bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral topotecan in children with recurrent or progressive high‐grade glioma
Authors: Wagner Sabine , Erdlenbruch Bernhard , Längler Alfred , Gnekow Astrid , Kühl Joachim , Albani Michael , Völpel Sigrid , Bucsky Peter , Emser Angela , Peters Ove , Wolff Johannes E. A. 
Published: March 2004

AbstractBACKGROUNDContinuous oral treatment with topotecan may be more effective than the typical 1‐day and 5‐day treatment schedules. In previous studies of continuous treatment with topotecan, increased intestinal side effects were reported in adult patients; however, the experience in pediatric patients and patients with high‐grade glioma is quite limited.METHODSThirty‐two pediatric patients with recurrent high‐grade glioma (16 females and 16 males; median age, 9.5 years) were enrolled in the current Phase I/II study. Tumor locations included the cerebral cortex (n = 5), pons (n = 18), and other sites (n = 9). An injectable formulation of topotecan was administered orally, in ice‐cold orange juice, once daily. The starting dose of 0.4 mg/m2 per day was escalated on a patient‐by‐patient basis. At each patient's maximum dose, blood samples were obtained for the determination of plasma hydroxytopotecan and topotecan lactone concentrations and for the calculation of pharmacokinetic quantities.RESULTSThe toxicity criteria for a maximum tolerated topotecan dose were met in only 19 patients. The primary toxicity type was hematologic. The median maximum tolerated dose was 0.9 mg/m2 per day (n = 19). The calculated maximum total plasma topotecan concentration was 3.8 ng/mL (n = 7), with an area under the concentration‐time curve of 38.4 ng · hours/mL and a half‐life of 4.1 hours, which would result in the complete disappearance of topotecan from the plasma after 12 hours. Objective responses were observed in 2 of 13 evaluable patients and lasted for 2.5 and 9 months, respectively (continuous clinical remission, 1 of 14 patients; partial response, 2 of 14 patients; stable disease, 7 of 14 patients; progressive disease, 4 of 14 patients).CONCLUSIONSOral topotecan (median dose, 0.9 mg/m2 per day) administered once daily was well tolerated and somewhat effective in children with recurrent high‐grade glioma. A schedule in which the daily dose is split so that dosing is performed twice daily may be superior to the current schedule. Cancer 2004. © 2004 American Cancer Society.
Alterations in the expression of the cell cycle regulatory protein cyclin kinase subunit 1 in colorectal carcinoma
Authors: Shapira Ma'anit , Ben‐Izhak Ofer , Bishara Bishara , Futerman Boris , Minkov Ira , Krausz Michael M. , Pagano Michele , Hershko Dan D. 
Published: March 2004

AbstractBACKGROUNDLow levels of p27Kip1 are associated with high aggressiveness and poor prognosis in various malignancies, including colorectal carcinoma. The authors showed that S phase kinase protein 2 (Skp2), the specific ubiquitin ligase subunit that targets p27Kip1 for degradation, was overexpressed and was inversely related to p27Kip1 levels in patients with colorectal carcinoma. The essential role of cyclin kinase subunit 1 (Cks1) in Skp2‐dependent p27 degradation was recently discovered, but its role in human malignancies is unknown.METHODSQuick‐frozen colorectal tumor samples from 30 patients were separated by electrophoresis on sodium dodecyl sulfate–polyacrylamide gels, transferred to nitrocellulose, and probed with highly specific monoclonal antibodies directed against Cks1, Skp2, and p27Kip1. The expression of Cks1 was also examined by immunohistochemistry using formalin‐fixed, paraffin‐embedded tissue sections from the same patients.RESULTSA strong correlation was found between Cks1 levels and Skp2 expression and loss of tumor differentiation. A significant inverse relation was also observed between levels of Cks1 and p27Kip1 and overall survival.CONCLUSIONSThe results of the current study suggest that increased expression of Cks1 may have an important causative role in decreasing levels of p27 in patients with aggressive colorectal carcinoma. Cancer 2004. © 2004 American Cancer Society.
The natural history of breast carcinoma in the elderly
Authors: Singh Rachana , Hellman Samuel , Heimann Ruth 
Published: March 2004

