gebhart/patrepeval huggingface dataset:
Discontinuation of Antihyperlipidemic Drugs — Do Rates Reported in Clinical Trials Reflect Rates in Primary Care Settings? (1995)

The discontinuation rates reported in randomized clinical trials may not reflect the rates actually observed in primary care settings. The effectiveness and tolerability of antihyperlipidemic medications should be studied further in populations that typically use the agents.
Suppression of Melatonin Secretion in Some Blind Patients by Exposure to Bright Light (1995)

The visual subsystem that mediates light-induced suppression of melatonin secretion remains functionally intact in some sightless patients. The absence of photic input to the circadian system thus constitutes a distinct form of blindness, associated with periodic insomnia, that afflicts most but not all patients with no conscious perception of light.
Isolation of a cDNA clone encoding a high molecular weight precursor to a 6-kDa pulmonary surfactant-associated protein. (1987)

Mammalian surfactant is an incompletely defined mixture of lipids and associated proteins of molecular mass 35,000 Da and approximately 6,000 Da. Surfactant preparations which are highly effective in treating respiratory distress syndrome in premature infants lack the 35-kDa proteins, but contain the 6-kDa proteins. We isolated and partially sequenced one of these low molecular weight proteins from the lung lavage material of an alveolar proteinosis patient. Oligonucleotides deduced from the sequence were used as probes to isolate a human cDNA clone. The clone codes for a 42-kDa protein which contains the sequence of the 6-kDa protein. Messenger RNA coding for the 42-kDa protein was identified in human lung RNA by in vitro translation and immunoprecipitation of the translation products with an antiserum against purified bovine surfactant 6-kDa proteins. Immunoprecipitation of the 42-kDa primary translation product is inhibited by the presence of the bovine 6-kDa protein. These observations suggest a precursor-product relationship of the 42-kDa protein to one of the 6-kDa proteins.
The 5HT2 receptor defines a family of structurally distinct but functionally conserved serotonin receptors. (1990)

Serotonin exerts its diverse physiological effects by interacting with multiple distinct receptor subtypes. We have isolated a rat brain 5HT2 serotonin receptor cDNA by virtue of its homology with the 5HT1c receptor. The 5HT2 receptor is a member of the family of receptors that are linked to guanine nucleotide-binding proteins and are predicted to span the lipid bilayer seven times. Overall sequence identity between the 5HT2 and 5HT1c receptors is 49%, but identity within the transmembrane domains is 80%. Expression of both the 5HT2 and 5HT1c receptors in transfected mouse fibroblasts activates phospholipase C signaling pathways and promotes cellular transformation. However, RNA blotting shows that these two receptor subtypes are differentially expressed in the central nervous system. In this manner, structurally and functionally homologous receptor subtypes may elicit distinct physiologic actions.
Glossopexy for Upper Airway Obstruction in Robin Sequence (1992)

A modified glossopexy is described with results of the operation in 24 patients who were specifically selected based on nasopharyngoscopic examination of the upper airway. Only patients with documented glossoptosis on endoscopy were selected for glossopexy. The procedure is designed to use two points of attachment for the tongue, one at the mandibular alveolus and the other at the lower lip. The genioglossus is also released to lengthen the tongue. All patients had resolution of their upper airway obstruction. There was only one partial dehiscence. The glossopexies were all released at the time of palate repair, usually before the first birthday.
Comparison of the Yields of Blood Cultures Using Serum or Plasma from Patients with Early Lyme Disease (2000)

In an initial experiment, culture-grown Borrelia burgdorferi was added to freshly collected uninfected human blood. This in vitro study demonstrated that more spirochetes were distributed into the plasma than into the serum fraction. In a subsequent clinical study, B. burgdorferi was recovered from plasma cultures of approximately 50% of 42 patients with early Lyme disease associated with erythema migrans. The rate of recovery from plasma cultures was significantly greater than that from serum cultures (P < 0.001).
High-throughput Agrobacterium-mediated barley transformation (2008)

