tbuckley/cabot-search huggingface dataset:
Pegfilgrastim ± ciprofloxacin for primary prophylaxis with TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy for breast cancer. Results from the GEPARTRIO study
Authors: G. von Minckwitz, S. Kümmel, A. du Bois, W. Eiermann, H. Eidtmann, B. Gerber, J. Hilfrich, J. Huober, S.D. Costa, C. Jackisch, S.-T. Grasshoff, S. Vescia, T. Skacel, S. Loibl, K.M. Mehta, M. Kaufmann
Journal: Annals of Oncology (2007)
Multidisciplinary biopsychosocial rehabilitation for chronic low back pain: Cochrane systematic review and meta-analysis
Authors: Steven J Kamper, A T Apeldoorn, A Chiarotto, R J E M Smeets, R W J G Ostelo, J Guzman, M W van Tulder
Journal: BMJ (2015)

<b>Objective</b> To assess the long term effects of multidisciplinary biopsychosocial rehabilitation for patients with chronic low back pain. <b>Design</b> Systematic review and random effects meta-analysis of randomised controlled trials. <b>Data sources</b> Electronic searches of Cochrane Back Review Group Trials Register, CENTRAL, Medline, Embase, PsycINFO, and CINAHL databases up to February 2014, supplemented by hand searching of reference lists and forward citation tracking of included trials. <b>Study selection criteria</b> Trials published in full; participants with low back pain for more than three months; multidisciplinary rehabilitation involved a physical component and one or both of a psychological component or a social or work targeted component; multidisciplinary rehabilitation was delivered by healthcare professionals from at least two different professional backgrounds; multidisciplinary rehabilitation was compared with a non- multidisciplinary intervention. <b>Results</b> Forty one trials included a total of 6858 participants with a mean duration of pain of more than one year who often had failed previous treatment. Sixteen trials provided moderate quality evidence that multidisciplinary rehabilitation decreased pain (standardised mean difference 0.21, 95% confidence interval 0.04 to 0.37; equivalent to 0.5 points in a 10 point pain scale) and disability (0.23, 0.06 to 0.40; equivalent to 1.5 points in a 24 point Roland-Morris index) compared with usual care. Nineteen trials provided low quality evidence that multidisciplinary rehabilitation decreased pain (standardised mean difference 0.51, −0.01 to 1.04) and disability (0.68, 0.16 to 1.19) compared with physical treatments, but significant statistical heterogeneity across trials was present. Eight trials provided moderate quality evidence that multidisciplinary rehabilitation improves the odds of being at work one year after intervention (odds ratio 1.87, 95% confidence interval 1.39 to 2.53) compared with physical treatments. Seven trials provided moderate quality evidence that multidisciplinary rehabilitation does not improve the odds of being at work (odds ratio 1.04, 0.73 to 1.47) compared with usual care. Two trials that compared multidisciplinary rehabilitation with surgery found little difference in outcomes and an increased risk of adverse events with surgery. <b>Conclusions</b> Multidisciplinary biopsychosocial rehabilitation interventions were more effective than usual care (moderate quality evidence) and physical treatments (low quality evidence) in decreasing pain and disability in people with chronic low back pain. For work outcomes, multidisciplinary rehabilitation seems to be more effective than physical treatment but not more effective than usual care.
Common variants in ZNF365 are associated with both mammographic density and breast cancer risk
Authors: Sara Lindström, Celine M Vachon, Jingmei Li, Jajini Varghese, Deborah Thompson, Ruth Warren, Judith Brown, Jean Leyland, Tina Audley, Nicholas J Wareham, Ruth J F Loos, Andrew D Paterson, Johanna Rommens, Darryl Waggott, Lisa J Martin, Christopher G Scott, V Shane Pankratz, Susan E Hankinson, Aditi Hazra, David J Hunter, John L Hopper, Melissa C Southey, Stephen J Chanock, Isabel dos Santos Silva, JianJun Liu, Louise Eriksson, Fergus J Couch, Jennifer Stone, Carmel Apicella, Kamila Czene, Peter Kraft, Per Hall, Douglas F Easton, Norman F Boyd, Rulla M Tamimi
Journal: Nature Genetics (2011)
Regulation of the expression of MHC class I-related chain A, B (MICA, MICB) via chromatin remodeling and its impact on the susceptibility of leukemic cells to the cytotoxicity of NKG2D-expressing cells
Authors: N Kato, J Tanaka, J Sugita, T Toubai, Y Miura, M Ibata, Y Syono, S Ota, T Kondo, M Asaka, M Imamura
Journal: Leukemia (2007)
COMPARATIVE ANALYSIS BETWEEN FRAMINGHAM RISK SCORE AND A NEW BIOMARKER-BASED RISK SCORE (HARM SCORE) FOR CORONARY HEART DISEASE MORTALITY RISK PREDICTION
Authors: Sandip K. Zalawadiya, Vikas Veeranna, Ashutosh Niraj, Sidakpal S. Panaich, Naga V.A. Kommuri, Sony Jacob, Luis Afonso
Journal: Journal of the American College of Cardiology (2011)
Epithelial-to-Mesenchymal Transition Induced by TGF-β1 Is Mediated by Blimp-1–Dependent Repression of BMP-5
Authors: Mathilde Romagnoli, Karine Belguise, Ziyang Yu, Xiaobo Wang, Esther Landesman-Bollag, David C. Seldin, Dany Chalbos, Sophie Barillé-Nion, Pascal Jézéquel, Margaret L. Seldin, Gail E. Sonenshein
Journal: Cancer Research (2012)

