gebhart/patrepeval huggingface dataset:
Combined treatment in advanced stages (IIIb-IV) of non-small cell lung cancer. (2003)

Chemotherapy regimens based on platinum represent the reference standards in Non-Small Cell Lung Cancer (NSCLC) and when it is associated with radiotherapy and/or surgery (combined treatment) it improves survival of patients. Aim of this study was to estimate the efficacy of chemotherapy, based on high-dose epirubicin plus cisplatin, associated with surgery and/or radiotherapy. Twenty-four inoperable NSCLC patients (15 pts in stage IIIb and 9 in stage IV) were treated with epirubicin (120 mg/m2) plus cisplatin (60 mg/m2), every three weeks for at least 3 cycles up to a maximum of 6. A total of 109 treatment cycles (epirubicin plus cisplatin) were administered and two of 24 patients achieved full response (CR), 9 showed partial response (PR), for an overall response rate of 45.8%, 8 patients (33.4%) achieved stable disease (SD) and 5 (20.8%) progressive disease (PD). Leukopenia aroses in 81.9% of the cycles, anaemia in 36.6% and thrombocytopenia in 14%. After chemotherapy, nausea/vomiting was present in 33.3% of patients, while in a small number of cases there were also mucositis, diarrhea, fever, phlebitis, transaminase increase and electrocardiographic anomalies. Upon entry, at the end of therapy patients underwent restaging (CT, bronchoscopy, bone scintiscan) to evaluate the possibility of surgical resection; 15 out of 24 patients completed treatment with radiotherapy (40-60 Gy) and then were re-evaluated for surgery. Five patients underwent complete surgical resection of the neoplasia (4 after chemotherapy and one after radiotherapy). After 1 year survival was 66.6% for all patients. Combined treatment in advanced NSCLC showed a good response and survival after 1 year.
Glial cells : their role in behaviour (1998)

Preface 1. Changing concepts on the role of glia Peter Laming 2. The phylogeny of glial-neuronal relationships and behaviour Betty Roots and Peter Laming 3. Glial cells in brain development and plasticity Christian Muller 4. The retina as a model of glial function in the brain Andreas Reichenbach, Serguei N. Skatchkov and Winfried Reichelt 5. Metabolic trafficking between neurons and glia Stephen R. Robinson, Arne Schousboe, Ralf Dringen, Pierre Magistretti, Jonathan Coles and Leif Hertz 6. Transmitter receptor and uptake systems in astrocytes and their relation to behaviour Harold K. Kimelberg, Tuula O. Jalonen, Chiye Aoki and Ken McCarthy 7. Glial regulation of the neuronal microenvironment Eva Sykova, Elisabeth Hansson, Lars Ronnback and Charles Nicholson 8. Role of periaxonal glia in nerve conduction Joan Abbott 9. Transplantation of myelin-forming glial cells into the spinal cord: restoration of normal conduction in previously demyelinated axons Jeffery D. Kocsis and Stephen G. Waxman 10. Contributions of potassium currents and glia to slow potential shifts Uwe Heinemann and Wolfgang Walz 11. Acid alkaline transients and pH regulation glia Joachim Deitmer 12. Intra-cranial slow potential shifts and behavioural state Peter Laming, Alister Nichol and John Roughan 13. Slow brain potentials, sensory processing and cognition Herbert Bauer, Niels Birbaumer and Frank Roesler 14. Recent evidence from around the brain for structural plasticity of astrocytes in the adult CNS Adrienne Salm, N. Hawrylak, J. B. Bobak, G. I. Hatton and C. Aoki 15. Astrocytic involvement in learning Kim Ng, Ciaran Regan and Brona O'Dowd References Index.
Review article: the role of serotonergic agents in the treatment of patients with primary chronic constipation (2005)

