bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase 2 study of carboplatin, docetaxel, and bevacizumab as frontline treatment for advanced nonsmall‐cell lung cancer
Authors: William William N. , Kies Merrill S. , Fossella Frank V. , Liu Diane D. , Gladish Gregory , Tse Warner H. , Lee J. Jack , Hong Waun K. , Lippman Scott M. , Kim Edward S.
Published: March 2010

BACKGROUND:

Bevacizumab has recently been demonstrated to prolong overall survival when added to carboplatin and paclitaxel for chemotherapy‐naïve patients with nonsquamous nonsmall‐cell lung cancer (NSCLC). However, the effects of combining bevacizumab with other standard, front‐line, platinum‐based doublets have not been extensively explored. We designed this single treatment arm, phase 2 trial to determine whether the combination of carboplatin, docetaxel, and bevacizumab is tolerable and prolongs progression‐free survival of chemotherapy‐naïve patients with advanced, nonsquamous NSCLC.

METHODS:

Forty patients were treated with up to 6 cycles of carboplatin (AUC 6), docetaxel (75 mg/m2), and bevacizumab (15 mg/kg) on Day 1 every 21 days. Patients with an objective response or stable disease received maintenance bevacizumab (15 mg/kg) every 21 days until disease progression. The primary endpoint was median progression‐free survival. Secondary endpoints included safety, response rates, and overall survival.

RESULTS:

The median number of chemotherapy and maintenance bevacizumab cycles/patient was 6 and 2, respectively. Grades 3‐5 adverse events included febrile granulocytopenia (10%), infections (13%), bleeding (13%), thrombotic events (13%), hypertension (5%), bowel perforation (5%), and proteinuria (3%). Median progression‐free survival was 7.9 months and median overall survival was 16.5 months. Partial responses were observed in 21 patients (53%), and stable disease ≥6 weeks occurred in another 17 patients (43%), for a disease control rate of 95%.

CONCLUSIONS:

Carboplatin, docetaxel, and bevacizumab were feasible and effective for front‐line treatment of advanced, nonsquamous NSCLC. These data provide further evidence that bevacizumab may be used in combination with multiple standard, platinum‐based doublets in this setting. Cancer 2010. © 2010 American Cancer Society.
High‐dose proton therapy and carbon‐ion therapy for stage I nonsmall cell lung cancer
Authors: Iwata Hiromitsu , Murakami Masao , Demizu Yusuke , Miyawaki Daisuke , Terashima Kazuki , Niwa Yasue , Mima Masayuki , Akagi Takashi , Hishikawa Yoshio , Shibamoto Yuta
Published: March 2010

BACKGROUND:

A study was undertaken to evaluate the clinical outcome of particle therapy for stage I nonsmall cell lung cancer (NSCLC).

METHODS:

From April 2003 to April 2007, 80 patients with stage I NSCLC were treated with proton therapy or carbon‐ion therapy (57 with proton therapy and 23 with carbon‐ion therapy) using 3 treatment protocols. In the first protocol, 80 gray equivalents (GyE) of proton therapy was given in 20 fractions, and the second proton therapy protocol used 60 GyE in 10 fractions. For carbon‐ion therapy, 52.8 GyE was given in 4 fractions. After achieving promising preliminary results for the first protocol, the authors started to use the second proton therapy protocol to shorten the overall treatment time. Carbon‐ion therapy was started in 2005, and thereafter, both proton and carbon‐ion therapy plans were made for each patient, and the 1 that appeared superior was adopted. Patient age ranged from 48 to 89 years (median, 76 years). Thirty‐seven patients were medically inoperable, and 43 refused surgery. Forty‐two patients had T1 tumors, and 38 had T2 tumors.

RESULTS:

The median follow‐up period for living patients was 35.5 months. For all 80 patients, the 3‐year overall survival, cause‐specific survival, and local control rates were 75% (IA: 74%; IB: 76%), 86% (IA: 84%; IB: 88%), and 82% (IA: 87%; IB: 77%), respectively. There were no significant differences in treatment results among the 3 protocols. Grade 3 pulmonary toxicity was observed in only 1 patient.

