gebhart/patrepeval huggingface dataset:
Post Hoc Analyses of Intention-to-Treat Population in Phase III Comparison of NovoTTF-100A™ System Versus Best Physician’s Choice Chemotherapy (2014)

We performed a treatment-based analysis of data from the pivotal phase III trial of the NovoTTF-100A System™ versus best physician's choice (BPC) chemotherapy in patients with recurrent glioblastoma multiforme (GBM), with particular focus on efficacy in patients using NovoTTF Therapy as intended. Median overall survival (OS) was compared for recurrent GBM patients receiving at least one full cycle of treatment with NovoTTF-100A System or BPC chemotherapy (modified intention-to-treat [mITT] population) in the recently reported phase III trial. The relationship between NovoTTF-100A System compliance and OS was evaluated in the ITT population. Kaplan-Meier analyses examined treatment-related differences in OS for various patient subgroups. Median OS was significantly higher in patients receiving≥1 course of NovoTTF Therapy versus BPC (7.7 v 5.9 months; hazard ratio, 0.69; 95% confidence interval [CI], 0.52-0.91; P = .0093). Median OS was also significantly higher in patients receiving NovoTTF Therapy with a maximal monthly compliance rate≥75% (≥18 hours daily) versus those with a<75% compliance rate (7.7 v 4.5 months; P = .042), and Kaplan-Meier analysis demonstrated a significant trend for improved median OS with higher compliance (P = .039). Additional post hoc analysis showed significantly higher median OS with NovoTTF Therapy than with BPC for patients with prior low-grade glioma, tumor size≥18 cm(2), Karnofsky performance status≥80, and those who had previously failed bevacizumab therapy. When used as intended in mITT patients with recurrent GBM, NovoTTF Therapy provides an OS benefit compared with chemotherapy in patients with recurrent GBM. This contrasts with the equivalent efficacy reported previously based on analysis of all randomized ITT subjects, including many who did not receive a full cycle of treatment. Higher NovoTTF Therapy compliance corresponds with greater survival benefit in the present study.
Blind source separation combining frequency-domain ICA and beamforming (2002)

We describe a new method of blind source separation (BSS) on a microphone array combining subband independent component analysis (ICA) and beamforming. The proposed array system consists of the following three sections: (1) subband-ICA-based BSS section with direction-of-arrival (DOA) estimation; (2) null beamforming section based on the estimated DOA information; and (3) integration of (1) and (2) based on the algorithm diversity. Using this technique, we can resolve the low-convergence problem through optimization in ICA. The results of the signal separation experiments reveal that a noise reduction rate (NRR) of about 18 dB is obtained under the nonreverberant condition, and NRR of 8 dB and 6 dB are obtained in the case that the reverberation times are 150 msec and 300 msec. These performances are superior to those of both simple ICA-based BSS and simple beamforming method.
Non-surgical management of uterine fibroids (2008)

Good quality evidence supports the safety and effectiveness of UAE for women with symptomatic fibroids. The current available data are insufficient to routinely offer UAE to women who wish to preserve or enhance their fertility. Newer treatments are still investigational.
Retrospective Analysis of Topoisomerase IIa Amplifications and Deletions As Predictive Markers in Primary Breast Cancer Patients Randomly Assigned to Cyclophosphamide, Methotrexate, and Fluorouracil or Cyclophosphamide, Epirubicin, and Fluorouracil: Danish Breast Cancer Cooperative Group (2005)

TOP2A amplification-and possibly deletion-seems to be predictive markers for the effect of adjuvant epirubicin containing therapy in primary breast cancer, but a final conclusion has to await a confirmative study or a meta-analysis.
NMDA receptor‐dependent CREB activation in survival of cerebellar granule cells during<i>in vivo</i>and<i>in vitro</i>development (2002)

