gebhart/patrepeval huggingface dataset:
Cabazitaxel vs docetaxel in chemotherapy-naive (CN) patients with metastatic castration-resistant prostate cancer (mCRPC): A three-arm phase III study (FIRSTANA). (2016)

5006 Background: The Phase III TROPIC study (NCT00417079) reported significant improvement in overall survival (OS) for cabazitaxel 25 mg/m2IV Q3W plus prednisone 10 mg PO QD (P) vs. mitoxantrone plus P in mCRPC pts previously treated with a docetaxel (D)-containing regimen. The FIRSTANA study examined if cabazitaxel 20 mg/m² (C20) or 25 mg/m² (C25) IV Q3W plus P is superior to docetaxel 75 mg/m² (D75) IV Q3W plus P in terms of OS in CN mCRPC pts. Methods: In this multinational, open label phase III study, mCRPC pts, ECOG PS 0-2, who had progressed after castration were randomized 1:1:1 to C20, C25 or D75 IV Q3W plus P. The primary endpoint was OS. Key secondary endpoints were safety, progression free survival (PFS), tumor PFS, tumor response (RECIST 1.1), PSA response, PSA PFS, pain response, pain PFS, time to skeletal-related events (SRE) and health-related quality of life (HRQOL). Results: Between May 2011 and April 2013, 1168 pts were randomized (C20=391, C25=389, D75=388). Baseline demographics and disease characteristics were similar across cohorts. The median number of treatment cycles was 9 for all dose groups. In the ITT analysis, median OS was 24.5 months for C20, 25.2 months for C25 and 24.3 months for D75. HR for C20 vs. D75 was 1.009 (0.85 to 1.197, p=0.9967) and for C25 vs. D75 was 0.97 (0.819 to 1.16, p=0.7574), indicating that C20 and C25 were not superior to D75 in terms of OS. PFS was 4.4 months for C20, 5.1 months for C25 and 5.3 months for D75 (NS). Tumor responses were superior in C25 (41.6%) compared to D75 (30.9%), p=0.0370. Other secondary endpoints did not significantly differ across dose groups. Adverse events (AEs) grade 3-4 were 41.2% in C20, 60.1% in C25 and 46.0% in D75; pts discontinuing treatment due to an AE were 25.2% in C20, 31.7% in C25 and 33.9% in D75. Febrile neutropenia, diarrhea and hematuria were more frequent in C25; peripheral neuropathy, peripheral edema, alopecia and nail disorders were more frequent in D75. Conclusions: C20 and C25 did not demonstrate superiority for OS compared to D75 in CN mCRPC pts. Among secondary endpoints only tumor responses were significantly superior for C25. AEs were less frequent in C20 for most categories. Clinical trial information: NCT01308567.
Impact of adding prophylactic probiotics to a bundle of standard preventative measures for Clostridium difficile infections: enhanced and sustained decrease in the incidence and severity of infection at a community hospital (2013)

Specific probiotic product added to SPM and antibiotic stewardship activities resulted in a further reduction in CDI rates and was shown to be safe.
Engineering Cytoplasmic Male Sterility via the Chloroplast Genome by Expression of β-Ketothiolase (2005)

While investigating expression of the polydroxybutyrate pathway in transgenic chloroplasts, we addressed the specific role of beta-ketothiolase. Therefore, we expressed the phaA gene via the chloroplast genome. Prior attempts to express the phaA gene in transgenic plants were unsuccessful. We studied the effect of light regulation of the phaA gene using the psbA promoter and 5' untranslated region, and evaluated expression under different photoperiods. Stable transgene integration into the chloroplast genome and homoplasmy were confirmed by Southern analysis. The phaA gene was efficiently transcribed in all tissue types examined, including leaves, flowers, and anthers. Coomassie-stained gel and western blots confirmed hyperexpression of beta-ketothiolase in leaves and anthers, with proportionately high levels of enzyme activity. The transgenic lines were normal except for the male-sterile phenotype, lacking pollen. Scanning electron microscopy revealed a collapsed morphology of the pollen grains. Floral developmental studies revealed that transgenic lines showed an accelerated pattern of anther development, affecting their maturation, and resulted in aberrant tissue patterns. Abnormal thickening of the outer wall, enlarged endothecium, and vacuolation affected pollen grains and resulted in the irregular shape or collapsed phenotype. Reversibility of the male-sterile phenotype was observed under continuous illumination, resulting in viable pollen and copious amount of seeds. This study results in the first engineered cytoplasmic male-sterility system in plants, offers a new tool for transgene containment for both nuclear and organelle genomes, and provides an expedient mechanism for F(1) hybrid seed production.
Miniature underwater glider: Design, modeling, and experimental results (2012)

