and observed response of the individual patient score was evaluated by means of Harrell's c-index. Calibration was performed using simulated data via bootstrap.Median age of the patients was 77 years (range, 70 to 94 years). In our model, age (hazard ratio [HR], 1.04; 95% CI, 1.01 to 1.07), abnormal albumin level (HR, 1.97; 95% CI, 1.23 to 3.15), poor Eastern Cooperative Oncology Group performance status (≥ 2 v < 2: HR, 1.77; 95% CI, 1.15 to 2.72), abnormal geriatric depression scale status (HR, 1.81; 95% CI, 1.29 to 2.56), high malnutrition risk (high v low risk: HR, 1.84; 95% CI, 1.17 to 2.87), and advanced disease stage (late v early: HR, 1.71; 95% CI, 0.98 to 2.95) were independent predictors of survival.Results confirm the importance of the CGA in assessment of elderly patients with cancer. The development of this nomogram incorporating these prognostic factors helps predict OS of patients, for further intervention.
Assessment of Aortic Valve Stenosis Severity
Authors: Damien Garcia, Philippe Pibarot, Jean G. Dumesnil, Frédéric Sakr, Louis-Gilles Durand
Journal: Circulation (2000)

Background —Fluid energy loss across stenotic aortic valves is influenced by factors other than the valve effective orifice area (EOA). We propose a new index that will provide a more accurate estimate of this energy loss. Methods and Results —An experimental model was designed to measure EOA and energy loss in 2 fixed stenoses and 7 bioprosthetic valves for different flow rates and 2 different aortic sizes (25 and 38 mm). The results showed that the relationship between EOA and energy loss is influenced by both flow rate and aortic cross-sectional area (A A ) and that the energy loss is systematically higher (15±2%) in the large aorta. The coefficient (EOA×A A )/(A A −EOA) accurately predicted the energy loss in all situations ( r 2 =0.98). This coefficient is more closely related to the increase in left ventricular workload than EOA. To account for varying flow rates, the coefficient was indexed for body surface area in a retrospective study of 138 patients with moderate or severe aortic stenosis. The energy loss index measured by Doppler echocardiography was superior to the EOA in predicting the end points, which were defined as death or aortic valve replacement. An energy loss index ≤0.52 cm 2 /m 2 was the best predictor of adverse outcomes (positive predictive value of 67%). Conclusions —This new energy loss index has the potential to reflect the severity of aortic stenosis better than EOA. Further prospective studies are necessary to establish the relevance of this index in terms of clinical outcomes.
Effect of endogenous angiotensin II on renal nerve activity and its cardiac baroreflex regulation.
Authors: G F Dibona, S Y Jones, L L Sawin
Journal: Journal of the American Society of Nephrology (1998)

The effects of physiologic alterations in endogenous angiotensin II activity on basal renal sympathetic nerve activity and its cardiac baroreflex regulation were studied. The effect of angiotensin II type 1 receptor blockade with intracerebroventricular losartan was examined in conscious rats consuming a low, normal, or high sodium diet that were instrumented for the simultaneous measurement of right atrial pressure and renal sympathetic nerve activity. The gain of cardiac baroreflex regulation of renal sympathetic nerve activity (% delta renal sympathetic nerve activity/mmHg mean right atrial pressure) was measured during isotonic saline volume loading. Intracerebroventricular losartan did not decrease arterial pressure but significantly decreased renal sympathetic nerve activity in low (-36+/-6%) and normal (-24+/-5%), but not in high (-2+/-3%) sodium diet rats. Compared with vehicle treatment, losartan treatment significantly increased cardiac baroreflex gain in low (-3.45+/-0.20 versus -2.89+/-0.17) and normal (-2.89+/-0.18 versus -2.54+/-0.14), but not in high (-2.27+/-0.15 versus -2.22+/-0.14) sodium diet rats. These results indicate that physiologic alterations in endogenous angiotensin II activity tonically influence basal levels of renal sympathetic nerve activity and its cardiac baroreflex regulation.
Abstract 3752: Folate receptor expression prevalence across multiple tumor types and concordance between matched primary and metastatic tumor pairs
Authors: Hewei Li, Qiuyan Wu, Guan Xing, Vic Teslenko, Jan Van Tornout, Christoph M. Ahlers, Fei Huang
Journal: Cancer Research (2010)

