tbuckley/cabot-search huggingface dataset:
Abatacept for Rheumatoid Arthritis Refractory to Tumor Necrosis Factor α Inhibition
Authors: Mark C. Genovese, Jean-Claude Becker, Michael Schiff, Michael Luggen, Yvonne Sherrer, Joel Kremer, Charles Birbara, Jane Box, Kannan Natarajan, Isaac Nuamah, Tracy Li, Richard Aranda, David T. Hagerty, Maxime Dougados
Journal: New England Journal of Medicine (2005)

A substantial number of patients with rheumatoid arthritis have an inadequate or unsustained response to tumor necrosis factor alpha (TNF-alpha) inhibitors. We conducted a randomized, double-blind, phase 3 trial to evaluate the efficacy and safety of abatacept, a selective costimulation modulator, in patients with active rheumatoid arthritis and an inadequate response to at least three months of anti-TNF-alpha therapy.Patients with active rheumatoid arthritis and an inadequate response to anti-TNF-alpha therapy were randomly assigned in a 2:1 ratio to receive abatacept or placebo on days 1, 15, and 29 and every 28 days thereafter for 6 months, in addition to at least one disease-modifying antirheumatic drug. Patients discontinued anti-TNF-alpha therapy before randomization. The rates of American College of Rheumatology (ACR) 20 responses (indicating a clinical improvement of 20 percent or greater) and improvement in functional disability, as reflected by scores for the Health Assessment Questionnaire (HAQ) disability index, were assessed.After six months, the rates of ACR 20 responses were 50.4 percent in the abatacept group and 19.5 percent in the placebo group (P<0.001); the respective rates of ACR 50 and ACR 70 responses were also significantly higher in the abatacept group than in the placebo group (20.3 percent vs. 3.8 percent, P<0.001; and 10.2 percent vs. 1.5 percent, P=0.003). At six months, significantly more patients in the abatacept group than in the placebo group had a clinically meaningful improvement in physical function, as reflected by an improvement from baseline of at least 0.3 in the HAQ disability index (47.3 percent vs. 23.3 percent, P<0.001). The incidence of adverse events and peri-infusional adverse events was 79.5 percent and 5.0 percent, respectively, in the abatacept group and 71.4 percent and 3.0 percent, respectively, in the placebo group. The incidence of serious infections was 2.3 percent in each group.Abatacept produced significant clinical and functional benefits in patients who had had an inadequate response to anti-TNF-alpha therapy.
A Case of Bronchial Adenoma with Liver Metastasis
Authors: P. Kincaid-Smith, J.-J. Brossy
Journal: Thorax (1956)

Distant metastases from bronchial " adenomas " are sufficiently uncommon to warrant reporting a patient in whom a liver metastasis after apparently successful treatment of a bronchial adenoma caused diagnostic difficulties. CASE REPORTA shorthand-typist, then aged 58, was first seen in February, 1948, complaining that three months pre- viously she had caught a cold which had "gone into her chest" and persisted, with the development of a cough productive of sputum which had latterly been blood-streaked.Clinical examination suggested some collapse at the right lung base, and radiography of the chest confirmed that this involved mainly the middle lobe.At bronchoscopy a large polypoid tumour was found in the right main bronchus, just above the middle lobar and apical lower segmental orifices.A biopsy speci- men was reported as bronchial adenoma.A right middle and lower lobectomy was performed (March, 1948).Convalescence after this operation was smooth.At a routine follow-up visit in September, 1954, the patient reported having had intermittent diarrhoea for 10 weeks, the stools being watery, without blood or slime.She had also suffered flatulence associated with colicky rumblings in the upper abdomen.There was no history of dyspepsia, pain, or weight loss.Palpation of the abdomen showed a mobile, smooth, rounded tumour about 10 cm. in diameter projecting from under the left costal margin near the midline.It moved freely on respiration and could be pushed from side to side of the abdomen.There was no asso- ciated tenderness or pain.A few rales were audible over the right lung, and the trachea was slightly displaced to the right, but air entry on both sides of the chest was good and radio- graphy confirmed the absence of gross disease in the chest.A barium meal and enema showed that the stomach and colon were displaced by but not attached to the mass, which appeared to be in a more posterior plane.An intravenous pyelogram showed that the left kidney area there was a definite papillary pattern.From the tumour in the medial branch of the middle lobe bronchus the surrounding lung was extensively on July 22,
Polo-Like Kinase 1 is a Therapeutic Target in High-Risk Neuroblastoma
Authors: Sandra Ackermann, Felix Goeser, Johannes H. Schulte, Alexander Schramm, Volker Ehemann, Barbara Hero, Angelika Eggert, Frank Berthold, Matthias Fischer
Journal: Clinical Cancer Research (2010)

