bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prophylactic Oophorectomy Reduces Breast Cancer Penetrance During Prospective, Long-Term Follow-Up of BRCA1 Mutation Carriers
Authors: Kramer Joan L. , Velazquez Isela A. , Chen Bingshu E. , Rosenberg Philip S. , Struewing Jeffery P. , Greene Mark H. 
Published: November 2005

Purpose Breast cancer penetrance estimates in BRCA1 mutation carriers have varied from 40% to 85%; this heterogeneity has been attributed to variations in risk among different study populations. No study has taken oophorectomy status into account in estimating penetrance. Because prophylactic oophorectomy reduces breast cancer risk by approximately 50%, we hypothesized that population differences in oophorectomy prevalence might significantly influence breast cancer penetrance estimates. Methods Females from multiple-case breast/ovarian cancer families that segregate deleterious BRCA1 mutations were observed prospectively for breast cancer incidence and oophorectomy. Results Within this cohort, 33 cases of breast cancer developed in 98 women with deleterious BRCA1 mutations during follow-up, yielding an estimated cumulative lifetime breast cancer risk of 80%. This estimate increased to 94% when the study participants were censored at the time of oophorectomy. Six of the 33 mutation-positive women who underwent oophorectomy during follow-up developed breast cancer, compared with 27 of 65 mutation carriers with intact ovaries (hazard ratio = 0.38; 95% CI, 0.15 to 0.97). Estimates of absolute breast cancer risk demonstrated that the protective effect of oophorectomy was strongest among women who were premenopausal at the time of surgery. When surgical status was ignored, the strong protective effect of oophorectomy, coupled with the high prevalence of the procedure in these families, led to a significantly lower estimate of the breast cancer penetrance in BRCA1 mutation carriers. Conclusion Differing rates of oophorectomy likely represent an underappreciated basis for a portion of the heterogeneity in estimated breast cancer penetrance described in BRCA mutation carriers, particularly mutation carriers from extensively affected, multiple-case families.
Genetic Testing in Pheochromocytoma or Functional Paraganglioma
Authors: Amar Laurence , Bertherat Jérôme , Baudin Eric , Ajzenberg Christiane , Bressac-de Paillerets Brigitte , Chabre Olivier , Chamontin Bernard , Delemer Brigitte , Giraud Sophie , Murat Arnaud , Niccoli-Sire Patricia , Richard Stéphane , Rohmer Vincent , Sadoul Jean-Louis , Strompf Laurence , Schlumberger Martin , Bertagna Xavier , Plouin Pierre-François , Jeunemaitre Xavier , Gimenez-Roqueplo Anne-Paule 
Published: November 2005

Purpose To assess the yield and the clinical value of systematic screening of susceptibility genes for patients with pheochromocytoma (pheo) or functional paraganglioma (pgl). Patients and Methods We studied 314 patients with a pheo or a functional pgl, including 56 patients having a family history and/or a syndromic presentation and 258 patients having an apparently sporadic presentation. Clinical data and blood samples were collected, and all five major pheo-pgl susceptibility genes (RET, VHL, SDHB, SDHD, and SDHC) were screened. Neurofibromatosis type 1 was diagnosed from phenotypic criteria. Results We have identified 86 patients (27.4%) with a hereditary tumor. Among the 56 patients with a family/syndromic presentation, 13 have had neurofibromatosis type 1, and germline mutations on the VHL, RET, SDHD, and SDHB genes were present in 16, 15, nine, and three patients, respectively. Among the 258 patients with an apparently sporadic presentation, 30 (11.6%) had a germline mutation (18 patients on SDHB, nine patients on VHL, two patients on SDHD, and one patient on RET). Mutation carriers were younger and more frequently had bilateral or extra-adrenal tumors. In patients with an SDHB mutation, the tumors were larger, more frequently extra-adrenal, and malignant. Conclusion Genetic testing oriented by family/sporadic presentation should be proposed to all patients with pheo or functional pgl. We suggest an algorithm that would allow the confirmation of suspected inherited disease as well as the diagnosis of unexpected inherited disease.
Efficacy of Fractionated Stereotactic Reirradiation in Recurrent Gliomas: Long-Term Results in 172 Patients Treated in a Single Institution
Authors: Combs Stephanie E. , Thilmann Christoph , Edler Lutz , Debus Jürgen , Schulz-Ertner Daniela 
Published: November 2005

