gebhart/patrepeval huggingface dataset:
AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Psychiatry: Update 2011 (2011)

Therapeutic drug monitoring (TDM), i. e., the quantification of serum or plasma concentrations of medications for dose optimization, has proven a valuable tool for the patient-matched psychopharmacotherapy. Uncertain drug adherence, suboptimal tolerability, non-response at therapeutic doses, or pharmacokinetic drug-drug interactions are typical situations when measurement of medication concentrations is helpful. Patient populations that may predominantly benefit from TDM in psychiatry are children, pregnant women, elderly patients, individuals with intelligence disabilities, forensic patients, patients with known or suspected genetically determined pharmacokinetic abnormalities or individuals with pharmacokinetically relevant comorbidities. However, the potential benefits of TDM for optimization of pharmacotherapy can only be obtained if the method is adequately integrated into the clinical treatment process. To promote an appropriate use of TDM, the TDM expert group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued guidelines for TDM in psychiatry in 2004. Since then, knowledge has advanced significantly, and new psychopharmacologic agents have been introduced that are also candidates for TDM. Therefore the TDM consensus guidelines were updated and extended to 128 neuropsychiatric drugs. 4 levels of recommendation for using TDM were defined ranging from "strongly recommended" to "potentially useful". Evidence-based "therapeutic reference ranges" and "dose related reference ranges" were elaborated after an extensive literature search and a structured internal review process. A "laboratory alert level" was introduced, i. e., a plasma level at or above which the laboratory should immediately inform the treating physician. Supportive information such as cytochrome P450 substrate- and inhibitor properties of medications, normal ranges of ratios of concentrations of drug metabolite to parent drug and recommendations for the interpretative services are given. Recommendations when to combine TDM with pharmacogenetic tests are also provided. Following the guidelines will help to improve the outcomes of psychopharmacotherapy of many patients especially in case of pharmacokinetic problems. Thereby, one should never forget that TDM is an interdisciplinary task that sometimes requires the respectful discussion of apparently discrepant data so that, ultimately, the patient can profit from such a joint effort.
Cysteinyl‐tRNA formation: the last puzzle of aminoacyl‐tRNA synthesis (1999)

With the exception of the methanogenic archaea Methanococcus jannaschii and Methanobacterium thermoautotrophicum deltaH, all organisms surveyed contain orthologs of Escherichia coli cysteinyl-tRNA synthetase (CysRS). The characterization of CysRS-encoding (cysS) genes and the demonstration of their ability to complement an E. coli cysSts mutant reveal that Methanococcus maripaludis and Methanosarcina barkeri, two other methanogenic archaea, possess canonical CysRS proteins. A molecular phylogeny inferred from 40 CysRS sequences indicates that the CysRS of M. maripaludis and Methanosarcina spp. are specific relatives of the CysRS of Pyrococcus spp. and Chlamydia, respectively. This result suggests that the CysRS gene was acquired by lateral gene transfer in at least one euryarchaeotic lineage.
Naltrexone Reduces Binge Eating and Purging in Adolescents in an Eating Disorder Program (2019)

<b><i>Objective:</i></b> Little evidence exists for pharmacologic treatment of binge eating and purging in adolescents with eating disorders. Given the role of the opioid reward system in compulsive binge eating and purging, naltrexone, an opioid antagonist, may be effective in reducing these behaviors. Previous studies have demonstrated that naltrexone reduces binge eating and purging in adults, yet evidence for its use in adolescents is lacking. This case series describes naltrexone utilization, response, and safety in adolescents with eating disorders. <b><i>Methods:</i></b> A retrospective chart review of adolescent patients prescribed naltrexone at an academic eating disorder program was completed. <b><i>Results:</i></b> Thirty-three adolescents aged 15.3 ± 1.49 years, 94% female gender identity, were treated with naltrexone with the most common expected outcome "to reduce vomiting." Naltrexone was prescribed for 129 ± 125 days. Over half of patients (52%, <i>n</i> = 17) had liver function tests during follow-up, all of which were within normal limits. Three patients (9.1%) experienced nausea related to naltrexone. Just over half of adolescents (67%; <i>n</i> = 22) had documentation of positive naltrexone response (e.g., reduced purging or urge to purge). The mean Clinical Global Impressions-Improvement score was 2.7 ± 1.3 (2 = much improved; 3 = minimally improved). <b><i>Conclusions:</i></b> Naltrexone is safe, well tolerated, and effective for the treatment of adolescents with binge eating and/or purging as part of a comprehensive eating disorder treatment plan. Further study is necessary to confirm the effectiveness of naltrexone prospectively and evaluate factors contributing to naltrexone response vs. nonresponse to promote an individualized approach to treatment of binge eating and purging behavior.
Dual Role of CCR2 during Initiation and Progression of Collagen-Induced Arthritis: Evidence for Regulatory Activity of CCR2+ T Cells (2004)

