tbuckley/cabot-search huggingface dataset:
Stereotactic body radiation therapy for management of spinal metastases in patients without spinal cord compression: a phase 1–2 trial
Authors: Xin Shelley Wang, Laurence D Rhines, Almon S Shiu, James N Yang, Ugur Selek, Ibrahima Gning, Ping Liu, Pamela K Allen, Syed S Azeem, Paul D Brown, Hadley J Sharp, David C Weksberg, Charles S Cleeland, Eric L Chang
Journal: The Lancet Oncology (2012)

Spinal stereotactic body radiation therapy (SBRT) is increasingly used to manage spinal metastases, yet the technique's effectiveness in controlling the symptom burden of spinal metastases has not been well described. We investigated the clinical benefit of SBRT for managing spinal metastases and reducing cancer-related symptoms.149 patients with mechanically stable, non-cord-compressing spinal metastases (166 lesions) were given SBRT in a phase 1-2 study. Patients received a total dose of 27-30 Gy, typically in three fractions. Symptoms were measured before SBRT and at several time points up to 6 months after treatment, by the Brief Pain Inventory (BPI) and the M D Anderson Symptom Inventory (MDASI). The primary endpoint was frequency and duration of complete pain relief. The study is completed and is registered with ClinicalTrials.gov, number NCT00508443.Median follow-up was 15·9 months (IQR 9·5-30·3). The number of patients reporting no pain from bone metastases, as measured by the BPI, increased from 39 of 149 (26%) before SBRT to 55 of 102 (54%) 6 months after SBRT (p<0·0001). BPI-reported pain reduction from baseline to 4 weeks after SBRT was clinically meaningful (mean 3·4 [SD 2·9] on the BPI pain-at-its-worst item at baseline, 2·1 [2·4] at 4 weeks; effect size 0·47, p=0·00076). These improvements were accompanied by significant reduction in opioid use during the first 6 months after SBRT (43 [28·9%] of 149 patients with strong opioid use at baseline vs 20 [20·0%] of 100 at 6 months; p=0·011). Ordinal regression modelling showed that patients reported significant pain reduction according to the MDASI during the first 6 months after SBRT (p=0·00003), and significant reductions in a composite score of the six MDASI symptom interference with daily life items (p=0·0066). Only a few instances of non-neurological grade 3 toxicities occurred: nausea (one event), vomiting (one), diarrhoea (one), fatigue (one), dysphagia (one), neck pain (one), and diaphoresis (one); pain associated with severe tongue oedema and trismus occurred twice; and non-cardiac chest pain was reported three times. No grade 4 toxicities occurred. Progression-free survival after SBRT was 80·5% (95% CI 72·9-86·1) at 1 year and 72·4% (63·1-79·7) at 2 years.SBRT is an effective primary or salvage treatment for mechanically stable spinal metastasis. Significant reductions in patient-reported pain and other symptoms were evident 6 months after SBRT, along with satisfactory progression-free survival and no late spinal cord toxicities.National Cancer Institute of the US National Institutes of Health.
THE ABILITY OF BACTERIAL LIPOPOLYSACCHARIDE TO MODULATE THE INDUCTION OF UNRESPONSIVENESS TO A STATE OF IMMUNITY
Authors: J. A. Louis, J. M. Chiller, W. O. Weigle
Journal: The Journal of Experimental Medicine (1973)