High-risk neuroblastoma remains a therapeutic challenge for pediatric oncologists. The Polo-like kinase 1 (PLK1) is highly expressed in many human cancers and is a target of the novel small-molecule inhibitor BI 2536, which has shown promising anticancer activity in adult malignancies. Here, we investigated the effect of BI 2536 on neuroblastoma cells in vitro and in vivo to explore PLK1 as a potential target in high-risk neuroblastoma therapy.PLK1 transcript levels were analyzed by microarrays in 476 primary neuroblastoma specimens, and correlation with prognostic markers and patient outcome was examined. To explore the effect of PLK1 inhibition on neuroblastoma cells, 7 cell lines were treated with BI 2536 and changes in growth properties were determined. Furthermore, nude mice with IMR-32 and SK-N-AS xenografts were treated with BI 2536.PLK1 is highly expressed in unfavorable neuroblastoma and in neuroblastoma cell lines. Expression of PLK1 is associated with unfavorable prognostic markers such as stage 4, age >18 months, MYCN amplification, unfavorable gene expression-based classification, and adverse patient outcome (P < 0.001 each). On treatment with nanomolar doses of BI 2536, all neuroblastoma cell lines analyzed showed significantly reduced proliferation, cell cycle arrest, and cell death. Moreover, BI 2536 abrogated growth of neuroblastoma xenografts in nude mice.Elevated PLK1 expression is significantly associated with high-risk neuroblastoma and unfavorable patient outcome. Inhibition of PLK1 using BI 2536 exhibits strong antitumor activity on human neuroblastoma cells in vitro and in vivo, opening encouraging new perspectives for the treatment of high-risk neuroblastoma.
TRAF6 Is a Critical Factor for Dendritic Cell Maturation and Development
Authors: Takashi Kobayashi, Patrick T Walsh, Matthew C Walsh, Kendra M Speirs, Elise Chiffoleau, Carolyn G King, Wayne W Hancock, Jorge H Caamano, Christopher A Hunter, Phillip Scott, Laurence A Turka, Yongwon Choi
Journal: Immunity (2003)
<scp>l</scp>-Amino Acid Transporter-1 and Boronophenylalanine-Based Boron Neutron Capture Therapy of Human Brain Tumors
Authors: Allah Detta, Garth S. Cruickshank
Journal: Cancer Research (2009)

Abstract The system l-amino acid transporter-1 (LAT-1) imports p-boronophenylalanine (BPA) into cells and may play a major role in the effectiveness of BPA-based boron neutron capture therapy. The functional status of LAT-1 and its relationship to cell proliferation were simultaneously examined in the same section of human tumor material using a dual-labeling technique. The uptake of BPA (boron inductively coupled plasma mass spectrometry) was profiled in the presence of agonists and antagonists in fresh tumor explants. The number of LAT-1–expressing cells (mean ± SD) was three times higher than that of proliferating cell nuclear antigen (PCNA)–expressing cells (71.5 ± 17.02% versus 23.8 ± 16.5%; P &amp;lt; 0.0001; n = 38 glioblastoma and metastatic tumors). There was no correlation between PCNA cells and the number of LAT-1/PCNA double-stained cells, and not all PCNA-expressing cells coexpressed LAT-1. Boron uptake reached 30 ± 15 μg/g of wet weight of tissue by 4 hours both in tumor and brain around tumor tissue containing tumor cells compared with time 0 (P &amp;lt; 0.005; n = 4 glioblastoma tumors). This uptake was inhibited by both phenylalanine and 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid. These LAT-1 data indicate that BPA-based boron neutron capture therapy might affect up to 70% of tumor cells, representing a three times higher proportion of tumor cells than their cell cycle status might suggest. Cells expressing PCNA, but not LAT-1, will require a different therapeutic strategy. [Cancer Res 2009;69(5):2126–32]
Evaluation of inflammatory infiltrate and fibrogenic cytokines in pseudopelade of Brocq suggests the involvement of T-helper 2 and 3 cytokines
Authors: S. Moretti, L. Amato, D. Massi, B. Bianchi, I. Gallerani, P. Fabbri
Journal: British Journal of Dermatology (2004)

