bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of the pharmacokinetics, safety and tolerability of two concentrations of a new liquid recombinant human growth hormone formulation versus the freeze-dried formulation
Authors: Liedert Bernd , Forssmann Ulf , Wolna Peter , Golob Michaela , Kovar Andreas 
Published: October 2010

Abstract

Background
Somatropin is recombinant human growth hormone (GH) used for the treatment of growth failure in children and GH deficiency in adults. Two concentrations of a liquid formulation have been developed: 5.83 and 8.0 mg/mL. This trial compared the pharmacokinetics (PK), safety and tolerability of these two liquid concentrations against the freeze-dried (FD) formulation in healthy volunteers.

Methods
In an open-label, single-centre, three-way crossover study, volunteers (aged 18-45 years) were given subcutaneous injections of the reconstituted FD and two liquid formulations in random sequential order, each at 4 mg/dose, with a 1-week wash-out period between doses. To suppress endogenous GH secretion, intravenous somatostatin was infused continuously 1 hour before to 24 hours after each dose, achieving a cumulative dose of 3 mg. Primary PK endpoints were area under the serum concentration-time curve (AUC0-t) and maximum serum concentration (Cmax). For each of the two liquid formulations, bioequivalence with the FD formulation was concluded if the 95% confidence intervals (CIs) for the estimated test/reference ratios of geometric means of AUC0-t and Cmax were within the standard pre-specified acceptance range (0.80-1.25).

Results
Fifteen men and 15 women enrolled (safety population, n = 30; PK population, n = 28). Bioequivalence with the FD formulation could be shown for both liquid formulations. The ratios of geometric means (95% CI) were 1.046 (0.980, 1.117) and 0.991 (0.929, 1.058) for AUC0-t and 0.954 (0.875, 1.040) and 0.955 (0.876, 1.041) for Cmax for the 5.83 and 8.0 mg/mL formulations, respectively. No significant differences between the three treatments in half-lives, time to reach Cmax, clearance or volume of distribution were observed. After injection, the most common side-effects were pain or injection-site reactions (all of mild intensity). There were no clinically significant abnormal vital signs, ECG or laboratory findings. There were 56 treatment-related adverse events (AEs): 49 mild, 6 moderate and 1 severe (vomiting). No serious AEs occurred. The pattern of AEs was as expected and all resolved by study end.

Conclusion
Both concentrations of a new liquid multi-dose formulation are bioequivalent to the FD reference formulation and all are well tolerated.

Trial registration number
NCT01034735.
Ecmo-assisted carinal resection and reconstruction after left pneumonectomy
Authors: Lei Jie , Su Kai , Li Xiao F , Zhou Yong A , Han Yong , Huang Li J , Wang Xiao P 
Published: October 2010

Abstract
Extracorporeal Membrane Oxygenation (ECMO) has become an increasingly important technique for patients with respiratory or cardiac failure for a variety of causes. In addition, there are many reports about the use of ECMO in surgical operation on neonates and children patients with tracheal obstruction. In this report we present a case about an adult patient who underwent a carinal resection and reconstruction after left pneumonectomy with ECMO assistance successfully. To our knowledge, this case is the first of its kind to use ECMO in adult carinal resection and reconstruction after pneumonectomy. In this report, we try to illustrate that ECMO is effective in operations of this kind.
Zebrafish model of tuberous sclerosis complex reveals cell-autonomous and non-cell-autonomous functions of mutant tuberin
Authors: Kim Seok-Hyung , Speirs Christina K. , Solnica-Krezel Lilianna , Ess Kevin C. 
Published: October 2010