Studies were performed to define the cellular parameters involved in the interference with the induction of immunologic unresponsiveness to human gamma globulin (HGG) by bacterial lipopolysaccharide (LPS). Mice which were injected with deaggregated HGG (tolerogen) and with LPS did not become tolerant to that antigen, but rather became primed to a subsequent challenge with immunogen. The ability to prime with tolerogen and LPS was also demonstrated in an adoptive transfer system. The temporal relationship between the injection of tolerogen and that of LPS was critical for priming to occur. The injection of tolerogen and LPS not only primed mice to HGG, but also resulted in a primary antibody response to HGG. The capacity of LPS to interfere with the induction of tolerance was restricted to B cells and did not affect the ability to induce unresponsiveness in T cells. The secondary response to HGG in mice primed by tolerogen and LPS was found to be T-cell independent. These observations are interpreted and discussed from the standpoint of the ability of LPS to circumvent required T-cell cooperation and to modulate to tolerogenic stimulus into an immunogenic signal.
Multivariate analysis of the association of acid and duodeno-gastro-oesophageal reflux exposure with the presence of oesophagitis, the severity of oesophagitis and Barrett's oesophagus
Authors: G H Koek, D Sifrim, T Lerut, J Janssens, J Tack
Journal: Gut (2008)

<h3>Background:</h3> Exposure to acid and duodeno-gastro-oesophageal reflux (DGOR) both increase with oesophageal lesions in gastro-oesophageal reflux disease (GORD). It is unknown whether DGOR exposure is an independent risk factor for oesophageal lesions. A multivariate analysis was performed on the relationship between oesophageal lesions and demographics and acid and DGOR exposure. <h3>Methods:</h3> In 422 patients with suspected GORD, upper endoscopy, oesophageal manometry, and pH and DGOR monitoring were performed. Stepwise logistic regression was used to identify factors associated with the presence of oesophagitis, severity of oesophagitis and the presence of Barrett's oesophagus. ORs and 95% CIs were computed at different cut-offs. <h3>Results:</h3> 54% of the patients had no oesophagitis, 36% had grade A–B oesophagitis, 3% had grade C–D oesophagitis and 7% had Barrett's oesophagus. In multivariate analysis, oesophagitis was associated with hiatal hernia (OR 3.621, 95% CI 2.263 to 5.794) and DGOR exposure (OR up to 2.236, 95% CI 1.356–3.685), while a low body mass index (BMI) seemed protective (OR for BMI &gt;first quartile 2.245, 95% CI 1.371 to 3.677). Severity of oesophagitis was only associated with acid exposure (OR up to 5.038, 95% CI 1.452 to 17.480). The presence of Barrett's oesophagus was associated with male sex (OR 3.621, 95% CI 2.263 to 5.794), DGOR (OR up to 5.017, 95% CI 2.051 to 12.274) and acid exposure (OR up to 3.031, 95% CI 1.216 to 7.556). <h3>Conclusions:</h3> Several independent factors are associated with oesophageal lesions in GORD. The risk of oesophagitis is associated with hiatal hernia, BMI and DGOR exposure; severity of oesophagitis depends on acid exposure; and Barrett's oesophagus is associated with male sex and exposure to both acid and DGOR.
Smart MoS<sub>2</sub>/Fe<sub>3</sub>O<sub>4</sub> Nanotheranostic for Magnetically Targeted Photothermal Therapy Guided by Magnetic Resonance/Photoacoustic Imaging
Authors: Jie Yu, Wenyan Yin, Xiaopeng Zheng, Gan Tian, Xiao Zhang, Tao Bao, Xinghua Dong, Zhongliang Wang, Zhanjun Gu, Xiaoyan Ma, Yuliang Zhao
Journal: Theranostics (2015)