Abstract Background: The human folate receptor (FR) is selectively overexpressed in a number of human epithelial malignancies, including ovarian, renal, and prostate cancers. Folate-conjugated therapies provide a strategy for targeting patients with FR expressing tumors. Identification of patients with FR expressing tumors is important to increase the opportunity for clinical benefit from folate conjugated therapies. The goals of this study are to determine the prevalence of FRα expression in various solid tumors, and to determine the concordance of FRα expression between primary and matched metastatic tumors. This concordance could help to determine if primary tumor samples would be suitable for assessing FR expression in metastatic tumors. Little information on this is currently available. Methods: FRα expression was analyzed by immunohistochemistry (IHC) in 339 primary tumors covering a wide range of human tumor types. Concordance of FRα status in 86 archived primary and matched metastatic breast, renal, endometrial and ovarian tumors was assessed by IHC. Results: FRα expression prevalence was moderate to high in primary tumors of lung (13/29; 45%), renal (66/115; 57%), colon (17/27; 63%), prostate (8/12; 67%) and ovarian (22/29; 76%). FRα expression frequency was found relatively low in breast tumor (26/127; 20%) which is consistent with previous reports. Furthermore, for the first time, we showed a good concordance (81.4%) of FRα expression between paired primary and metastatic ovarian, endometrial, renal and breast malignancies. Conclusions: FRα is frequently overexpressed in ovarian, prostate, colon and renal tumors, suggesting these tumor patients might benefit more from folate conjugated therapies. New findings from this study show that FRα expression is maintained in metastatic tumors, indicating the utility of archived primary tumor samples for determining the FR positivity of metastatic tumors in patients receiving a folate conjugated agent. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3752.
S-adenosyl-L-methionine synthetase and phospholipid methyltransferase are inhibited in human cirrhosis
Authors: Antonio Martín Duce, Pablo Ortíz, Carmen Cabrero, José M. Mato
Journal: Hepatology (1988)

We have measured the activity S -adenosyl-L-methio-nine synthetase in liver biopsies from a group of controls (n = 17) and in 26 cirrhotics (12 alcoholic and 14 posthepatitic). The activity of this enzyme was markedly reduced in the group of cirrhotics (285 ± 32 pmoles per min per mg protein) when compared with that observed in controls (505 ± 37 pmoles per min per mg protein). No differences in S -adenosyl-L-methionine synthetase was observed between both groups of cirrhotics. Similarly, a marked reduction in the activity phospholipid methyltransferase was also observed in liver biopsies from the same group of cirrhotics (105 ± 12 pmoles per min per mg protein) when compared with the control subjects (241 ± 13 pmoles per min per mg protein). Again, no difference in the activity of this enzyme was observed between both groups of cirrhotics. These results indicated a marked deficiency in the metabolism of S -adenosyl-L-methionine in cirrhosis.
The superoxide scavenger TEMPOL induces urokinase receptor (uPAR) expression in human prostate cancer cells
Authors: Danielle Lejeune, Mohammad Hasanuzzaman, Amanda Pitcock, Joseph Francis, Inder Sehgal
Journal: Molecular Cancer (2006)

Abstract There is little understanding of the effect that reactive oxygen metabolites have on cellular behavior during the processes of invasion and metastasis. These oxygen metabolites could interact with a number of targets modulating their function such as enzymes involved in basement membrane dissolution, adhesion molecules involved in motility or receptors involved in proliferation. We investigated the effect of increased scavenging of superoxide anions on the expression of the urokinase receptor (uPAR) in PC-3M human prostate cancer cells. Urokinase receptor is a GPI-linked cell surface molecule which mediates multiple functions including adhesion, proliferation and pericellular proteolysis. Addition of the superoxide scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy (TEMPOL) to PC-3M cultures stimulated expression of uPAR protein peaking between 48 and 72 hours. Cell surface expression of the uPAR was also increased. Surprisingly, uPAR transcript levels increased only slightly and this mild increase did not coincide with the striking degree of protein increase. This disparity indicates that the TEMPOL effect on uPAR occurs through a post-transcriptional mechanism. TEMPOL presence in PC-3M cultures reduced intracellular superoxide-type species by 75% as assayed by NBT dye conversion; however this reduction significantly diminished within hours following TEMPOL removal. The time gap between TEMPOL treatment and peak uPAR protein expression suggests that reduction of reactive oxygen metabolites in prostate cancer cells initiates a multistep pathway which requires several hours to culminate in uPAR induction. These findings reveal a novel pathway for uPAR regulation involving reactive oxygens such as superoxide anion.
US states get healthcare ratings
Authors: Janice Hopkins Tanne
Journal: BMJ (2005)