Purpose To evaluate the efficacy of fractionated stereotactic radiotherapy (FSRT) performed as reirradiation in 172 patients with recurrent low- and high-grade gliomas. Patients and Methods Between 1990 and 2004, 172 patients with recurrent gliomas were treated with FSRT as reirradiation in a single institution. Seventy-one patients suffered from WHO grade 2 gliomas. WHO grade 3 gliomas were diagnosed in 42 patients, and 59 patients were diagnosed with glioblastoma multiforme (GBM). The median time between primary radiotherapy and reirradiation was 10 months for GBM, 32 months for WHO grade 3 tumors, and 48 months for grade 2 astrocytomas. FSRT was performed with a median dose of 36 Gy in a median fractionation of 5 × 2 Gy/wk. Results Median overall survival after primary diagnosis was 21 months for patients with GBM, 50 months for patients with WHO grade 3 gliomas, and 111 months for patients with WHO grade 2 gliomas. Histologic grading was the strongest predictor for overall survival, together with the extent of neurosurgical resection and age at primary diagnosis. Median survival after reirradiation was 8 months for patients with GBM, 16 months for patients with grade 3 tumors, and 22 months for patients with low-grade gliomas. Only time to progression and histology were significant in influencing survival after reirradiation. Progression-free survival after FSRT was 5 months for GBM, 8 months for WHO grade 3 tumors, and 12 months for low-grade gliomas. Conclusion FSRT is well tolerated and may be effective in patients with recurrent gliomas. Prospective studies are warranted for further evaluation.
Recent Chemotherapy Reduces the Sensitivity of [18F]Fluorodeoxyglucose Positron Emission Tomography in the Detection of Colorectal Metastases
Authors: Akhurst Timothy , Kates Tara J. , Mazumdar Madhu , Yeung Henry , Riedel Elyn R. , Burt Bryan M. , Blumgart Leslie , Jarnagin William , Larson Steven M. , Fong Yuman 
Published: November 2005

Purpose [18F]2-fluoro-2-deoxyglucose (FDG) –positron emission tomography (PET) has become a useful tool in the assessment of patients with colorectal cancer. Patients often undergo chemotherapy as treatment for primary or metastatic colorectal malignancy. Because cytotoxic chemotherapy may decrease the cellular metabolic activity of tumor, we assessed the effects of chemotherapy on PET imaging. Patients and Methods This is a prospective study examining detection of hepatic colorectal metastases by FDG-PET as related to use of chemotherapy. Pathologic analysis of the liver resection specimens was used as gold standard. Results There was significantly decreased tumor FDG uptake (as measured by the maximal standardized uptake value) in patients treated preoperatively with chemotherapy, resulting in less efficient detection of cancerous lesions. One biologic basis of this change in accuracy of PET was a significant decrease in the activity of the key glycolytic enzyme hexokinase in tumors from patients treated with chemotherapy. Conclusion These results indicate that FDG-PET scanning should be interpreted in the context of concurrent cytotoxic therapy. FDG-PET scanning results may also be useful in assessment of response to such cytotoxic therapies.
The dissociation of the Fgf-feedback loop controls the limbless state of the neck
Authors: Lours Corinne , Dietrich Susanne 
Published: November 2005