Chemokines play an important role in the recruitment of leukocytes and have recently been shown to also attract regulatory T cells. Using blocking mAbs, we analyzed the role of the chemokine receptor CCR2 during initiation and progression of collagen-induced arthritis in mice. Blockade of CCR2 from days 0 to 15 markedly improved clinical signs of arthritis and histological scores measuring leukocyte infiltration, synovial hyperplasia, and bone and cartilage erosion. CCR2 blockade during disease initiation significantly reduced plasma titers of collagen Abs in vivo. In vitro CCR2 blockade also interfered with collagen-specific activation and proliferation of T cells. Surprisingly, CCR2 blockade from days 21 to 36 markedly aggravated clinical and histological signs of arthritis and increased the humoral immune response against collagen. We show that CCR2 is expressed on regulatory T cells. Purified CCR2+ T cells are fully anergic toward polyclonal and collagen-specific activation and potently suppress activation of other T and B cells. The subpopulation of CCR2+ CD25+ regulatory T cells increases approximately 5-fold in the progression phase, while CCR2 expression on other leukocyte populations remains unchanged. These findings identify CCR2+ T cells as regulatory T cells and indicate that CCR2 also plays an important role in down-modulating an inflammatory response.
Excessive production of amyloid beta-protein by peripheral cells of symptomatic and presymptomatic patients carrying the Swedish familial Alzheimer disease mutation. (1994)

The 39- to 43-amino acid amyloid beta-protein (A beta), which is progressively deposited in cerebral plaques and blood vessels in Alzheimer disease (AD), is secreted by cultured human cells during normal metabolism. In studies of cell lines transfected with beta-amyloid precursor protein (beta APP) cDNAs, the beta APP mutation K670N/M671L found in a Swedish familial AD (FAD) pedigree has previously been shown to cause a marked augmentation of A beta secretion. Here, we have conducted blinded analyses of beta APP metabolism in primary skin fibroblasts from affected members of the Swedish FAD pedigree and their unaffected siblings or spouses. These fibroblasts continuously secrete a homogenous population of A beta molecules starting at Asp-1 (D672 of beta APP). We found a consistent and significant approximately 3-fold elevation of A beta release from all biopsied skin fibroblasts bearing the FAD mutation. No significant alterations of other metabolic derivatives of beta APP were detected. The elevated A beta levels were found in cells from both patients with clinical AD and presymptomatic subjects. Thus, A beta overproduction in this FAD pedigree is not a secondary event but is consistent with a causal role in the development of the disease. Increased A beta secretion can begin many years prior to onset of symptoms, even in peripheral tissues, indicating that it does not require preexisting neural abnormalities.
Electrophilic reactions at single bonds. 20. Selective monohalogenation of methane over supported acidic or platinum metal catalysts and hydrolysis of methyl halides over .gamma.-alumina-supported metal oxide/hydroxide catalysts. A feasible path for the oxidative conversion of methane into methyl alcohol/dimethyl ether (1985)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectrophilic reactions at single bonds. 20. Selective monohalogenation of methane over supported acidic or platinum metal catalysts and hydrolysis of methyl halides over .gamma.-alumina-supported metal oxide/hydroxide catalysts. A feasible path for the oxidative conversion of methane into methyl alcohol/dimethyl etherGeorge A. Olah, Balaram Gupta, Jeff D. Felberg, Wai M. Ip, Altaf Husain, Richard Karpeles, Koop Lammertsma, Ashok K. Melhotra, Nirupam J. Trivedi, and Cite this: J. Am. Chem. Soc. 1985, 107, 24, 7097–7105Publication Date (Print):November 1, 1985Publication History Published online1 May 2002Published inissue 1 November 1985https://pubs.acs.org/doi/10.1021/ja00310a057https://doi.org/10.1021/ja00310a057research-articleACS PublicationsRequest reuse permissionsArticle Views1401Altmetric-Citations158LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Optical imaging of pre-invasive breast cancer with a combination of VHHs targeting CAIX and HER2 increases contrast and facilitates tumour characterization (2016)