CONCLUSIONS:

Proton therapy and carbon‐ion therapy are safe and effective for stage I NSCLC. Further investigation of particle therapy for stage I NSCLC is warranted. Cancer 2010. © 2010 American Cancer Society.
A note from history
Authors: Hajdu Steven I.
Published: March 2010

Antonio Benivieni, an Italian physician, Theophilus Boneti, a Swiss physician, and Giovanni Battista Mogagni, an Italian physician, pioneered postmortem examination for finding hidden causes of diseases. By correlating the results of their clinical and postmortem examinations, they established the foundation of anatomic pathology, clinical medicine, and oncology. Cancer 2010. © 2010 American Cancer Society.
A novel therapeutic combination for neuroblastoma
Authors: Zage Peter E. , Zeng Lizhi , Palla Shana , Fang Wendy , Nilsson Monique B. , Heymach John V. , Zweidler‐McKay Patrick A.
Published: March 2010

BACKGROUND:

High‐risk cases of neuroblastoma have poor survival rates, and novel therapies are needed. Vandetanib (ZD6474, Zactima) is an inhibitor of the vascular endothelial growth factor receptor, epidermal growth factor receptor, and rearranged during transfection (RET) tyrosine kinases, which have each been implicated in neuroblastoma pathogenesis. The authors hypothesized that vandetanib combined with 13‐cis‐retinoic acid (CRA), a differentiating agent used in most current neuroblastoma treatment regimens, would be effective against neuroblastoma tumor models.

METHODS:

The authors evaluated the effects of vandetanib with and without CRA on RET phosphorylation and on the proliferation and survival of human neuroblastoma cell lines in vitro. Using a subcutaneous mouse xenograft model of human neuroblastoma, they analyzed tumors treated with CRA, vandetanib, and the combination of vandetanib plus CRA for growth, gross and histologic appearance, vascularity, and apoptosis.

RESULTS:

Vandetanib treatment inhibited RET phosphorylation and resulted in induction of apoptosis in the majority of neuroblastoma cell lines in vitro, whereas CRA treatment induced morphologic differentiation and cell‐cycle arrest. Treatment with vandetanib plus CRA resulted in more significant reduction in neuroblastoma cell viability than either alone. In a mouse xenograft model, the combination of vandetanib with CRA demonstrated significantly more growth inhibition than either alone, via both reduction in tumor vascularity and induction of apoptosis.

CONCLUSIONS:

Vandetanib induces neuroblastoma tumor cell death in vitro and reduces tumor growth and vascularity in vivo. The combination of vandetanib with CRA was more effective in reducing tumor growth than either treatment alone. The antitumor effects of vandetanib plus CRA suggest a novel combination for use in neuroblastoma patients. Cancer 2010. © 2010 American Cancer Society.
Efficacy of radiotherapy for painful bone metastases during the last 12 weeks of life
Authors: Meeuse Jan J. , van der Linden Yvette M. , van Tienhoven Geertjan , Gans Rijk O. B. , Leer Jan Willem H. , Reyners An K. L.
Published: March 2010

BACKGROUND:

Radiotherapy is an effective treatment for painful bone metastases. Whether this applies also in patients with limited survival remains to be investigated. This study analyzed the effect of radiotherapy for painful bone metastases in patients with a survival ≤12 weeks.

METHODS:

In the Dutch Bone Metastasis Study, 1157 patients with painful bone metastases were randomized to single fraction (1 × 8 grays [Gy]) or multiple fraction (6 × 4 Gy) radiotherapy. Patients who died within 12 weeks after randomization were included in this analysis. Patients were classified as responders or nonresponders, based on their pain response to radiotherapy. This response was calculated considering changes in pain intensity (measured with an 11‐point numeric rating scale) and analgesic usage. Cox proportional hazards models were used to analyze pain response and survival.