The ability to selectively destroy cancer cells while sparing normal tissue is highly desirable during the cancer therapy.Here, magnetic targeted photothermal therapy was demonstrated by the integration of MoS 2 (MS) flakes and Fe 3 O 4 (IO) nanoparticles (NPs), where MoS 2 converted near-infrared (NIR) light into heat and Fe 3 O 4 NPs served as target moiety directed by external magnetic field to tumor site.The MoS 2 /Fe 3 O 4 composite (MSIOs) functionalized by biocompatible polyethylene glycol (PEG) were prepared by a simple two-step hydrothermal method.And the as-obtained MSIOs exhibit high stability in bio-fluids and low toxicity in vitro and in vivo.Specifically, the MSIOs can be applied as a dual-modal probe for T 2 -weighted magnetic resonance (MR) and photoacoustic tomography (PAT) imaging due to their superparamagnetic property and strong NIR absorption.Furthermore, we demonstrate an effective result for magnetically targeted photothermal ablation of cancer.All these results show a great potential for localized photothermal ablation of cancer spatially/timely guided by the magnetic field and indicated the promise of the multifunctional MSIOs for applications in cancer theranostics.
Human alveolar macrophages synthesize factor VII in vitro. Possible role in interstitial lung disease.
Authors: H A Chapman, C L Allen, O L Stone, D S Fair
Journal: Journal of Clinical Investigation (1985)

Both fibrin and tissue macrophages are prominent in the histopathology of chronic inflammatory pulmonary disease. We therefore examined the procoagulant activity of freshly lavaged human alveolar macrophages in vitro. Intact macrophages (5 X 10(5) cells) from 13 healthy volunteers promoted clotting of whole plasma in a mean of 65 s. Macrophage procoagulant activity was at least partially independent of exogenous Factor VII as judged by a mean clotting time of 99 s in Factor VII-deficient plasma and by neutralization of procoagulant activity by an antibody to Factor VII. Immunoprecipitation of extracts of macrophages metabolically labeled with [35S]methionine by Factor VII antibody and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a labeled protein consistent in size with the known molecular weight of blood Factor VII, 48,000. The addition of 50 micrograms of unlabeled, purified Factor VII blocked recovery of the 48,000-mol wt protein. In addition, supernatants of cultured macrophages from six normal volunteers had Factor X-activating activity that was suppressed an average of 71% after culture in the presence of 50 microM coumadin or entirely by the Factor VII antibody indicating that Factor VII synthesized by the cell was biologically active. Endotoxin in vitro induced increases in cellular tissue factor but had no consistent effect on macrophage Factor VII activity. We also examined the tissue factor and Factor VII activities of freshly lavaged alveolar cells from nine subjects with clinical and/or histologic evidence of sarcoidosis. Four of the nine subjects expressed increased tissue factor and seven of nine had increased Factor VII activity over the normal range (P less than 0.01). We estimate the mean Factor VII associated with the cells of sarcoid patients to be 4.7 ng/10(6) cells (range 0.4-20) as compared to a mean of 0.74 ng/10(6) cells (range 0.2-2) for that of normal subjects. Along with previous data showing synthesis of plasminogen activator, these findings indicate that human alveolar macrophages normally synthesize and express measurable amounts of the initial enzymes of proteolytic reactions regulating both fibrin deposition and fibrin resorption. Abnormalities in Factor VII activity in a small group of patients with sarcoidosis raise the possibility that modulation of fibrin turnover by macrophages may contribute to the pathology of this and perhaps other interstitial lung diseases.
Predicting pneumococcal community-acquired pneumonia in the emergency department
Authors: S.M. Huijts, W.G. Boersma, D.E. Grobbee, W.C. Gruber, K.U. Jansen, J.A.J.W. Kluytmans, B.A.F. Kuipers, F. Palmen, M.W. Pride, C. Webber, M.J.M. Bonten
Journal: Clinical Microbiology and Infection (2014)
Meta-Analysis of the Significance of Asymptomatic Bacteriuria in Diabetes
Authors: Marjo Renko, Päivi Tapanainen, Päivi Tossavainen, Tytti Pokka, Matti Uhari
Journal: Diabetes Care (2010)