Induction of epithelial-to-mesenchymal transition (EMT) by TGF-β1 requires Ras signaling. We recently identified the transcriptional repressor Blimp-1 (PRDM1) as a downstream effector of the NF-κB, RelB/Bcl-2/Ras-driven pathway that promotes breast cancer cell migration. As the RelB/Blimp-1 pathway similarly required Ras signaling activation, we tested whether Blimp-1 plays a role in TGF-β1-mediated EMT. Here, TGF-β1 treatment of untransformed NMuMG mammary epithelial and MDA-MB-231 breast cancer cells was shown to induce Blimp-1 expression, which promoted an EMT signature and cell migration. TGFB1 and BLIMP1 RNA levels were correlated in patient breast tumors. BLIMP1 gene transcription was activated by TGF-β1 via a c-Raf (RAF1) to AP-1 pathway. Blimp-1 induced expression of the EMT master regulator Snail (SNAI1) via repressing BMP-5, which inhibited Snail expression upon TGF-β1 treatment. Interestingly, a similar cascade was observed during postnatal mouse mammary gland development. RelB expression was detected early in pregnancy followed progressively by Blimp-1 and then Snail; whereas, BMP-5 levels were high in nulliparous and regressing glands. Finally, lower BMP5 RNA levels were detected in patient breast tumors versus normal tissues, and correlated with cancer recurrence. Thus, the Ras effector Blimp-1 plays an essential role in TGF-β1-induced EMT via repression of BMP-5 in breast cancer.
Immunoglobulin synthesis by salivary gland lymphoid cells in Sjögren's syndrome
Authors: Norman Talal, Richard Asofsky, Philip Lightbody
Journal: Journal of Clinical Investigation (1970)

The synthesis of immunoglobulins by cells infiltrating the labial salivary glands has been studied by radioimmunoelectrophoresis in 20 patients with Sjögren's syndrome (SS) and in 14 control patients with related disorders. The patients with SS were producing significantly greater quantities of IgG, IgM, and IgA. Synthesis of IgG and IgM correlated with the degree of lymphoid infiltration but not with serum immunoglobulin concentration. Patients with SS and rheumatoid arthritis (RA) showed greater synthesis of IgG and IgM than those with uncomplicated RA. The only extensive lymphoid infiltration was seen in patients with SS. One patient with SS and primary macroglobulinemia was synthesizing the paraprotein in the lip biopsy as well as in the bone marrow. These results establish the immunologic competence of the infiltrating lymphoid cells and suggest their origin from an extrasalivary source.
Can the English NHS meet the 18-week waiting list target?
Authors: Richard Lewis, John Appleby
Journal: Journal of the Royal Society of Medicine (2005)

Waiting lists for hospital treatment are often viewed as a peculiarly British disease. While it is erroneous to think that other developed countries do not suffer waiting lists,1 there is little doubt that long waits for hospital treatment have dogged the National Health Service for many years and are a source of dissatisfaction among patients.

Waiting lists for treatment have grown steadily since the inception of the NHS. Only since 1999 has there been a sustained decline in the numbers of people waiting. Waiting times for treatment, perhaps a better measure of system performance, have waxed and waned over the last decade as various initiatives by governments of all political hues have sought to tackle the problem of service access.

