tbuckley/cabot-search huggingface dataset:
Vulnerability to malaria, tuberculosis, and HIV/AIDS infection and disease. Part 1: determinants operating at individual and household level
Authors: Imelda Bates, Caroline Fenton, Janet Gruber, David Lalloo, Antonieta Medina Lara, S Bertel Squire, Sally Theobald, Rachael Thomson, Rachel Tolhurst
Journal: The Lancet Infectious Diseases (2004)
Endobronchial ultrasound and positron emission tomography positive mediastinal lymph nodes
Authors: G. Plat, P. Pierard, A. Haller, J. Hutsebaut, J. Faber, M. Dusart, P. Eisendrath, J-P. Sculier, V. Ninane
Journal: European Respiratory Journal (2006)

Positron emission tomography with 18F-fluoro-2-deoxy- d -glucose (FDG-PET) is more accurate than computed tomography for staging of mediastinal (hilar) lymph nodes. In the case of positive findings, tissue sampling of lymph nodes is required. The diagnostic/staging yield of transbronchial needle aspiration (TBNA) following endobronchial ultrasound (EBUS) localisation was assessed in this particular clinical setting. The number of avoided surgical procedures was evaluated. All consecutive patients referred for staging and/or diagnosis of mediastinal FDG-PET positive lesions were included. Data were prospectively collected. TBNA sampling of lymph nodes was performed after EBUS localisation. If no diagnosis was reached, further surgical sampling or adequate follow-up was performed. From January 2003 to June 2004, 33 patients were included. The average number of TBNA samples per patient was 4.2±1.5. Cytological or histological diagnoses were obtained in 27 (82%) of the patients, of which 78% were obtained after previous EBUS localisation. In 25 (76%) of the 33 patients, surgical staging procedures were suppressed. In conclusion, transbronchial needle aspiration after endobronchial ultrasound localisation should be considered as a primary method of evaluation of lymph nodes positive by positron emission tomography with 18F-fluoro-2-deoxy- d -glucose, and may replace the majority of surgical mediastinal staging/diagnostic procedures.
Motivations and Methods for Analyzing Pulsatile Hormone Secretion
Authors: Johannes D. Veldhuis, Daniel M. Keenan, Steven M. Pincus
Journal: Endocrine Reviews (2008)

Endocrine glands communicate with remote target cells via a mixture of continuous and intermittent signal exchange. Continuous signaling allows slowly varying control, whereas intermittency permits large rapid adjustments. The control systems that mediate such homeostatic corrections operate in a species-, gender-, age-, and context-selective fashion. Significant progress has been made in understanding mechanisms of adaptive interglandular signaling in vivo. Principal goals are to understand the physiological origins, significance, and mechanisms of pulsatile hormone secretion. Key analytical issues are: 1) to quantify the number, size, shape, and uniformity of pulses, nonpulsatile (basal) secretion, and elimination kinetics; 2) to evaluate regulation of the axis as a whole; and 3) to reconstruct dose-response interactions without disrupting hormone connections. This review will focus on the motivations driving and the methodologies used for such analyses.
A novel leukocyte adhesion deficiency caused by expressed but nonfunctional β2 integrins Mac-1 and LFA-1
Authors: Nancy Hogg, Mairi P. Stewart, Sarah L. Scarth, Rebecca Newton, Jacqueline M. Shaw, S.K. Alex Law, Nigel Klein
Journal: Journal of Clinical Investigation (1999)

In the leukocyte adhesion deficiency (LAD)-1 syndrome, there is diminished expression of β2(CD18) integrins. This is caused by lesions in the β2-subunit gene and gives rise to recurrent bacterial infections, impaired pus formation, and poor wound healing. We describe a patient with clinical features compatible with a moderately severe phenotype of LAD-1 but who expresses the β2 integrins lymphocyte function– associated molecule (LFA)-1 and Mac-1 at 40%–60% of normal levels. This level of expression should be adequate for normal integrin function, but both the patient's Mac-1 on neutrophils and LFA-1 on T cells failed to bind ligands such as fibrinogen and intercellular adhesion molecule (ICAM)-1, respectively, or to display a β2-integrin activation epitope after adhesion-inducing stimuli. Unexpectedly, divalent cation treatment induced the patient's T cells to bind to ICAM-2 and ICAM-3. Sequencing of the patient's two CD18 alleles revealed the mutations S138P and G273R. Both mutations are in the β2-subunit conserved domain, with S138P a putative divalent cation coordinating residue in the metal ion–dependent adhesion site (MIDAS) motif. After K562 cell transfection with α subunits, the mutated S138P β subunit was coexpressed but did not support function, whereas the G273R mutant was not expressed. In summary, the patient described here exhibits failure of the β2 integrins to function despite adequate levels of cell-surface expression.
Oral contraceptives and risk of endometriosis: a systematic review and meta-analysis
Authors: P. Vercellini, B. Eskenazi, D. Consonni, E. Somigliana, F. Parazzini, A. Abbiati, L. Fedele
Journal: Human Reproduction Update (2010)

