tbuckley/cabot-search huggingface dataset:
Pembrolizumab for the Treatment of Non–Small-Cell Lung Cancer
Authors: Edward B. Garon, Naiyer A. Rizvi, Rina Hui, Natasha Leighl, Ani S. Balmanoukian, Joseph Paul Eder, Amita Patnaik, Charu Aggarwal, Matthew Gubens, Leora Horn, Enric Carcereny, Myung-Ju Ahn, Enriqueta Felip, Jong-Seok Lee, Matthew D. Hellmann, Omid Hamid, Jonathan W. Goldman, Jean-Charles Soria, Marisa Dolled-Filhart, Ruth Z. Rutledge, Jin Zhang, Jared K. Lunceford, Reshma Rangwala, Gregory M. Lubiniecki, Charlotte Roach, Kenneth Emancipator, Leena Gandhi
Journal: New England Journal of Medicine (2015)

We assessed the efficacy and safety of programmed cell death 1 (PD-1) inhibition with pembrolizumab in patients with advanced non–small-cell lung cancer enrolled in a phase 1 study. We also sought to define and validate an expression level of the PD-1 ligand 1 (PD-L1) that is associated with the likelihood of clinical benefit.
Insulin-sensitizing thiazolidinedione improves coronary endothelial dysfunction in insulin resistance by PET measurements of myocardial blood flow
Authors: Miguel Hernandez-Pampaloni, Manuel Quiñones, Isabel Bulnes-Enriquez, Xotohil Jimenez, Gustavo Hernandez, Roxana De la Rosa, Zoe Sarnat, Willa Hsueh, Heinrich R. Schelbert
Journal: Journal of the American College of Cardiology (2002)
Detection of immune complexes in systemic sclerosis and Raynaud's phenomenon
Authors: PAULINE M. DOWD, J.D. KIRBY, E.J. HOLBOROW, E.D. COOKE, S.A. BOWCOCK
Journal: British Journal of Dermatology (1981)

Phagocytosed immune complexes in polymorphonuclear leukocytes of nineteen patients with Raynaud's phenomenon were detected by scoring the cells for IgG and C3 inclusions. Parallel estimations of circulating immune complexes were made by liquid phase C1q binding and polyethylene glycol (PEG) precipitation methods. The results were compared with the degree of cold stress-induced vasospasm measured by quantified infra-red thermography. Thirteen of nineteen patients with Raynaud's phenomenon compared with only one of seventeen normal controls showed significantly elevated levels of phagocytosed IgG. The correlation of IgG and C3 scores for individual patients was high and the IgG and C3 scores correlated well with the thermographic assessment of the severity of the Raynaud's phenomenon. Two of the patients had elevated levels of circulating immune complexes detectable by raised levels of C1q binding, four patients had raised IgG and three patients raised IgM complexes detectable by PEG precipitation. None of the controls had elevated levels of circulating immune complexes detectable by either method. There was no correlation between the levels of circulating and phagocytosed immune complexes.
The unpredictability paradox: review of empirical comparisons of randomised and non-randomised clinical trials
Authors: R. Kunz, A. D Oxman
Journal: BMJ (1998)

To summarise comparisons of randomised clinical trials and non-randomised clinical trials, trials with adequately concealed random allocation versus inadequately concealed random allocation, and high quality trials versus low quality trials where the effect of randomisation could not be separated from the effects of other methodological manoeuvres.Systematic review.Cohorts or meta-analyses of clinical trials that included an empirical assessment of the relation between randomisation and estimates of effect.Cochrane Review Methodology Database, Medline, SciSearch, bibliographies, hand searching of journals, personal communication with methodologists, and the reference lists of relevant articles.Relation between randomisation and estimates of effect.Eleven studies that compared randomised controlled trials with non-randomised controlled trials (eight for evaluations of the same intervention and three across different interventions), two studies that compared trials with adequately concealed random allocation and inadequately concealed random allocation, and five studies that assessed the relation between quality scores and estimates of treatment effects, were identified. Failure to use random allocation and concealment of allocation were associated with relative increases in estimates of effects of 150% or more, relative decreases of up to 90%, inversion of the estimated effect and, in some cases, no difference. On average, failure to use randomisation or adequate concealment of allocation resulted in larger estimates of effect due to a poorer prognosis in non-randomly selected control groups compared with randomly selected control groups.Failure to use adequately concealed random allocation can distort the apparent effects of care in either direction, causing the effects to seem either larger or smaller than they really are. The size of these distortions can be as large as or larger than the size of the effects that are to be detected.
Failure of Topical Testosterone in Male-Pattern Alopecia
Authors: Robert A. Berger
Journal: JAMA (1968)