In tetrapods, limbs develop at two specific positions along the anteroposterior axis of the embryo, whereas other regions of the embryo, most prominently the neck and the flank, are limbless. However, the flank can generate an ectopic limb when the Fgf-feedback loop crucial for the initiation of limb budding is activated. Thus, despite its limblessness, the flank is a limb-competent area.Using the chick embryo as model, we investigated whether the neck, as the flank, has the competence to form a limb, and what mechanism may regulate its limblessness. We show that forelimb lateral mesoderm plus ectoderm grafted into the neck can continue limb development, suggesting that the neck does not actively inhibit this process. However, neck tissues themselves do not support or take part in limb formation. Hence, the neck is limb-incompetent. This is due to the dismantling of Fgf signalling at distinct points of the MAPK signalling cascade in the neck lateral mesoderm and ectoderm.
Efficient Sonochemical Degradation of 4-Chlorophenol Catalyzed by Titanium Dioxide Hydrate
Authors: Dai Zhiming , Chen Aiping , Kisch Horst 
Published: November 2005

Abstract
A nanocrystalline anatase hydrate (Titanhydrat-0, TH) is a highly efficient catalyst for low intensity sonochemical degradation of 4-chlorophenol (4-CP). The initial disappearance rate of 4-CP increases by a factor of 95 under the TH dosage of 0.5 g dm−3. After 120 min of ultrasonic irradiation 63% of 4-CP is completely mineralized under the TH dosage of 0.5 g dm−3. However, in homogeneous sonochemical degradation, no mineralization at all occurs. Moreover, we deduce that the process of sonochemical mineralization mainly occurs at the interface region of TH. The process of sonocatalytic degradation is simple and inexpensive, and appears to be a potentially powerful method of remediation of contaminants in water.
Kinetics of electrophile-nucleophile combinations: A general approach to polar organic reactivity
Authors: Mayr Herbert , Ofial Armin R. 
Published: November 2005

Abstract
Benzhydrylium ions (Ar2CH+) and structurally related quinone methides are employed as reference electrophiles for comparing the nucleophilicities of a large variety of compounds, e.g., alkenes, arenes, alkynes, allylsilanes, allylstannanes, enol ethers, enamines, diazo compounds, carbanions, transition-metal π-complexes, hydride donors, phosphanes, amines, alkoxides, etc., using the correlation equation log k (20 °C) = s(N + E), where s and N are nucleophile-dependent parameters and E is an electrophilicity parameter. The same equation was employed to derive the electrophilicity parameter E for different types of carbocations, cationic transition-metal π-complexes, typical Michael acceptors, and electron-deficient arenes. The E, N, and s parameters thus obtained can be used for predicting rates and selectivities of polar organic reactions.
Is the single transition-state model appropriate for the fundamental reactions of organic chemistry?
Authors: Parker Vernon D. 
Published: November 2005

Abstract
In recent years, we have reported that a number of organic reactions generally believed to follow simple second-order kinetics actually follow a more complex mechanism. This mechanism, the reversible consecutive second-order mechanism, involves the reversible formation of a kinetically significant reactant complex intermediate followed by irreversible product formation. The mechanism is illustrated for the general reaction between reactant and excess reagent under pseudo-first-order conditions in eq. i where k
f' is the pseudo-first-order rate constant equal to k
f[Excess Reagent].
Reactant + Excess reagent = Reactant complex = Products (i)
The mechanisms are determined for the various systems, and the kinetics of the complex mechanisms are resolved by our "non-steady-state kinetic data analysis". The basis for the non-steady-state kinetic method will be presented along with examples. The problems encountered in attempting to identify intermediates formed in low concentration will be discussed.
Cycloproparenyl anions: From models to real systems
Authors: Eckert-Maksic Mirjana , Glasovac Zoran 
Published: November 2005

Abstract
An overview of our recent work on cycloproparenyl anions is given. Preparation, the electronic structure, and the properties of the progenitor of the series, cyclopropabenzenyl anion, are discussed. It is shown that the cyclopropabenzenyl anion is by ca. 145 kJ mol-1 more stable than the parent cyclopropenyl anion according to results of the MP2/6-31+G(d) calculations. This finding was attributed to a delicate balance of two opposing effects: (a) propensity of the aromatic ring to alleviate unfavorable 4π electron interaction within the three-membered ring by the anionic resonance effect and (b) a pyramidalization of the anionic center, which tends to maximize the s-character of the lone pair. We have also shown that stability of the cyclopropabenzenyl anion could be considerably enhanced by substitution of the aromatic ring with fluorine and cyano groups, as well as by a linear extension of the aromatic backbone. Finally, the impact of the fusion of additional cyclopropenyl ring to the benzene moiety to acidity of the benzylic position in cyclopropabenzene is discussed.
Advanced opto-electronics materials by fullerene and acetylene scaffolding
Authors: Diederich François 
Published: November 2005