During both in vivo and in vitro development, cerebellar granule cells depend on the activity of the NMDA glutamate receptor subtype for survival and full differentiation. With the present results, we demonstrate that CREB activation, downstream of the NMDA receptor, is a necessary step to ensure survival of these neurons. The levels of CREB expression and activity increase progressively during the second week of postnatal cerebellar development and the phosphorylated form of CREB is localized selectively to cerebellar granule cells during the critical developmental stages examined. Chronically blocking the NMDA receptor through systemic administration of the competitive antagonist, CGP 39551, during the in vivo critical developmental period, between 7-11 postnatal days, results in increased apoptotic elimination of differentiating granule neurons in the cerebellum [Monti & Contestabile, Eur. J. Neurosci., 12, 3117-3123 (2000)]. We report here that this event is accompanied by a significant decrease of CREB phosphorylation in the cerebellum of treated rat pups. When cerebellar granule neurons are explanted and maintained in dissociated cultures, the levels of CREB phosphorylation increase with differentiation, similar to that which happens during in vivo development. When granule cells are kept in non-trophic conditions, their viability is affected and both CREB phosphorylation and transcriptional activity are decreased significantly. The neuronal viability and the deficiency of CREB activity, are both rescued by the pharmacological activation of the NMDA receptor. These results provide good circumstantial evidence for a functional link between the NMDA receptor and CREB activity in promoting neuronal survival during development.
Genetic Features of B‐Cell Chronic Lymphocytic Leukemia (2000)

The genetic features of B-cell chronic lymphocytic leukemia (CLL) are currently being reassessed by molecular cytogenetic techniques such as fluorescence in situ hybridization (FISH). Conventional cytogenetic studies by chromosome banding are difficult in CLL mainly because of the low in vitro mitotic activity of the tumor cells, which leads to poor quantity and quality of metaphase spreads. Molecular genetic analyses are limited because candidate genes are known for only a few chromosomal aberrations that are observed in CLL. FISH was found to be a powerful tool for the genetic analysis of CLL as it overcomes both the low mitotic activity of the CLL cells and the lack of suitable candidate genes for analysis. Using FISH, the detection of chromosomal aberrations can be performed at the single cell level in both dividing and non-dividing cells, thus circumventing the need of metaphase preparations from tumor cells. Probes for the detection of trisomies, deletions and translocation breakpoints can be applied to the regions of interest with the growing number of clones available from genome-wide libraries. Using the interphase cytogenetic FISH approach with a disease specific set of probes, chromosome aberrations can be found in more than 80% of CLL cases. The most frequently observed abnormalities are losses of chromosomal material, with deletions in band 13q14 being the most common, followed by deletions in 11q22-q23, deletions in 17p13 and deletions in 6q21. The most common gains of chromosomal material are trisomies 12q, 8q and 3q. Translocation breakpoints, in particular involving the immunoglobulin heavy chain locus at 14q32, which are frequently observed in other types of non-Hodgkin's lymphoma, are rare events in CLL. Genes affected by common chromosome aberrations in CLL appear to be p53 in cases with 17p deletion and ataxia telangiectasia mutated (ATM), which is mutated in a subset of cases with 11q22-q23 aberrations. However, for the other frequently affected genomic regions, the search for candidate genes is ongoing. In parallel, the accurate evaluation of the incidence of chromosome aberrations in CLL by FISH allows the correlation of genetic abnormalities with clinical disease manifestations and outcome. In particular, 17p abnormalities and deletions in 11q22-q23 have already been shown to be among the most important independent prognostic factors identifying subgroups of patients with rapid disease progression and short survival. In addition, deletion 17p has been associated with resistance to treatment with purine analogs. Therefore, genetic abnormalities may allow a risk assessment for individual patients at the time of diagnosis, thus giving the opportunity for a risk-adapted management.
The role of the school nurse in the management of diabetes: Assessing a position statement (2014)

The UK is facing a huge increase in the number of people with diabetes. The purpose of this study was to identify the degree of implementation of the National Association of School Nurse's (NASN) position statement in the US and the school nurse's role. The results support the need for the nurse's role in schools to improve the student with diabetes’ care management. The NASN position statement could be a good basis for designing an instrument to measure the impact of nursing's professional role in the academic community. Other school nurse organisations, including in the UK, could also benefit from a similar position statement clrealy defining the role of the school nurses in the care of children with diabetes.
PI3K integrates the action of insulin and leptin on hypothalamic neurons (2005)