BACKGROUNDCombined oral contraceptives (OCs) inhibit ovulation, substantially reduce the volume of menstrual flow and may hypothetically interfere with implantation of refluxed endometrial cells. The aim of this review is to establish if OC use influences the risk of endometriosis.
Assessment of progression of asbestosis in the sheep model by bronchoalveolar lavage and pulmonary function tests.
Authors: R Begin, M Rola-Pleszczynski, S Masse, D Nadeau, G Drapeau
Journal: Thorax (1983)

To study the relationship between the results of bronchoalveolar lavage and pulmonary function tests during induction and progression of asbestosis, three groups of six sheep were exposed repeatedly by intratracheal injection to either saline (controls), low doses of Canadian chrysotile UICC asbestos (cumulative exposure 328 mg) (low-dose group), or high doses of the same fibres (cumulative dose 2282 mg) (high-dose group) until there was clear evidence of alveolitis from the lung biopsy specimens of all sheep of the high-dose group. During the course of this induction and for the following eight months lung biopsies, bronchoalveolar lavage and pulmonary function tests were performed at two-month intervals. At the time of initial alveolitis in the high-dose group there was no significant change in the cellularity of the bronchoalveolar lavage fluid, but static lung compliance (Cst), vital capacity (VC), arterial oxygen tension (Pao2), and diffusion capacity (DL/VA) were significantly lower than in the other groups. In the following months, as the alveolitis evolved into a fibrosing process, macrophages and neutrophils from the bronchoalveolar lavage fluid increased significantly and pulmonary function deteriorated. Proteins and enzymes in the bronchoalveolar lavage fluid also increased significantly in the high-dose group. These data show that in the sheep model of asbestosis simple tests of pulmonary function correlate well with histological changes and changes in the bronchoalveolar lavage fluid in the course of the disease and can be used to assess progression of asbestosis.
5-Amino-4-Imidazolecarboxamide Riboside Potentiates Both Transport of Reduced Folates and Antifolates by the Human Reduced Folate Carrier and Their Subsequent Metabolism
Authors: John J. McGuire, William H. Haile, Chen-Chen Yeh
Journal: Cancer Research (2006)

Abstract Transport is required before reduced folates and anticancer antifolates [e.g., methotrexate (MTX)] exert their physiologic functions or cytotoxic effects. The folate/antifolate transporter with the widest tissue distribution and greatest activity is the reduced folate carrier (RFC). There is little evidence that RFC-mediated influx is posttranscriptionally regulated. We show that [3H]MTX influx in CCRF-CEM human childhood T-leukemia cells is potentiated up to 6-fold by exogenous 5-amino-4-imidazolecarboxamide riboside (AICAr) in a AICAr and MTX concentration–dependent manner. Metabolism to more biologically active polyglutamate forms is also potentiated for MTX and other antifolates. That potentiation of influx by AICAr is mediated by effects on the RFC is supported by analyses ±AICAr showing (a) similarity and magnitude of kinetic constants for [3H]MTX influx; (b) similarity of inhibitory potency of known RFC substrates; (c) lack of potentiation in a CCRF-CEM subline that does not express the RFC; and (d) similarity of time and temperature dependence. Potentiation occurs rapidly and does not require new protein synthesis. Effects of specific inhibitors of folate metabolism and the time and sequence of AICAr incubation with cells suggest that both dihydrofolate reductase inhibition and metabolism of AICAr are essential for potentiation. Acute folate deficiency or incubation of CCRF-CEM with AICAr-related metabolites (e.g., adenosine) does not initiate potentiation. AICAr increases growth inhibitory potency of MTX and aminopterin against CCRF-CEM cells when both AICAr and antifolate are present for the first 24 hours of a 120-hour growth period. AICAr is the first small molecule that regulates RFC activity. (Cancer Res 2006; 66(7): 3836-44)
A Show of Confidence
Authors: J. Rothman
Journal: New England Journal of Medicine (1978)