AbstractBACKGROUNDThe authors evaluated the two indicators of metastatic proclivity (namely, virulence [V; the rate of appearance of distant metastases] and metastagenicity [M; the ultimate likelihood of developing distant metastases]) of breast carcinoma in elderly women. The authors then compared these characteristics with the corresponding characteristics in a cohort of younger women to determine whether breast carcinoma was more indolent in women age > 70 years, as is commonly believed in the medical community.METHODSThe authors examined 2136 women who underwent mastectomy without adjuvant systemic therapy at The University of Chicago Hospitals (Chicago, IL) between 1927 and 1987. The median follow‐up period was 12.3 years. Distant disease–free survival (DDFS) was determined for women who did not receive systemic therapy. V and M were obtained from log‐linear plots of DDFS.RESULTSNo significant difference in tumor size at presentation was observed among women age < 40 years, women ages 40–70 years, and women age > 70 years (P = 0.86), whereas significantly fewer women age > 70 years presented with positive lymph nodes compared with younger women (P = 0.05). In women with negative lymph node status, there was a higher DDFS rate among patients ages 40–70 years (81% at 10 years) compared with patients age > 70 years (65% at 10 years; P = 0.018). There was no significant age‐related difference among women with lymph node–positive disease (P = 0.2). For example, the 10‐year DDFS rate for women ages 40–70 years was 33%, compared with 38% for women age > 70 years. Among those with lymph node–negative disease, V was 3% per year for women ages 40–70 years as well as women age > 70 years. Among women with lymph node–negative disease, M was 0.20 for patients ages 40–70 years and 0.35 for patients age > 70 years. In women with positive lymph node status, both V (11% per year vs. 10% per year) and M (0.70 vs. 0.65) were similar in both age groups.CONCLUSIONSFewer women age > 70 years had lymph node involvement at presentation. However, when this finding was taken into account, the authors found no evidence that breast carcinoma was more indolent in women age > 70 years. These results support the use of similar diagnostic and therapeutic efforts for elderly women and younger women, with modification for elderly women based only on comorbidity. Cancer 2004. © 2004 American Cancer Society.
Parallel program debugging by specification
Authors: Huband Simon , McDonald Chris 
Published: April 2004

AbstractMost message passing parallel programs employ logical process topologies with regular characteristics to support their computation. Since process topologies define the relationship between processes, they present an excellent opportunity for debugging. The primary benefit is that process behaviours can be correlated, allowing expected behaviour to be abstracted and identified, and undesirable behaviour reported. However, topology support is inadequate in most message passing parallel programming environments, including the popular Message Passing Interface (MPI) and the Parallel Virtual Machine (PVM). Programmers are forced to implement topology support themselves, increasing the possibility of introducing errors.This paper proposes a trace‐ and topology‐based approach to parallel program debugging, driven by four distinct types of specifications. Trace specifications allow trace data from a variety of sources and message passing libraries to be interpreted in an abstract manner, and topology specifications address the lack of explicit topology knowledge, whilst also facilitating the construction of user‐consistent views of the debugging activity. Loop specifications express topology‐consistent patterns of expected trace events, allowing conformance testing of associated trace data, and error specifications specify undesirable event interactions, including mismatched message sizes and mismatched communication pairs. Both loop and error specifications are simplified by having knowledge of the actual topologies being debugged.The proposed debugging framework enables a wealth of potential debugging views and techniques. Copyright © 2004 John Wiley & Sons, Ltd.
A comparison of the efficacy and acceptability of group versus individual cognitive behaviour therapy in the treatment of panic disorder and agoraphobia in primary care
Authors: Sharp D. M. , Power K. G. , Swanson V. 
Published: March 2004