Summary Chronic constipation is a highly prevalent disorder that is associated with significant direct and indirect costs and has substantial impact on patient quality of life. It is more common among women and non‐white populations and is evenly distributed across adult age groups. Constipation is a heterogeneous disorder associated with multiple symptoms and aetiologies. Recent research has increased our understanding of the pathogenesis of this disorder and the central role of the neurotransmitter serotonin in mediating gastrointestinal motility, secretion and sensation. Abnormal serotonin signalling and reuptake appear to play central roles in the symptoms of a subset of patients with chronic constipation. This observation provides a rationale for the use of targeted serotonergic agents for the treatment of chronic constipation. As the role of serotonin in gastrointestinal function is further elucidated and additional candidate drugs are developed, it is likely that serotonergic agents will afford additional treatment options for patients with chronic constipation. This article provides a concise review of the evidence supporting a role for serotonin in the pathogenesis of chronic constipation and a summary of the currently available evidence supporting the use of serotonergic agents for this disorder.
The Carrot Vs. the Stick in Work (2000)

Recombinant human DNase (rhDNase) reduces viscosity of sputum. Effect has been documented in cystic fibrosis and postoperatively in paediatric heart disease. Single dose treatment with rhDNase in paediatric asthma has no effect. In respiratory syncytial virus infection, treatment with rhDNase may be associated with increased need for supplemental oxygen. In adults with idiopathic bronchiectasis, treatment with rhDNase leads to more pulmonary exacerbations and a greater decline in pulmonary function tests. There are no controlled studies on rhDNase in primary ciliary dyskinesia or atelectasis.
Analytical Effectiveness of Mathematical Models for R&D Project Selection (1973)

Four mathematical programming models for R&amp;D project selection and funding are developed, based on similar models and results in the literature. Project selection and funding decision planning data for thirty actual R&amp;D projects are collected and the models are used with these data to ascertain which of the available projects to select and how much to spend on them. The portfolios prescribed by each model are compared with a prorata benchmark allocation, an ex post optimum allocation based on the success/fail project outcomes and the allocations actually used by management. The results indicate that these models may be effective decision aids when used at appropriate project life cycle periods, with the choice of the particular model form being influenced by the manager's objectives and viewpoints of the project selection problem.
Energy metabolism in heart failure and remodelling (2008)

Myocytes of the failing heart undergo impressive metabolic remodelling. The time line for changes in the pathways for ATP synthesis in compensated hypertrophy is: flux through the creatine kinase (CK) reaction falls as both creatine concentration ([Cr]) and CK activity fall; increases in [ADP] and [AMP] lead to increases in glucose uptake and utilization; fatty acid oxidation either remains the same or decreases. In uncompensated hypertrophy and in other forms of heart failure, CK flux and fatty acid oxidation are both lower; any increases in glucose uptake and utilization are not sufficient to compensate for overall decreases in the capacity for ATP supply and [ATP] falls. Metabolic remodelling is under transcriptional and post-transcriptional control. The lower metabolic reserve of the failing heart contributes to impaired contractile reserve.
Chemistry and biology of asparagine-linked glycosylation (1999)

The biosynthesis of glycoprotein conjugates is a complex process that involves the collective action of numerous enzymes. Recent research on the chemistry and biology of asparagine-linked glycosylation in our group has been focused on two specific areas. These are the development of potent inhibitors of oligosaccharyl transferase and the investigation of the conformational consequences of the glycosylation process. Since asparagine-linked glycosylation is an essential eukaryotic process, an understanding of the details of this complex transformation is of utmost importance both to fundamental biochemistry and to a consideration of the mechanisms of homeostatic control.
Issues in text-to-speech synthesis (2002)

The ultimate goal of text-to-speech synthesis is to convert ordinary orthographic text into an acoustic signal that is indistinguishable from human speech. Originally, synthesis systems were architected around a system of rules and models that were based on research on human language and speech production and perception processes. The quality of speech produced by such systems is inherently limited by the quality of the rules and the models. Given that our knowledge of human speech processes is still incomplete, the quality of text-to-speech is far from natural-sounding. Hence, today's interest in high quality speech for applications, in combination with advances in computer resource, has caused the focus to shift from rules and model-based methods to corpus-based methods that presumably bypass rules and models. For example, many systems now rely on large word pronunciation dictionaries instead of letter-to-phoneme rules and large prerecorded sound inventories instead of rules predicting the acoustic correlates of phonemes. Because of the need to analyze large amounts of data, this approach relies on automated techniques such as those used in automatic speech recognition.
Liver transplantation for the treatment of urea cycle disorders (1998)

