gebhart/patrepeval huggingface dataset:
Safety and efficacy of cervical 10 kHz spinal cord stimulation in chronic refractory primary headaches: a retrospective case series (2016)

Paresthesia-free high cervical HF10 SCS appears to be a long-term safe and likely effective therapeutic approach for patients with chronic refractory primary headache disorders. These results warrant further prospective studies in larger series of patients.
In Vivo Mapping of Nucleosomes Using Psoralen-DNA Crosslinking and Primer Extension (2003)

In the nucleus of eukaryotic cells, DNA is packaged into a nucleoprotein complex known as chromatin (). This complex provides the compaction and structural organization of the DNA for processes such as replication, transcription, recombination, and repair. The highly compact structure of chromatin does not only restrict the access of DNA to enzymes and regulating factors, it can even act as an activating principle bringing distant DNA-protein binding sites into close proximity.
Modeling Combined Radiopharmaceutical Therapy: A Linear Optimization Framework (2009)

In this paper, we investigate a previously proposed mathematical model describing the effects that an innovative combined radiopharmaceutical therapy might have on the delivery of radiation to the tumor and limiting critical organs. While focused on a specific dual agent therapy, this investigation will prove mathematically that for any two therapeutic radiopharmaceuticals with different limiting critical organs the model provides patient specific conditions under which combination therapy is superior to single agent therapy. In addition, this paper outlines general methods for calculating the amounts of administered radioactivity for each drug required to optimize tumor radiation dose. We also consider extensions of this model to include an arbitrary number of independent radiopharmaceuticals and/or other treatment factors.
Characterization of Diverse Subvariants of the Meningococcal Factor H (fH) Binding Protein for Their Ability To Bind fH, To Mediate Serum Resistance, and To Induce Bactericidal Antibodies (2010)

Neisseria meningitidis is a commensal of the human nasopharynx but is also a major cause of septicemia and meningitis. The meningococcal factor H binding protein (fHbp) binds human factor H (fH), enabling downregulation of complement activation on the bacterial surface. fHbp is a component of two serogroup B meningococcal vaccines currently in clinical development. Here we characterize 12 fHbp subvariants for their level of surface exposure and ability to bind fH, to mediate serum resistance, and to induce bactericidal antibodies. Flow cytometry and Western analysis revealed that all strains examined expressed fHbp on their surface to different extents and bound fH in an fHbp-dependent manner. However, differences in fH binding did not always correlate with the level of fHbp expression, indicating that this is not the only factor affecting the amount of fH bound. To overcome the issue of strain variability in fHbp expression, the MC58ΔfHbp strain was genetically engineered to express different subvariants from a constitutive heterologous promoter. These recombinant strains were characterized for fH binding, and the data confirmed that each subvariant binds different levels of fH. Surface plasmon resonance revealed differences in the stability of the fHbp-fH complexes that ranged over 2 orders of magnitude, indicating that differences in residues between and within variant groups can influence fH binding. Interestingly, the level of survival in human sera of recombinant MC58 strains expressing diverse subvariants did not correlate with the level of fH binding, suggesting that the interaction of fHbp with fH is not the only function of fHbp that influences serum resistance. Furthermore, cross-reactive bactericidal activity was seen within each variant group, although the degree of activity varied, suggesting that amino acid differences within each variant group influence the bactericidal antibody response.
Efficacy of Locally Delivered Polyclonal Immunoglobulin against Pseudomonas aeruginosa Peritonitis in a Murine Model (1999)