OBJECTIVE To evaluate whether asymptomatic bacteriuria (ASB) is more common in patients with diabetes than among control subjects. In addition, we wanted to clarify the clinical significance of ASB in patients with diabetes. RESEARCH DESIGN AND METHODS We conducted a systematic review and meta-analysis of published data since 1966. Twenty-two studies fulfilled the inclusion criteria of the meta-analysis. RESULTS ASB was present in 439 of 3,579 (12.2%) patients with diabetes and in 121 of 2,702 (4.5%) healthy control subjects. ASB was more common both in patients with type 1 diabetes (odds ratio 3.0 [95% CI 1.1–8.0]) and type 2 diabetes (3.2 [2.0–5.2]) than in control subjects. The point prevalence of ASB was higher in both women (14.2 vs. 5.1%; 2.6 [1.6–4.1]) and men (2.3 vs. 0.8%; 3.7 [1.3–10.2]) as well as in children and adolescents (12.9 vs. 2.7%; 5.4 [2.7–11.0]) with diabetes than in healthy control subjects. Albuminuria was more common in patients with diabetes and ASB than those without ASB (2.9 [1.7–4.8]). History of urinary tract infections was associated with ASB (1.6 [1.1–2.3]). CONCLUSIONS We were able to show that the prevalence of ASB is higher in all patients with diabetes compared with control subjects. We also found that diabetic subjects with ASB more often had albuminuria and symptomatic urinary tract infections.
Emerging Concepts on the Role of Innate Immunity in the Prevention and Control of HIV Infection
Authors: Margaret E. Ackerman, Anne-Sophie Dugast, Galit Alter
Journal: Annual Review of Medicine (2011)

While neutralizing antibodies can provide sterilizing protection from HIV infection via their variable domains, the antibody constant domain provides a functional link between innate and adaptive immunity and offers a means to harness the potent antiviral properties of a wide spectrum of innate immune effector cells. There has been a growing appreciation of the role of these effector mechanisms across fields from cancer immunotherapy to autoimmunity and infectious disease, as well as speculation that this mechanism may be responsible for the protection observed in the RV144 HIV vaccine trial. This review summarizes these extraneutralizing humoral immune activities, progress in defining the importance of these effector mechanisms during progression in HIV infection, and the potential impact that such vaccine-induced immune responses may have on protection from infection.
Clinical Application of the 70-Gene Profile: The MINDACT Trial
Authors: Fatima Cardoso, Laura Van't Veer, Emiel Rutgers, Sherene Loi, Stella Mook, Martine J. Piccart-Gebhart
Journal: Journal of Clinical Oncology (2008)

The 70-gene profile is a new prognostic tool that has the potential to greatly improve risk assessment and treatment decision making for early breast cancer. Its prospective validation is currently ongoing through the MINDACT (Microarray in Node-Negative Disease May Avoid Chemotherapy) trial, a 6,000-patient randomized, multicentric trial. This article reviews the several steps in the development of the profile from its discovery to its clinical validation.
Could we abandon cyclophosphamide in systemic vasculitis and lupus nephritis?
Authors: Cees G M Kallenberg
Journal: Annals of the Rheumatic Diseases (2012)

Cyclophosphamide has greatly improved prognosis in anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV) and proliferative lupus nephritis (LN). However, the side effects of long-term cyclophosphamide treatment are considerable prompting a search for alternatives to cyclophosphamide. For maintenance treatment in AAV, azathioprine is the preferred drug with methotrexate as an alternative in the case of intolerance to azathioprine. Data on mycophenolate mofetil (MMF) for the induction of remission in AAV are being awaited, but rituximab appears as effective as cyclophosphamide in newly diagnosed patients with AAV, and is probably even better for relapsing patients, while the possibility of maintenance treatment with intermittent low-dose infusions of rituximab is being explored. In LN, low-dose intravenous cyclophosphamide is as effective as high-dose cyclophosphamide for the induction of remission, with azathioprine being used for maintenance treatment. MMF can be used in the case of intolerance to cyclophosphamide and might be the first choice in black and Hispanic patients. In the case of intolerance to both cyclophosphamide and MMF, azathioprine with pulses of methylprednisolone can be used. Here, the role of rituximab has not been established. In conclusion, alternatives are available for cyclophosphamide both in AAV and proliferative LN.
Photodynamic Therapy for Focal Retinal Pigment Epithelial Leaks Secondary to Central Serous Chorioretinopathy
Authors: Michael D. Ober, Lawrence A. Yannuzzi, Diana V. Do, Richard F. Spaide, Neil M. Bressler, Lee M. Jampol, Allison Angelilli, Chiara M. Eandi, Alice T. Lyon
Journal: Ophthalmology (2005)
Trends in the Diabetes Quality Improvement Project Measures in Maine From 1994 to 1999
Authors: Monica R. McClain, David E. Wennberg, Roger W. Sherwin, William C. Steinmann, Janet C. Rice
Journal: Diabetes Care (2003)