It has long been recognized that male hormone is both a prerequisite and an incitant in pattern alopecia occurring in genetically predisposed men.<sup>1-4</sup>The report by Papa and Kligman<sup>5</sup>in 1965 of stimulation of hair growth in common baldness was, therefore, a most startling and unexpected one, on two grounds. First, because no reliably effective topical medication had ever been found previously for this condition: second, because good results were claimed for the very hormone whose systemic action was known to be a necessary condition for this type of baldness to develop. Papa and Kligman were fully aware of the paradoxical implications of their findings and suggested that perhaps the stimulating topical action of the hormone could be explained on the basis of a local pharmacological action on the scalp tissues. They reported the regrowth of coarse terminal hairs in an estimated 10% to 15% of the affected
The Electrocardiogram, Vectorcardiogram, and Ventricular Gradient in the Tetralogy of Fallot
Authors: N. P. DEPASQUALE, G. E. BURCH
Journal: Circulation (1961)

The electrocardiogram, ventricular gradient, and spatial vectorcardiogram were studied in 140 patients with proved tetralogy of Fallot. The patients were separated into three groups according to hemodynamic data. The salient features of the electrocardiogram in patients of group I consisted of diminutive R waves in leads I and V 6 , a deep Q wave and high R wave in lead III, a prominent R wave in lead V 1 , which was not wide, and the absence of Q waves in leads I, V 1 , and V 6 . The electrocardiogram in patients of group II was similar to that of the patients of group I except for the appearance of more signs of left ventricular electric activity and less clock-wise rotation of the heart. The electrocardiogram of the patients of group III was similar to that previously described for ventricular septal defect. Â QRS , Â T , Ĝ, and sVCG reflected the same general trend as the electrocardiograms. The electrophysiologic data presented support clinical observations indicating that the tetralogy of Fallot includes patients with a wide range of hemodynamic differences.
Decision Analysis: A Progress Report
Authors: JEROME P. KASSIRER
Journal: Annals of Internal Medicine (1987)

Since its introduction into medicine 15 years ago, decision analysis has been applied to difficult clinical problems. Several important advances have made the process more practical and acceptable: computer programs that eliminate the need for burdensome calculations, improved techniques for designing analytic models, the ability to carry out sensitivity analyses over several dimensions simultaneously, and the elaboration of clinically relevant measures of utility. Using these techniques, analysts have addressed many important clinical issues including screening for and prevention of disease, tradeoffs among tests and treatments, and the interpretation of clinical data under conditions of uncertainty. Problems with the approach remain and applications have not been extensive, but decision analysis is evolving as a powerful clinical tool and gradually is gaining acceptance in medical practice.
Rising to the challenge: will the NHS support people with long term conditions?
Authors: Tim Wilson, David Buck, Chris Ham
Journal: BMJ (2005)

The NHS is waking to the challenge of chronic diseases. Three researchers who have worked in the Department of Health discuss how the NHS might rise to the challenge of better supporting people with long term conditions The health gains experienced over the past 50 or so years are now presenting health systems around the world with a new challenge: how best to support people with long term conditions. An ageing population is testimony to improvements in public health through improved housing, sanitation and diet, and better health services—resulting in more patients surviving previously fatal events like serious infections but creating increasing numbers with long term conditions (fig 1). Over the past few years the British government has responded to issues that are foremost in the minds of the electorate, such as access to specialist services, especially in patient waiting times. This has evidently paid off.1 Now the NHS is waking to the challenge of chronic diseases. The NHS Improvement Plan, launched in June 2004, outlined the importance of supporting people with long term conditions. In the foreword, John Reid, the secretary of state for health, outlines how a "major investment in services closer to home will ensure much better support for patients who have long-term conditions, enabling them to minimise the impact of these on their lives."2 We discuss how the NHS might rise to this challenge. Fig 1 Percentage of respondents to general household survey 2002 (n=13 000) reporting a chronic condition. Data from 1998 onwards are weighted Analysis of the British household panel survey (2001), the health survey for England (2001), and general household survey (2002) has given us a great insight into how long term conditions affect people in England.3–5 The data show that:
Immunoreactive gastrin components in human serum
Authors: J. F. Rehfeld, F. Stadil, J. Vikelsoe
Journal: Gut (1974)