AbstractFunctional π-systems with unusual opto-electronic properties are intensively investigated from both fundamental research and technological application viewpoints. This article reports on novel π-conjugated systems obtained by acetylenic and fullerene scaffolding. Linearly conjugated acetylenic nanorods, consisting of monodisperse poly(triacetylene) (PTA) oligomers and extending up to 18 nm length, were prepared to investigate the limits of effective conjugation and to explore at which length a monodisperse oligomer reaches the properties of an infinite polydisperse polymer. With the cyanoethynylethenes (CEEs), a powerful new class of electron acceptors is introduced that undergo intense intramolecular charge-transfer (CT) interactions with appended donors. Macrocyclic scaffolds with unusual opto-electronic properties are perethynylated dehydroannulenes, expanded radialenes, and radiaannulenes bearing peripheral dialkylanilino donor groups. Extended porphyrin-fullerene conjugates are investigated for their novel photophysical and efficient multicharge storage properties. Self-assembly of fullerenes and porphyrins, governed by weak interactions between the two components, leads to unprecedented nanopatterned surfaces that are investigated by scanning tunneling microscopy (STM).
Cyclodextrin-based catalysts and molecular reactors
Authors: Easton Christopher J. 
Published: November 2005

Abstract
The naturally occurring cyclodextrins and their derivatives have been developed as miniature reaction vessels, to manipulate the outcomes of chemical transformations at the molecular level. In this manner, the rate of hydrolysis of a phosphate triester has been enhanced by almost five orders of magnitude, and the ratios of products obtained from electrophilic aromatic substitution reactions, from competing reactions to give indigoid dyes, and from nitrile oxide cycloadditions have all been changed, by factors of up to 3500 times.
An alternative view of enzyme catalysis
Authors: Menger Fredric M. 
Published: November 2005

Abstract
This paper begins with a brief review of theories and concepts that have influenced today's view of enzyme catalysis: transition-state stabilization, entropy, orbital steering, proximity, and intramolecularity. The discussion then launches into the "spatiotemporal" model of enzyme catalysis in which fast intramolecular and enzymatic rates are ascribed to short distances that are imposed rigidly upon the reacting entities. An equation relating rate and distance is set forth, as are experimental and computational data supporting this relationship. Finally, enzyme systems themselves are analyzed in terms of the distance parameter and the so-called "split-site" model in which ground-state geometries play a crucial role. Among the many surprising conclusions is a transition-state stabilization by noncovalent forces (e.g., hydrogen-bonding) that are positioned far away from the actual transition-state chemistry. The model also confronts and dismisses the claim in classical enzymology that the ubiquitous enzyme-substrate complex is either inconsequential or inhibitory to the overall reaction rate.
Bioantioxidants: From chemistry to biology
Authors: Zhou Bo , Liu Zhong-Li 
Published: November 2005

Abstract
Bioantioxidants, or dietary antioxidants, are dietary substances in food that significantly decrease the adverse effects of reactive oxygen species (ROS) on normal physiological functions in humans. Inhibition of ROS-induced oxidative damages by supplementation of bioantioxidants, the so-called "antioxidant therapy", has become an attractive therapeutic strategy to reduce the risk of ROS-related diseases and has led to flourishing research in the past decade. However, many questions dealing with the correlation between chemical and biological activities, the bioavailability and "non-antioxidant" effects of bioantioxidants are still under debate.
This article outlines our current kinetic and mechanistic studies on naturally occurring antioxidants, including vitamin E, green tea polyphenols (GOHs), and resveratrol, as well as their synthetic analogs in micelles, in red blood cells, in low-density lipoprotein (LDL) and in microsomes. The cytotoxicity and apoptosis-inducing activity of these antioxidants against cancer cells were also studied. It was found that there was significant correlation between the chemical and biological antioxidant activities, as well as between the antioxidant activity and the cytotoxic and apoptosis-inducing activities.
Stability in chemistry and biology: Life as a kinetic state of matter
Authors: Pross Addy 
Published: November 2005