This protocol demonstrates significant improvements in both efficiency and ease of use over existing barley transformation methods. This opens up opportunities for the development of functional genomics resources in barley.
Relationship between DNA-Transfection Efficiency and Chemical Structures of Aromatic Cationic Lipids (2012)

Abstract Gene therapy by introducing a foreign DNA into a cell with defective gene has been expected to treat various incurable diseases such as cancers, inherited diseases, and cardiovascular disease. Cationic lipids have been used as a carrier of therapeutic DNAs because they can form a complex with DNA and such a complex can be incorporated into cells and transport the bound DNA to cytosol. This complex is called lipoplex and categorized as a nonviral vector. We synthesized various kinds of cationic lipids with aromatic ring attached different hydrophilic groups, alkyl chain length and position of alkyl chains and evaluated their transfection efficiency. The lipids with primary amine and ethylenediamine-attached C12 at meta–meta position showed the highest transfection efficiencies, which reaches the same level as commercially available transfection reagent. The order of transfection efficiency in terms of alkyl chain length is follows: C12 C9 ≈ C18. The lipids with a primary amine showed better transfection efficiency than that with a quaternary ammonium salt. These results show that these cationic lipids with amine group attached aromatic structure can be used for novel transfection reagents.
Insertion of a rabbit β-globin gene sequence into an E.coli plasmid (1975)

Double stranded DNA has been synthesized in vitro from rabbit globin messenger RNA and elongated with homopolymeric dG tails. An E. coli plasmid was cleaved by EcoRI. The cohesive ends were repaired and dC tails added, to permit reconstitution of the EcoRI sites upon annealing with the dG elongated globin DNA. Transformation of E. coli with the globin-plasmid DNA hybrid has yielded a clone which harbours a recombinant plasmid (pCR1-betaG1), as demonstrated by hybridization experiments with radioactive globin cDNA. The sequence carried by the recombinant plasmid corresponds to part of the gene sequence coding for the beta chain of rabbit globin. Circular DNA of the purified recombinant plasmid exhibits sensitivity to EcoRI.
Phase 2 study of romiplostim in patients with low- or intermediate-risk myelodysplastic syndrome receiving azacitidine therapy (2010)

We evaluated the efficacy and safety of romiplostim, a thrombopoietin mimetic, in patients with low- or intermediate-risk myelodysplastic syndromes (MDS) receiving azacitidine therapy. Forty patients with low- or intermediate-risk MDS were stratified by baseline platelet counts (< 50 vs ≥ 50 × 10(9)/L) and randomized to romiplostim 500 μg or 750 μg or placebo subcutaneously once weekly during 4 cycles of azacitidine. The primary endpoint was the incidence of clinically significant thrombocytopenic events, defined by grade 3 or 4 thrombocytopenia starting on day 15 of the first cycle or platelet transfusion at any time during the 4-cycle treatment period. No formal hypothesis testing was planned. The incidence of clinically significant thrombocytopenic events in patients receiving romiplostim 500 μg, romiplostim 750 μg, or placebo was 62%, 71%, and 85%, respectively. The incidence of platelet transfusions was 46%, 36%, and 69%, respectively. These differences were not statistically significant with the small numbers in each group. Romiplostim 750 μg significantly raised median platelet counts during cycle 3 on day 1 (P = .0373) and at the nadir (P = .0035) compared with placebo. Grade 3 rash and arthralgia each were reported in 1 romiplostim-treated patient (4%). This study suggests romiplostim may provide clinical benefits in MDS patients during azacitidine therapy.
Hydrogen peroxide mediates the cell growth and transformation caused by the mitogenic oxidase Nox1 (2001)