Pseudopelade of Brocq (PB) is an acquired progressive cicatricial alopecia which is characterized by some distinctive clinical features. It may represent either a distinct entity, i.e. an idiopathic primary scarring alopecia, or the end stage of various forms of scarring alopecia such as discoid lupus erythematosus (DLE) or lichen planopilaris (LPP).The aim of the study was to evaluate a set of patients with a clinically defined PB, to ascertain whether their PB was idiopathic or secondary, and then to study the phenotype of the inflammatory infiltrate and the presence of any fibrogenic and antifibrogenic cytokines to identify idiopathic or secondary forms in more detail.Twelve female patients with PB were studied by means of histology, direct immunofluorescence (DIF) and immunohistochemistry, by using monoclonal antibodies to cell markers (lymphocyte subtypes, Langerhans cells, macrophages, fibroblasts, mastocytes and activation markers) and fibrogenic and antifibrogenic cytokines.Using histology and DIF, we diagnosed two cases as DLE and three cases as LPP. Seven cases had nonspecific histology or DIF appearances and were classified as noncharacterized pseudopelade (NCPB). Two major phenotypic patterns of dermal infiltrate were identified by immunohistochemistry. These were: (i) a conspicuous infiltrate of CD3+ cells with a high CD4+/CD8+ ratio, variable numbers of macrophages, mast cells and fibroblasts always fewer than lymphocytes; (ii) an infiltrate of CD3+ cells with variable CD4+/CD8+ ratio and conspicuous amounts of macrophages, mast cells and fibroblasts, more numerous than infiltrating lymphocytes. The first pattern was typical of DLE and LPP, the second one was typical of NCPB. Fibrogenic cytokines were observed in all cases, but basic fibroblastic growth factor (bFGF) and transforming growth factor (TGF)-beta were more strongly expressed in NCPB. Interferon (IFN)-gamma was found in LPP.In our PB patients we identified five of 12 secondary PB and seven of 12 idiopathic PB by means of histology and DIF. The phenotypic pattern of infiltration allowed us to further differentiate secondary (richer in lymphocytes) from idiopathic PB (richer in resident cells). The pattern of cytokine expression showed the presence of fibrogenic molecules (interleukins 4 and 6, bFGF and TGF-beta) in all cases, suggesting the involvement of mechanisms mediated by T-helper 2 and 3 cytokines in PB.
Left Ventricular Geometry Predicts Cardiovascular Outcomes Associated with Anemia Correction in CKD
Authors: Kai-Uwe Eckardt, Armin Scherhag, Iain C. Macdougall, Dimitrios Tsakiris, Naomi Clyne, Francesco Locatelli, Michael F. Zaug, Hans U. Burger, Tilman B. Drueke
Journal: Journal of the American Society of Nephrology (2009)

Partial correction of anemia in patients with chronic kidney disease (CKD) reduces left ventricular hypertrophy (LVH), which is a risk factor for cardiovascular (CV) morbidity, but complete correction of anemia does not improve CV outcomes. Whether LV geometry associates with CV events in patients who are treated to different hemoglobin (Hb) targets is unknown. One of the larger trials to study the effects of complete correction of anemia in stages 3 to 4 CKD was the Cardiovascular Risk Reduction by Early Anemia Treatment with Epoetin Beta (CREATE) trial. Here, we analyzed echocardiographic data from CREATE to determine the prevalence, dynamics, and prognostic implications of abnormal LV geometry in patients who were treated to different Hb targets. The prevalence of LVH at baseline was 47%, with eccentric LVH more frequent than concentric. During the study, LVH prevalence and mean left ventricular mass index did not change significantly, but LV geometry fluctuated considerably within 2 yr in both groups. CV event-free survival was significantly worse in the presence of concentric LVH and eccentric LVH compared with the absence of LVH (P = 0.0009 and P < or = 0.0001, respectively). Treatment to the higher Hb target associated with reduced event-free survival in the subgroup with eccentric LVH at baseline (P = 0.034). In conclusion, LVH is common and associates with poor outcomes among patients with stages 3 to 4 CKD, although both progression and regression of abnormal LV geometry occur. Complete anemia correction may aggravate the adverse prognosis of eccentric LVH.
The Physiology of the Axon Initial Segment
Authors: Kevin J. Bender, Laurence O. Trussell
Journal: Annual Review of Neuroscience (2012)