To examine changes in the management of patients with diabetes from 1994 to 1999 using the claims-based Diabetes Quality Improvement Project (DQIP) accountability measures.Administrative claims from an employer-based health insurance cohort in Maine were used to describe the prevalence of claims-based DQIP accountability measures-HbA(1c) testing, dilated eye examination, lipid profile, and monitoring for diabetic nephropathy-from 1994 (n = 1151) to 1999 (n = 2221) in a 100% sample of adults (18-64 years of age) with diabetes. The Mantel-Haenszel chi(2) test for trend was performed on each measure. Prevalence estimates were also stratified by three insurance products: health maintenance organization (HMO), point of service, and indemnity.There was a positive trend for all outcome measures (P < 0.001). The baseline and final frequencies (percent increase) for lipid testing, HbA(1c), dilated eye examination, and screening for diabetic nephropathy were as follows: 13-50% (257%), 37-69% (92%), 30-46% (53%), and 37-50% (36%), respectively. Individuals with diabetes and indemnity insurance were much less likely to receive these measures than individuals with other types of insurance, whereas people in HMOs were more likely to receive HbA(1c) testing and lipid profiles.The proportion of patients with diabetes receiving DQIP accountability measures significantly increased from 1994 to 1999. There is large variation in prevalence among these measures and insurance products. It is urgent to identify effective mechanisms for delivering consistent preventive care that are congruent with defined standards of benefit.
Translational Crossroads for Biomarkers
Authors: Robert C. Bast, Hans Lilja, Nicole Urban, David L. Rimm, Herbert Fritsche, Joe Gray, Robert Veltri, George Klee, Andrew Allen, Nam Kim, Steven Gutman, Mark A. Rubin, Andrew Hruszkewycz
Journal: Clinical Cancer Research (2005)

Abstract A group of investigators met at a Specialized Programs of Research Excellence Workshop to discuss key issues in the translation of biomarker discovery to the development of useful laboratory tests for cancer care. Development and approval of several new markers and technologies have provided informative examples that include more specific markers for prostate cancer, more sensitive tests for ovarian cancer, more objective analysis of tissue architecture and an earlier indication of response to treatment in breast cancer. Although there is no clear paradigm for biomarker development, several principles are clear. Marker development should be driven by clinical needs, including early cancer detection, accurate pretreatment staging, and prediction of response to treatment, as well as monitoring disease progression and response to therapy. Development of a national repository that uses carefully preserved, well-annotated tissue specimens will facilitate new marker development. Reference standards will be an essential component of this process. Both hospital-based and commercial laboratories can play a role in developing biomarkers from discovery to test validation. Partnering of academe and industry should occur throughout the process of biomarker development. The National Cancer Institute is in a unique position to bring together academe, industry, and the Food and Drug Administration to (a) define clinical needs for biomarkers by tumor type, (b) establish analytic and clinical paradigms for biomarker development, (c) discuss ways in which markers from different companies might be evaluated in combination, (d) establish computational methods to combine data from multiple biomarkers, (e) share information regarding promising markers developed in National Cancer Institute–supported programs, and (f) exchange data regarding new platforms and techniques that can accelerate marker development.
Detection of Life-Threatening Prostate Cancer With Prostate-Specific Antigen Velocity During a Window of Curability
Authors: H. Ballentine Carter, Luigi Ferrucci, Anna Kettermann, Patricia Landis, E. James Wright, Jonathan I. Epstein, Bruce J. Trock, E. Jeffrey Metter
Journal: JNCI Journal of the National Cancer Institute (2006)