Abstract
Despite the considerable advances in our understanding of biological processes, the physicochemical relationship between living and nonliving systems remains uncertain and a continuing source of controversy. In this review, we describe a kinetic model based on the concept of dynamic kinetic stability that attempts to incorporate living systems within a conventional physicochemical framework. Its essence: all replicating systems, both animate and inanimate, represent elements of a replicator space. However, in contrast to the world of nonreplicating systems (all inanimate), where selection is fundamentally thermodynamic, selection within replicator space is effectively kinetic. As a consequence, the nature of stability within the two spaces is of a distinctly different kind, which, in turn, leads to different physicochemical patterns of aggregation. Our kinetic approach suggests: (a) that all living systems may be thought of as manifesting a kinetic state of matter (as apposed to the traditional thermodynamic states associated with inanimate systems), and (b) that key Darwinian concepts, such as fitness and natural selection, are particular expressions of more fundamental physicochemical concepts, such as kinetic stability and kinetic
selection. The approach appears to provide an improved basis for understanding the physicochemical process of complexification by which life on earth emerged, as well as a means of relating life's defining characteristics - its extraordinary complexity, its far-from-equilibrium character, and its purposeful (teleonomic) nature - to the nature of that process of complexification.
International collaboration in drug discovery and development from natural sources
Authors: Cragg Gordon M. , Newman David J. 
Published: November 2005

Abstract
Nature has been a source of medicinal agents for thousands of years, and an impressive number of modern drugs have been isolated from natural sources, particularly plants, with many based on their use in traditional medicine. The past century, however, has seen an increasing role played by microorganisms in the production of the antibiotics and other drugs for the treatment of serious diseases, and more recently, marine organisms have proved to be a rich source of novel bioactive agents. Natural products will continue to play a crucial role in meeting this demand through the expanded investigation of the world's biodiversity, much of which remains unexplored. By using medicinal chemistry, and combinatorial chemical and biosynthetic technology, novel natural product leads will be optimized on the basis of their biological activities to yield effective chemotherapeutic and other bioactive agents. With much of the biological diversity found in tropical and subtropical regions, the investigation of these resources requires multidisciplinary international collaboration in the discovery and development process. Such collaboration can result in substantial short-term benefits accruing to source countries, with the potential for the generation of significant longer-term benefits in the select cases of those agents that proceed into advanced development, and possible commercialization.
Unusual metabolites from some Tanzanian indigenous plant species
Authors: Nkunya Mayunga H. H. 
Published: November 2005

Abstract
In this paper, the chemistry of some unusual natural products that were isolated from various Tanzanian indigenous plant species during the past 20 years is reviewed. Among the compounds covered in this review are cyclohexane epoxides; heptane derivatives; oxygenated pyrenes; phenanthrene derivatives; flavonoids with uncommon structural frameworks; mono-, bis-, and dimeric prenylated indoles; and variously substituted mono-, sesqui-, and diterpenoids.
Protein profiling as a diagnostic tool in clinical chemistry: a review
Authors: Bons Judith A. P. , Wodzig Will K. W. H. , van Dieijen-Visser Marja P. 
Published: November 2005

AbstractSerum protein profiling by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) appears to be an important diagnostic tool for a whole range of diseases. Sensitivities and specificities obtained with this new technology often seem superior to those obtained with current biomarkers. However, reproducibility and standardization are still problematic. The present review gives an overview of the diagnostic value of protein profiles obtained with SELDI in studies on prostate and ovarian cancer. To identify aspects important for protein profiling, we compare and discuss differences in pre- and post-analytical conditions presented in the literature supplemented with some of our own data. Further progress in protein profiling as a diagnostic tool requires a more comprehensive description of technical details in all future studies.