Infectious peritonitis results from bacterial contamination of the abdominal cavity. Conventional antibiotic treatment is complicated both by the emergence of antibiotic-resistant bacteria and by increased patient populations intrinsically at risk for nosocomial infections. To complement antibiotic therapies, the efficacy of direct, locally applied pooled human immunoglobulin G (IgG) was assessed in a murine model (strains CF-1, CD-1, and CFW) of peritonitis caused by intraperitoneal inoculations of 10(6) or 10(7) CFU of Pseudomonas aeruginosa (strains IFO-3455, M-2, and MSRI-7072). Various doses of IgG (0.005 to 10 mg/mouse) administered intraperitoneally simultaneously with local bacterial challenge significantly increased survival in a dose-dependent manner. Local intraperitoneal application of 10 mg of IgG increased animal survival independent of either the P. aeruginosa or the murine strains used. A local dose of 10 mg of IgG administered up to 6 h prophylactically or at the time of bacterial challenge resulted in 100% survival. Therapeutic 10-mg IgG treatment given up to 12 h postinfection also significantly increased survival. Human IgG administered to the mouse peritoneal cavity was rapidly detected systemically in serum. Additionally, administered IgG in peritoneal lavage fluid samples actively opsonized and decreased the bacterial burden via phagocytosis at 2 and 4 h post-bacterial challenge. Tissue microbial quantification studies showed that 1.0 mg of locally applied IgG significantly reduced the bacterial burden in the liver, peritoneal cavity, and blood and correlated with reduced levels of interleukin-6 in serum.
Is it possible to exclude a diagnosis of myocardial damage within six hours of admission to an emergency department? Diagnostic cohort study (2001)

The six hour rule-out protocol for myocardial infarction is accurate and efficacious. It can be used in patients presenting to emergency departments with chest pain indicating a low to moderate risk of myocardial infarction.
Brain‐derived neurotrophic factor and nerve growth factor correlate with T‐cell activation in primary Sjögren's syndrome (2008)

NT levels are potential biomarkers for lymphocyte activation in pSS patients.
Unstable and stable chromosomal aberrations in lymphocytes of people e exposed to Chernobyl fallout in Bryansk, Russia (1997)

Analyses of unstable and stable chromosomal aberrations in peripheral blood lymphocytes were used in the assessment of radiation exposure of residents of a village situated in the Chernobyl fallout-contamination zone of Bryansk, Russia. Blood samples were taken from subjects residing in villages with high (> 1100 kBq/m2 137 Cs; Mirnyi) and very low (< 37 kBq/m2 137 Cs; Krasnyi Rog) contamination, 7 years after the Chernobyl accident. The groups were matched by age, sex, smoking habits and previous medical radiological exposures. A total of 200 people (100 exposed, 100 controls) were analysed for the presence of unstable aberrations from Giemsa-stained slides. To study stable aberrations, chromosome painting analyses were performed on 100 subjects (50 exposed, 50 controls), using painting probes for chromosomes 1, 2 and 4 and a pancentromeric probe. People living in the contaminated area showed significantly higher rates of unstable chromosome-type aberrations but not chromatid-type aberrations in their lymphocytes, indicating radiation exposure as a causative factor for the observed difference. No significant differences were found in the aberration rates between the two areas by the chromosome painting method. The levels of chromosome exchanges were low in both populations, but consistently higher in Mirnyi compared with the control area. The magnitude of radiation exposure resulting from Chernobyl fallout was estimated on the basis of excess stable chromosomal aberrations in the lymphocytes of the Mirnyi population compared with the controls.
Adaptive Space Deformations Based on Rigid Cells (2007)

Abstract We propose a new adaptive space deformation method for interactive shape modeling. A novel energy formulation based on elastically coupled volumetric cells yields intuitive detail preservation even under large deformations. By enforcing rigidity of the cells, we obtain an extremely robust numerical solver for the resulting nonlinear optimization problem. Scalability is achieved using an adaptive spatial discretization that is decoupled from the resolution of the embedded object. Our approach is versatile and easy to implement, supports thin‐shell and solid deformations of 2D and 3D objects, and is applicable to arbitrary sample‐based representations, such as meshes, triangle soups, or point clouds.
PSI-7851, a Pronucleotide of β- d -2′-Deoxy-2′-Fluoro-2′- C -Methyluridine Monophosphate, Is a Potent and Pan-Genotype Inhibitor of Hepatitis C Virus Replication (2010)