AbstractPanic disorder and agoraphobia is a prevalent clinical condition which places heavy demands on treatment resources in primary care. The efficient delivery of evidence‐based psychological treatment for this disorder is therefore important. Previous research has investigated both individual and group treatment formats for cognitive behaviour therapy (CBT) for panic disorder and agoraphobia. These two modalities of treatment delivery are, however, rarely compared within the same study format. Also little is known of patients' preferences regarding treatment delivery formats. The present study investigated the relative efficacy of a group treatment CBT and an individual treatment CBT in comparison with a waiting list control group in the treatment of panic disorder with or without agoraphobia in primary care. Ninety‐seven patients suffering from DSM‐IV panic disorder with or without agoraphobia were randomly allocated to receive either group CBT, individual CBT, or waiting list control. All patients were seen by the same therapist and all received an identical treatment manual. Treatment response was measured by blind assessor, therapist and patient‐rated measures of anxiety, depression, and agoraphobic avoidance, and was analysed in terms of both traditional statistical significance and clinical significance of outcome. At treatment end‐point, in terms of traditional statistical significance, both the group and individual CBT were significantly superior to waiting list control but did not differ significantly from each other. When clinical significance of outcome at treatment end‐point was considered, individual CBT showed a significant advantage over both group CBT and waiting list control. At 3‐month follow‐up, however, the individual CBT treatment group showed significant superiority to the group CBT treatment on clinical significance of outcome on one outcome measure only. This was principally due to a reduction in the proportion of patients achieving criteria of clinically significant change in the individual CBT treatment group over the 3‐month follow‐up period. When given a free choice of group or individual CBT at the end of the waiting list period, the overwhelming majority (95%) of the waiting list patients chose individual CBT. The implications of these findings for future research and for wider clinical practice are discussed. Copyright © 2004 John Wiley & Sons, Ltd.
Positive life goals and plans in parasuicide
Authors: Vincent Paula J. , Boddana Pradeep , MacLeod Andrew K. 
Published: March 2004

AbstractParasuicidal individuals lack positive expectations about the future. This study set out to examine two aspects of positive future thinking—the ability to think of goals and the presence of cognitions related to achieving those goals, including plans, perceived control and perceived likelihood. Individuals who had recently engaged in an episode of parasuicide (N = 24) were compared with matched, hospital controls (N = 24) on a range of measures to assess number and type of goals, ability to think of plans to achieve goals, sense of control over goal outcomes, and perceived likelihood of achieving goals, as well as self‐report measures of hope, hopelessness, depression and anxiety. The two groups did not differ in the number of goals they could identify, especially after controlling for unemployment. The groups did differ in the quality of goals with the parasuicide patients' goals being less specific and more self‐focused in important goals, though these effects were confounded by group differences in employment status. Compared to controls, and after controlling for employment, parasuicide patients gave less specific plans, could think of more obstacles to achieving their goals and gave lower ratings of control and likelihood of achieving their goals. Parasuicide patients appear able to think of positive life goals but have clear problems in being able to think of how to achieve those goals. Copyright © 2004 John Wiley & Sons, Ltd.
Dose meta‐cognition or responsibility predict obsessive–compulsive symptoms: a test of the metacognitive model
Authors: Gwilliam Petra , Wells Adrian , Cartwright‐Hatton Samantha 
Published: March 2004

AbstractCognitive models of Obsessive–Compulsive disorder (OCD) have emphasized inflated responsibility (Salkovskis, 1985), thought–action fusion (Rachman, 1993), and metacognitive beliefs (Wells, 1997; Wells & Matthews, 1994), as factors contributing to disorder. The metacognitive model views responsibility as a by‐product of metacognitions that make little additional contribution to OCD, and gives rise to the following hypotheses: (1) responsibility and meta‐cognitive beliefs are positively correlated with obsessive–compulsive symptoms, (2) the relationship between responsibility and obsessive–compulsive symptoms is statistically dependent on meta‐cognition, (3) meta‐cognitions positively correlate with obsessive–compulsive symptoms independently of responsibility. The results supported each of these hypotheses and exploratory analyses were conducted to find the best unique set of predictors among a range of metacognitive dimensions. Metacognitive beliefs concerning need to control thoughts, thought–action fusion, and negative beliefs about cognitive competence emerged as reliable predictors. An additional contribution was made by thought–event fusion in one equation. The results provide support for the meta‐cognitive model. Copyright © 2004 John Wiley & Sons, Ltd.
Synthesis, Solution‐State and Solid‐State Structural Characterization of Monocationic Nitrido Heterocomplexes [M(N)(DTC)(PNP)]+ (M = 99Tc, Re; DTC = Dithiocarbamate; PNP = Heterodiphosphane)
Authors: Bolzati Cristina , Refosco Fiorenzo , Cagnolini Aldo , Tisato Francesco , Boschi Alessandra , Duatti Adriano , Uccelli Licia , Dolmella Alessandro , Marotta Ester , Tubaro Michela 
Published: March 2004