Prostate-specific antigen (PSA) level is typically used as a dichotomous test for prostate cancer, resulting in overdiagnosis for a substantial number of men. The rate at which serum PSA levels change (PSA velocity) may be an important indicator of the presence of life-threatening disease.
15N studies of endogenous faecal nitrogen in infants
Authors: W. W. C. Read, D. S. McLaren, M. Tchalian
Journal: Gut (1974)

<sup>15</sup>N from labelled yeast protein, fed to marasmic and recovered infants, appeared in the stool shortly after administration and continued to be excreted for 100 hours. Unabsorbed dietary <sup>15</sup>N, which appeared with carmine-marked stools, formed only part of this excretion. Calculations of the endogenous nitrogen content of infant stool agreed closely with those of previous workers. The use of intravenously injected <sup>15</sup>N showed that part of the stool nitrogen was derived from this source. It was excreted as urea, ammonia, and other compounds, and totalled about 2% of the administered urea. The persistence of the <sup>15</sup>N in the stool suggests that it had in part been incorporated into cellular material.
Clinical and Biological Features Associated With Epidermal Growth Factor Receptor Gene Mutations in Lung Cancers
Authors: H. Shigematsu, L. Lin, T. Takahashi, M. Nomura, M. Suzuki, I. I. Wistuba, K. M. Fong, H. Lee, S. Toyooka, N. Shimizu, T. Fujisawa, Z. Feng, J. A. Roth, J. Herz, J. D. Minna, A. F. Gazdar
Journal: JNCI Journal of the National Cancer Institute (2005)

Background: Mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR) gene in lung cancers are associated with increased sensitivity of these cancers to drugs that inhibit EGFR kinase activity. However, the role of such mutations in the pathogenesis of lung cancers is unclear. Methods: We sequenced exons 18–21 of the EGFR TK domain from genomic DNA isolated from 617 non-small-cell lung cancers (NSCLCs) and 524 normal lung tissue samples from the same patients and 36 neuroendocrine lung tumors collected from patients in Japan, Taiwan, the United States, and Australia and from 243 other epithelial cancers. Mutation status was compared with clinicopathologic features and with the presence of mutations in KRAS, a gene in the EGFR signaling pathway that is also frequently mutated in lung cancers. All statistical tests were two sided. Results: We detected a total of 134 EGFR TK domain mutations in 130 (21%) of the 617 NSCLCs but not in any of the other carcinomas, nor in nonmalignant lung tissue from the same patients. In NSCLC patients, EGFR TK domain mutations were statistically significantly more frequent in never smokers than ever smokers (51% versus 10%), in adenocarcinomas versus cancer of other histologies (40% versus 3%), in patients of East Asian ethnicity versus other ethnicities (30% versus 8%), and in females versus males (42% versus 14%; all P < .001). EGFR TK domain mutation status was not associated with patient age at diagnosis, clinical stage, the presence of bronchioloalveolar histologic features, or overall survival. The EGFR TK domain mutations we detected were of three common types: in-frame deletions in exon 19, single missense mutations in exon 21, and in-frame duplications/insertions in exon 20. Rare missense mutations were also detected in exons 18, 20, and 21. KRAS gene mutations were present in 50 (8%) of the 617 NSCLCs but not in any tumors with an EGFR TK domain mutation. Conclusions: Mutations in either the EGFR TK domain or the KRAS gene can lead to lung cancer pathogenesis. EGFR TK domain mutations are the first molecular change known to occur specifically in never smokers.