Many medical researchers believe that it would be fruitless to submit for publication any paper that lacks statistical tests of significance. Their belief is not ill founded: editors and referees commonly rely on tests of significance as indicators of a sophisticated and meaningful statistical analysis, as well as the primary means to assess sampling variability in a study. The preoccupation with significance tests is embodied in the focus on whether the P value is less than 0.05; results are considered "significant" or "not significant" according to whether or not the P value is less than or greater than 0.05. Dr. . . .
Dose Intensity Analysis of Melphalan and Prednisone in Multiple Myeloma
Authors: M. Palmer, A. Belch, J. Hanson, L. Brox
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Dose Intensity Analysis of Melphalan and Prednisone in Multiple Myeloma Get access M. Palmer, M. Palmer Search for other works by this author on: Oxford Academic PubMed Google Scholar A. Belch, A. Belch Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Hanson, J. Hanson Search for other works by this author on: Oxford Academic PubMed Google Scholar L. Brox L. Brox * 3Cancer Research Group (McEachern Laboratory) and Cross Cancer Institute, University of AlbertaEdmonton, AB, Canada. *Correspondence to: L. Brox, Cancer Research Group (McEachern Laboratory), University of Alberta, Edmonton, AB, Canada, T6G 2H7. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 6, 18 May 1988, Pages 414–418, https://doi.org/10.1093/jnci/80.6.414 Published: 18 May 1988 Article history Received: 13 November 1987 Revision received: 15 January 1988 Accepted: 21 January 1988 Published: 18 May 1988
Diaphragm electromyogram in infants with abdominal wall defects and congenital diaphragmatic hernia
Authors: Z. Kassim, C. Jolley, J. Moxham, A. Greenough, G.F. Rafferty
Journal: European Respiratory Journal (2010)

Measurement of the diaphragm electromyogram (EMGdi) elicited by phrenic nerve stimulation could be useful to assess neonates suffering from respiratory distress due to diaphragm dysfunction, as observed in infants with abdominal wall defects (AWD) or congenital diaphragmatic hernia (CDH). The study aims were to assess the feasibility of recording EMGdi using a multipair oesophageal electrode catheter and examine whether diaphragm muscle and/or phrenic nerve function was compromised in AWD or CDH infants. Diaphragm compound muscle action potentials elicited by magnetic phrenic nerve stimulation were recorded from 18 infants with surgically repaired AWD (n = 13) or CDH (n = 5), median (range) gestational age 36.5 (34–40) weeks. Diaphragm strength was assessed as twitch transdiaphragmatic pressure (Tw P di ). One AWD patient had prolonged phrenic nerve latency (PNL) bilaterally (left 9.31 ms, right 9.49 ms) and two CDH patients had prolonged PNL on the affected side (10.1 ms and 10.08 ms). There was no difference in left and right Tw P di in either group. PNL correlated significantly with Tw P di in CDH (r = 0.8; p = 0.009). Oesophageal EMG and magnetic stimulation of the phrenic nerves can be useful to assess phrenic nerve function in infants. Reduced phrenic nerve conduction accompanies the reduced diaphragm force production observed in infants with CDH.
Reply to F. Ades
Authors: Zhongzhen Guan
Journal: Journal of Clinical Oncology (2013)

This study was carried out from 2006 mostly in Asian countries, especially in China.Unfortunately, anti-human epidermal growth factor receptor 2 drugs were not universally available at that time in developing countries.The study was approved by a national accredited ethics review board.In addition, although disease progression occurred, investigators had the option to unblind the patient's treatment, and those on placebo plus paclitaxel could continue on open-label lapatinib monotherapy.
Paclitaxel After Doxorubicin Plus Cyclophosphamide As Adjuvant Chemotherapy for Node-Positive Breast Cancer: Results From NSABP B-28
Authors: Eleftherios P. Mamounas, John Bryant, Barry Lembersky, Louis Fehrenbacher, Scot M. Sedlacek, Bernard Fisher, D. Lawrence Wickerham, Greg Yothers, Atilla Soran, Norman Wolmark
Journal: Journal of Clinical Oncology (2005)

