bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biologic Cost of Caring for a Cancer Patient: Dysregulation of Pro- and Anti-Inflammatory Signaling Pathways
Authors: Rohleder Nicolas , Marin Teresa J. , Ma Roy , Miller Gregory E. 
Published: May 2009

Purpose Caring for a family member with cancer is a psychologically demanding experience. However, it remains unclear whether the distress that caregiving provokes also takes a physiologic toll on the body. This study observed familial caregivers of patients with brain cancer for a year after diagnosis and tracked changes in neurohormonal and inflammatory processes. Patients and Methods Eighteen caregivers (age 50.4 ± 3.5 years) and 19 controls (age 50.2 ± 2.6 years) were assessed four times during a year (before and after radiotherapy, as well as 6 weeks and 4 months thereafter). Salivary biomarkers of hypothalamus-pituitary-adrenal axis and sympathetic nervous system (SNS) activity were collected, and blood was drawn for assessment of the systemic inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6). Blood was also used to monitor in vitro IL-6 production by endotoxin-stimulated leukocytes and expression of mRNA for pro- and anti-inflammatory signaling molecules. Results Caregivers showed marked changes over time in diurnal output of salivary amylase, a marker of SNS activity, whereas secretions in controls were stable during follow-up. Cortisol output was similar in caregivers and controls. During the year, caregivers showed a profound linear increase in systemic inflammation, as indexed by CRP. At the same time, they displayed a linear decline in mRNA for anti-inflammatory signaling molecules and diminished in vitro glucocorticoid sensitivity. Conclusion These preliminary data show that familial caregivers of patients with cancer experience marked changes in neurohormonal and inflammatory processes in the year after diagnosis. These changes may place them at risk for morbidity and mortality from diseases fostered by excessive inflammation.
Cognitive Deficits and Predictors 3 Years After Diagnosis of a Pilocytic Astrocytoma in Childhood
Authors: Aarsen Femke K. , Paquier Philippe F. , Arts Willem-Frans , Van Veelen Marie-Lise , Michiels Erna , Lequin Maarten , Catsman-Berrevoets Coriene E. 
Published: May 2009

Purpose To prospectively study cognitive deficits and predictors 3 years after diagnosis in a large series of pediatric patients treated for pilocytic astrocytoma (PA). Patients and Methods Sixty-one of 67 children were grouped according to infratentorial, supratentorial midline, and supratentorial hemispheric site. Intelligence, memory, attention, language, visual-spatial, and executive functions were assessed. Included predictors were sex, age, relapse, diagnosis-assessment interval, hydrocephalus, kind of treatment, and tumor variables. Results All children with PA had problems with sustained attention and speed. In the infratentorial group, there also were deficits in verbal intelligence, visual-spatial memory, executive functioning, and naming. Verbal intelligence and verbal memory problems occurred in the brainstem tumor group. The supratentorial hemispheric tumor group had additional problems with selective attention and executive functioning, and the supratentorial midline tumor group displayed no extra impairments. More specifically, the dorsal supratentorial midline tumor group displayed problems with language and verbal memory. Predictors for lower cognitive functioning were hydrocephalus, radiotherapy, residual tumor size, and age; predictors for better functioning were chemotherapy or treatment of hydrocephalus. Almost 60% of children had problems with academic achievement, for which risk factors were relapse and younger age at diagnosis. Conclusion Despite normal intelligence at long-term follow-up, children treated for PA display invalidating cognitive impairments. Adequate treatment of hydrocephalus is important for a more favorable long-term cognitive outcome. Even children without initial severe deficits may develop cognitive impairments years after diagnosis, partly because of the phenomenon of growing into deficit, which has devastating implications for academic achievement and quality of life (QOL).
Adjuvant Therapy With Pegylated Interferon Alfa-2b Versus Observation in Resected Stage III Melanoma: A Phase III Randomized Controlled Trial of Health-Related Quality of Life and Symptoms by the European Organisation for Research and Treatment of Cancer Melanoma Group
Authors: Bottomley Andrew , Coens Corneel , Suciu Stefan , Santinami Mario , Kruit Willem , Testori Alessandro , Marsden Jeremy , Punt Cornelis , Salès François , Gore Martin , MacKie Rona , Kusic Zvonko , Dummer Reinhard , Patel Poulam , Schadendorf Dirk , Spatz Alain , Keilholz Ulrich , Eggermont Alexander 
Published: May 2009