SUMMARYTuberous sclerosis complex (TSC) is an autosomal dominant disease caused by mutations in either the TSC1 (encodes hamartin) or TSC2 (encodes tuberin) genes. Patients with TSC have hamartomas in various organs throughout the whole body, most notably in the brain, skin, eye, heart, kidney and lung. To study the development of hamartomas, we generated a zebrafish model of TSC featuring a nonsense mutation (vu242) in the tsc2 gene. This tsc2vu242 allele encodes a truncated Tuberin protein lacking the GAP domain, which is required for inhibition of Rheb and of the TOR kinase within TORC1. We show that tsc2vu242 is a recessive larval-lethal mutation that causes increased cell size in the brain and liver. Greatly elevated TORC1 signaling is observed in tsc2vu242/vu242 homozygous zebrafish, and is moderately increased in tsc2vu242/+ heterozygotes. Forebrain neurons are poorly organized in tsc2vu242/vu242 homozygous mutants, which have extensive gray and white matter disorganization and ectopically positioned cells. Genetic mosaic analyses demonstrate that tsc2 limits TORC1 signaling in a cell-autonomous manner. However, in chimeric animals, tsc2vu242/vu242 mutant cells also mislocalize wild-type host cells in the forebrain in a non-cell-autonomous manner. These results demonstrate a highly conserved role of tsc2 in zebrafish and establish a new animal model for studies of TSC. The finding of a non-cell-autonomous function of mutant cells might help explain the formation of brain hamartomas and cortical malformations in human TSC.
pH-dependent localization of Btn1p in the yeast model for Batten disease
Authors: Wolfe Devin M. , Padilla-Lopez Sergio , Vitiello Seasson Phillips , Pearce David A. 
Published: October 2010

SUMMARY
Btn1p the yeast homolog of human CLN3, which is associated with juvenile Batten disease has been implicated in several cellular pathways. Yeast cells lacking BTN1 are unable to couple ATP hydrolysis and proton pumping activities by the vacuolar ATPase (V-ATPase). In this work, we demonstrate that changes in extracellular pH result in altered transcription of BTN1, as well as a change in the glycosylation state and localization of Btn1p. At high pH, Btn1p expression was increased and the protein was mainly located in vacuolar membranes. However, low pH decreased Btn1p expression and changed its location to undefined punctate membranes. Moreover, our results suggest that differential Btn1p localization may be regulated by its glycosylation state. Underlying pathogenic implications for Batten disease of altered cellular distribution of CLN3 are discussed.
Label-free Rapid Semiquantitative Detection of Proteins Down to Sub-monolayer Coverage by Using Surface-enhanced Raman Scattering of Nitrate Ion
Authors: Zhou Zhen , Huang Genin Gary , Ozaki Yukihiro 
Published: October 2010

Abstract
A novel heat-induced SERS method was used to selectively enhance a band of NO3− at 1049 cm−1 for semi-quantitative detection of lysozyme and insulin down to 10−9 and 10−8 M, respectively, and bell shape variations of SERS intensities were observed for the concentration dependency of the proteins.
Acetylated Cyclodextrins as New Organogelators
Authors: Kida Toshiyuki , Kishimoto Koichiro , Hatano Koji , Muraoka Masahiro , Nakatsuji Yohji , Akashi Mitsuru 
Published: October 2010

Abstract
Acetylated cyclodextrins (CDs), including peracetylated α- and β-CDs as well as 2,3-O-diacetylated α- and β-CDs, were found to function as organogelators for organic solvents such as benzene, toluene, and xylenes at ambient temperature. Their organogelation capability was strongly affected by both the CD ring size and the degree of acetylation. Peracetylated α-CD showed the highest organogelation capability among these acetylated CDs, possibly due to the effective construction of three-dimensional networks by the pillar-like assemblies in the organic solvents.
Invasive Spindle Cell Thymomas (WHO Type A)
Authors: Moran Cesar A. , Kalhor Neda , Suster Saul 
Published: October 2010

Abstract
We report 41 cases of invasive spindle cell thymomas (World Health Organization type A). The patients were 16 women and 25 men between the ages of 38 and 80 years. Clinically, the patients had diverse symptomatology, including chest pain, cough, and dyspnea. None of the patients had a history of myasthenia gravis. According to the Mazaoka surgical staging system, 34 patients had stage II disease, 6 had stage III, and 1 had stage IV. Follow-up information showed that 30 patients were alive after a period ranging from 12 to 96 months; for 8 patients who are alive, the follow-up was less than 12 months; 1 patient died 10 months after initial diagnosis. For 2 patients, no follow-up information was obtained. This study stresses the fact that histologic features do not correlate with invasion or encapsulation because all thymomas, regardless of their histologic type, are capable of invasion.
Oral and Extraoral Plasmablastic Lymphoma
Authors: Hansra Damien , Montague Naomi , Stefanovic Alexandra , Akunyili Ikechukwu , Harzand Arash , Natkunam Yasodha , de la Ossa Margarita , Byrne Gerald E. , Lossos Izidore S. 
Published: October 2010