The concept of gliding robotic fish combines gliding and fin-actuation mechanisms to realize energy-efficient locomotion and high maneuverability, and holds strong promise for mobile sensing in versatile aquatic environments. In this paper we present the modeling and design of a miniature fish-like glider, a key enabling component for gliding robotic fish. The full dynamics of the glider is first derived and then reduced to the sagittal plane, where the lift, drag, and pitch moment coefficients are obtained as linear or quadratic functions of the attack angle based on computational fluid dynamics (CFD) analysis. The model is used to design the glider by accommodating stringent constraints on dimensions yet meeting the desired specification on speed. A fully untethered prototype of underwater glider is developed, with a weight of 4 kg and length of 40 cm. With a net buoyancy of 20 g, it realizes a steady gliding speed of 20 cm/s. The volume and net buoyancy of this glider are less than 10% and 5%, respectively, of those of reported gliders in the literature, and its speed per unit net buoyancy is over 9 times of those other vehicles. Experimental results have shown that the model is able to capture well both the steady glide behavior under different control inputs, and the dynamics during transients.
Recombinant Factor IX Fc Fusion Protein Maintains Full Procoagulant Properties and Exhibits Prolonged Efficacy in Hemophilia B Mice (2016)

The activation by factor XIa or factor VIIa/tissue factor, inhibition by AT, interaction profiles with phospholipids, affinities for factor VIIIa within the context of the Xase complex, and thrombin generation profiles were similar for rFIXFc and rFIX. Xase complexes formed with either molecule exhibited similar kinetic profiles for factor Xa generation. In acute efficacy models, mice infused with rFIXFc or rFIX were equally protected from bleeding. However, in prophylactic efficacy models, protection from bleeding was maintained approximately three times longer in rFIXFc-dosed mice than in those given rFIX; this prolonged efficacy correlates with the previously observed half-life extension. We conclude that rFIXFc retains critical FIX procoagulant attributes and that the extension in rFIXFc half-life translates into prolonged efficacy in hemophilia B mice.
Transcriptional control of viral gene therapy by cisplatin (2002)

Ionizing radiation (IR) and radical oxygen intermediates (ROIs) activate the early growth response-1 (Egr1) promoter through specific cis-acting sequences termed CArG elements. Ad.Egr.TNF.11D, a replication-deficient adenoviral vector containing CArG elements cloned upstream of the cDNA for human recombinant TNF-α was used to treat human esophageal adenocarcinoma and rat colon adenocarcinoma cells in culture and as xenografts in athymic nude mice. Cisplatin, a commonly used chemotherapeutic agent, causes tumor cell death by producing DNA damage and generating ROIs. The present studies demonstrate induction of TNF-α production in tumor cells and xenografts treated with the combination of Ad.Egr.TNF.11D and cisplatin. The results show that the Egr1 promoter is induced by cisplatin and that this induction is mediated in part through the CArG elements. These studies also demonstrate an enhanced antitumor response without an increase in toxicity following treatment with Ad.Egr.TNF.11D and cisplatin, compared with either agent alone. Chemo-inducible cancer gene therapy thus provides a means to control transgene expression while enhancing the effectiveness of commonly used chemotherapeutic agents.
Tumor-Reactive CD4+ T Cell Responses to the Melanoma-Associated Chondroitin Sulphate Proteoglycan in Melanoma Patients and Healthy Individuals in the Absence of Autoimmunity (2007)