Central control of energy balance depends on the ability of proopiomelanocortin (POMC) or agouti-related protein (Agrp) hypothalamic neurons to sense and respond to changes in peripheral energy stores. Leptin and insulin have been implicated as circulating indicators of adiposity, but it is not clear how changes in their levels are perceived or integrated by individual neuronal subtypes. We developed mice in which a fluorescent reporter for PI3K activity is targeted to either Agrp or POMC neurons and used 2-photon microscopy to measure dynamic regulation of PI3K by insulin and leptin in brain slices. We show that leptin and insulin act in parallel to stimulate PI3K in POMC neurons but in opposite ways on Agrp neurons. These results suggest a new view of hypothalamic circuitry, in which the effects of leptin and insulin are integrated by anorexigenic but not by orexigenic neurons.
Perfusion imaging with a freely diffusible hyperpolarized contrast agent (2011)

Contrast agents that can diffuse freely into or within tissue have numerous attractive features for perfusion imaging. Here we present preliminary data illustrating the suitability of hyperpolarized (13)C labeled 2-methylpropan-2-ol (also known as dimethylethanol, tertiary butyl alcohol and tert-butanol) as a freely diffusible contrast agent for magnetic resonance perfusion imaging. Dynamic (13)C images acquired in rat brain with a balanced steady-state free precession sequence following administration of hyperpolarized 2-methylpropan-2-ol show that this agent can be imaged with 2-4 s temporal resolution, 2 mm slice thickness, and 700 μm in-plane resolution while retaining adequate signal-to-noise ratio. (13)C relaxation measurements on 2-methylpropan-2-ol in blood at 9.4 T yield T(1) = 46 ± 4s and T(2) = 0.55 ± 0.03 s. In the rat brain at 4.7 T, analysis of the temporal dynamics of the balanced steady-state free precession image intensity in tissue and venous blood indicate that 2-methylpropan-2-ol has a T(2) of roughly 2-4s and a T(1) of 43 ± 24 s. In addition, the images indicate that 2-methylpropan-2-ol is freely diffusible in brain and hence has a long residence time in tissue; this in turn makes it possible to image the agent continuously for tens of seconds. These characteristics show that 2-methylpropan-2-ol is a promising agent for robust and quantitative perfusion imaging in the brain and body.
Understanding Diversion with a Novel Fiber-Laden Acid System for Matrix Acidizing of Carbonate Formations (2010)

Abstract Recently, a new fiber-laden, self-diverting, and viscoelastic acid has been successfully used for matrix acidizing of highly heterogeneous carbonate formations The fibers have been designed to be inert under surface and pumping conditions, and their geometry allows them to form strong and stable fiber networks that can effectively bridge across natural fractures, wormholes, and perforation tunnels. Eventually, the fibers degrade into a water-soluble organic liquid that is produced back to the surface during flowback. In the case of perforated wells, experiments suggest that diversion with fibers operates in three phases. First, as the early volumes of fiber-laden acid reach the perforations, the acid penetrates the reservoir as if no fibers were present. Second, as the fibers bridge, they accumulate inside the perforations and form a fiber cake. Third, the fibers plug the perforation, and the injectivity decreases locally, promoting diversion into other perforations. The pressure drop through a plugged perforation was analyzed by performing 340 separate fine-scale 3D simulations. The original work was based on theoretical and laboratory-based experiments, considering typical perforation schemes and for various permeability ratios between the generated fiber cake and the formation's original permeability. The results were compiled, and a correlation was made to model the resulting skin. The model was implemented into an acid placement simulator and was extensively tested and validated in the field. In this paper, we present the model that describes the effect of fiber accumulation within perforations and explain how some of the model parameters such as formation-permeability contrast, fiber-cake permeability, and total permeability thickness (kh) may affect diversion efficiency. Case studies from field testing of the model illustrate methods of pressure history matching, job design, and treatment history evaluation.
Proton Conduction of Acid/Salt Doped Silica Gels (1995)

Composite silica gels containing perchloric acid HClO4, dodecatungstophosphoric acid H3PW12O40⋅29H2O (WPA), or tetra-n-buthylammonium perchlorate (n-Bu)4NClO4 were prepared by the sol-gel method from tetraethoxysilane and each dopant. For all the systems no changes in conductivities were observed during gelation where the transformation from liquid to solid occurred macroscopically. The conductivities of silica gels doped with HClO4 or WPA, the values of which were about 10-2S·cm-1 at room temperature and higher than those of the pure silica gels and (n-Bu)4NClO4-doped silica gels (10-7S·cm-1), did not change in the drying process from wet to dried gels.
Structural studies of class I major histocompatibility complex proteins: insights into antigen presentation (1995)