The apparent molecular size and charge of immunoreactive gastrin components were studied in sera from patients with pernicious anaemia or gastrinomas (the Zollinger-Ellison syndrome) by Sephadex gel filtration and aminoethylcellulose chromatography. The following serum components were distinguished: (1) a monophasic component I similar in size to proinsulin which was converted into ;little' gastrin I by trypsin digestion; (2) a biphasic component II, corresponding to ;big' gastrins I and II (Gregory and Tracy); (3) a biphasic component III corresponding to ;little' gastrins I and II (Gregory and Tracy); and (4) a biphasic component IV, corresponding to ;minigastrins' I and II (Gregory and Tracy). ;Big, big' gastrin, a plasma component found in the void volume of the Sephadex G-50 column by Yalow and Berson (1972) was undetectable in the sera investigated. A component in gastrinoma and antral mucosa extracts corresponding in size to ;big big' gastrin was detectable by the assay; the ;big big' gastrin fraction from gastrinoma tissue was heterogenous, with components of apparent MW 30 000-100 000. It is concluded that serum gastrin circulates in the form of at least four components, of which the three smaller ones are in pairs.
Endovascular Aortic Repair Versus Open Surgical Repair for Descending Thoracic Aortic Disease
Authors: Davy Cheng, Janet Martin, Hani Shennib, Joel Dunning, Claudio Muneretto, Stephan Schueler, Ludwig Von Segesser, Paul Sergeant, Marko Turina
Journal: Journal of the American College of Cardiology (2010)
Abstract LB-99: EGF receptor tyrosine kinase defines critical prognostic genes of stage IA lung adenocarcinoma
Authors: Asuka Nakata, Mai Yamauchi, Rui Yamaguchi, Takashi Kohno, Masao Nagasaki, Teppei Shimamura, Seiya Imoto, Ayumu Saito, Kazuko Ueno, Yousuke Hatanaka, Ryo Yoshida, Tomoyuki Higuchi, Masaharu Nomura, David G. Beer, Jun Yokota, Satoru Miyano, Noriko Gotoh
Journal: Cancer Research (2012)

Abstract Non-small cell lung cancer (NSCLC) is the commonest and the most fatal histological subtype of lung cancer. About 10-30% of patients diagnosed as stage IA (the earliest stage of a lung tumor, smaller than three centimeters in diameter with no evidence of regional lymph node and/or regional metastasis) and submitted to surgery die due to recurrence. Therefore, the identification of prognostic biomarkers for stage IA lung adenocarcinoma with poor prognosis is of great importance to select patients who will be benefited by adjuvant therapy. To the best of our knowledge, there is not a set of genes that identifies these patients. It is known that epidermal growth factor (EGF) signaling pathway is closely related to aggressive phenotypes of lung and other cancers. EGFR tyrosine kinase-specific inhibitor, namely gefitinib is expected to alter the gene expression patterns caused by EGFR tyrosine kinase activity. We performed microarray assays in order to obtain the entire gene expression time course profile of human primary lung epithelial cells that were stimulated with EGF in both the presence and absence of gefitinib. The time courses are composed of 19 time points along 48 hours. The data were subjected to a mathematical analysis, namely the State Space Model (SSM) in order to select genes with gene expressions altered by gefitinib. One hundred thirty nine genes were identified. These genes were used as expression signatures to train a risk scoring model that classifies patients in high- or low-risk (risk of dying in five years). This model was trained by using a data set composed of 253 North American patients with lung adenocarcinomas. Then, the predictive ability of the risk scoring model was examined in two independent cohorts composed of North American and Japanese patients. The model enabled the statistically significant identification of high-risk stage IA lung adenocarcinoma in both cohorts, with hazard ratios (HRs) for death of 7.16 (P=0.029) for North American and 10.98 (P=0.008) for Japanese. The set of 139 genes altered by gefitinib includes several ones that are involved in biological aspects of cancer phenotypes but are yet unknown to be involved in EGF signaling. This result strongly re-emphasizes that EGF signaling status underlies aggressive phenotype of cancer cells, and also suggests the first set of genes that are useful for the identification of stage IA lung adenocarcinoma patients with poor prognosis. 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 LB-99. doi:1538-7445.AM2012-LB-99
Plasmid Releasing Multiple Channel Bridges for Transgene Expression After Spinal Cord Injury
Authors: Laura De Laporte, Yang Yang, Marina L Zelivyanskaya, Brian J Cummings, Aileen J Anderson, Lonnie D Shea
Journal: Molecular Therapy (2008)