Purpose Interferon (IFN) -based adjuvant therapy in melanoma is associated with significant side effects, which necessitates evaluation of health-related quality of life (HRQOL). Our trial examined the HRQOL effects of adjuvant pegylated IFN-α-2b (PEG-IFN-α-2b) versus observation in patients with stage III melanoma. Methods A total of 1,256 patients with stage III melanoma were randomly assigned after full lymphadenectomy to receive either observation (n = 629) or PEG-IFN-α-2b (n = 627): induction 6 μg/kg/wk for 8 weeks then maintenance 3 μg/kg/wk for an intended total duration of 5 years. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 was used to assess HRQOL. Results At 3.8 years of median follow-up, for the primary end point, recurrence-free survival (RFS), risk was reduced by 18% (hazard rate = 0.82; P = .01) in the PEG-IFN-α-2b arm compared with observation. Significant and clinically meaningful differences occurred with the PEG-IFN-α-2b treatment arm compared with the observation group, showing decreased global HRQOL at month 3 (−11.6 points; 99% CI, −8.2 to −15.0) and year 2 (−10.5 points; 99% CI, −6.6 to −14.4). Many of the other scales showed statistically significant differences between scores when comparing the two arms. From a clinical point of view, important differences were found for five scales: two functioning scales (social and role functioning) and three symptom scales (appetite loss, fatigue, and dyspnea), with the PEG-IFN-α-2b arm being most impaired. Conclusion PEG-IFN-α-2b leads to a significant and sustained improvement in RFS. There is an expected negative effect on global HRQOL and selected symptoms when patients undergo PEG-IFN-α-2b treatment.
Phase III Study by the Norwegian Lung Cancer Study Group: Pemetrexed Plus Carboplatin Compared With Gemcitabine Plus Carboplatin As First-Line Chemotherapy in Advanced Non–Small-Cell Lung Cancer
Authors: Grønberg Bjørn H. , Bremnes Roy M. , Fløtten Øystein , Amundsen Tore , Brunsvig Paal Fr. , Hjelde Harald H. , Kaasa Stein , von Plessen Christian , Stornes Frøydis , Tollåli Terje , Wammer Finn , Aasebø Ulf , Sundstrøm Stein 
Published: May 2009