Abstract
Plasmablastic lymphoma (PBL), initially characterized as an aggressive lymphoma arising in the jaw and oral mucosa in HIV-infected patients, was recently reported to occur with extraoral manifestations, heterogeneous histologic findings, and variable association with immunodeficiency states. We reviewed clinical, morphologic, and immunophenotypic features of 13 cases of PBL to determine whether these different subtypes represent distinct morphologic and clinical entities. Two distinct subtypes of PBL were identified and classified as oral and extraoral PBL. The oral PBLs were strongly associated with HIV infection and commonly demonstrated plasmablastic morphologic features without plasmacytic differentiation. Extraoral PBLs tended to occur in patients with underlying non–HIV-related immunosuppression and universally demonstrated plasmacytic differentiation. The patients with oral PBL demonstrated better overall survival compared with patients with extraoral PBL (P = .02). Our findings suggest that PBL with oral and extraoral manifestation represent 2 distinct clinicopathologic entities.
Nighttime and Weekend Medication Error Rates in an Inpatient Pediatric Population
Authors: Miller April D , Piro Christina C , Rudisill Celeste N , Bookstaver P Brandon , Bair Jennifer D , Bennett Charles L 
Published: October 2010

Background: Nighttime and weekend admission has been associated with increased morbidity and mortality and has been linked to a variety of factors. Medication errors in hospitalized patients occur frequently, but the association between error rates and time of day and day of week (weekday vs weekend) has not been extensively studied. Objective: To compare reported medication error rates over a 1-year period between daytime versus nighttime shifts and weekday versus weekend in a children's hospital and to characterize the types of errors that occurred. Methods: One hundred forty errors reported between January and December 2008 were retrospectively reviewed and classified by error type and severity according to established standards. Two investigators independently classified errors, and a third investigator with pediatric pharmacy expertise resolved discrepancies. Data on doses dispensed were collected from pharmacy records. Results: Over the study period, the reported error rate during daytime nursing shifts was 1.17 errors per 1000 doses dispensed versus 2.12 errors per 1000 doses dispensed for nighttime nursing shifts (p = 0.005). The error rates during pharmacy shifts (1st, 2nd, and 3rd) were 1.01, 2.24, and 1.88 per 1000 doses dispensed, respectively (p = 0.0019). Reported errors for weekday versus weekend were 1.9 errors per 1000 weekday doses versus 2.55 errors per 1000 doses, respectively (p = 0.181), and error rate for weekend shifts relative to first shift on weekdays was greater (p = 0.0004). Errors in medication administration, followed by dispensing errors, occurred most frequently. Conclusions: There was an increase in medication error rate during evening and nighttime shifts relative to day shift and during weekends relative to weekdays at this institution. Additional studies to validate this finding are needed; however, error prevention efforts should be instituted now for evening, nighttime, and weekend medication dispensing and administration.
Grading the Severity of Drug-Drug Interactions in the Intensive Care Unit: A Comparison Between Clinician Assessment and Proprietary Database Severity Rankings
Authors: Smithburger Pamela L , Gill Sandra L Kane , Benedict Neal J , Falcione Bonnie A , Seybert Amy L 
Published: October 2010

Background: Computerized provider order entry with decision support software offers an opportunity to identify and prevent medication-related errors, including drug-drug interactions (DDIs), through alerting mechanisms. However, the number of alerts generated can overwhelm and lead to “alert fatigue.” A DDI alert system based on severity rankings has been shown to reduce alert fatigue; however, the best method to populate this type of database is unclear. Objective: To compare the severity ranking of proprietary databases to clinician assessment for DDIs occurring in critically ill patients. Methods: This observational, prospective study was conducted over 8 weeks in the cardiac and cardiothoracic intensive care unit. Medication profiles of patients were screened for the presence of DDIs and a severity evaluation was conducted using rankings of proprietary databases and clinician opinion using a DDI severity assessment tool. The primary outcome measure was the number of DDIs considered severe by both evaluation methods. Results: A total of 1150 DDIs were identified after 400 patient medication profiles were evaluated. Of these, 458 were unique drug pairs. Overall, 7.4% (34/458) were considered a severe interaction based upon proprietary database ratings. The assessment by clinicians ranked 6.6% (30/458) of the unique DDIs as severe. Only 3 interactions, atazanavir–simvastatin, atazanavir–tenofovir, and aspirin–warfarin, were considered severe by both evaluation methods. Conclusions: Since proprietary databases and clinician assessment of severe DDIs do not agree, developing a knowledge base for a DDI alert system likely requires proprietary database information in conjunction with clinical opinion.
Determination of daptomycin in human plasma by liquid chromatography-tandem mass spectrometry. Clinical application
Authors: Verdier Marie-Clémence , Bentué-Ferrer Danièle , Tribut Olivier , Collet Nicolas , Revest Matthieu , Bellissant Eric 
Published: October 2010

Abstract

Background: Daptomycin is a recently developed cyclic lipopeptide antibiotic active against most Gram-positive pathogens including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. To optimize treatment efficacy and safety, especially in patients undergoing multiple drug regimens and/or co-morbidities, a specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the quantification of daptomycin in plasma.