The three-dimensional structures of three human and two murine class I molecules, in complex with single peptides and with mixtures of endogenous peptides, have now been determined to high resolution. These structures have afforded important insights into the way in which antigenic peptides are bound by an MHC class I molecule, and how a given MHC molecule can bind a large number and variety of peptides, for presentation to a T cell receptor. Peptides are bound in a cleft located in the alpha 1/alpha 2 domain of a class I molecule. They are tethered by an array of hydrogen bonding interactions many of which are conserved among the different structures. Binding is also accomplished through van der Waals interactions between two or three peptide residues and complementary pockets in the cleft. The location and the characteristics of its pockets are unique to a given MHC class I molecule, and so determine the identity of the anchor residues of the set of peptides that bind. The antigenic epitope recognized by the TCR consists of residues on the MHC as well as the side chains of those peptide residues that point out from the cleft. The various strategies used to expand the repertoire of peptides bound and presented are discussed.
Predominance of HLA-Restricted Cytotoxic T-Lymphocyte Responses to Serotype-Cross-Reactive Epitopes on Nonstructural Proteins following Natural Secondary Dengue Virus Infection (1998)

We examined the memory cytotoxic T-lymphocytic (CTL) responses of peripheral blood mononuclear cells (PBMC) obtained from patients in Thailand 12 months after natural symptomatic secondary dengue virus infection. In all four patients analyzed, CTLs were detected in bulk culture PBMC against nonstructural dengue virus proteins. Numerous CD4+ and CD8+ CTL lines were generated from the bulk cultures of two patients, KPP94-037 and KPP94-024, which were specific for NS1.2a (NS1 and NS2a collectively) and NS3 proteins, respectively. All CTL lines derived from both patients were cross-reactive with other serotypes of dengue virus. The CD8+ NS1.2a-specific lines from patient KPP94-037 were HLA B57 restricted, and the CD8+ NS3-specific lines from patient KPP94-024 were HLA B7 restricted. The CD4+ CTL lines from patient KPP94-037 were HLA DR7 restricted. A majority of the CD8+ CTLs isolated from patient KPP94-024 were found to recognize amino acids 221 to 232 on NS3. These results demonstrate that in Thai patients after symptomatic secondary natural dengue infections, CTLs are mainly directed against nonstructural proteins and are broadly cross-reactive.
Low Magnesium Levels and FGF-23 Dysregulation Predict Mitral Valve Calcification as well as Intima Media Thickness in Predialysis Diabetic Patients (2015)

Background. Mitral valve calcification and intima media thickness (IMT) are common complications of chronic kidney disease (CKD) implicated with high cardiovascular mortality. Objective. To investigate the implication of magnesium and fibroblast growth factor-23 (FGF-23) levels with mitral valve calcification and IMT in CKD diabetic patients. Methods. Observational, prospective study involving 150 diabetic patients with mild to moderate CKD, divided according to Wilkins Score. Carotid-echodoppler and transthoracic echocardiography were used to assess calcification. Statistical tests used to establish comparisons between groups, to identify risk factors, and to establish cut-off points for prediction of mitral valve calcification. Results. FGF-23 values continually increased with higher values for both IMT and calcification whereas the opposite trend was observed for magnesium. FGF-23 and magnesium were found to independently predict mitral valve calcification and IMT (P < 0.05). Using Kaplan-Meier analysis, the number of deaths was higher in patients with lower magnesium levels and poorer Wilkins score. The mean cut-off value for FGF-23 was 117 RU/mL and for magnesium 1.7 mg/dL. Conclusions. Hypomagnesemia and high FGF-23 levels are independent predictors of mitral valve calcification and IMT and are risk factors for cardiovascular mortality in this population. They might be used as diagnostic/therapeutic targets in order to better manage the high cardiovascular risk in CKD patients.
Drosophila gene related to the major heat shock-induced gene is transcribed at normal temperatures and not induced by heat shock. (1982)