Successive governments have tended to focus on reducing the maximum waiting times for outpatient appointments and inpatient treatments. The current Labour government has now raised the stakes further. It has pledged that by 2008 there will be a maximum wait of only 18 weeks from any referral of a patient by a general practitioner to treatment in hospital if required. Such a target represents a large step up in expected performance. Current targets are that by the end of this year, no patient will wait more than 3 months for an outpatient appointment and a further 3 months for any inpatient or day-case treatment. Meeting the new target will require a massive effort, and despite considerable success to date, could it be a target too far? And, moreover, is there now a case for a change in focus on waiting times to address broader issues such as equity of access?
Immunosuppression for liver transplantation
Authors: E K Geissler, H J Schlitt
Journal: Gut (2008)

In the last few decades liver transplantation (LTx) has become a reliable life-saving procedure for patients with chronic end-stage liver diseases. LTx has an outstanding success rate in the first few years after allografting, especially considering that many patients are on the brink of survival at the time of transplantation. The success of LTx is owed to the pioneers who developed the surgical procedures and to researchers who discovered the medications to help prevent immunological rejection of allografts. However, several problems continue to impose serious limits on LTx today, including a shortage of donor livers, recurrence of disease (eg, hepatitis, hepatocellular cancer), preservation of long-term allograft function and the side effects of anti-rejection drugs. While the dilemma of organ shortage is not a focus of this review, we will address the latter issues as they relate to the "oldest" and "newest" approaches to immunosuppression, and discuss the prospect that recipients could potentially be made immunologically tolerant to liver transplants. Due to the critical shortage of organs, new strategies to preserve transplanted liver allografts for the longest possible time are of paramount importance.
Cellular Action of Vasopressin in Medullary Tubules of Mice with Hereditary Nephrogenic Diabetes Insipidus
Authors: Brian A. Jackson, Richard M. Edwards, Heinz Valtin, Thomas P. Dousa
Journal: Journal of Clinical Investigation (1980)

Our previous studies (1974. J. Clin. Invest.54: 753-762.) suggested that impaired metabolism of cyclic AMP (cAMP) may be involved in the renal unresponsiveness to vasopressin (VP) in mice with hereditary nephrogenic diabetes insipidus (NDI). To localize such a defect to specific segments of the nephron, we studied the activities of VP-sensitive adenylate cyclase, cAMP phosphodiesterase (cAMP-PDIE), as well as accumulation of cAMP in medullary collecting tubules (MCT) and in medullary thick ascending limbs of Henle's loop (MAL) microdissected from control mice with normal concentrating ability and from mice with hereditary NDI.
Polyethylene glycol-modified bilirubin oxidase improves hepatic energy charge and urinary prostaglandin levels in rats with obstructive jaundice
Authors: Toshinori Kamisako, Shozo Miyawaki, Esteban C. Gabazza, Tomoaki Ishihara, Akira Kamei, Noriko Kawamura, Yukihiko Adachi
Journal: Journal of Hepatology (1998)
Predictive value of image cytometry for diagnosis of lung cancer in heavy smokers
Authors: S. Xing, B. Khanavkar, J. A. Nakhosteen, Z. Atay, K-H. Jöckel, W. Marek
Journal: European Respiratory Journal (2005)

The Research Institute for Diagnosis and Treatment of Early Lung Cancer (RIDTELC) Lung Study was initiated to determine whether lung cancer screening by automated sputum cytometry combined with conventional sputum cytology and auto-fluorescence in addition to white light bronchoscopy could enhance the detection rate of early lung cancer. The present study analyses the initial findings to evaluate the efficiency of automated sputum cytology in predicting the diagnosis of lung cancer. In this study, malignancy grade was used as a predictive parameter for lung cancer. In total, 2,480 heavy smokers (&gt;30 pack-yrs), aged 50–74 yrs, with no previous cancer in the last 5 yrs, received chest radiology, conventional sputum cytology and sputum cytometry screening. In total, twenty-seven lung cancers were diagnosed, representing a prevalence of 1.1%, 25 of which provided sputum samples. Positive automated sputum cytology results were seen in 176 smokers (7.2%), 10 (0.4%) of whom had severe dysplasia or higher lesions (positive results) by conventional sputum cytology examination. Out of 25 tumour cases, 20 had suspicious results using automated sputum cytology, representing 80% sensitivity. One patient out of 24 with tumours had positive results on conventional sputum cytology, representing a sensitivity of 4.2%. For all stages of squamous cell lung cancer and later stage adenocarcinoma the sensitivity of automated sputum cytology was 100%. For adenocarcinoma stage I sensitivity was 25%. In conclusion, DNA analysis of sputum slides by automated sputum cytology may be a suitable tool for the detection of early lung cancer and the characterisation of a high-risk group with pre-invasive lesions for follow-up.
The varicocele dilemma
Authors: S. J. Silber
Journal: Human Reproduction Update (2001)