Purpose To compare pemetrexed/carboplatin with a standard regimen as first-line therapy in advanced non–small-cell lung cancer NSCLC. Patients and Methods Patients with stage IIIB or IV NSCLC and performance status of 0 to 2 were randomly assigned to receive pemetrexed 500 mg/m2 plus carboplatin area under the curve (AUC) = 5 (Calvert's formula) on day 1 or gemcitabine 1,000 mg/m2 on days 1 and 8 plus carboplatin AUC = 5 on day 1 every 3 weeks for up to four cycles. The primary end point was health-related quality of life (HRQoL) defined as global quality of life, nausea/vomiting, dyspnea, and fatigue reported on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and the lung cancer–specific module LC13 during the first 20 weeks. Secondary end points were overall survival and toxicity. Results Four hundred thirty-six eligible patients were enrolled from April 2005 to July 2006. Patients who completed the baseline questionnaire were analyzed for HRQoL (n = 427), and those who received ≥ one cycle of chemotherapy were analyzed for toxicity (n = 423). Compliance of HRQoL questionnaires was 87%. There were no significant differences for the primary HRQoL end points or in overall survival between the two treatment arms (pemetrexed/carboplatin, 7.3 months; gemcitabine/carboplatin, 7.0 months; P = .63). The patients who received gemcitabine/carboplatin had more grade 3 to 4 hematologic toxicity than patients who received pemetrexed/carboplatin, including leukopenia (46% v 23%, respectively; P < .001), neutropenia (51% v 40%, respectively; P = .024), and thrombocytopenia (56% v 24%, respectively; P < .001). More patients on the gemcitabine/carboplatin arm received transfusions of RBCs and platelets, whereas the frequencies of neutropenic infections and thrombocytopenic bleedings were similar on both arms. Conclusion Pemetrexed/carboplatin provides similar HRQoL and survival when compared with gemcitabine/carboplatin with less hematologic toxicity and less need for supportive care.
Prospective Randomized Multicenter Adjuvant Dermatologic Cooperative Oncology Group Trial of Low-Dose Interferon Alfa-2b With or Without a Modified High-Dose Interferon Alfa-2b Induction Phase in Patients With Lymph Node–Negative Melanoma
Authors: Hauschild Axel , Weichenthal Michael , Rass Knuth , Linse Ruthild , Ulrich Jens , Stadler Rudolf , Volkenandt Matthias , Grabbe Stephan , Proske Ulrike , Schadendorf Dirk , Brockmeyer Norbert , Vogt Thomas , Rompel Rainer , Kaufmann Roland , Kaatz Martin , Näher Helmut , Mohr Peter , Eigentler Thomas , Livingstone Elisabeth , Garbe Claus 
Published: May 2009

Purpose Interferon alfa (IFN-α) has shown clinical efficacy in the adjuvant treatment of patients with high-risk melanoma in several clinical trials, but optimal dosing and duration of treatment are still under discussion. It has been argued that in high-dose IFN-α (HDI), the intravenous (IV) induction phase might be critical for the clinical benefit of the regimen. Patients and Methods In an attempt to investigate the potential role of a modified high-dose induction phase, lymph node–negative patients with resected primary malignant melanoma of more than 1.5-mm tumor thickness were included in this prospective randomized multicenter Dermatologic Cooperative Oncology Group trial. Six hundred seventy-four patients were randomly assigned to receive 4 weeks of a modified HDI scheme. This schedule consisted of 5 times weekly 10 MU/m2 IFN-α-2b IV for 2 weeks and 5 times weekly 10 MU/m2 IFN-α-2b administered subcutaneously (SC) for another 2 weeks followed by 23 months of low-dose IFN-α-2b (LDI) 3 MU SC three times a week (arm A). LDI 3 MU three times a week was given for 24 months in arm B. Results Of 650 assessable patients, there were 92 relapses among the 321 patients receiving high-dose induction as compared with 95 relapses among the 329 patients receiving LDI only. Five-year relapse-free survival rates were 68.0% (arm A) and 67.1% (arm B), respectively. Likewise, melanoma-related fatalities were similar between both groups, resulting in 5-year overall survival rates of 80.2% (arm A) and 82.9% (arm B). Conclusion The addition of a 4-week modified HDI induction phase to a 2-year low-dose adjuvant IFN-α-2b treatment schedule did not improve the clinical outcome.
Dinogunellins A-D: Putative ichthyootoxic phospholipids of northern blenny Stichaeus grigorjewi eggs
Authors: Matsunaga Shigeki , Takahashi Nobutaka , Fusetani Nobuhiro 
Published: May 2009

Abstract
Dinogunellins A-D, ichthyootoxic phospholipids, have been isolated from the mature eggs of the northern blenny Stichaeus grigorjewi. Their structures were determined based on spectral and chemical methods as a mixture of 2’- or 3’-acylated adenosine 5’-phosphate linked to the α-carboxyl group of L-asparagine through a P-N bond.
Recent developments in EU competition law (2006–2008): Single-firm dominance and the interpretation of Article 82
Authors: Schweitzer Heike 
Published: May 2009