Methods: A C18 column was used for separation, with a mobile phase initially consisting of 0.1% formic acid, water, and acetonitrile (ACN) in a linear gradient from 20% to 70%. After protein precipitation with ACN, the clear upper layer was diluted in water:ACN (50:50, v/v) before injection. Detection was performed using an electrospray ionization technique. MS/MS transitions, monitored in the positive ion mode were m/z 811.1 → m/z 313.1 for daptomycin, and m/z 609.4 → m/z 194.9 for reserpine, used as internal standard.

Results: Elution of daptomycin and reserpine occurred at 4.5 and 3.9 min, respectively. The method was validated over a range of concentrations from 1 mg/L to 120 mg/L. The assay met recommended acceptance criteria: coefficients of variation were <6.3% and <7.4%, and accuracies were between –5.9% and +11.2% and between –3.5% and +3.7%, for intra- and inter-day validations, respectively.

Conclusions: This method appears well-adapted to routine hospital practice for therapeutic drug monitoring of daptomycin considering its time of analysis, range of concentrations measured, precision and accuracy.
Age- and gender-dependent changes in circulating concentrations of tumor necrosis factor-α, soluble tumor necrosis factor receptor-1 and sulfated glycosaminoglycan in healthy people
Authors: Komosinska-Vassev Katarzyna , Olczyk Pawel , Winsz-Szczotka Katarzyna , Klimek Katarzyna , Olczyk Krystyna 
Published: October 2010

Abstract

Background: In this study, the effect of gender and physio-logical ageing on circulating concentrations of plasma sulfated glycosaminoglycans (sGAG) as well as molecules involved in pro- (tumor necrosis factor-α; TNF-α) and anti-inflammatory responses (soluble tumor necrosis factor receptor-1, sTNF-RI) were assessed. The relationships between sGAG and molecules involved in age-dependent extracellular matrix (ECM) remodeling during physiological ageing were also investigated.

Methods: Circulating TNF-α and sTNF-RI were measured in 91 healthy volunteers using enzyme-linked immunosorbent assays. sGAG were quantified using an Alcian blue-binding assay.

Results: A linear age-related decline in plasma sGAG was found during the first five decades of life (r=–0.61, p<0.05), followed by an increase occurring only in females (r=0.46, p<0.05). Circulating TNF-α concentrations were inversely correlated with age (r=–0.24, p<0.05) over the lifetime. For TNF-α, the observed changes were gender specific. Serum sTNF-RI concentrations were not affected by age in either men or women. A significant positive correlation was found between the concentrations of TNF-α and both sGAG (r=0.22, p<0.05) and sTNF-RI (r=0.21, p<0.05).

Conclusions: Our data demonstrate that physiological ageing is associated with ECM remodeling, reflected by plasma sGAGs concentrations. Changes in the ECM metabolism during the ageing process were influenced by circulating TNF-α. Furthermore, serum concentrations of biomolecules involved in pro- and anti-inflammatory responses are not increased in healthy elderly subjects.
Development of a fluorescent microsphere immunoassay for cystatin B (CSTB) in serum of patients with hepatocellular carcinoma
Authors: Ji Na Young , Kang Yun Hee , Park Mi-Young , Lee Chung Il , Kim Mi Kyung , Kim Dae Ghon , Kim Jong Wan , Song Eun Young 
Published: October 2010

Abstract

Background: Serum cystatin B (CSTB) concentrations have been reported to be increased in patients with hepatocellular carcinoma compared to concentrations seen in normal subjects. In this study, we developed a “fluorescent microsphere immunoassay” (FMI) capable of specifically detecting CSTB in serum.

Methods: The FMI used a microparticle conjugated polyclonal antibody to CSTB and biotinylated monoclonal antibody as capture protein and probe protein, respectively. The results were obtained using the Bio-Plex200 system.