These results establish the feasibility of the use of VHH 'cocktails' to increase T/B ratios and improve early detection of heterogeneous tumours and the use of multispectral molecular imaging to facilitate the assessment of the target expression status of tumours and metastases, both invasive or non-invasively.
Large-scale structure of genomic methylation patterns (2005)

The mammalian genome depends on patterns of methylated cytosines for normal function, but the relationship between genomic methylation patterns and the underlying sequence is unclear. We have characterized the methylation landscape of the human genome by global analysis of patterns of CpG depletion and by direct sequencing of 3073 unmethylated domains and 2565 methylated domains from human brain DNA. The genome was found to consist of short (<4 kb) unmethylated domains embedded in a matrix of long methylated domains. Unmethylated domains were enriched in promoters, CpG islands, and first exons, while methylated domains comprised interspersed and tandem-repeated sequences, exons other than first exons, and non-annotated single-copy sequences that are depleted in the CpG dinucleotide. The enrichment of regulatory sequences in the relatively small unmethylated compartment suggests that cytosine methylation constrains the effective size of the genome through the selective exposure of regulatory sequences. This buffers regulatory networks against changes in total genome size and provides an explanation for the C value paradox, which concerns the wide variations in genome size that scale independently of gene number. This suggestion is compatible with the finding that cytosine methylation is universal among large-genome eukaryotes, while many eukaryotes with genome sizes <5 x 10(8) bp do not methylate their DNA.
Highly efficient blue electroluminescence from a distyrylarylene emitting layer with a new dopant (1995)

We report that organic electroluminescence devices with a distyrylarylene (DSA) emitting layer including a new dopant realized highly efficient and bright emission in blue region. This dopant was amino-substituted DSA. The luminous efficiency was obtained to be 1.5 lm/W. The external quantum efficiency was estimated to be 2.4%, which is one of the highest efficiencies ever reported in blue emitting organic EL devices.
Differential N-Glycan Patterns of Secreted and Intracellular IgG Produced in Trichoplusia ni Cells (1997)

Structures of the N-linked oligosaccharide attached to the heavy chain of a heterologous murine IgG2a produced from Trichoplusia ni (TN-5B1-4, High Five) insect cells were characterized. Coexpression of the chaperone immunoglobulin heavy chain-binding protein (BiP) in the baculovirus-infected insect cells increased the soluble intracellular and secreted IgG level. This facilitated the detailed analysis of N-glycans from both intracellular and secreted IgG. Following purification of the immunoglobulins using Protein A-Sepharose, glycopeptides, prepared by trypsin-chymotrypsin digestion, were further digested with glycoamidase from sweet almond emulsin to obtain the oligosaccharide moieties. The resulting oligosaccharides were then reductively aminated with 2-aminopyridine and the structures identified by two-dimensional high performance liquid chromatography mapping (Tomiya, N., Awaya, J., Kurono, M., Endo, S., Arata, Y., and Takahashi, N. (1988) Anal. Biochem. 171, 73-90). The N-glycans obtained from the secreted IgG contain 35% complex type, some with terminal galactose residues at either alpha1, 3-Man or alpha1,6-Man branches of the Man3GlcNAc2 core. The remaining oligosaccharides detected in the secreted IgG were principally hybrid (30%) and paucimannosidic (35%) type N-glycans. Most (84%) of these secreted glycoforms contained fucose alpha1, 6-linked to the innermost GlcNAc residue and the presence of a potentially allergenic fucose alpha1,3-linked to the innermost GlcNAc residue was also detected. In contrast, the intracellular immunoglobulins included 50% high mannose-type N-glycans with lower levels of complex, hybrid, and paucimannosidic-type structures. Reverse phase one-dimensional high performance liquid chromatography analysis of the IgG N-glycans in the absence of heterologous BiP exhibited a similar distribution of intracellular and secreted glycoforms. These studies indicate that Trichoplusia ni TN-5B1-4 cells are capable of terminal galactosylation. However, the processing pathways in these cell lines appear to diverge from mammalian cells in the formation of paucimannosidic structures, in the presence of alpha1,3-fucose linkages, and in the absence of sialylation.
Functional characterization of NCAM fibronectin type III domains: Demonstration of modulatory effects of the proline‐rich sequence encoded by alternatively spliced exons a and AAG (1996)