The principal goal of therapy when liver transplantation is used for the treatment of metabolic disease is to correct the metabolic error. By doing so, liver transplantation eliminates the hepatic and peripheral consequences of the error. Inborn errors involving the urea cycle appear on theoretical grounds to be amenable to treatment using liver transplantation and, indeed, published data demonstrate that this approach to therapy can be successful. The purpose of this study is to examine the outcome of liver transplantation done for the indication of urea cycle defects in a large group of patients. The first goal of the study is to determine with certainty that liver transplantation corrects hyperammonaemia and halts the progress of disease. A second goal is to determine the extent of neurological recovery in children previously injured by hyperammonaemia. The final goal is to understand whether the quality of life is improved and medical expense is reduced by transplantation. The study involved a survey of major transplantation centres. Four centres provided data about 16 patients, 14 of whom were alive 11 months to 6 years after transplantation. The results demonstrate that liver transplantation resulted in correction of hyperammonaemia in all patients. The neurological outcome after transplantation correlated closely with the condition prior to transplantation. This population of patients has had relatively few problems in the long term related to the liver transplant itself. The quality of life seems to be much improved, but further study will be needed to confirm this. Limited data involving two patients show a reduction in the cost of care. We conclude from our experience that liver transplantation can be an effective treatment for children with urea cycle defects.
The Intranuclear Binding of Testosterone and 5α-Androstan-17β-ol-3-one by Rat Prostate (1968)

Abstract The intranuclear binding of radioactive hormone in prostate after the intravenous administration of testosterone-1,2-3H to rats has been studied. Nuclei obtained by sucrose density gradient centrifugation were extracted with buffer containing 0.6 m NaCl, and the soluble radioactivity was separated into bound and free fractions by gel filtration on Sephadex G-25 or G-200. As early as 15 min after testosterone administration, the radioactivity recovered in the bound form was predominantly dihydrotestosterone. By gel filtration of nuclear extracts on Sephadex G-200 and by the use of digestive enzymes, it was shown that dihydrotestosterone was bound to an acidic nuclear protein. Finally, several characteristics of this binding phenomenon were defined; the binding was stable to freezing for as long as 8 days, stable to short term incubation at 20° but not at 37°, and partially stable to repeated gel filtration on Sephadex.
STRUCTURE‐ACTIVITY RELATIONSHIPS IN A SERIES OF 6‐THIOXANTHINES WITH BRONCHODILATOR AND CORONARY DILATOR PROPERTIES (1961)

The bronchodilator activity of 47 compounds on the isolated guinea-pig tracheal ring preparation and the coronary dilator activity on the dog heart-lung preparation is described. 1,3-Disubstituted xanthines and 6-thioxanthines (theophyllines and 6-thiotheophyllines) were more active as bronchodilators and as coronary dilators than were 3,7-disubstituted 6-thioxanthines (6-thiotheobromines) or 1,3,7-trisubstituted 6-thioxanthines (6-thiocaffeines). None of the 6-thioxanthines was of any interest as a diuretic and none of the 6-thiocaffeines was of any interest as a central stimulant. Structure-activity requirements for potent bronchodilator and coronary dilator activity are discussed.
Reducing the caesarean delivery risk in elective inductions of labour: a decision analysis (2002)