Abstract
In December 2008, the Commission published a ‘Guidance on the Commission's Enforcement Priorities in Applying Article 82 EC Treaty to Abusive Exclusionary Conduct by Dominant Undertakings’. The communication appears to conclude a debate on a ‘more economic approach’ towards Article 82 which has occupied the competition law community for the last three years. This article reviews the proposals contained in the ‘Priorities Paper’ in the light of the important judgments on the abuse of single-firm dominance which the CFI and the ECJ have issued between 2006 and 2008, including the Microsoft judgment. It strives to ascertain the current state of the law on Article 82, and the room it leaves for a ‘more economic approach’.
Hyperinsulinismus bei Säuglingen und Kindern: wenn ein Insulinspiegel nicht immer ausreicht / Hyperinsulinism in infancy and childhood: when an insulin level is not always enough1)
Authors: Palladino Andrew A. , Bennett Michael J. , Stanley Charles A. 
Published: May 2009

ZusammenfassungHypoglykämie bei Säuglingen und Kindern kann zu Krampfanfällen, Entwicklungsverzögerungen und anhaltenden Hirnschäden führen. Häufigste Ursache sowohl transienter als auch permanenter Hypoglykämien ist ein Hyperinsulinismus (HI). Der HI ist durch eine fehlregulierte Insulinsekretion gekennzeichnet, die zu einer persistierenden milden bis schweren Hypoglykämie führt. Die verschiedenen Formen des HI stellen eine Gruppe klinisch, genetisch und morphologisch heterogener Erkrankungen dar.Kongenitaler Hyperinsulinismus steht mit Mutationen der Gene für SUR-1 und Kir6.2, Glukokinase, Glutamatdehydrogenase, kurzkettige 3-Hydroyacyl-CoA-Dehydrogenase sowie mit einer ektopischen Expression vonSLC16A1auf der Plasmamembran der β-Zelle im Zusammenhang. Ein Hyperinsulinismus kann mit perinatalem Stress, wie Geburtsasphyxie, mütterlicher Toxinämie, Frühgeburtlichkeit oder einer intrauterinen Wachstumsretardierung assoziiert sein, was zu einer prolongierten anhaltenden neonatalen Hypoglykämie führt. Zu den Mimikris eines Hyperinsulinismus gehören neonataler Panhypopituitarismus, medikamenteninduzierte Hypoglykämie, ein Insulinom, Anti-Insulin- und Insulin-Rezeptor-stimulierende Antikörper, das Beckwith-Wiedemann-Syndrom sowie angeborene Erkrankungen der Glykosylierung. Laboratoriumsuntersuchungen bei einem Hyperinsulinismus umfassen die Bestimmung des Blutzuckers, der Konzentrationen von Insulin, β-Hydroxybutyrat, Fettsäuren, Ammoniak und des Acylcarnitin-Profils im Plasma sowie die Untersuchung auf organische Säuren im Urin. Über Speziallaboratorien stehen genetische Untersuchungen der bekannten, mit Hyperinsulinismus assoziierten Gene zur Verfügung. Bestimmungen der akuten Insulinantwort (AIR) sind nützlich für eine phänotypische Charakterisierung. Bildgebende Verfahren und histologische Methoden stehen für eine Diagnose und Klassifizierung des Hyperinsulinismus ebenfalls zur Verfügung. Das Ziel der Behandlung bei Säuglingen mit Hyperinsulinismus ist die Prävention von hypoglykämiebedingten Hirnschäden durch Aufrechterhaltung eines Blutzuckerspiegels von über 700 mg/L (70 mg/dL) mit einer medikamentösen oder operativen Therapie.Das Management des Hyperinsulinismus erfordert einen multidisziplinären Ansatz, an dem pädiatrische Endokrinologen, Radiologen, Chirurgen und Pathologen, beteiligt werden sollten, die mit der Diagnosestellung, Klassifizierung und Behandlung eines Hyperinsulinismus vertraut sind.
Multiparametrische Diagnostik in der Pathologie / Multiparametric diagnostic methods in pathology
Authors: Cullen Paul , Funke Harald , Klein Hanns-Georg , Langmann Thomas , Miethke Thomas , Neumaier Michael , Sauter Guido 
Published: May 2009