Results: The dose-response relationship between CSTB and fluorescent intensity showed linearity in the range 0–1000 pg/mL and 7 pg/mL, sensitivity lower than 11.2 pg/mL. This result revealed that the FMI system was more sensitive than enzyme-linked immunoassay (ELISA). Additionally, the FMI system used smaller sample volumes compared to ELISA.

Conclusions: We measured CSTB with both the FMI and an ELISA procedure and compared the two methods. The CSTB concentrations in serum specimens as measured with the FMI assay system were similar to those measured with ELISA. Thus, the new FMI using the Bio-Plex system may be useful for detection of CSTB in human serum.
Prevalence and course of pseudothrombocytopenia in outpatients
Authors: Froom Paul , Barak Mira 
Published: October 2010

Abstract

Background: The prevalence and course of pseudothrombocytopenia in outpatients is uncertain.

Methods: In a cohort study of 687,955 members of a health maintenance organization, we extracted 36,780 consecutive automated complete blood count test results and determined the point prevalence of pseudothrombocytopenia during a one-month period. We also calculated a retrospective cumulative prevalence over the past 5 years.

Results: There were 1105 (2.7%) patients with platelet counts of 100–149×109/L and 304 (0.8%) with counts <100×109/L, of whom 12.8% (n=39) had pseudothrombocytopenia newly discovered or in the past. There were 40 additional patients with a history of pseudothrombocytopenia, but now showing platelet counts of 150×109/L or more, and another 21 with platelet counts of 100–149×109/L. The total cumulative prevalence of pseudothrombocytopenia was 0.27% (100/36,780), 2.5-fold higher than the point prevalence of 0.11% (39/36,780). Platelet counts were extremely variable in these patients during the 5-year follow-up period.

Conclusions: Physicians should be aware of the variability of platelet counts in patients with pseudothrombocytopenia in order to reduce unnecessary retesting. Since pseudothrombocytopenia can result in platelet counts between 100 and 149×109/L, peripheral smears should be done in all patients with such values, or the reference limit value should be lowered to 100×109/L.
On the inversion formulas of Pestov and Uhlmann for the geodesic ray transform
Authors: Krishnan Venkateswaran P. 
Published: October 2010

Abstract
We generalize the inversion formulas obtained by Pestov–Uhlmann for the geodesic ray transform of functions and vector fields on 2-dimensional manifolds with boundary of constant curvature. Our formulas hold for simple 2-dimensional manifolds whose curvatures are close to a constant.
Mit Kopf, Körper und Hand: Herausforderungen Humanoider Roboter
Authors: Ritter Helge , Steil Jochen J. , Sagerer Gerhard 
Published: October 2010

Zusammenfassung
Humanoide Roboter stellen uns vor die Herausforderung, komplexe Embodiment-Funktionen zu beherrschen: Koordination von Ganzkörperbewegungen, Benutzung anthropomorpher Hände und Steuerung ausdrucksfähiger Gesichtsgestik. Wir stellen einige Beiträge und Forschungslinien des Bielefelder CoR-Lab und des Exzellenzclusters CITEC zu diesen Themenfeldern vor und beleuchten einige disziplinübergreifende Bezüge zur Erforschung kognitiver Systeme.
Invariants and Bonnet-type theorem for surfaces in ℝ4
Authors: Ganchev Georgi , Milousheva Velichka 
Published: October 2010

Abstract
In the tangent plane at any point of a surface in the four-dimensional Euclidean space we consider an invariant linear map ofWeingarten-type and find a geometrically determined moving frame field. Writing derivative formulas of Frenet-type for this frame field, we obtain eight invariant functions. We prove a fundamental theorem of Bonnet-type, stating that these eight invariants under some natural conditions determine the surface up to a motion. We show that the basic geometric classes of surfaces in the four-dimensional Euclidean space, determined by conditions on their invariants, can be interpreted in terms of the properties of two geometric figures: the tangent indicatrix, which is a conic in the tangent plane, and the normal curvature ellipse. We construct a family of surfaces with flat normal connection.
Ideals which generalize (v
0)
Authors: Kalemba Piotr , Plewik Szymon 
Published: October 2010

Abstract
Countable products of finite discrete spaces with more than one point and ideals generated by Marczewski-Burstin bases (assigned to trimmed trees) are examined, using machinery of base tree in the sense of B. Balcar and P. Simon. Applying Kulpa-Szymanski Theorem, we prove that the covering number equals to the additivity or the additivity plus for each of the ideals considered.