AbstractMono‐cationic nitrido heterocomplexes of general formula [M(N)(DTC)(PNP)]+ (where M is 99Tc or Re, DTC is the mono‐anionic form of a dithiocarbamate ligand, and PNP is a diphosphane ligand with a tertiary amine‐containing five‐membered spacer) were prepared by ligand‐exchange reactions with the labile precursors [M(N)Cl2(PPh3)2] in dichloromethane/alcohol mixtures. The molecular structure of the representative rhenium complex [Re(N)(dedc)(pnp2)][PF6] (1) displays a distorted, square‐pyramidal geometry with the dithiocarbamate sulfur and the diphosphane phosphorus atoms spanning the four coordination positions on the equatorial plane. If the additional interactions between the nitrido nitrogen and the weakly bonded trans N‐diphosphane heteroatom, the molecular geometry can be viewed as pseudo‐octahedral. The structure in solution, as established by multinuclear NMR spectroscopy and ESI spectrometry, is monomeric, and identical to that shown in the solid state. Replacement of the phenyl groups on the phosphorous atoms in complexes 1, 2, 5, and 6 with alkyl groups modified neither the course of the reaction nor the composition of the resulting complexes. These results, together with the observation that no symmetrical complexes containing two identical bidentate ligands were produced in these reactions, strongly supports the conclusion that a mixed coordination sphere, composed by a combination of π‐donor and π‐acceptor atoms around the [M≡N]2+ group, constitutes a highly stable system. Compounds containing dangling alkyl‐substituted groups in the outer sphere (3, 4, 7, and 8) were fully characterized by multinuclear NMR spectroscopy and ESI mass spectrometry. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Hetero‐Diels−Alder Reactions of Ketones — A Challenge for Chemists
Authors: Jørgensen Karl Anker 
Published: April 2004

AbstractThe recent developments of mainly catalytic and enantioselective hetero‐Diels−Alder reactions of ketones are presented. First, direct reactions of unactivated ketones are presented, focusing on the recent hydrogen bond‐promoted hetero‐Diels−Alder reactions with activated conjugated dienes. Then, direct catalytic enantioselective hetero‐Diels−Alder reactions of activated ketones with conjugated dienes are outlined. The use of different chiral copper(II) and zinc(II) catalysts are shown and the use of the hetero‐Diels−Alder adducts in organic synthesis presented. Finally, the inverse‐electron demand hetero‐Diels−Alder reactions of α,β‐unsaturated ketone functionalities are discussed. The different chiral Lewis‐acid complexes and chiral amines used for catalytic asymmetric hetero‐Diels−Alder reactions are presented and the scope of these reactions in the synthesis of optically active α‐hydroxy lactones, formyl esters and carbohydrates are demonstrated. The mechanistic aspects of the catalytic enantioselective hetero‐Diels−Alder reactions are also discussed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Shellfish Toxins − Chemical Studies on Northern Adriatic Mussels
Authors: Ciminiello Patrizia , Fattorusso Ernesto 
Published: April 2004

AbstractDuring our investigation on toxic mussels from the Northern Adriatic sea, initiated about ten years ago, a number of polyether toxins have been isolated and characterized, some of which represent new additions to the diarrhetic shellfish poisoning (DSP) class of biotoxins and seem to be specific to the Adriatic. In addition, we have also isolated new types of toxins, oxazinins and chlorosulfolipids, whose structures were elucidated by extensive use of 1D and 2D NMR spectroscopic techniques. Some of them could represent a further risk to public health due to their cytotoxic activity. A liquid‐chromatography mass‐spectrometry (LC‐MS) method was proposed for the sensitive, specific and direct detection of yessotoxin and its analogs. In addition, the proposed method allows us highlight the possible presence of new analogs, and enables us to propose an effective structural hypothesis even when full structural elucidation of new toxins by NMR spectroscopy is hampered by the limited amount of material available. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)
Ein Horchposten ins Universum
Authors: Aufmuth Peter 
Published: March 2004

AbstractErst seit wenigen Jahren ist es möglich, Gravitationswellen nachzuweisen. Ein neu entwickelter Gravitationswellendetektor zeichnet sich durch besondere Empfindlichkeit aus. Mit seiner Hilfe lassen sich wichtige Informationen über Schwarze Löcher, dunkle Materie und den Ursprung des Alls gewinnen
Keratin 14 Cre transgenic mice authenticate keratin 14 as an oocyte‐expressed protein
Authors: Hafner Martin , Wenk Jutta , Nenci Arianna , Pasparakis Manolis , Scharffetter‐Kochanek Karin , Smyth Neil , Peters Thorsten , Kess Daniel , Holtkötter Olaf , Shephard Pierre , Kudlow Jeffrey E. , Smola Hans , Haase Ingo , Schippers Angela , Krieg Thomas , Müller Werner 
Published: April 2004