Zusammenfassung
Die Arbeitsgruppen Chipdiagnostik und Bioinformatik der DGKL haben sich bei ihrer Jahrestagung 2008 mit Anwendungen der arraybasierten Technologie in der Pathologie beschäftigt. Hauptthemen waren neue Entwicklungen auf dem Feld der Gewebematrices oder Multigewebeblöcken (engl. tissue arrays), Anwendungen der multiparametrischen Analytik in der epigenetischen Regulation der Genaktivität, sowie die arraybasierte vergleichende genomische Hybridisierungstechnologie (engl. array comparative genomic hybridization oder Array-CGH). Diese Methoden finden bereits heute besonders in der Charakterisierung von Tumorzellen und -gewebe einen breiten Einsatz und haben die Krebsdiagnostik erheblich vorangebracht. Eine wichtiges Ergebnis der Tagung war die Erkenntnis, dass bei der hochparallelen Analytik die technischen Möglichkeiten der klinischen Anwendung voraus sind. Deshalb besteht ein erheblicher Bedarf vor allem an begleitender klinischer Forschung, um die Anwendbarkeit und die Bedeutung dieser Diagnostik zu präzisieren.
Changes in Fluid Penetrability and Mechanical Properties of Concrete due to High Temperature Exposure
Authors: Recalde Juan José , Leming Michael L. 
Published: May 2009

Abstract
This paper examines the relationship between changes in mechanical properties and fluid penetrability of a conventional and a high strength concrete mixture resulting from exposure to temperatures of 150°C, 300°C, or both, using a unique experimental technique. Measurements were taken before and after exposure on 100 mm diameter disks, approximately 25 mm thick. The dynamic modulus of elasticity (Ed) was measured using resonant frequency techniques. Fluid penetrability of the disks was characterized by air permeability index (API) and rate of water absorption (sorptivity). The nondestructive nature of these tests allowed multiple testing on the same samples. The changes in API and Ed of high strength concrete disks were greater than those of conventional strength. Damaged high strength concrete was found to have a lower residual rate of water absorption than damaged conventional strength concrete. However, the rate of water absorption of high strength concrete did not show as large an increase as was found with air permeability. The API identified differences between high strength concrete specimens exposed to both 150°C and 300°C compared to similar specimens exposed to 300°C only. This difference was also identified by changes in Ed, but was not identified using the rate of water absorption. The test methods for API and Ed described in this paper are simple and easy to conduct, and appear to provide useful information in studying changes in microstructure of concrete exposed to elevated temperatures.
Multiple Metal Cations as Spray Deposit Tracers and Evaluation of the AGDISP Ground Boom Spray Drift Model
Authors: Zabkiewicz J. A. , Steele K. D. , Connell R. J. 
Published: May 2009

AbstractThe determination of spray drift by agrichemicals in field applications is laborious and expensive. Dyes have been used as tracers to reduce workloads and costs, but these methods have technical drawbacks. Metal cations have also been used as tracers and this method is promising, especially if a number of distinct cations from consecutive spray applications can be collected cumulatively by the same collectors. This study evaluated the use of various water soluble metal cation salts and plastic tape as a cost-effective collector for spray drift deposits. Measured deposit values were compared with calculated outputs from the AGDISP ground boom spray drift model. The comparisons showed that AGDISP over estimated downwind deposition and under estimated deposition within the last swathe in the spray block. Increasing boom height above the canopy improved within spray block deposition estimates. Varying wind direction had negligible effect; increasing relative humidity gave greater deposition closer to the spray block. These trends are discussed, together with the pros and cons of the metal cation and plastic tape collector system.
Genomewide Analysis Reveals Novel Pathways Affecting Endoplasmic Reticulum Homeostasis, Protein Modification and Quality Control
Authors: Čopič Alenka , Dorrington Mariana , Pagant Silvere , Barry Justine , Lee Marcus C S , Singh Indira , Hartman John L , Miller Elizabeth A 
Published: May 2009