The hepatitis C virus (HCV) NS5B RNA polymerase facilitates the RNA synthesis step during the HCV replication cycle. Nucleoside analogs targeting the NS5B provide an attractive approach to treating HCV infections because of their high barrier to resistance and pan-genotype activity. PSI-7851, a pronucleotide of beta-D-2'-deoxy-2'-fluoro-2'-C-methyluridine-5'-monophosphate, is a highly active nucleotide analog inhibitor of HCV for which a phase 1b multiple ascending dose study of genotype 1-infected individuals was recently completed (M. Rodriguez-Torres, E. Lawitz, S. Flach, J. M. Denning, E. Albanis, W. T. Symonds, and M. M. Berry, Abstr. 60th Annu. Meet. Am. Assoc. Study Liver Dis., abstr. LB17, 2009). The studies described here characterize the in vitro antiviral activity and cytotoxicity profile of PSI-7851. The 50% effective concentration for PSI-7851 against the genotype 1b replicon was determined to be 0.075+/-0.050 microM (mean+/-standard deviation). PSI-7851 was similarly effective against replicons derived from genotypes 1a, 1b, and 2a and the genotype 1a and 2a infectious virus systems. The active triphosphate, PSI-7409, inhibited recombinant NS5B polymerases from genotypes 1 to 4 with comparable 50% inhibitory concentrations. PSI-7851 is a specific HCV inhibitor, as it lacks antiviral activity against other closely related and unrelated viruses. PSI-7409 also lacked any significant activity against cellular DNA and RNA polymerases. No cytotoxicity, mitochondrial toxicity, or bone marrow toxicity was associated with PSI-7851 at the highest concentration tested (100 microM). Cross-resistance studies using replicon mutants conferring resistance to modified nucleoside analogs showed that PSI-7851 was less active against the S282T replicon mutant, whereas cells expressing a replicon containing the S96T/N142T mutation remained fully susceptible to PSI-7851. Clearance studies using replicon cells demonstrated that PSI-7851 was able to clear cells of HCV replicon RNA and prevent viral rebound.
Mouse models for human lung cancer (2005)

In recent years several new mouse models for lung cancer have been described. These include models for both non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Tumorigenesis in these conditional mouse tumor models can be initiated in adult mice through Cre-recombinase-induced activation of oncogenic mutations in a subset of the cells. They present a marked improvement over mouse models that depend on carcinogen induction of tumors. These models permit us to study the consecutive steps involved in initiation and progression and allow us to address questions like the cell of origin, and the role of cancer stem cells in the maintenance of these tumors. They now need to be validated as suitable preclinical models for intervention studies in which questions with respect to therapy response and resistance can be addressed.
Glutamate neurotoxicity in cortical cell culture (1987)

The central neurotoxicity of the excitatory amino acid neurotransmitter glutamate has been postulated to participate in the pathogenesis of the neuronal cell loss associated with several neurological disease states, but the complexity of the intact nervous system has impeded detailed analysis of the phenomenon. In the present study, glutamate neurotoxicity was studied with novel precision in dissociated cell cultures prepared from the fetal mouse neocortex. Brief exposure to glutamate was found to produce morphological changes in mature cortical neurons beginning as quickly as 90 sec after exposure, followed by widespread neuronal degeneration over the next hours. Quantitative dose-toxicity study suggested an ED50 of 50-100 microM for a 5 min exposure to glutamate. Immature cortical neurons and glia were not injured by such exposures to glutamate. Uptake processes probably do not limit GNT in culture, as the uptake inhibitor dihydrokainate did not potentiate GNT. Possibly reflecting the lack of uptake limitation, glutamate was found to be actually more potent than kainate as a neurotoxin in these cultures, a dramatic reversal of the in vivo potency rank order. Some neurons regularly survived brief glutamate exposure; these possibly glutamate-resistant neurons had electrophysiologic properties, including chemosensitivity to glutamate, that were grossly similar to those of the original population.
Temperature-sensitive phenotype of the human parainfluenza virus type 3 candidate vaccine strain (cp45) correlates with a defect in the L gene (1996)