Nox1, a homologue of gp91phox, the catalytic moiety of the superoxide (O(2)(-))-generating NADPH oxidase of phagocytes, causes increased O(2)(-) generation, increased mitotic rate, cell transformation, and tumorigenicity when expressed in NIH 3T3 fibroblasts. This study explores the role of reactive oxygen species (ROS) in regulating cell growth and transformation by Nox1. H(2)O(2) concentration increased approximately 10-fold in Nox1-expressing cells, compared with <2-fold increase in O(2)(-). When human catalase was expressed in Nox1-expressing cells, H(2)O(2) concentration decreased, and the cells reverted to a normal appearance, the growth rate normalized, and cells no longer produced tumors in athymic mice. A large number of genes, including many related to cell cycle, growth, and cancer (but unrelated to oxidative stress), were expressed in Nox1-expressing cells, and more than 60% of these returned to normal levels on coexpression of catalase. Thus, H(2)O(2) in low concentrations functions as an intracellular signal that triggers a genetic program related to cell growth.
Inhibition of pulmonary surfactant function by phospholipases (1991)

Previous studies have shown that respiratory failure associated with disorders such as acute pancreatitis correlates well with increased levels of phospholipase A2 (PLA2) in lung lavages and that intratracheal administration of PLA2 generates an acute lung injury. In addition, bacteria such as Pseudomonas have been shown to secrete phospholipase C (PLC). We studied the effects of these phospholipases on pulmonary surfactant activity using a pulsating bubble surfactometer. Concentrations greater than or equal to 0.1 unit/ml PLA2 destroyed surfactant biophysical activity, increasing surface tension at minimum bubble size from less than 1 to 15 mN/m. This surfactant inactivation was predominantly related to the effect of lysophosphatidylcholine on the surface film, although the fatty acids released with higher PLA2 concentrations also had a detrimental effect on surfactant function. Similarly, as little as 0.1 unit PLC increased the surface tension at minimal size of an oscillating bubble from less than 1 to 15 mN/m, an effect that could be mimicked by the addition of dipalmitin to surfactant in the absence of PLC. Moreover, lower, noninhibitory concentrations (0.01 unit/ml) of PLA2 and PLC increased the sensitivity of surfactant to other inhibitory agents, such as albumin. Thus, relatively low concentrations of PLC and PLA2 can cause severe breakdown of surfactant function and may contribute significantly to some forms of lung injury.
Development of Buckwheat Bread : 3. Effects of the Thermal Process of Dough Making on Baking Properties (1999)

The quality of the buckwheat bread made with previously heated (55℃) and cooled buckwheat flour dough with the addition of ascorbic acid (AA) or/and sodium stearoyl lactylate (SSL) was evaluated. With heat treatment, handling property of dough and grain of the bread crumb were markedly improved and stickiness of the dough decreased. The optimum resting time to produce the best loaf volume and grain was found to be 3hr for both unheated and heated doughs. Heat treated dough showed higher dough expansion rate during fermentation than unheated dough, even though heated dough had lower loaf volume, probably because of an improper oven spring. Increase in shortening of dough formula from 3% to 5% improved loaf volume without improvement of handling property. With the addition of 100 ppm AA or/and 0.5% SSL, loaf volume and crumb grain were improved for both unheated and heated doughs. Microscopic analysis of a mixed dough by scanning electron microscope (SEM) showed that heated dough had a continuous network whereas unheated dough was discontinuous. The addition of AA and SSL gave the dough a more continuous structure with strengthened strands or interactions between the starch granule and protein. Therefore, it appears that the presence of continuity in heated buckwheat bread dough is related to the improved loaf volume and crumb grain without dough stickiness.
Human and economic burden of generalized anxiety disorder (2006)