Americans can now get information about how well their state is providing vaccinations, prenatal care, pneumococcal vaccine for elderly people—and many more details.

The quality of health care that Americans get varies widely from state to state, according to statistics from the second annual report comparing the 50 states and the District of Columbia. The report, from the Agency for Health Care Research and Quality, looks at …
Bone loss before the clinical onset of rheumatoid arthritis in subjects with anticitrullinated protein antibodies
Authors: Arnd Kleyer, Stephanie Finzel, Jürgen Rech, Bernhard Manger, Manuel Krieter, Francesca Faustini, Elisabeth Araujo, Axel J Hueber, Ulrike Harre, Klaus Engelke, Georg Schett
Journal: Annals of the Rheumatic Diseases (2013)

Anticitrullinated protein antibodies (ACPA) are a major risk factor for bone loss in rheumatoid arthritis (RA). We have recently shown that ACPA directly induce bone loss by stimulating osteoclast differentiation. As ACPA precede the clinical onset of RA by years, we hypothesised that ACPA positive healthy individuals may already show skeletal changes.We performed a comparative micro-CT analysis of the bone microstructure in the metacarpophalangeal joints of ACPA positive and ACPA negative healthy individuals without clinical signs of arthritis.ACPA positive (n=15) and negative (n=15) healthy individuals were not different in age (48.2±4.1 vs 51.4±3.8 years, p=0.57) or gender (eight women and two men in both groups). Bone mineral density was significantly reduced in ACPA positive individuals (mean±SEM 280±11 mg/cm(3)) compared with controls (327±6). Bone loss was based on cortical bone changes, with significant (p=0.044) reduction in cortical thickness in the ACPA positive group (mean±SEM 0.22±0.03 mm) compared with controls (0.32±0.03 mm). Areas of cortical porosity were significantly (p=0.0005) more widespread in ACPA positive (mean±SEM 7.4±1.4%) than in ACPA negative individuals (1.0±0.3%).Structural bone damage starts before the clinical onset of arthritis in subjects with ACPA. These findings revise the concept that bone damage is an exclusive consequence of synovitis in patients with RA.
Responsiveness to anti-tumour necrosis factor α therapy is related to pre-treatment tissue inflammation levels in rheumatoid arthritis patients
Authors: T C van der Pouw Kraan, C A Wijbrandts, L G van Baarsen, F Rustenburg, J M Baggen, C L Verweij, P P Tak
Journal: Annals of the Rheumatic Diseases (2007)