AbstractSummary: Three mouse lines expressing Cre recombinase under the control of the human K14 promoter induced specific deletion of loxP flanked target sequences in the epidermis, in tongue, and thymic epithelium of the offspring where the Cre allele was inherited from the father. Where the mother carried the Cre allele, loxP flanked sequences were completely deleted in all tissues of the offspring, even in littermates that did not inherit the Cre allele. This maternally inherited phenotype indicates that the human K14 promoter is transcriptionally active in murine oocytes and that the enzyme remains active until after fertilization, even when the Cre allele becomes transmitted to the polar bodies during meiosis. Detection of K14 mRNA by RT‐PCR in murine ovaries and immunohistochemical identification of the K14 protein in oocytes demonstrates that the human K14 promoter behaves like its murine homolog, thus identifying K14 as an authentic oocytic protein. genesis 38:176–181, 2004. © 2004 Wiley‐Liss, Inc.
Generation of Pax2‐Cre mice by modification of a Pax2 bacterial artificial chromosome
Authors: Ohyama Takahiro , Groves Andrew K. 
Published: April 2004

AbstractSummary: The Pax2 gene is expressed in the developing otocyst, kidney, and midbrain–hindbrain boundary. We generated Pax2‐Cre transgenic lines by modification of a Pax2 bacterial artificial chromosome (BAC). In one Pax2‐Cre line, Cre mRNA starts to be expressed in the otic placode at the late presomite stage. R26R reporter mouse analysis revealed that the Cre expression is sufficient to delete the loxP‐flanked sequences in most of the cells in the inner ear. Reporter‐positive cells are also detected in other Pax2‐expressing tissues such as midbrain, cerebellum, olfactory bulb, and kidney, suggesting that these cells are the descendants of Pax2‐expressing cells in these tissues and that Pax2‐Cre transgenic mice can delete genes efficiently in these tissues. genesis 38:195–199, 2004. © 2004 Wiley‐Liss, Inc.
Impaired associative memory in temporal lobe epilepsy subjects after lesions of hippocampus, parahippocampal gyrus, and amygdala
Authors: Weniger Godehard , Boucsein Katrin , Irle Eva 
Published: April 2004

AbstractThere has been growing interest in the differential role of medial temporal lobe structures in learning and memory. The goal of the present study was to clarify how lesions of hippocampus, parahippocampal gyrus, and amygdala interfere with associative learning and memory. Thirty subjects with pharmacoresistant medial temporal lobe epilepsy (TLE) and temporal lobe removal were compared with 30 matched healthy control subjects. A set of neuropsychological test measures and an associative learning task requiring the learning and recall of objects and faces were administered. The lesions of hippocampus, parahippocampal gyrus, amygdala, and fusiform gyrus of TLE subjects were determined by three‐dimensional magnetic resonance imaging (3‐D MRI) volumetric assessment. The results indicate that TLE subjects with combined large hippocampal lesions, large parahippocampal gyrus (i.e., perirhinal/entorhinal) lesions, and large amygdala lesions learned and recalled the associative task significantly worse than control subjects or subjects with small lesions of the hippocampus, parahippocampal gyrus, and amygdala. Regression analysis revealed that larger lesions of the parahippocampal gyrus (i.e., perirhinal/entorhinal cortices) were significantly related to increasing deficits on the task, and that hippocampal and amygdala lesion size did not significantly improve the prediction. Our results suggest that perirhinal and entorhinal cortices may contribute predominantly to the associative learning and recall of objects and faces. © 2004 Wiley‐Liss, Inc.
Long‐term hydrological simulation based on the Soil Conservation Service curve number
Authors: Mishra Surendra Kumar , Singh Vijay P. 
Published: April 2004

AbstractPresenting a critical review of daily flow simulation models based on the Soil Conservation Service curve number (SCS‐CN), this paper introduces a more versatile model based on the modified SCS‐CN method, which specializes into seven cases. The proposed model was applied to the Hemavati watershed (area = 600 km2) in India and was found to yield satisfactory results in both calibration and validation. The model conserved monthly and annual runoff volumes satisfactorily. A sensitivity analysis of the model parameters was performed, including the effect of variation in storm duration. Finally, to investigate the model components, all seven variants of the modified version were tested for their suitability. Copyright © 2004 John Wiley & Sons, Ltd.