We have previously demonstrated that the temperature sensitivity of a human parainfluenza virus type 3 (HPIV-3) candidate vaccine strain (cp45), which is currently under evaluation in humans, is associated with poor transcriptional activity of the virus at the nonpermissive temperature (R. Ray, K. Meyer, F. Newman, and R. B. Belshe, J. Virol. 69:1959-1963, 1995). In this study, the temperature sensitivity of cp45 virus was further investigated by the complementation of a specific gene function. CV-1 cells were transfected with cloned genes from wild-type HPIV-3 encoding the large protein (L), phosphoprotein (P), and nucleocapsid protein (NP), alone or together, for the expression of biologically active proteins. Only cells expressing the L gene were able to rescue cp45 replication when incubated at the nonpermissive temperature (39.5 degrees C), whereas cells transiently expressing NP or P were incapable of rescuing the virus. The virus titers obtained following complementation of the L protein were 190 to 2,300 PFU/ml of culture medium, compared with the undetectable growth of the cp45 temperature-sensitive mutant at the nonpermissive temperature. Rescued progeny virus still maintained the temperature-sensitive phenotype. Results from this study suggest that the temperature sensitivity of the cp45 candidate vaccine strain is associated primarily with L-protein function and that the defect can be complemented by transient expression of the wild-type protein. This study underscores the importance of the L protein in RNA polymerase activity and its critical role in virus replication.
Hydrogenation Processes in the Synthesis of Perfumery Ingredients (2007)

Homogeneous catalytic hydrogenation has played an important role in the development of modern organic synthesis. Indeed, the discovery of highly regio- and stereoselective catalysts for C=C and C=O bonds reductions has allowed the efficient synthesis of optically active compounds. As the fragrance industry has turned to synthetic ingredients to fulfill the need for novel, cost-effective, and environment-friendly products, the use of catalytic processes are more and more in demand. In this Account, we thus highlight the application of catalytic hydrogenation in the synthesis of fragrance ingredients.
Pharmacokinetics and Disposition of Rilpivirine (TMC278) Nanosuspension as a Long-Acting Injectable Antiretroviral Formulation (2010)

The next-generation human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase inhibitor rilpivirine (TMC278) was administered in rats and dogs as single intramuscular (IM) or subcutaneous (SC) injections, formulated as a 200-nm nanosuspension. The plasma pharmacokinetics, injection site concentrations, disposition to lymphoid tissues, and tolerability were evaluated in support of its potential use as a once-monthly antiretroviral agent in humans. Rilpivirine plasma concentration-time profiles showed sustained and dose-proportional release over 2 months in rats and over 6 months in dogs. The absolute bioavailability approached 100%, indicating a complete release from the depot, in spite of rilpivirine concentrations still being high at the injection site(s) 3 months after administration in dogs. For both species, IM administration was associated with higher initial peak plasma concentrations and a more rapid washout than SC administration, which resulted in a stable plasma-concentration profile over at least 6 weeks in dogs. The rilpivirine concentrations in the lymph nodes draining the IM injection site exceeded the plasma concentrations by over 100-fold 1 month after administration, while the concentrations in the lymphoid tissues decreased to 3- to 6-fold the plasma concentrations beyond 3 months. These observations suggest uptake of nanoparticles by macrophages, which generates secondary depots in these lymph nodes. Both SC and IM injections were generally well tolerated and safe, with observations of a transient inflammatory response at the injection site. The findings support clinical investigations of rilpivirine nanosuspension as a long-acting formulation to improve adherence during antiretroviral therapy and for preexposure prophylaxis.
Leigh Syndrome Associated With Mitochondrial Complex I Deficiency Due to a Novel Mutation in the NDUFS1 Gene (2005)

Identifying nuclear mutations as a cause of respiratory chain disorders will enhance the possibility of prenatal diagnosis and help us understand how molecular defects can lead to complex I deficiency.
Disruption of the MMAC1/PTEN gene by deletion or mutation is a frequent event in malignant melanoma. (1997)