To avoid immune escape by down-regulation or loss of Ag by the tumor cells, target Ags are needed, which are important for the malignant phenotype and survival of the tumor. We could identify a CD4(+) T cell epitope derived from the human melanoma-associated chondroitin sulfate proteoglycan (MCSP) (also known as high m.w.-melanoma-associated Ag), which is strongly expressed on >90% of human melanoma lesions and is important for the motility and invasion of melanoma cells. However, MCSP is not strictly tumor specific, because it is also expressed in a variety of normal tissues. Therefore, self tolerance should prevent the induction of strong T cell responses against these Ags by vaccination strategies. In contrast, breaking self tolerance to this Ag by effectively manipulating the immune system might mediate antitumor responses, although it would bear the risk of autoimmunity. Surprisingly, we could readily isolate CD4(+) Th cells from the blood of a healthy donor-recognizing peptide MCSP(693-709) on HLA-DR11-expressing melanoma cells. Broad T cell reactivity against this Ag could be detected in the peripheral blood of both healthy donors and melanoma patients, without any apparent signs of autoimmune disease. In some patients, a decline of T cell reactivity was observed upon tumor progression. Our data indicate that CD4(+) T cells are capable of recognizing a membrane glycoprotein that is important in melanoma cell function, and it may be possible that the sizable reactivity to this Ag in most normal individuals contributes to immune surveillance against cancer.
Role of CDMP-1 in Skeletal Morphogenesis: Promotion of Mesenchymal Cell Recruitment and Chondrocyte Differentiation (1999)

Cartilage provides the template for endochondral ossification and is crucial for determining the length and width of the skeleton. Transgenic mice with targeted expression of recombinant cartilage-derived morphogenetic protein-1 (CDMP-1), a member of the bone morphogenetic protein family, were created to investigate the role of CDMP-1 in skeletal formation. The mice exhibited chondrodysplasia with expanded cartilage, which consists of the enlarged hypertrophic zone and the reduced proliferating chondrocyte zone. Histologically, CDMP-1 increased the number of chondroprogenitor cells and accelerated chondrocyte differentiation to hypertrophy. Expression of CDMP-1 in the notochord inhibited vertebral body formation by blocking migration of sclerotome cells to the notochord. These results indicate that CDMP-1 antagonizes the ventralization signals from the notochord. Our study suggests a molecular mechanism by which CDMP-1 regulates the formation, growth, and differentiation of the skeletal elements.
Oxygen and Lactate Concentrations Measured in Vivo in the Intervertebral Discs of Patients With Scoliosis and Back Pain (1998)

Concentrations of metabolites depend on cellular activity and on transport of the metabolite between the blood supply and the cell. The correlation between degeneration and nutrition cannot be determined only from metabolite concentrations; measurements of metabolic activity and nutrient transport rates also are required.
Scalable microfluidics for single-cell RNA printing and sequencing (2015)

Many important biological questions demand single-cell transcriptomics on a large scale. Hence, new tools are urgently needed for efficient, inexpensive manipulation of RNA from individual cells. We report a simple platform for trapping single-cell lysates in sealed, picoliter microwells capable of printing RNA on glass or capturing RNA on beads. We then develop a scalable technology for genome-wide, single-cell RNA-Seq. Our device generates pooled libraries from hundreds of individual cells with consumable costs of $0.10-$0.20 per cell and includes five lanes for simultaneous experiments. We anticipate that this system will serve as a general platform for single-cell imaging and sequencing.
Expression of Biologically Active Human Follitropin in Chinese Hamster Ovary Cells (1989)

To study the structure-function relationships of follitropin (FSH), we expressed the hormone in a heterologous cell system. A genomic clone bearing a 3.7-kilobase FSH beta insert containing the entire coding sequence was transfected alone or together with the alpha subunit gene into Chinese hamster ovary cells and stable lines expressing either FSH beta or FSH dimer were selected. Pulse-chase experiments revealed that, when transfected alone FSH beta was very slowly secreted similar to lutropin beta and thyrotropin beta but unlike choriogonadotropin beta which is efficiently secreted. However, cotransfection of the FSH beta and alpha subunit genes resulted in "rescue" of the beta subunit and rapid secretion of dimer. These data support the hypothesis that the glycoprotein hormones of pituitary origin have determinants for secretion that differ from those on the placental hormone, choriogonadotropin. Recombinant FSH stimulated steroidogenesis comparable to purified human FSH isolated from pituitaries in an in vitro rat granulosa cell assay and appears more homogeneous by chromatofocusing. Human FSH produced by this cell line provides a source of bioactive FSH for experimental and clinical use.
Monoallelic TP53 inactivation is associated with poor prognosis in chronic lymphocytic leukemia: results from a detailed genetic characterization with long-term follow-up (2008)