RESULTS:

Two hundred seventy‐4 patients were included in this analysis. At randomization, the mean pain intensity score (±standard deviation) was 7 (±2). The proportion showing a pain response did not differ between the single fraction and multiple fraction groups. Toward death, pain intensity score decreased to 5 (±3) in responders (45%), whereas in nonresponders (55%) no change was observed. Despite the benefit in responders, in 60% of all patients pain intensity remained 5 after randomization.

CONCLUSIONS:

Pain responded in about half of the patients who survived ≤12 weeks after randomization into the Dutch Bone Metastasis Study. When considering radiotherapy, single fraction should be preferred. Additional palliative measures remain essential for adequate pain control. Cancer 2010. © 2010 American Cancer Society.
Association ofp53codon 72 polymorphism with risk of second primary malignancy in patients with squamous cell carcinoma of the head and neck
Authors: Li Fanglin , Sturgis Erich M. , Chen Xingming , Zafereo Mark E. , Wei Qingyi , Li Guojun
Published: March 2010

BACKGROUND:

p53 plays a critical role in cellular anticancer mechanisms, and has been correlated with second primary malignancy (SPM) development. A common polymorphism in codon 72 ofp53results in an amino acid substitution and could influence p53 function. The authors hypothesized thatp53codon 72 polymorphism may be associated with risk of SPMs and SPM‐free survival among patients with squamous cell carcinoma of the head and neck (SCCHN).

METHODS:

A total of 1271 patients, who were diagnosed with incident SCCHN between May 1995 and January 2007, were genotyped and observed for SPM development. Log‐rank test and Cox proportional hazard models were used to compare SPM‐free survival and SPM risk between the different genotype groups.

RESULTS:

The authors found significantly reduced SPM‐free survival for patients with variant proline (Pro) 72 allele compared with patients with arginine (Arg) 72 homozygous genotype (log‐rank test,P= .005). Compared with SCCHN patients with thep5372Arg/Arg genotype, there was a significantly greater risk of SPM associated with thep5372Arg/Pro genotype (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.17‐2.61) and combinedp5372Arg/Pro + Pro/Pro (HR, 1.58; 95% CI, 1.07‐2.34). Furthermore, stratification analyses showed that the risk of SPM associated withp53variant genotypes (Arg/Pro + Pro/Pro) was more pronounced in several subgroups.

CONCLUSIONS:

p53codon 72 polymorphism could be a risk marker for genetic susceptibility to SPM in patients with primary SCCHN. Cancer 2010. © 2010 American Cancer Society.
Weekly alternating therapy with irinotecan plus cisplatin and etoposide plus cisplatin in the treatment of patients with extensive small cell lung carcinoma
Authors: William William N. , Uyeki James , Johnson Faye M. , Feng Lei , Peeples Beverly O. , Fossella Frank V. , Karp Daniel D. , Blumenschein George R. , Stewart David J. , Glisson Bonnie S.
Published: March 2010

BACKGROUND:

Irinotecan has significant activity in small‐cell lung cancer (SCLC). The authors' previous phase 1 study of alternating weekly therapy with irinotecan/cisplatin (IP), etoposide/cisplatin (EP), and granulocyte–colony‐stimulating factor (G‐CSF) support was well tolerated and active in patients with SCLC. A phase 2 trial was conducted to estimate the efficacy of this regimen in previously untreated patients with extensive SCLC.

METHODS:

A total of 33 patients were treated between June 2002 and July 2007. Patients received 12 weeks of therapy with cisplatin (20 mg/m2) on Day 1 and irinotecan (100 mg/m2) on Day 1 and G‐CSF on Days 2 to 5 (Weeks 1, 3, 5, 7, 9, and 11) followed by cisplatin (20 mg/m2) on Day 1 and etoposide (60 mg/m2) on Days 1 to 3 with G‐CSF on Days 4 to 7 (Weeks 2, 4, 6, 8, 10, and 12). The primary endpoint was 1‐year survival rate.