The primary aim of National Surgical Adjuvant Breast and Bowel Project (NSABP) B-28 was to determine whether four cycles of adjuvant paclitaxel (PTX) after four cycles of adjuvant doxorubicin/cyclophosphamide (AC) will prolong disease-free survival (DFS) and overall survival (OS) compared with four cycles of AC alone in patients with resected operable breast cancer and histologically positive axillary nodes.Between August 1995 and May 1998, 3,060 patients were randomly assigned (AC, 1,529; AC followed by PTX [AC --> PTX], 1,531). Patients > or = 50 years and those younger than 50 years with estrogen receptor (ER) or progesterone receptor (PR) -positive tumors also received tamoxifen for 5 years, starting with the first dose of AC. Postlumpectomy radiotherapy was mandated. Postmastectomy or regional radiotherapy was prohibited. Median follow-up is 64.6 months.The addition of PTX to AC significantly reduced the hazard for DFS event by 17% (relative risk [RR], 0.83; 95% CI, 0.72 to 0.95; P = .006). Five-year DFS was 76% +/- 2% for patients randomly assigned to AC --> PTX compared with 72% +/- 2% for those randomly assigned to AC. Improvement in OS was small and not statistically significant (RR, 0.93; 95% CI, 0.78 to 1.12; P = .46). Five-year OS was 85% +/- 2% for both groups. Subset analysis of the effect of paclitaxel according to hormone receptors or tamoxifen administration did not reveal statistically significant interaction (for DFS, P = .30 and P = .44, respectively). Toxicity with the AC --> PTX regimen was acceptable for the adjuvant setting.The addition of PTX to AC resulted in significant improvement in DFS but no significant improvement in OS with acceptable toxicity. No significant interaction between treatment effect and receptor status or tamoxifen administration was observed.
Association of Inflammation and Malnutrition with Cardiac Valve Calcification in Continuous Ambulatory Peritoneal Dialysis Patients
Authors: ANGELA YEE MOON WANG, JEAN WOO, MEI WANG, MANDY MAN MEI SEA, RICKY IP, PHILIP KAM TAO LI, SIU FAI LUI, JOHN ELSBY SANDERSON
Journal: Journal of the American Society of Nephrology (2001)