AbstractTo gain new mechanistic insight into ER homeostasis and the biogenesis of secretory proteins, we screened a genomewide collection of yeast mutants for defective intracellular retention of the ER chaperone, Kar2p. We identified 87 Kar2p-secreting strains, including a number of known components in secretory protein modification and sorting. Further characterization of the 73 nonessential Kar2p retention mutants revealed roles for a number of novel gene products in protein glycosylation, GPI-anchor attachment, ER quality control, and retrieval of escaped ER residents. A subset of these mutants, required for ER retrieval, included the GET complex and two novel proteins that likely function similarly in membrane insertion of tail-anchored proteins. Finally, the variant histone, Htz1p, and its acetylation state seem to play an important role in maintaining ER retrieval pathways, suggesting a surprising link between chromatin remodeling and ER homeostasis.
External Morphology and Development of Immature Stages of Diadegma semiclausum (Hymenoptera: Ichneumonidae), an Important Endoparasitoid of Plutella xylostella (Lepidoptera: Plutellidae)
Authors: Huang Fang , Shi Min , Chen Xue-Xin , Ye Gong-Yin , He Jun-Hua 
Published: May 2009

Abstract
Diadegma semiclausum (Hellén) (Hymenoptera: Ichneumonidae) is one of the most important biological control agents of the diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae). Each immature stage of D. semiclausum was studied by dissecting parasitized hosts in the laboratory at 22 ± 1°C and 70–75% RH. Results show that the egg is hymenopteriform, lacking appendages. The larvae seem to be hypermetamorphic, with four instars. The pupal period has two distinct phases: 1) phase I, larval-like with remarkable groups of urate cells; and 2) phase II, exarate pupal appearance with a pigmentation sequence of eyes, ocelli, mandibles, thorax, abdomen, and antennae. All stages and sequences are illustrated with detailed photomicrographs.
Primary CNS Lymphoma in Immunocompetent Patients
Authors: Sierra del Rio Monica , Rousseau Audrey , Soussain Carole , Ricard Damien , Hoang-Xuan Khê 
Published: May 2009

AbstractPrimary central nervous system lymphoma (PCNSL) constitutes a rare group of extranodal non-Hodgkin’s lymphomas (NHLs), primarily of B cell origin, whose incidence has markedly increased in the last three decades. Immunodeficiency is the main risk factor, but the large majority of patients are immunocompetent. Recent evidence suggests a specific tumorigenesis that may explain their particular clinical behavior compared with systemic NHL. The addition of i.v. high-dose methotrexate (MTX) chemotherapy to whole-brain radiotherapy (WBRT) has considerably improved the prognosis, leading to a threefold longer median survival time compared with WBRT alone and represents the current standard of care. However, this combined treatment exposes the patient, especially the elderly, to a high risk for delayed neurotoxicity. In the older population (&gt;60 years), there is growing evidence that MTX-based chemotherapy alone as initial treatment is the best approach to achieve effective tumor control without compromising patient quality of life. In the younger population, the risk for neurotoxicity is much lower, and this strategy is controversial because it may be associated with higher relapse rates. Future efforts should focus on the development of new polychemotherapy regimens allowing the reduction or deferral of WBRT in order to minimize the risk for delayed neurotoxicity. In this setting, intensive chemotherapy with autologous blood stem cell transplantation was recently demonstrated to be feasible and efficient as salvage therapy and is currently being evaluated as part of primary treatment. This review highlights the recent advances in the pathogenesis and treatment of PCNSL in the immunocompetent population.