The action potential generally begins in the axon initial segment (AIS), a principle confirmed by 60 years of research; however, the most recent advances have shown that a very rich biology underlies this simple observation. The AIS has a remarkably complex molecular composition, with a wide variety of ion channels and attendant mechanisms for channel localization, and may feature membrane domains each with distinct roles in excitation. Its function may be regulated in the short term through the action of neurotransmitters, in the long term through activity- and Ca 2+ -dependent processes. Thus, the AIS is not merely the beginning of the axon, but rather a key site in the control of neuronal excitability.
Psychosomatic Implications in Chronic Haemodialysis
Authors: C.L. Cazzullo, G. Invernizzi, R. Ventura, M. Sostero
Journal: Psychotherapy and Psychosomatics (1973)

Chronic haemodialysis raises many psychologic and psychosomatic problems. They are: selection of the patients, dependence from the Center, impossibility of developing an adequate work, decline of sexual activity. This situation is very demoralizing and the patient may retire in his illness, giving up his role in the social environment. Very important is the presence of a psychiatric doctor in the Center not only for the patients, but also in the discussion with colleagues and the assistential staff, when he can give useful news as concerning the behaviour of the patients and the team with an interpretation of the psychodynamics of their interpersonal relationship.
THE SKIN AND FRICTION: DEVIATIONS FROM AMONTON'S LAWS, AND THE EFFECTS OF HYDRATION AND LUBRICATION
Authors: STANLEY COMAISH, EVA BOTTOMS
Journal: British Journal of Dermatology (1971)

SUMMARY.— The coefficient of friction has been determined for skin and various materials. It has been established that the behaviour of skin is not portrayed by the simple laws of friction, but by a more complex relationship of the type F =μWn. This is probably because skin is subject to viscoelastic rather than purely plastic deformation. Friction may be altered by the type of material in contact with skin and is further influenced by surface lubrication. Dry talcum powder reduces friction slightly for certain materials against skin, but increases friction when it becomes wetted.
IScore
Authors: Gustavo Saposnik, Moira K. Kapral, Ying Liu, Ruth Hall, Martin O'Donnell, Stavroula Raptis, Jack V. Tu, Muhammad Mamdani, Peter C. Austin
Journal: Circulation (2011)

Background— A predictive model of stroke mortality may be useful for clinicians to improve communication with and care of hospitalized patients. Our aim was to identify predictors of mortality and to develop and validate a risk score model using information available at hospital presentation. Methods and Results— This retrospective study included 12 262 community-based patients presenting with an acute ischemic stroke at multiple hospitals in Ontario, Canada, between 2003 and 2008 who had been identified from the Registry of the Canadian Stroke Network (8223 patients in the derivation cohort, 4039 in the internal validation cohort) and the Ontario Stroke Audit (3720 for the external validation cohort). The mortality rates for the derivation and internal validation cohorts were 12.2% and 12.6%, respectively, at 30 days and 22.5% and 22.9% at 1 year. Multivariable predictors of 30-day and 1-year mortality included older age, male sex, severe stroke, nonlacunar stroke subtype, glucose ≥7.5 mmol/L (135 mg/dL), history of atrial fibrillation, coronary artery disease, congestive heart failure, cancer, dementia, kidney disease on dialysis, and dependency before the stroke. A risk score index stratified the risk of death and identified low- and high- risk individuals. The c statistic was 0.850 for 30-day mortality and 0.823 for 1-year mortality for the derivation cohort, 0.851 for the 30-day model and 0.840 for the 1-year mortality model in the internal validation set, and 0.790 for the 30-day model and 0.782 for the 1-year model in the external validation set. Conclusion— Among patients with ischemic stroke, factors identifiable within hours of hospital presentation predicted mortality risk at 30 days and 1 year. The predictive score may assist clinicians in estimating stroke mortality risk and policymakers in providing a quantitative tool to compare facilities.
Induction Chemotherapy and Dose Intensification of the Radiation Boost in Locally Advanced Anal Canal Carcinoma: Final Analysis of the Randomized UNICANCER ACCORD 03 Trial
Authors: Didier Peiffert, Laetitia Tournier-Rangeard, Jean-Pierre Gérard, Claire Lemanski, Eric François, Marc Giovannini, Frédérique Cvitkovic, Xavier Mirabel, Olivier Bouché, Elisabeth Luporsi, Thierry Conroy, Christine Montoto-Grillot, Françoise Mornex, Antoine Lusinchi, Jean-Michel Hannoun-Lévi, Jean-François Seitz, Antoine Adenis, Christophe Hennequin, Bernard Denis, Michel Ducreux
Journal: Journal of Clinical Oncology (2012)