In order to characterize the functions of the two fibronectin type III (F3) homology domains of the neural cell adhesion molecule (NCAM), we investigated the effects of two variants, expressed as fusion proteins, of the NCAM-F3 domains on attachment and spreading of NCAM-expressing fibroblasts, cerebellar cell aggregation and fiber formation, and on growth cones. The two fusion proteins were different with regard to a short proline-rich insert of six amino acids between the two F3 domains. Immobilized NCAM-F3 fusion proteins were found to mediate attachment of both transmembrane and lipid-anchored NCAM expressing fibroblasts. Also NCAM-negative cells adhered to the NCAM-F3 substratum, although to a lesser extent, implying the possibility of a heterophilic ligand to NCAM-F3 domains on the surface of fibroblasts. Cellular spreading on NCAM-F3 substratum was selectively increased in fibroblasts expressing transmembrane NCAM, and only the NCAM-F3 fusion protein lacking the proline-rich insert was able to elicit this effect. Primary cultures of mouse cerebellum were strongly inhibited with regard to formation of cellular aggregates and fibers, when incubated in the presence of either of the two NCAM-F3 fusion proteins, the fusion protein with the proline-rich insert being the more effective one. Finally, the morphology of growth cones from rat cerebellar granule cells changed significantly when grown on NCAM-F3 substrata as revealed by computer-assisted image analysis. Thus, our data indicate that the NCAM-F3 domains are involved in cell-cell adhesion, and that insertion of the proline-rich sequence has a modulatory effect on NCAM-F3 domain functions.
Hybridization of an immobilized PNA probe with its complementary oligodeoxyribonucleotide on the surface of silica glass (2003)

A 16mer sequence of peptide nucleic acid (PNA) was immobilized onto the surface of silica glass to supply solid supports for DNA chip and biosensor constructions. To the surface, 3-aminopropyltriethoxysilane (APTES), succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxy-(6-amidocaproate) (LC-SMCC), and cysteinyl-PNA were introduced in order. Hybridization of the immobilized PNA with its complementary oligodeoxyribonucleotide (ODN) should be done in a solution containing 15-20% dimethylformamide (DMF) at pH 9.5. This combination of hybridization conditions enabled specific adsorption of the target ODN of at least 50 pM to the surface.
Hahb-10, a Sunflower Homeobox-Leucine Zipper Gene, is Regulated by Light Quality and Quantity, and Promotes Early Flowering when Expressed in Arabidopsis (2005)