Objective: The response of rheumatoid arthritis (RA) patients to treatment with neutralising antibodies to tumour necrosis factor α (TNFα) is highly variable. The underlying mechanism for therapy responsiveness is currently unknown. We therefore evaluated the relationship between baseline molecular profiles of synovial tissues from RA patients and the clinical response to treatment with infliximab. Methods: Synovial biopsies were obtained by arthroscopy from 18 RA patients with active disease (28 joint count Disease Activity Score (DAS28)⩾3.2) before initiation of treatment with infliximab. All patients were on stable methotrexate treatment. Clinical response at 16 weeks was defined as a reduction in DAS28 of ⩾1.2, non-response as reduction in DAS28 &lt;1.2. Large-scale gene expression profiling using microarrays was performed on synovial tissue samples. To identify biological processes in synovial biopsies that could discriminate between responders and non-responders, we performed pathway analysis on the expression profiles. Results: A total of 12 patients responded to therapy, while 6 patients failed to fulfil the response criteria. We identified several biological processes, related to inflammation, which were up-regulated in patients who responded to therapy, compared to those who did not show clinical improvement. Conclusion: These results indicate that patients with a high level of tissue inflammation are more likely to benefit from anti-TNFα treatment.
Notch signalling regulates fibroblast activation and collagen release in systemic sclerosis
Authors: C. Dees, M. Tomcik, P. Zerr, A. Akhmetshina, A. Horn, K. Palumbo, C. Beyer, J. Zwerina, O. Distler, G. Schett, J. H. W. Distler
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> Dermal fibroblasts from patients with systemic sclerosis (SSc) release excessive amounts of collagen resulting in tissue fibrosis. The molecular mechanisms underlying this pathological activation are incompletely understood. <h3>Objective</h3> To investigate whether Notch signalling contributes to the uncontrolled activation of fibroblasts in SSc. <h3>Methods</h3> Activation of the Notch pathway was assessed by immunohistochemistry or Western blot for the Notch intracellular domain and the Notch ligand Jagged-1 (Jag-1) and real-time PCR for the target gene hes-1. Differentiation of resting dermal fibroblasts into myofibroblasts was assessed by staining for α-smooth muscle actin. The synthesis of collagen was quantified by real-time PCR and Sircol assays. <h3>Results</h3> Notch signalling was activated in lesional skin of patients with SSc. The activation persisted in cultured dermal SSc fibroblasts. Stimulation of healthy dermal fibroblasts with recombinant human Jag-1-Fc chimera resulted in an SSc-like phenotype with increased release of collagen and differentiation of resting fibroblasts into myofibroblasts. Consistent with the selective activation of the Notch pathway in dermal SSc fibroblasts, DAPT or siRNA against Notch strongly reduced the basal collagen expression in SSc fibroblasts, but not in fibroblasts from healthy volunteers. <h3>Conclusion</h3> It was shown that Notch signalling is activated in SSc and plays an important role in fibroblast activation and collagen release. Inhibition of Notch signalling might be an effective strategy to selectively prevent the aberrant activation of SSc fibroblasts.
THE TREATMENT OF PAINFUL "FROST-BITE."
Authors: W. C. Davis
Journal: BMJ (1915)

j per cent., and most recently in metlhod (1) sterile water.The urea and quinine hydrochloride requires a little longer to act, but its effect is more prolonged than that produced by novocain, otherwise thero is nothing to choose between them; whil&t for an intradermiiic injection, water alone is perfectly satisfactory.At first we were doubtful of the action of this anaesthetic on the vitality of tlle grafts, btit even whlen transferred direct to the wound they took perfectly, altlhoucgh as a matter of convenience in lhandling, we, as a rule, puit tlhem first into warm saline.Tbe advantages of a local over a general anaestlhetic for this purpose are obviotus.There is Ino need of an assistant, of previous preparation of the patient, or of moving the p)atient from his bed.In the eyes of the patient it appears a iuielh nmore triffinr btisiness-an imiportant point if it hias to be done frequiently, as in the case of large wounds, or repeated if the first grafts fail to take.Lastly, perlhaps, if one can skin-graft witlh no more trotuble than doitig a dressing, one will be inclined to graft even sm11all wNounds, wlicilh would lheal perfectly well witlh- out it, but in wlichl, nevertlheless, a weelk or ten days can tlhereby be saved.
Long term effects of smoke inhalation in survivors of the King's Cross underground station fire.
Authors: P W Fogarty, P J George, M Solomon, S G Spiro, R F Armstrong
Journal: Thorax (1991)