A gene related to the major heat shock-induced (hsp70) gene of Drosophila has been isolated from the sibling species D. melanogaster and D. simulans. This heat shock-cognate (hsc70) gene is present at cytological locus 70C. The primary sequence of approximately one-third of the protein-coding region has been compared with that of the hsp70 gene; 72% homology of the base sequence and 74% homology of the deduced amino acid sequence was found. In the codon specifying amino acid 66, the hsc70 gene contains an insertion of 1.7 kilobases; the hsp70 genes contain no intervening sequences. The sequence at the 5' and 3' junctions of the insertion is similar to that found in many intervening sequences. cDNA extension experiments indicate that the hsc70 gene is transcribed at normal temperatures in adult flies and that transcription is not enhanced by heat treatment.
Insurability of electronic commerce risks (2003)

New kinds of risks increasingly threaten electronic commerce. The traditional instrument for risk transfer is insurance. Research is needed to determine whether new Internet risks are insurable. In this article, starting with damage scenarios and damage dimensions, Internet risks are classified and their properties are evaluated by means of decision-oriented insurability criteria. The definition of basic goal-oriented risk sees risk as a violation of the technical protection goals of the multilateral security concept (confidentiality, integrity, availability, accountability). These technical security risks, which form the foundation for further economic and social risks, are being further examined. On the basis of the protection goals of multilateral security, existing insurance offers are analysed and statements regarding the insurability of potential violation of individual protection goals are made. The article works out problems resulting from insurability and shows solution approaches regarding the insurability.
Oxyopinins, Large Amphipathic Peptides Isolated from the Venom of the Wolf Spider Oxyopes kitabensis with Cytolytic Properties and Positive Insecticidal Cooperativity with Spider Neurotoxins (2002)

Five amphipathic peptides with antimicrobial, hemolytic, and insecticidal activity were isolated from the crude venom of the wolf spider Oxyopes kitabensis. The peptides, named oxyopinins, are the largest linear cationic amphipathic peptides from the venom of a spider that have been chemically characterized at present. According to their primary structure Oxyopinin 1 is composed of 48 amino acid residues showing extended sequence similarity to the ant insecticidal peptide ponericinL2 and to the frog antimicrobial peptide dermaseptin. Oxyopinins 2a, 2b, 2c, and 2d have highly similar sequences. At least 27 out of 37 amino acid residues are conserved. They also show a segment of sequence similar to ponericinL2. Circular dichroism analyses showed that the secondary structure of the five peptides is essentially alpha-helical. Oxyopinins showed disrupting activities toward both biological membranes and artificial vesicles, particularly to those rich in phosphatidylcholine. Electrophysiological recordings performed on insect cells (Sf9) showed that the oxyopinins produce a drastic reduction of cell membrane resistance by opening non-selective ion channels. Additionally, a new paralytic neurotoxin named Oxytoxin 1 was purified from the same spider venom. It contains 69 amino acid residue cross-linked by five disulfide bridges. Application of mixtures containing oxyopinins and Oxytoxin 1 to insect larvae showed a potentiation phenomenon, by which an increase lethality effect is observed. These results suggest that the linear amphipathic peptides in spider venoms and neuropeptides cooperate to capture insects efficiently.
Humanpharmakologische Untersuchungen von rekombinantem Hirudin (HBW 023) (1991)

Zusammenfassung Rekombinantes Hirudin (HBW 023) wurde in Dosierungen von 0,01 bis 0,5 mg/kg Körpergewicht intravenös bei 40 gesunden Freiwilligen auf Toleranz, Pharmakokinetik und Pharmakodynamik hin untersucht. Bei klinischen, ophthalmoskopischen, klinisch-chemischen und hämatologischen sowie EKG-Untersuchungen ergaben sich keine Hinweise auf Unverträglichkeit. Antikörper gegen Hirudin oder verunreinigende Hefeproteine konnten bei mehrfachen Untersuchungen nach Gabe von Hirudin nicht nachgewiesen werden. Hirudin zeigte eine lineare Kinetik mit dosisproportionalem Anstieg von Cmax und AUC. Die Eliminationshalbwertszeit lag bei etwa einer Stunde, die totale Clearance bei etwa 200 ml/min, die renale Clearance bei 90 ml/min. 50% der gegebenen Dosis wurden als Hirudin im Urin wiedergefunden. Hirudin bewirkte eine plasmaspiegelabhängige Verlängerung der aktivierten partiellen Thromboplastinzeit.