The goal of the current work is to provide a comprehensive review and interpretation of the literature on the human and economic burden of generalized anxiety disorder (GAD) and how it compares with that of other mental disorders. The term "human burden" is used to describe quantified impairments in role functioning and quality of life (QOL). "Economic burden" describes costs related to health care resource utilization and lost work. A review of 34 studies reporting original quantitative data on associations between GAD and role functioning, QOL, and/or economic costs was undertaken. GAD was defined by DMS-III-R, DSM-IV, or ICD-10 DCR. Persons with GAD (both with and without a comorbid mental disorder) described significant impairments due to both physical and emotional problems. Studies typically showed that role and QOL impairments of GAD were at least comparable in magnitude to those of other anxiety disorders, somatoform disorders, and physical conditions, and greater than those of substance use disorders. Large representative studies showed that role impairments of pure GAD were similar in magnitude to those of pure MDD. Studies of DSM-IV disorders showed that QOL impairments of GAD were at least comparable in magnitude to those of MDD; studies of DSM-III-R disorders showed the opposite pattern. GAD was associated with considerable economic costs owing to lost work productivity and high medical resource use. Quality of care initiatives that have been implemented to increase recognition and improve treatment outcomes for persons with MDD should be extended to the effective management of GAD.
Clinical implications of glucocorticoid receptors in human leukemia. (1978)

Glucorticoid receptors were studied in various populations of normal human peripheral blood lymphocytes and leukemic lymphoblasts. Normal lymphocytes contain low levels of glucocorticoid receptor (approximately 2,500 sites/cell) which are identical in T- and non-T-fractions. Phytohemagglutinin treatment increases levels about 3-fold. Leukemic lymphoblasts contain larger numbers of receptor sites. Presence of receptor is correlated with in vitro sensitivitiy to glucocorticoids and in vivo response to therapy. Quantity of receptor is also correlated with complete remission duration independently of leukemic cell type (T or null), initial WBC, or age of patient. Quantitative determination of glucocorticoid receptor levels in acute lymphoblastic leukemia may be of value both as an independent prognostic variable and in suggesting which patients should receive glucocorticoid therapy.
Degenerate target sites mediate rapid primed CRISPR adaptation (2014)

Prokaryotes encode adaptive immune systems, called CRISPR-Cas (clustered regularly interspaced short palindromic repeats-CRISPR associated), to provide resistance against mobile invaders, such as viruses and plasmids. Host immunity is based on incorporation of invader DNA sequences in a memory locus (CRISPR), the formation of guide RNAs from this locus, and the degradation of cognate invader DNA (protospacer). Invaders can escape type I-E CRISPR-Cas immunity in Escherichia coli K12 by making point mutations in the seed region of the protospacer or its adjacent motif (PAM), but hosts quickly restore immunity by integrating new spacers in a positive-feedback process termed "priming." Here, by using a randomized protospacer and PAM library and high-throughput plasmid loss assays, we provide a systematic analysis of the constraints of both direct interference and subsequent priming in E. coli. We have defined a high-resolution genetic map of direct interference by Cascade and Cas3, which includes five positions of the protospacer at 6-nt intervals that readily tolerate mutations. Importantly, we show that priming is an extremely robust process capable of using degenerate target regions, with up to 13 mutations throughout the PAM and protospacer region. Priming is influenced by the number of mismatches, their position, and is nucleotide dependent. Our findings imply that even outdated spacers containing many mismatches can induce a rapid primed CRISPR response against diversified or related invaders, giving microbes an advantage in the coevolutionary arms race with their invaders.
Telomere Fluorescence Measurements in Granulocytes and T Lymphocyte Subsets Point to a High Turnover of Hematopoietic Stem Cells and Memory T Cells in Early Childhood (1999)

To study telomere length dynamics in hematopoietic cells with age, we analyzed the average length of telomere repeat sequences in diverse populations of nucleated blood cells. More than 500 individuals ranging in age from 0 to 90 yr, including 36 pairs of monozygous and dizygotic twins, were analyzed using quantitative fluorescence in situ hybridization and flow cytometry. Granulocytes and naive T cells showed a parallel biphasic decline in telomere length with age that most likely reflected accumulated cell divisions in the common precursors of both cell types: hematopoietic stem cells. Telomere loss was very rapid in the first year, and continued for more than eight decades at a 30-fold lower rate. Memory T cells also showed an initial rapid decline in telomere length with age. However, in contrast to naive T cells, this decline continued for several years, and in older individuals lymphocytes typically had shorter telomeres than did granulocytes. Our findings point to a dramatic decline in stem cell turnover in early childhood and support the notion that cell divisions in hematopoietic stem cells and T cells result in loss of telomeric DNA.
“Less is More”: The Role of Purging in Hematopoietic Stem Cell Transplantation (1997)