There is probably no subject that is more controversial in the area of male infertility than varicocele. The overwhelming majority of non-urologist infertility specialists in the world are extremely sceptical of the role of varicocele or varicocelectomy in the treatment of male infertility. Directors of most assisted reproductive technologies (ART) programmes view the enthusiasm with which urologists approach varicocelectomy as a potential impediment to the couple that is getting older and do not have much time left to become pregnant using ART. There are many credible, well-controlled studies which show no effect of varicocelectomy on fertility. There are also a few ‘controlled’ studies that favour varicocelectomy, but all can be criticised on the basis of patient selection bias. Thus the great weight of evidence from controlled studies is against varicocelectomy and the reports supporting varicocelectomy are extremely weak. Finally, the reports that semen parameters are improved by varicocelectomy is flawed by uncontrolled observations and the failure to take into account the variability of semen analysis in infertile men and its regression toward the mean. Many control studies have demonstrated that, because of this variability, men with an initially low sperm count tend later to have higher sperm counts in the absence of any treatment whatsoever.
Redox signaling in angiogenesis: Role of NADPH oxidase
Authors: M USHIOFUKAI
Journal: Cardiovascular Research (2006)

Angiogenesis, a process of new blood vessel formation, is a key process involved in normal development and wound repair as well as in the various pathophysiologies such as ischemic heart and limb diseases and atherosclerosis. Reactive oxygen species (ROS) such as superoxide and H(2)O(2) function as signaling molecules in many aspects of growth factor-mediated responses including angiogenesis. Vascular endothelial growth factor (VEGF) is a key angiogenic growth factor and stimulates proliferation, migration, and tube formation of endothelial cells (ECs) primarily through the VEGF receptor type2 (VEGR2, KDR/Flk1). VEGF binding initiates autophosphorylation of VEGFR2, which results in activation of downstream signaling enzymes including ERK1/2, Akt, and eNOS in ECs, thereby stimulating angiogenesis. The major source of ROS in EC is a NADPH oxidase which consists of Nox1, Nox2 (gp91phox), Nox4, p22phox, p47phox, p67phox and the small G protein Rac1. The endothelial NADPH oxidase is activated by angiogenic factors including VEGF and angiopoietin-1. ROS derived from this enzyme stimulate diverse redox signaling pathways leading to angiogenesis-related gene induction as well as EC migration and proliferation, which may contribute to postnatal angiogenesis in vivo. The aim of this review is to provide an overview of the recent progress on the emerging area of the role of ROS derived from NADPH oxidase and redox signaling in angiogenesis. Understanding these mechanisms may provide insight into the NADPH oxidase and redox signaling components as potential therapeutic targets for treatment of angiogenesis-dependent cardiovascular diseases and for promoting angiogenesis in ischemic limb and heart diseases.
Otitis media and its consequences: beyond the earache
Authors: Anne Vergison, Ron Dagan, Adriano Arguedas, Jan Bonhoeffer, Robert Cohen, Ingeborg DHooge, Alejandro Hoberman, Johannes Liese, Paola Marchisio, Arto A Palmu, G Thomas Ray, Elisabeth AM Sanders, Eric AF Simões, Matti Uhari, Johan van Eldere, Stephen I Pelton
Journal: The Lancet Infectious Diseases (2010)
Oxygen treatment of sleep hypoxaemia in Duchenne muscular dystrophy.
Authors: P E Smith, R H Edwards, P M Calverley
Journal: Thorax (1989)