To determine whether the vaginal delivery rate is increased in nulliparous women who have positive fetal fibronectin (fFN) testing before elective induction of labour, we performed a decision analysis that tested three options: (1) spontaneous labour; (2) testing nulliparous candidates for elective induction of labour at 39 weeks gestation with fFN and inducing labour if fFN positive (women who are fFN negative are managed expectantly); (3) elective induction of labour for women who are at least 39 weeks. We found that spontaneous labour had a vaginal delivery rate of 90, elective induction 79 and fFN screening 83. At baseline, a mother must be willing to take an additional 7 risk of caesarean delivery to warrant fFN testing or an additional 11 risk of caesarean delivery to warrant elective induction. We conclude that spontaneous labour has the highest vaginal delivery rates. An fFN test in a nulliparous woman may help to raise her likelihood of a vaginal delivery in an elective induction.
Imaging of atherosclerosis. Elastography. (2002)

Intravascular ultrasound elastography is a method for measuring the local elastic properties of coronary atherosclerotic plaques using intravascular ultrasound (IVUS). Mechanical properties of the different tissues within a plaque are measured through strain. In the last decade, several groups have applied elastography intravascularly with various levels of success. In this paper, the approaches of the different research groups will be discussed and the focus will be on our approach to the application of intravascular elastography.
THE QUICK WESTERN BLOT, A NOVEL TRANSPORTABLE 50-MINUTE HIV-1 ANTIBODY TEST (1989)

HIV-1 antibody determination by ELISA screening takes 4 hr to complete and is not reliable. Regular Western blot can take up to 24 hr. This makes organ transplantation both difficult and risky with regard to HIV-1 transmission. We developed a modification of the Western blot technique that takes under 50 min, is transportable, is definitive on site, and does not delay organ retrieval. This test has been called the Quick Western Blot. We examined 459 serum specimens from referrals; from the AIDS Testing Proficiency Panel, Walter Reed Army Institute of Research; and from 36 organ donors. All specimens were tested by ELISA HIV-1 Ab screening, the regular Western blot, and by the Quick Western Blot. The organ donors were initially tested on-site during organ procurement by the Quick Western Blot and later had complete testing by the reference methods. Compared with regular Western blot, the ELISA showed a specificity of 78.4% and a positive predictive value of 65.5%, whereas the Quick Western Blot was as reliable and specific as the regular Western blot, but much quicker. Because of the rapidity and specificity of the test, this test has particular utility in the screening of organ donors, as was shown in a case of multiple organ donation where the ELISA was negative, but the Quick Western Blot was found positive and thereby prevented the donation of HIV-1 infected organs.
Outcome of Continuous Positive Airway Pressure Treatment with Suboptimal Pressure in Obstructive Sleep Apnea (2010)

Continuous positive airway pressure is the treatment of choice for obstructive sleep apnea, and is highly effective especially in moderateto-severe obstructive sleep apnea. Although continuous positive airway pressure treatment with optimal pressure is ideal, some patients undergo continuous positive airway pressure treatment with suboptimal pressure. We aimed to evaluate the treatment outcome of continuous positive airway pressure with suboptimal pressure in obstructive sleep apnea. In this study, although mean apnea-hypopnea index was reduced after 3 and 6 months of continuous positive airway pressure treatment with suboptimal pressure compared to that of diagnostic polysomnography, continuous positive airway pressure treatment with suboptimal pressure is effective to reduce mean apnea-hypopnea index to less than 5 only in 53.85% after 3 months of continuous positive airway pressure treatment, and 60% of patients after 6 months of continuous positive airway pressure treatment, respectively.
Dendritic Spine Abnormalities in Amyloid Precursor Protein Transgenic Mice Demonstrated by Gene Transfer and Intravital Multiphoton Microscopy (2005)