Cardiac valve calcification (VC) has long been regarded as a consequence of aging and abnormal calcium-phosphate metabolism in uremic patients. In view of the recent recognition of association among inflammation, malnutrition, and atherosclerosis, the possible role of inflammation and malnutrition in VC was investigated. Inflammatory markers (including C-reactive protein [CRP], fibrinogen, and basal metabolic rate) and nutritional status (assessed using serum albumin, subjective global nutrition assessment, and handgrip strength) were examined, in addition to calcium phosphate parameters and other traditional cardiovascular risk factors, including gender, smoking habits, BP, and lipid profile, in relation to VC in 137 patients who were on continuous ambulatory peritoneal dialysis. Compared with patients with no VC, patients with VC not only were older (60 [10] versus 54 [12] yr; P = 0.005), had higher plasma phosphate (1.89 [0.52] versus 1.64 [0.41] mmol/L; P = 0.003), and had higher parathyroid hormone (83 [40, 145] versus 38 [16, 71] pmol/L; P = 0.001) but also had higher CRP (4.5 [0.1, 13.4] versus 0.2 [0.1, 4.4] mg/L; P = 0.004), had higher fibrinogen (6.6 [1.9] versus 5.7 [1.3] g/L; P = 0.002), and had lower serum albumin (26 [4] versus 29 [3] g/L; P = 0004). Twenty-three percent of patients with VC versus 17% of patients with no VC were moderately to severely malnourished according to subjective global nutrition assessment (P = 0.05). Even after adjustment for patients' age, duration of continuous ambulatory peritoneal dialysis, diabetes, and calcium x phosphate product, cardiac VC remained strongly associated with CRP (odds ratio, 1.05; P = 0.026) and albumin (odds ratio, 0.85; P = 0.01). The data suggest that VC not only is a passive degenerative process but also involves active inflammation, similar to that seen in atherosclerosis. The presence of uncontrolled hyperphosphatemia and hyperparathyroidism further accelerates the progression of calcification. The data also indicate that VC and atherosclerosis should be considered as associated syndromes, sharing similar pathogenic mechanisms, namely active inflammation.
Increased Neutrophil Numbers and IL-8 Levels in Airway Secretions in Acute Severe Asthma
Authors: CLAUDIA L. ORDOÑEZ, THOMAS E. SHAUGHNESSY, MICHAEL A. MATTHAY, JOHN V. FAHY
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The inflammatory events in the airways at the time of acute respiratory failure from acute severe asthma are poorly understood. To determine the patterns of cellular inflammation in the airways in acute severe asthma, we analyzed tracheal aspirates collected within 12 h of intubation from patients intubated emergently for acute severe asthma (n = 10) and from patients intubated electively for nonpulmonary surgery (n = 14). The number of neutrophils in tracheal aspirates from asthma patients was 10 times higher than normal (4.2 [0.6 to 335.0] [median, range] versus 0.4 [0.009 to 9.4] × 106/ml, p = 0.001), and there was a strong trend for a positive relationship between neutrophil number and duration of intubation (rs = 0.64, p = 0.06). Although eosinophil numbers were also significantly higher than normal (0.5 [0.0 to 23.3] versus 0.0 [0.0 to 0.1] × 106/ml, p = 0.003), the numbers of eosinophils were 8-fold less than neutrophils, and there was no significant correlation between eosinophil number and duration of intubation (rs = 0.4, p = 0.26). Interleukin-8 (IL-8), a chemoattraction for neutrophils, was 19 times higher than normal in tracheal aspirates from asthmatic patients (75.0 [9.0 to 168.0] versus 4.0 [0.08 to 24.0] ng/ml, p < 0.05) and correlated significantly with the neutrophil number (rs = 0.77, p = 0.03). Furthermore, the IL-8 levels correlated positively with the duration of mechanical ventilation (rs = 0.74, p = 0.03). Surprisingly, the number of neutrophils increased significantly during the period of intubation in the asthmatic subjects, possibly because of intravenous corticosteroid treatment. We conclude that neutrophils are the dominant inflammatory leukocyte characterizing airway inflammation in acute severe asthma that requires mechanical ventilation, and that IL-8 is an important mediator of this neutrophilia.
CD44 Isoform Status Predicts Response to Treatment with Anti-CD44 Antibody in Cancer Patients
Authors: Fabian Birzele, Edgar Voss, Adam Nopora, Konrad Honold, Florian Heil, Sabine Lohmann, Henk Verheul, Christophe Le Tourneau, Jean-Pierre Delord, Carla van Herpen, Devalingam Mahalingam, Andrew L. Coveler, Valerie Meresse, Stefan Weigand, Valeria Runza, Michael Cannarile
Journal: Clinical Cancer Research (2015)

Abstract Purpose: CD44, a cell surface glycoprotein, plays important roles in the development, progression, and metastasis of various tumor types. The aim of this study was to investigate how the expression of CD44 isoforms influences the interaction with hyaluronic acid (HA) and how differential isoform expression impacts antitumoral responses in vivo to treatment with RG7356, a humanized anti-CD44 antibody inhibiting CD44–HA interaction. Experimental Design: CD44 isoform expression on various tumor cell lines was analyzed by RNASeq while data on patients with different tumor types were obtained from the publicly available TCGA RNASeq dataset as well as a phase I clinical study (NCT01358903). We analyzed the link between HA production and CD44 isoform expression as well as the consequences of blocking the CD44-mediated cell adhesion to HA using RG7356. The correlation between CD44 isoform expression and antitumor response to RG7356 treatment was investigated in the corresponding murine xenograft in vivo models as well as in a subset of patients treated with RG7356 from a recently completed phase I clinical trial. Results: CD44 isoform expression, in particular expression of CD44s, is associated with HA production and predicts response to treatment with RG7356 in tumor xenograft models. Furthermore, patient data suggest that CD44 isoform status is a potential predictive biomarker for clinical response to treatment with RG7356. Conclusions: We provide new insights into the close interplay between CD44 and HA and a potential biomarker to enrich patient responses to RG7356 in the clinic. Clin Cancer Res; 21(12); 2753–62. ©2015 AACR.
Adjuvant portal-vein infusion of fluorouracil and heparin in colorectal cancer: a randomised trial
Authors: Philippe Rougier, Tarek Sahmoud, Donato Nitti, Desmond Curran, Roberto Doci, B De Waele, Toshifusa Nakajima, Helmut Rauschecker, Roberto Labianca, Jean-Claude Pector, Giovanni Apolone, Philippe Lasser, Marie Laure Couvreur, Jacques Wils, Silvia Marsoni
Journal: The Lancet (1998)