The exact prognostic role of TP53 mutations (without 17p deletion) and any impact of the deletion without TP53 mutation in CLL are unclear. We studied 126 well-characterized CLL patients by direct sequencing and DHPLC to detect TP53 mutations (exons 2-11). Most patients with 17p deletions also had TP53 mutations (81%). Mutations in the absence of 17p deletions were found in 4.5%. We found a shorter survival for patients with TP53 mutation (n = 18; P = .002), which was more pronounced when analyzed from the time point of mutation detection (6.8 vs 69 months, P < .001). The survival was equally poor for patients with deletion 17p plus TP53 mutation (7.6 months, n = 13), TP53 mutation only (5.5 months, n = 5), and 17p deletion only (5.4 months, n = 3). The prognostic impact of TP53 mutation (HR 3.71) was shown to be independent of stage, VH status, and 11q and 17p deletion in multivariate analysis. Serial samples showed evidence of clonal evolution and increasing clone size during chemotherapy, suggesting that there may be patients where this treatment is potentially harmful. TP53 mutations are associated with poor sur-vival once they occur in CLL. The de-monstration of clonal evolution under selective pressure supports the biologic significance of TP53 mutations in CLL.
A field investigation of kennel cough: Incubation period and clinical signs (1991)

Abstract A study of the incubation period and clinical signs of kennel cough was undertaken by collating and analysing information obtained by postal questionnaires from a random sample of general veterinary practitioners in the United Kingdom. Agent‐specific incubation periods were inferred from the vaccinal status of affected dogs. The mean and range of the incubation period for Bordetella bronchiseptica infection were 6‐5 days and two to 14 days, respectively; similar descriptive statistics for canine parainfluenza virus (CPIV) infection were 4–5 days and one to eight days. Local clinical signs (cough, nasal discharge and gagging/retching) were present in animals in all vaccinal categories. One or more systemic clinical signs (pyrexia and anorexia) were identified in 32 per cent of cases. No association was detected between vaccinal status against B bronchiseptica and CPIV, and clinical signs.
Two modes of c-myb activation in virus-induced mouse myeloid tumors. (1986)

Two modes of disruption of the protooncogene c-myb by viral insertional mutagenesis in mouse myeloid tumor cells are described. The first mode was found in six tumors in which a Moloney murine leukemia virus component had inserted in the same transcriptional orientation upstream of the 5'-most exon with v-myb homology (vE1). cDNA sequence data indicate the presence of a truncated c-myb mRNA that is initiated in the upstream 5' long terminal repeat of the integrated provirus and processed via a cryptic splice donor sequence in the gag region to the splice acceptor site in vE1 of the c-myb gene, thus removing the remaining downstream viral and myb intronic sequences. Unlike most gag-onc transcripts, the gag and myb sequences in the hybrid transcript were not in the same reading frame. It is presumed that the gag sequence provides a cryptic translation initiation site for the novel amino-truncated c-myb protein. The second mode of disruption was by downstream virus insertion at the 3' side of the c-myb, which results in the synthesis of a small (approximately 2 kilobase) myb transcript. The 5' long terminal repeat of the inserted provirus provides a TGA termination codon that results in the elimination of 240 normal c-myb amino acid residues from the carboxyl terminus of the tumor-specific myb protein. These results suggest that truncated myb proteins play a role in neoplastic transformation of myeloid cells.
Stability of injectable medications after reconstitution (1976)

The stability of injectable medications after reconstitution is presented. The following information about each drug is given in tabular format: drug to be reconstituted and size of package; recommended route(s) of administration; recommended diluent, quantity to be used and resultant concentration; stability after initial dilution; and stability after further dilution; and stability of frozen antibiotics.
Characterization of the Mammalian YAP (Yes-associated Protein) Gene and Its Role in Defining a Novel Protein Module, the WW Domain (1995)