Accumulation of amyloid-beta (Abeta) into senile plaques in Alzheimer's disease (AD) is a hallmark neuropathological feature of the disorder, which likely contributes to alterations in neuronal structure and function. Recent work has revealed changes in neurite architecture associated with plaques and functional changes in cortical signaling in amyloid precursor protein (APP) expressing mouse models of AD. Here we developed a method using gene transfer techniques to introduce green fluorescent protein (GFP) into neurons, allowing the investigation of neuronal processes in the vicinity of plaques. Multiphoton imaging of GFP-labeled neurons in living Tg2576 APP mice revealed disrupted neurite trajectories and reductions in dendritic spine density compared with age-matched control mice. A profound deficit in spine density (approximately 50%) extends approximately 20 mum from plaque edges. Importantly, a robust decrement (approximately 25%) also occurs on dendrites not associated with plaques, suggesting widespread loss of postsynaptic apparatus. Plaques and dendrites remained stable over the course of weeks of imaging. Postmortem analysis of axonal immunostaining and colocalization of synaptophysin and postsynaptic density 95 protein staining around plaques indicate a parallel loss of presynaptic and postsynaptic partners. These results show considerable changes in dendrites and dendritic spines in APP transgenic mice, demonstrating a dramatic synaptotoxic effect of dense-cored plaques. Decreased spine density will likely contribute to altered neural system function and behavioral impairments observed in Tg2576 mice.
Activation of two distinct Sox9-EGFP-expressing intestinal stem cell populations during crypt regeneration after irradiation (2012)

Recent identification of intestinal epithelial stem cell (ISC) markers and development of ISC reporter mice permit visualization and isolation of regenerating ISCs after radiation to define their functional and molecular phenotypes. Previous studies in uninjured intestine of Sox9-EGFP reporter mice demonstrate that ISCs express low levels of Sox9-EGFP (Sox9-EGFP Low), whereas enteroendocrine cells (EEC) express high levels of Sox9-EGFP (Sox9-EGFP High). We hypothesized that Sox9-EGFP Low ISCs would expand after radiation, exhibit enhanced proliferative capacities, and adopt a distinct gene expression profile associated with rapid proliferation. Sox9-EGFP mice were given 14 Gy abdominal radiation and studied between days 3 and 9 postradiation. Radiation-induced changes in number, growth, and transcriptome of the different Sox9-EGFP cell populations were determined by histology, flow cytometry, in vitro culture assays, and microarray. Microarray confirmed that nonirradiated Sox9-EGFP Low cells are enriched for Lgr5 mRNA and mRNAs enriched in Lgr5-ISCs and identified additional putative ISC markers. Sox9-EGFP High cells were enriched for EEC markers, as well as Bmi1 and Hopx, which are putative markers of quiescent ISCs. Irradiation caused complete crypt loss, followed by expansion and hyperproliferation of Sox9-EGFP Low cells. From nonirradiated intestine, only Sox9-EGFP Low cells exhibited ISC characteristics of forming organoids in culture, whereas during regeneration both Sox9-EGFP Low and High cells formed organoids. Microarray demonstrated that regenerating Sox9-EGFP High cells exhibited transcriptomic changes linked to p53-signaling and ISC-like functions including DNA repair and reduced oxidative metabolism. These findings support a model in which Sox9-EGFP Low cells represent active ISCs, Sox9-EGFP High cells contain radiation-activatable cells with ISC characteristics, and both participate in crypt regeneration.
New vaccine technologies. (2002)

New vaccine development for potential use in human medicine is buoyant. New science (genomics and proteomics) is presenting major new opportunities. New approaches (DNA vaccines, new combination vaccines, new formulations, novel delivery routes, new adjuvants) are being vigorously explored. New needs (defence vaccines) are being identified. One common element in all these varied areas is that pre-clinical evaluation of a candidate new vaccine is a pre-requisite before initiation of clinical trials in humans. Laboratory evaluation also usually continues during the clinical phase of vaccine development. Pre-clinical and laboratory evaluations often involve animals. Data from these studies are used to support an application for marketing authorisation. Regulatory Authorities use precedent to help assess these applications. Where no precedent exists the Regulatory Authorities apply risk-benefit analyses based on the perceived risks of a new product or process. These perceived risks are constantly reviewed as experience is gained. The World Health Organisation facilitates the development of scientific consensus on issues that have an impact on the quality and safety of biological medicines, including vaccines. New vaccine technologies often present new challenges for the safety and efficacy evaluation of candidate preparations. Animal models are usually very important in this process. The number of new vaccine candidates seems set to increase in the short-term.