The regeneration of tissues with complex architectures requires strategies that promote the appropriate cellular processes, and can direct their organization. Plasmid-loaded multiple channel bridges were engineered for spinal cord regeneration with the ability to support and direct cellular processes and promote gene transfer at the injury site. The bridges were manufactured with a gas foaming technique, and had multiple channels with controllable diameter and encapsulated plasmid. Initial studies investigating bridge implantation subcutaneously (SC) indicated transgene expression in vivo for 44 days, with gene expression dependent upon the pore size of the bridge. In the rat spinal cord, bridges implanted into a lateral hemisection supported substantial cell infiltration, aligned cells within the channels, axon growth across the channels, and high levels of transgene expression at the implant site with decreasing levels rostral and caudal. Immunohistochemistry revealed that the transfected cells at the implant site were present in both the pores and channels of the bridge and were mainly identified as Schwann cells, fibroblasts, and macrophages, in descending order of transfection. This synergy between gene delivery and the scaffold architecture may enable the engineering of tissues with complex architectures. The regeneration of tissues with complex architectures requires strategies that promote the appropriate cellular processes, and can direct their organization. Plasmid-loaded multiple channel bridges were engineered for spinal cord regeneration with the ability to support and direct cellular processes and promote gene transfer at the injury site. The bridges were manufactured with a gas foaming technique, and had multiple channels with controllable diameter and encapsulated plasmid. Initial studies investigating bridge implantation subcutaneously (SC) indicated transgene expression in vivo for 44 days, with gene expression dependent upon the pore size of the bridge. In the rat spinal cord, bridges implanted into a lateral hemisection supported substantial cell infiltration, aligned cells within the channels, axon growth across the channels, and high levels of transgene expression at the implant site with decreasing levels rostral and caudal. Immunohistochemistry revealed that the transfected cells at the implant site were present in both the pores and channels of the bridge and were mainly identified as Schwann cells, fibroblasts, and macrophages, in descending order of transfection. This synergy between gene delivery and the scaffold architecture may enable the engineering of tissues with complex architectures.
Prognosis in myocardial infarction--the benefits of exercise as seen in non-randomised trials.
Authors: R. J. Shephard, T. Kavanagh, J. Kennedy, S. Qureshi
Journal: British Journal of Sports Medicine (1981)

Previous uncontrolled studies suggest that exercise rehabilitation reduces recurrence rates in post-myocardial infarction patients. Six hundred and ten consecutive post-coronary patients referred to an exercise rehabilitation programme have been followed for an average of 36.5 months (1-8 years). Total deaths amounted to 36 (1.89% p.a.) of which 23 were cardiac deaths, with an annual death rate averaging only 0.85% after the first year of conditioning had been completed. There were also a total of 21 non-fatal recurrences of infarction. comparison has been made with 700 patients enrolled in the Health Insurance Plan of New York. On the basis of smoothed probabilities for the risk factors reported in the New York series, we should have seen 89 deaths (P less than 0.001). Correcting for differences between the two groups (age and number of diabetics) gives a predicted mortality for the Toronto series of 63.5 deaths (3.42% p.a.). This discrepancy in favour of the exercised group is significant in terms of an infinitely large control population (P less than 0.001) and also sample sizes of 610 exercised and 700 control patients (0.01 greater than P greater than 0.001). Unfortunately, formally to prove such a 45% reduction in mortality by way of a randomised control trial would be extremely costly, possibly prohibitively so.
The Genetic Trail of Osteoporosis
Authors: Darwin J. Prockop
Journal: New England Journal of Medicine (1998)