Homeodomain-leucine zipper proteins constitute a family of transcription factors found only in plants. Expression patterns of the sunflower homeobox-leucine zipper gene Hahb-10 (Helianthus annuus homeobox-10), that belongs to the HD-Zip II subfamily, were analysed. Northern blots showed that Hahb-10 is expressed primarily in mature leaves, although expression is clearly detectable in younger leaves and also in stems. Considerably higher expression levels were detected in etiolated seedlings compared with light-grown seedlings. Induction of Hahb-10 expression was observed when seedlings were subjected to treatment with gibberellins. Transgenic Arabidopsis thaliana plants that express Hahb-10 under the 35S cauliflower mosaic virus promoter show special phenotypic characteristics such as darker cotyledons and planar leaves. A reduction in the life cycle of about 25% allowing earlier seed collection was also observed, and this phenomenon is clearly related to a shortened flowering time. When the number of plants per pot increased, the difference in developmental rate between transgenic and non-transformed individuals became larger. After gibberellin treatment, the relative difference in life cycle duration was considerably reduced. Several light-regulated genes have been tested as possible target genes of Hahb-10. One of them, PsbS, shows a different response to illumination conditions in transgenic plants compared with the response in wild-type plants while the other genes behave similarly in both genotypes. We propose that Hahb-10 functions in a signalling cascade(s) that control(s) plant responses to light quality and quantity, and may also be involved in gibberellin transduction pathways.
Absence of γ-Interferon–inducible Lysosomal Thiol Reductase in Melanomas Disrupts T Cell Recognition of Select Immunodominant Epitopes (2002)

Long-lasting tumor immunity requires functional mobilization of CD8+ and CD4+ T lymphocytes. CD4+ T cell activation is enhanced by presentation of shed tumor antigens by professional antigen-presenting cells (APCs), coupled with display of similar antigenic epitopes by major histocompatibility complex class II on malignant cells. APCs readily processed and presented several self-antigens, yet T cell responses to these proteins were absent or reduced in the context of class II+ melanomas. T cell recognition of select exogenous and endogenous epitopes was dependent on tumor cell expression of gamma-interferon-inducible lysosomal thiol reductase (GILT). The absence of GILT in melanomas altered antigen processing and the hierarchy of immunodominant epitope presentation. Mass spectral analysis also revealed GILT's ability to reduce cysteinylated epitopes. Such disparities in the profile of antigenic epitopes displayed by tumors and bystander APCs may contribute to tumor cell survival in the face of immunological defenses.
Poor responses to oseltamivir treatment in a patient with influenza A (H7N9) virus infection (2013)

In March 2013, the cases of human infection with influenza A of H7N9 subtype were first reported. Preliminary data suggested that the H7N9 isolates are sensitive to neuraminidase inhibitors, such as oseltamivir, which is the recommended choice of treatment. On April 2(nd), a 56-year-old male patient was presented with fever and cough to our hospital. He had previous history of close contact with another H7N9 patient. After caring for his wife (a confirmed H7N9 infection case died on April 3(rd)), this patient showed flu like symptoms on April 2(nd). On the same day, oseltamivir (75 mg bid) treatment was started. Throat swab specimens were screened for H7N9 virus by real-time reverse transcriptase-polymerase chain reaction. The patient was hospitalized on April 4(th). Initial specimens on April 4(th) and April 5(th) were negative for H7N9. But the specimen collected on April 10(th) was tested positive for H7N9. The result was confirmed by Shanghai Municipal Center of Disease Control and Prevention. By April 25(th) when we submitted this report, swab specimens of this patient were still positive for H7N9. This case calls for increased awareness of potential resistance of H7N9 to oseltamivir.
High-performance hmm adaptation with joint compensation of additive and convolutive distortions via Vector Taylor Series (2007)

In this paper, we present our recent development of a model-domain environment-robust adaptation algorithm, which demonstrates high performance in the standard Aurora 2 speech recognition task. The algorithm consists of two main steps. First, the noise and channel parameters are estimated using a nonlinear environment distortion model in the cepstral domain, the speech recognizer’s “feedback” information, and the Vector-Taylor-Series (VTS) linearization technique collectively. Second, the estimated noise and channel parameters are used to adapt the static and dynamic portions of the HMM means and variances. This two-step algorithm enables Joint compensation of both Additive and Convolutive distortions (JAC). In the experimental evaluation using the standard Aurora 2 task, the proposed JAC/VTS algorithm achieves 91.11% accuracy using the clean-trained simple HMM backend as the baseline system for the model adaptation. This represents high recognition performance on this task without discriminative training of the HMM system. Detailed analysis on the experimental results shows that adaptation of the dynamic portion of the HMM mean and variance parameters is critical to the success of our algorithm.