RESULTS:

Grade 4 neutropenia (toxicities were determined using the National Cancer Institute Common Toxicity Criteria [version 2.0]) was noted in 5 (1.5%) of 343 courses with neutropenic fever in only 5 (1%) of 343 courses. One patient died of neutropenic sepsis. Nonhematologic toxicities grade ≥2 were observed in 15 (4%) of 343 courses and were limited to fatigue, hyponatremia, and diarrhea. The overall objective response rate was 89% in 28 assessable patients (no complete responses and 25 partial responses). The median progression‐free and overall survivals were 6.0 months and 10.9 months, respectively. The 1‐year survival rate was 33%.

CONCLUSIONS:

Weekly therapy with IP alternating with EP and G‐CSF support was well tolerated in patients with extensive SCLC, but did not demonstrate improved progression‐free or overall survival when compared with historical controls at the study institution. Cancer 2010. © 2010 American Cancer Society.
Detection of chromosomal anomalies in endometrial atypical hyperplasia and carcinoma by using fluorescence in situ hybridization
Authors: Qian Junqi , Weber Deena , Cochran Richard , Hossain Deloar , Bostwick David G.
Published: March 2010

BACKGROUND:

Endometrial cancer is the most common pelvic gynecological malignancy. The diagnosis of well‐differentiated endometrial adenocarcinoma, atypical hyperplasia, and hyperplasia is often challenging. The authors sought to investigate the utility of chromosomal anomalies for the detection of endometrial hyperplasia and carcinoma using multitarget fluorescence in situ hybridization (FISH).

METHODS:

Samples were collected by endometrial Tao brush and processed by liquid‐based cytological preparation protocol from consecutive cases to include 50 benign, 50 hyperplasia without atypia, 47 atypical hyperplasia, and 53 endometrial cancers. Each was hybridized using fluorescence‐labeled DNA probes to chromosomes 1, 8, and 10. The FISH signals were enumerated in 100 cells per case, and the chromosomal anomalies were correlated with pathologic findings, including histologic diagnoses on matched endometrial tissue samples.

RESULTS:

Numeric chromosomal anomalies were found in 0% (0 of 50) of benign, 20% (10 of 50) of hyperplasia, 74% (35 of 47) of atypical hyperplasia, and 87% (46 of 53) of carcinoma specimens. The mean percentage of cells with chromosomal changes was 55% in cancer specimens, which was significantly higher than that in hyperplasia without atypia (13%, P < .0001) and atypical hyperplasia (32%, P = .003). The most frequent chromosomal anomaly was gain of chromosome 1. FISH anomalies had an overall sensitivity of 81% and specificity of 90% for the detection of atypical hyperplasia and/or endometrial carcinoma. There was no association with grade of endometrial carcinoma.

CONCLUSIONS:

Multitarget FISH appears to be useful for the differential diagnosis of hyperplasia, atypical hyperplasia, and endometrial adenocarcinoma, with a high level of sensitivity and specificity. It is also a potential tool for the early detection of neoplastic cells in endometrial cytology specimens. Endometrial hyperplasia with FISH‐detected chromosomal anomalies may represent a clinically significant subset of cases that warrant close clinical follow‐up. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.
A process‐oriented architecture for complex system modelling
Authors: Ritson C. G. , Welch P. H.
Published: March 2010