The epithet "less is more" is usually applied to the essentials of good design, but it might be equally true of autologous blood or marrow transplantation. Ever since autologous marrow transplantation was first used to reconstitute recipients of high-dose chemotherapy or radiotherapy, there has been much discussion about the relative contribution of residual tumor cells in the graft to the occurrence of subsequent relapse. It was not until the early 1990s that this risk was finally confirmed by the use of gene marking [1]. A retroviral vector was used to mark a proportion of the autologous remission bone marrow from patients with acute myeloid leukemia (AML) before marrow infusion after high-dose therapy. Two recipients relapsed and both had leukemic blasts with the marker, the neomycin-resistance gene. As the safety of autologous hematopoietic stem cell transplantation has increased, the use of high-dose therapy followed by stem cell "rescue" is becoming more widespread. The malignancies treated in this way include leukemia, lymphoma, myeloma, neuroblastoma, breast cancer, and ovarian tumors. In each of these conditions a number of important questions should be addressed: Can we identify and quantitate tumor cells in the grafts and establish their oncogenic potential? If so, how best can we remove them? Can they be removed without compromising the graft, and will such purging produce a clinically significant reduction in relapse risk? Finally, will the procedure be cost-effective?
Adapting the acoustic model of a speech recognizer for varied proficiency non-native spontaneous speech using read speech with language-specific pronunciation difficulty (2009)

This paper presents a novel approach to acoustic model adaptation of a recognizer for non-native spontaneous speech in the context of recognizing candidates’ responses in a test of spoken English. Instead of collecting and then transcribing spontaneous speech data, a read speech corpus is created where non-native speakers of English read English sentences of different degrees of pronunciation difficulty with respect to their native language. The motivation for this approach is (1) to save time and cost associated with transcribing spontaneous speech, and (2) to allow for a targeted training of the recognizer, focusing particularly on those phoneme environments which are difficult to pronounce correctly by non-native speakers and hence have a higher likelihood of being misrecognized. As a criterion for selecting the sentences to be read, we develop a novel score, the “phonetic challenge score”, consisting of a measure for native language-specific difficulties described in the second-language acquisition literature and also of a statistical measure based on the cross-entropy between phoneme sequences of the native language and English. We collected about 23,000 read sentences from 200 speakers in four language groups: Chinese, Japanese, Korean, and Spanish. We used this data for acoustic model adaptation of a spontaneous speech recognizer and compared recognition performance between the unadapted baseline and the system after adaptation on a held-out set from the English test responses data set. The results show that using this targeted read speech material for acoustic model adaptation does reduce the word error rate significantly for two of four language groups of the spontaneous speech test set, while changes of the two other language groups are not significant. Insdex Terms: acoustic model adaptation, non-native spontaneous speech, cross-lingual phonetic difficulty
Dopamine Receptor Function in the Basal Ganglia (1995)

Clinical disorders that affect the basal ganglia, such as Parkinson's disease, are believed to result from an imbalance in the activity of the two main output pathways of the striatum, the direct and indirect striatal output pathways. Dopamine (DA) modulates the activity of these pathways through the select distribution of the D1 and D2 DA-receptor subtypes on neurons, which give rise to the direct and indirect striatal output pathways, respectively. Studies employing quantitative in situ hybridization histochemistry have been used to analyze changes in levels of gene-regulated peptides and immediate early genes in direct and indirect striatal output neurons in response to selective D1- and D2-agonist treatments. D2-receptor activation reverses and D1-receptor activation increases gene regulation in indirect and direct striatal output neurons, respectively. These findings suggest that functional activity in the two output pathways of the striatum are oppositely regulated by DA by segregation of the D1- and D2-receptor subtypes on different striatal neuron populations. A proposed pharmacologic strategy for the treatment of Parkinson's disease based on these findings is suggested.