Over the past decade, we have applied the power of molecular biology to the study of human diseases, and we have identified genetic defects causing over 100 different diseases. Evidence of genetic causes of osteoporosis has been with us for some time. Yet there still is considerable debate and confusion about whether osteoporosis is a genetic disease.Anecdotal evidence indicated many years ago that blacks are much less likely to have osteoporosis than whites and Asians, apparently because of differences in genetic background.1 In studies of monozygotic and dizygotic twins, moreover, approximately 80 percent of the age-specific variation in bone . . .
PREDICTION OF DEATH AND CONGESTIVE HEART FAILURE USING MULTIPLE CONCOMITANT ANGIOGRAPHIC BIOCHEMICAL AND ELECTROCARDIOGRAPHIC BIOMARKERS IN PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION TREATED WITH PRIMARY PERCUTANEOUS CORONARY INTERVENTION
Authors: Wichert J. Kuijt, Matthew T. Roe, Cindy L. Green, Karen S. Pieper, Susanna R. Stevens, Renato D. Lopes, Robert H. Christenson, Jan G. Tijssen, Greg W. Stone, A. Michael Lincoff, Robbert J. De Winter, Mitchell W. Krucoff
Journal: Journal of the American College of Cardiology (2011)
Abstract 5171: Restoration of fibronectin matrix assembly impedes invasion and reduces tumor-stromal cell affinity in prostate cancer
Authors: Dongxuan Jia, Ildiko Entersz, Christine Butler, Connan Vaca, Ramsey A. Foty
Journal: Cancer Research (2012)

Abstract Cell-cell and cell-ECM interactions are important regulators of cohesion, a property previously demonstrated to mediate malignant invasion. Intermixing of the epithelial and stromal compartments is often associated with increased invasive capacity and poor prognosis. The studies reported here propose a novel role for α5β1 integrin, the principle mediator of fibronectin matrix assembly (FNMA), as an invasion suppressor in prostate cancer cells. Employing a combination of biophysical and cell biological techniques we explore the relationship between cohesion, invasion, FNMA and tumor-stromal interactions, using a well-characterized prostate cancer model. We show that cohesion is inversely proportional to invasive capacity. We also show that the most invasive cells are deficient in FNMA and express reduced levels of α5β1 integrin. We generated cells over-expressing either wild-type α5 integrin or a non-functional α5 in which the cytoplasmic domain was replaced with that of α2. We show that only wild-type α5 was able to increase cohesion and reduce the invasiveness of aggressive cells. In order to further explore the influence of FNMA on tumor-stromal cell interaction we employed a liquid miscibility model in which interactions between tumor and stroma are rooted in the same thermodynamic principles that govern the mixing of simple fluids. In this model, whether tumor and stromal cells segregate or intermix depends on the ratio of the strength of self-cohesion to cross-adhesion; a high ratio corresponds with segregation, whereas a lower ratio denotes intermixing. We hypothesized that segregation between tumor and stroma can be promoted by increasing the strength of tumor cell cohesion. To test this hypothesis, we first showed that aggressive prostate cancer cells intermix with prostate fibroblasts. We then treated the cancer cells with MEK inhibitors (MEKi) and showed that treatment restored FNMA, leading to increased cell-cell cohesion. When mixed with prostate stromal cells, MEKi-treated cells segregated, suggesting that increasing cohesion between tumor cells is sufficient to reduce their affinity for stromal cells. These data suggest that by increasing tumor cell cohesion through a fibronectin matrix mediated adhesion mechanism, it may be possible to effectively reduce affinity of tumor cells for stroma, thus inhibiting invasion. 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 5171. doi:1538-7445.AM2012-5171