BACKGROUND: In most accidents causing smoke inhalation only a few victims actually inhale the smoke. The fire at King9s Cross provided an opportunity to assess the long term effects of smoke inhalation in a larger number of patients. METHODS: Fourteen survivors from the King9s Cross underground station fire were assessed for respiratory disability six months after the disaster and 10 were reassessed at two years. All had inhaled substantial quantities of smoke and 10 had skin burns of differing severity. RESULTS: Six months after the fire nine survivors admitted to one or more symptoms, which included hoarseness (two cases), cough (five cases), and breathlessness (six cases); and a survivor with asthma noted a worsening of his symptoms. The remaining five denied new symptoms. Peak expiratory flow, spirometric indices, and transfer factor for carbon monoxide were within the predicted normal ranges. The mean residual volume, however, was greater than the predicted value and the mean maximum expiratory flow at 25% of vital capacity (V25) less than predicted, with no significant differences between smokers (n = 7) and non-smokers (n = 7). At least one of these ventilatory defects, suggesting small airways obstruction, was present in 11 survivors at six months and they had persisted in the seven patients who were reassessed at two years. CONCLUSION: Smoke inhalation may be associated with injury to the small airways.
The Mitochondrial-Derived Peptide MOTS-c Promotes Metabolic Homeostasis and Reduces Obesity and Insulin Resistance
Authors: Changhan Lee, Jennifer Zeng, Brian G. Drew, Tamer Sallam, Alejandro Martin-Montalvo, Junxiang Wan, Su-Jeong Kim, Hemal Mehta, Andrea L. Hevener, Rafael de Cabo, Pinchas Cohen
Journal: Cell Metabolism (2015)
neu Antigen-Negative Variants Can Be Generated after neu-Specific Antibody Therapy in neu Transgenic Mice
Authors: Keith L. Knutson, Bond Almand, Yushe Dang, Mary L. Disis
Journal: Cancer Research (2004)

Abstract Prolonged administration of HER-2/neu-specific monoclonal antibody therapy is now widely used for the treatment of HER-2/neu-overexpressing tumors in advanced-stage breast cancer patients. Monoclonal antibody therapy has the potential to promote reduced tumor expression of HER-2/neu by receptor down-modulation and/or the generation of antigen-negative variants. Loss of antigen by either mechanism could potentially impact subsequent therapeutic strategies targeting HER-2/neu. In this study, the effects of chronic neu-specific monoclonal antibody therapy on tumor growth and neu protein expression were examined in a murine model of neu-overexpressing breast cancer. Treatment of neu-overexpressing tumors with neu-specific antibody, in vitro or in vivo, resulted in significant tumor growth inhibition. When neu antibody was used to treat neu-overexpressing tumor cells both in vitro and in vivo in tumor-bearing mice, neu receptor expression was not diminished after cessation of therapy. However, in the setting of clinically undetectable disease in a fraction of animals, antigen-negative variants were generated. An understanding of the effects of monoclonal antibodies on target antigen expression is critical for the future design and testing of novel HER-2/neu-targeted therapies administered in combination with or after HER-2/neu-specific monoclonal antibody therapy.
In vivo treatment of (NZB X NZW)F1 lupus-like nephritis with monoclonal antibody to gamma interferon.
Authors: C O Jacob, P H van der Meide, H O McDevitt
Journal: The Journal of Experimental Medicine (1987)

The (NZB X NZW)F1 mouse is recognized as an important animal model of the human disease systemic lupus erythematosus (SLE). Groups of NZB/W F1 mice were treated either with IFN-gamma or with PBS. The results demonstrate that IFN-treated animals have accelerated development of fatal immune complex glomerulonephritis relative to age-matched controls. On the other hand, administration of mAbs specific for IFN-gamma to such mice from 4 to 7 mo of age resulted in significant remission. Development of both proteinuria and anti-DNA antibodies were delayed and survival at 11 mo was increased from less than 20% to 95% in treated mice relative to controls (p less than or equal to 0.001). These findings may have therapeutic implications for the treatment of SLE.
Sex hormones, glucocorticoids and autoimmunity: facts and hypotheses.
Authors: J A Da Silva
Journal: Annals of the Rheumatic Diseases (1995)

Increasing knowledge on the regulation of immune responses over the past decade has made it clear that the immune system is involved in complex interactions with most, if not all, of the biological systems responsible for normal homeostasis.The evidence for important interplays between the immune and endocrine systems has launched the whole new field of neuroimmunoendocrinology which has attracted the interest of scientists and clinicians alike.The mechanisms involved in the interactions between adrenal and gonadal steroids and the immune system are poorly understood, however, and further clarification could have important implications in the understanding of the pathogenesis and treatment of auto- immune diseases.