Concomitant radiochemotherapy (RCT) is the standard for locally advanced anal canal carcinoma (LAACC). Questions regarding the role of induction chemotherapy (ICT) and a higher radiation dose in LAACC are pending. Our trial was designed to determine whether dose escalation of the radiation boost or two cycles of ICT before concomitant RCT lead to an improvement in colostomy-free survival (CFS).Patients with tumors ≥ 40 mm, or < 40 mm and N1-3M0 were randomly assigned to one of four treatment arms: (A) two ICT cycles (fluorouracil 800 mg/m(2)/d intravenous [IV] infusion, days 1 through 4 and 29 to 32; and cisplatin 80 mg/m(2) IV, on days 1 and 29), RCT (45 Gy in 25 fractions over 5 weeks, fluorouracil and cisplatin during weeks 1 and 5), and standard-dose boost (SD; 15 Gy); (B) two ICT cycles, RCT, and high-dose boost (HD; 20-25 Gy); (C): RCT and SD boost (reference arm); and (D) RCT and HD boost.Two hundred eighty-three of 307 patients achieved full treatment. With a median follow-up period of 50 months, the 5-year CFS rates were 69.6%, 82.4%, 77.1%, and 72.7% in arms A, B, C, and D, respectively. Considering the 2 × 2 factorial analysis, the 5-year CFS was 76.5% versus 75.0% (P = .37) in groups A and B versus C and D, respectively (ICT effect), and 73.7% versus 77.8% in groups A and C versus B and D, respectively (RT-dose effect; P = .067).Using CFS as our main end point, we did not find an advantage for either ICT or HD radiation boost in LAACC. Nevertheless, the results of the most treatment-intense arm B should prompt the design of further intensification studies.
Levels of Symptom Burden During Chemotherapy for Advanced Lung Cancer: Differences Between Public Hospitals and a Tertiary Cancer Center
Authors: Charles S. Cleeland, Tito R. Mendoza, Xin Shelley Wang, Jeanie F. Woodruff, Guadalupe R. Palos, Stephen P. Richman, Arlene Nazario, Garrett R. Lynch, Kai-Ping Liao, Gary M. Mobley, Charles Lu
Journal: Journal of Clinical Oncology (2011)

Purpose We compared risk factors for high disease- and treatment-related symptom burden over 15 weeks of therapy in medically underserved patients with advanced non–small-cell lung cancer and in patients treated at a tertiary cancer center. Patients and Methods We monitored symptom severity weekly during chemotherapy. Patients were recruited from a tertiary cancer center (n=101) and three public hospitals treating the medically underserved (n=80). We used a composite symptom-severity score and group-based trajectory analysis to form two groups: one with consistently more severe symptoms and another with less severe symptoms. We examined predictors of group membership. Results Seventy percent of the sample (n=126) reported low symptom-severity levels that decreased during therapy; 30% (n=55) had consistently severe symptoms throughout the study. In multivariate analysis, patients with good performance status being treated in public hospitals were significantly more likely than patients treated at the tertiary cancer center to be in the high-symptom group (odds ratio, 5.6; 95% CI, 2.1 to 14.6; P =.001) and to report significantly higher symptom interference (P =.001). Other univariate predictors of high-symptom group membership included variables associated with being medically underserved (eg, having less education, being single, and being nonwhite). No group differences by ethnicity were observed in the public hospitals. Medically underserved patients were less likely to receive adequate pain management. Conclusion Patients with advanced lung cancer and good performance status treated at public hospitals were more likely than those treated at a tertiary cancer center to experience substantial symptoms during chemotherapy.
C34T mutation of the<i>AMPD1</i>gene in an elite white runner: Figure 1
Authors: A Lucia, M A Martin, J Esteve-Lanao, A F San Juan, J C Rubio, J Oliván, J Arenas
Journal: British Journal of Sports Medicine (2006)

The case is reported of an elite, male, white endurance runner (28 years of age), who is one of the best non-African runners in the world despite carrying the C34T mutation in the gene ( AMPD1 ) that encodes the skeletal muscle specific isoform of AMP deaminase, an enzyme that plays an important role in muscle metabolism. The frequency of the mutant allele in sedentary white people is 8–11%. Previous research has shown that this mutation, at least in homozygotes, can impair the exercise capacity of untrained people and their trainability. The maximum oxygen uptake of the study subject was exceptionally high (83.6 ml/kg/min), whereas his ammonia and lactate concentrations at high submaximal running speeds were lower than those of other world class runners who are not carriers of the mutation. The partial metabolic deficiency of the study subject is possibly compensated for by his exceptionally favourable anthropometric characteristics (body mass index 18.2 kg/m 2 ).