We report cDNA cloning and characterization of the human and mouse orthologs of the chicken YAP (Yes-associated protein) gene which encodes a novel protein that binds to the SH3 (Src homology 3) domain of the Yes proto-oncogene product. Sequence comparison between mouse, human, and chicken YAP proteins showed an inserted sequence in the mouse YAP that represented an imperfect repeat of an upstream sequence. Further analysis of this sequence revealed a putative protein module that is found in various structural, regulatory, and signaling molecules in yeast, nematode, and mammals including human dystrophin. Because one of the prominent features of this sequence motif is two tryptophans (W), we named it the WW domain (Bork, P., and Sudol, M. (1994) Trends Biochem. Sci. 19, 531-533). Since its delineation, more proteins have been shown to contain this domain, and we report here on the widespread distribution of the WW module and present a discussion of its possible function. We have also shown that the human YAP gene is well conserved among higher eukaryotes, but it may not be conserved in yeast. Its expression at the RNA level in adult human tissues is nearly ubiquitous, being relatively high in placenta, prostate, ovary, and testis, but is not detectable in peripheral blood leukocytes. Using fluorescence in situ hybridization on human metaphase chromosomes and by analyzing rodent-human hybrids by Southern blot hybridization and polymerase chain reaction amplification, we mapped the human YAP gene to chromosome band 11q13, a region to which the multiple endocrine neoplasia type 1 gene has been mapped.
Global microRNA expression profiling of microdissected tissues identifiesmiR‐135bas a novel biomarker for pancreatic ductal adenocarcinoma (2011)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is known for its poor prognosis resulting from being diagnosed at an advanced stage. Accurate early diagnosis and new therapeutic modalities are therefore urgently needed. MicroRNAs (miRNAs), considered a new class of biomarkers and therapeutic targets, may be able to fulfill those needs. Combining tissue microdissection with global miRNA array analyses, cell type‐specific miRNA expression profiles were generated for normal pancreatic ductal cells, acinar cells, PDAC cells derived from xenografts and also from macrodissected chronic pancreatitis (CP) tissues. We identified 78 miRNAs differentially expressed between ND and PDAC cells providing new insights into the miRNA‐driven pathophysiological mechanisms involved in PDAC development. Having filtered miRNAs which are upregulated in the three pairwise comparisons of PDAC vs. ND, PDAC vs. AZ and PDAC vs. CP, we identified 15 miRNA biomarker candidates including miR‐135b. Using relative qRT‐PCR to measure miR‐135b normalized to miR‐24 in 75 FFPE specimens (42 PDAC and 33 CP) covering a broad range of tumor content, we discriminated CP from PDAC with a sensitivity and specificity of 92.9% [95% CI=(80.5, 98.5)] and 93.4% [95% CI=(79.8, 99.3)], respectively. Furthermore, the area under the curve (AUC) value reached of 0.97 was accompanied by positive and negative predictive values of 95% and 91%, respectively. In conclusion, we report pancreatic cell‐specific global miRNA profiles, which offer new candidate miRNAs to be exploited for functional studies in PDAC. Furthermore, we provide evidence that miRNAs are well‐suited analytes for development of sensitive and specific aid‐in‐diagnosis tests for PDAC.
The Tornado-X magnetic trap for plasma confinement and heating (1997)

A description of the Tornado-X magnetic trap for plasma confinement and heating is given. The results of the first investigations of a decaying plasma are presented, which lead to the conclusion that the plasma losses are determined by classical diffusion. The plasma is heated by utilizing the drift of charged particles in crossed magnetic and electric fields. The parameters of the rotating plasma obtained in the Tornado-650 facility are reproduced in the initial stage.
Effect of acute induced metabolic alkalosis on 800-m racing time (1983)

Medicine & Science in Sports & Exercise (MSSE), ACSM's flagship monthly peer-reviewed journal, is the leading multidisciplinary original research journal for members. Each issue features original investigations, clinical studies and comprehensive reviews on current topics in sports medicine and exercise science.
Brain volume abnormalities in major depressive disorder: A meta‐analysis of magnetic resonance imaging studies (2009)

This is the first comprehensive meta-analysis in major depressive disorder demonstrating structural brain abnormalities, particularly in those brain areas that are involved in emotion processing and stress-regulation.