The MMAC1/PTEN gene, located at 10q23.3, is a candidate tumor suppressor commonly mutated in glioma. We have studied the pattern of deletion, mutation, and expression of MMAC1/PTEN in 35 unrelated melanoma cell lines. Nine (26%) of the cell lines showed partial or complete homozygous deletion of the MMAC1/PTEN gene, and another six (17%) harbored a mutation in combination with loss of the second allele. Mutations could also be demonstrated in uncultured tumor specimens from which the cell lines had been established, and cell lines derived from two different metastases from one individual carried the same missense mutation. Collectively, these findings suggest that disruption of MMAC1/PTEN by allelic loss or mutation may contribute to the pathogenesis or neoplastic evolution in a large proportion of malignant melanomas.
Large Scale Gene Expression Analysis of Osteoclastogenesisin Vitro and Elucidation of NFAT2 as a Key Regulator (2002)

To understand the molecular events coupling between cell proliferation and differentiation by elucidating genes essential for the process, we conducted a large scale gene expression analysis of an in vitro osteoclastogenesis system consisting of recombinant RANKL and mouse RAW264 cells. The entire process leading to the formation of tartrate resistant acid phosphatase-positive multinucleated cells takes 3 days and plates become fully covered with multinucleated cells at 4 days. Microarray probing at eight time points revealed 635 genes that showed greater than 2-fold differential expression for at least one time point and they could be classified into six groups by the "k-means" clustering analysis. Among a group of 106 early inducible genes (within 2-5 h after RANKL stimulation), four genes including NFAT2 were identified as genes whose enhanced expressions were fairly correlated with an efficient induction of matured osteoclasts. Moreover, cyclosporin A significantly suppressed the multinucleated cell formation accompanying the reduction of the nuclear localization of NFAT2. When the expression of NFAT2 was suppressed by introducing antisense NFAT2, multinucleated cell formation was severely hampered. Functional analysis thus combined with gene analysis by microarray technology elucidated a key role of NFAT2 in osteoclastogenesis in vitro.
Efficacy of an intraperitoneal antibiotic to reduce the incidence of infection in the trauma patient: a prospective, randomized study. (1996)

Intraperitoneal kanamycin given to trauma patients requiring diagnostic peritoneal lavage within the first three hours following injury reduces the incidence of infectious complications and shortens intensive care unit and hospital stay.
A4 amyloid protein deposition and the diagnosis of Alzheimer's disease (1988)

The histologic diagnosis of Alzheimer's disease (AD) might be aided if a more sensitive marker of aberrant A4 amyloid protein deposition were available. We screened a sample of aged brains, using immunocytochemical methods to detect the A4 protein deposition, and found that, in comparison with conventional histologic techniques (silver impregnation and Congo red), immunocytochemistry is more sensitive and allows an easier demarcation between "normal" and "abnormal." If A4 protein deposition is accepted as a definitive marker for AD, then the age-related prevalence of AD increases dramatically. To what degree these prevalence rates are reflected in clinically detectable impairment of higher cortical function remains to be determined.
Amino acid sequence studies on the α chain of human fibrinogen. Location of four plasmin attack points and a covalent cross-linking site (1975)

The amino acid sequence of a 38-residue midsection piece of the alpha chain of human fibrinogen has been determined using a combination of plasmin-derived peptides and cyanogen bromide fragments. The segment contains several important features, including four early plasmin attack points, one of the two alpha-chain cross-linking acceptor sites, and a peptide homologous to one isolated from plasmin digests of bovine fibrinogen, and reported to have anticoagulant activity. The segment is sequentially adjacent to and overlapping with a large molecular weight (20000-25000) fragment released during plasminolysis. This latter material is very rich in glycine and serine and deficient in nonpolar amino acids. It also contains the other alpha-chain cross-linking acceptor site.
Automated Effect-Specific Mammographic Pattern Measures (2008)

We investigate the possibility to develop methodologies for assessing effect specific structural changes of the breast tissue using a general statistical machine learning framework. We present an approach of obtaining objective mammographic pattern measures quantifying a specific biological effect, such as hormone replacement therapy (HRT). We compare results using this approach to using standard density measures. We show that the proposed method can quantify both age related effects and effects caused by HRT. Age effects are significantly detected by our method where standard methodologies fail. The separation of HRT subpopulations using our approach is comparable to the best methodology, which is interactive.