Patients with Duchenne muscular dystrophy develop progressive ventilatory muscle weakness and often die of respiratory complications. Recurrent, often profound, hypoxaemia has been shown in a previous study by this group to occur during rapid eye movement (REM) sleep in these patients before they develop sleep symptoms. In this study the efficacy and physiological effects of nocturnal oxygen in such patients have been assessed. Seven patients with Duchenne muscular dystrophy (age range 16-22 years; mean vital capacity 1.37 litres) with normal arterial blood gas tensions when awake were investigated by standard overnight polysomnography on an acclimatization night followed by two successive nights on which they received room air and nasal oxygen (2 litres/min) respectively in random order. Total sleep time, proportion of REM and non-REM sleep, and frequency and duration of arousals were similar on the two nights. When breathing air six of the seven subjects developed oxygen desaturation of more than 5% during REM sleep. With oxygen only one subject showed any oxygen desaturation exceeding 2.5%. Oxygen desaturation was associated with periods of hypopnoea or cessation of respiratory effort. The mean duration of episodes of hypopnoea and apnoea was prolonged during oxygen breathing by 19% and the mean duration of episodes during REM sleep by 33% (the proportion of REM sleep associated with hypopnoea and apnoea increased in all subjects). Heart rate in non-REM sleep fell by 9.3%; heart rate variation in REM and non-REM sleep was unchanged. These acute studies show that oxygen reduces the sleep hypoxaemia associated with respiratory muscle weakness; whether long term treatment will be possible or desirable is not clear as oxygen potentiates the underlying ventilatory disturbance.
<i>MET</i> Amplification Status in Therapy-Naïve Adeno- and Squamous Cell Carcinomas of the Lung
Authors: Hans-Ulrich Schildhaus, Anne M. Schultheis, Josef Rüschoff, Elke Binot, Sabine Merkelbach-Bruse, Jana Fassunke, Wolfgang Schulte, Yon-Dschun Ko, Andreas Schlesinger, Marc Bos, Masyar Gardizi, Walburga Engel-Riedel, Michael Brockmann, Monika Serke, Ulrich Gerigk, Khosro Hekmat, Konrad F. Frank, Marcel Reiser, Holger Schulz, Stefan Krüger, Erich Stoelben, Thomas Zander, Jürgen Wolf, Reinhard Buettner
Journal: Clinical Cancer Research (2014)

MET is a potential therapeutic target in lung cancer and both MET tyrosine kinase inhibitors and monoclonal antibodies have entered clinical trials. MET signaling can be activated by various mechanisms, including gene amplification. In this study, we aimed to investigate MET amplification status in adeno- and squamous cell carcinomas of the lung. We propose clearly defined amplification scores and provide epidemiologic data on MET amplification in lung cancer.We evaluated the prevalence of increased MET gene copy numbers in 693 treatment-naïve cancers by FISH, defined clear cutoff criteria, and correlated FISH results to MET IHC.Two thirds (67%) of lung cancers do not have gains in MET gene copy numbers, whereas 3% show a clear-cut high-level amplification (MET/centromer7 ratio ≥2.0 or average gene copy number per nucleus ≥6.0 or ≥10% of tumor cells containing ≥15 MET copies). The remaining cases can be subdivided into intermediate- (6%) and low-level gains (24%). Importantly, MET amplifications occur at equal frequencies in squamous and adenocarcinomas without or with EGFR or KRAS mutations.MET amplification is not a mutually exclusive genetic event in therapy-naïve non-small cell lung cancer. Our data suggest that it might be useful to determine MET amplification (i) before EGFR inhibitor treatment to identify possible primary resistance to anti-EGFR treatment, and (ii) to select cases that harbor KRAS mutations additionally to MET amplification and, thus, may not benefit from MET inhibition. Furthermore, our study provides comprehensive epidemiologic data for upcoming trials with various MET inhibitors.
Altered Detoxification Status and Increased Resistance to Oxidative Stress by K-Ras Transformation
Authors: Christian V. Recktenwald, Roland Kellner, Rudolf Lichtenfels, Barbara Seliger
Journal: Cancer Research (2008)

Abstract Mutated K-ras is frequently found in human malignancies and plays a key role in many signal transduction processes resulting in an altered gene and/or protein expression pattern. Proteins controlled by a constitutive activated mitogen-activated protein kinase pathway are primarily related to alterations in the mitochondrial and nuclear compartments. Therefore, different K-Ras mutants and respective control cells were subjected to two-dimensional gel electrophoresis using basic pH gradients. This approach led to the identification of differentially expressed proteins, such as members of the heterogeneous ribonucleoprotein family, and enzymes involved in cellular detoxification as well as in oxidative stress. Increased expression of these enzymes was paralleled by an elevated tolerance of K-ras mutants against the cytotoxic potential of hydrogen peroxide and formaldehyde as well as an altered redox status based on enhanced intracellular glutathione (GSH) levels indicating an improved detoxification potential of defined K-ras transfectants, whereas down-regulation by RNA interference of candidate proteins reversed the tolerance against these compounds. This hypothesis is supported by an up-regulated expression of a key enzyme of the pentose phosphate pathway resulting in an increased production of NADPH required for anabolic processes as well as the rebuilding of oxidized GSH. Both the enhanced resistance against xenobiotic compounds as well as an altered oxidative pathway might confer growth advantages for tumor cells carrying dominant-positive K-ras mutations such as in lung or pancreatic adenocarcinoma. [Cancer Res 2008;68(24):10086–93]