A fine‐grained massively parallel and process‐oriented architecture for the modelling of complex systems is presented. We propose that the concurrency in the model simplifies its design and construction by directly reflecting the processes in the natural world. The architecture is based on CSP, extended with mechanisms for process mobility from the pi‐calculus; implementations are presented using the occam‐pi language. A case study, modelling platelets (possibly artificial) within a blood vessel, is described. The aim for this model is to engineer emergent behaviour: the clotting of platelets in response to a wound in the blood vessel wall and the staunching of blood loss. A three‐dimensional model is constructed, along with mechanisms for visualization and interaction. Its expressiveness and efficiency relies strongly on the dynamic and mobile capabilities of occam‐pi. General principles for the design of large and complex system models are drawn. The described case study runs to millions of processes engaged in ever‐changing communication topologies. It is free from deadlock, livelock, race hazards and starvation by design, employing a small set of synchronization patterns for which we have proven safety theorems. Compiled occam‐π codes automatically and efficiently exploit all cores in a shared‐memory multiprocessor system. They are also straightforward to distribute over standard cluster architectures. Copyright © 2007 CG Ritson & PH Welch.
Urinary biomarkers involved in type 2 diabetes: a review
Authors: Matheson Agnès , Willcox Mark D. P. , Flanagan Judith , Walsh Bradley J.
Published: March 2010

Diabetes mellitus is one of the most challenging health concerns of the 21st century. With at least 30% of the diabetic population remaining undiagnosed, effective and early diagnosis is of critical concern. Development of a diagnostic test, more convenient and reliable than those currently used, would therefore be highly beneficial. Urine as a diagnostic medium allows for non‐invasive detection of biomarkers, including some associated with type 2 diabetes and its complications. This review provides a synopsis of those urinary biomarkers that potentially may provide a basis for the development of improved diagnostic tests. Three main pathways for the sourcing of potential makers are identified: kidney damage, oxidative stress and low‐grade inflammation including atherosclerosis/vascular damage. This review briefly presents each pathway and some of the most relevant urinary biomarkers that may be used to monitor the development or progression of diabetes and its complications. In particular, biomarkers of renal dysfunction such as transferrin, type IV collagen and N‐acetyl‐β‐D‐glucosaminidase might prove to be more sensitive than urinary albumin, the current gold standard, in the detection of incipient nephropathy and risk assessment of cardiovascular disease. Inflammatory markers including orosomucoid, tumour necrosis factor‐α, transforming growth factor‐β, vascular endothelial growth factor and monocyte chemoattractant protein‐1, as well as oxidative stress markers such as 8‐hydroxy‐2′deoxyguanosine may also be useful biomarkers for diagnosis or monitoring of diabetic complications, particularly kidney disease. However, the sensitivity of these markers compared with albumin requires further investigation. Copyright © 2010 John Wiley & Sons, Ltd.
Relationship between insulin resistance, inflammation and liver cell apoptosis in patients with severe obesity
Authors: Civera M. , Urios A. , Garcia‐Torres M. L. , Ortega J. , Martinez‐Valls J. , Cassinello N. , del Olmo J. A. , Ferrandez A. , Rodrigo J. M. , Montoliu C.
Published: March 2010

Background

In obesity, insulin resistance appears frequently after activation of proinflammatory molecules. Caspase‐generated cytokeratin‐18 (CK‐18) fragments are produced during the apoptosis of hepatic cells. The main objective in the present study is to investigate the relationship between insulin resistance and caspase‐generated CK‐18 fragments in patients with severe obesity.

Methods

Sixty‐two patients selected for bariatric surgery were clinically studied (sex, age, weight, waist diameter, body mass index, arterial pressure and type 2 diabetes mellitus) and analytic parameters were measured in blood (glucose concentration, cholesterol, triglycerides, insulin, glycosylated hemoglobin, aspartate aminotransferase, alanine aminotransferase, high‐sensitivity C‐reactive protein, adiponectin, interleukin 6, interleukin 18 and CK‐18 fragments). Patient group division was based on 70th percentile of insulin resistance as measured by homeostasis model asssessment (HOMA) and also according to liver histology.

Results

Patients with greater insulin resistance (percentile > 70th) showed higher values of CK‐18 fragments, interleukin 6 and transaminases. A positive correlation between the HOMA score, value of CK‐18 fragments and triglyceride level was found. A correlation between CK‐18 fragments with interleukin 6, triglycerides and transaminases was also observed. HOMA score and value of CK‐18 fragments correlated with the degree of liver fibrosis.

Conclusions

Greater degree of insulin resistance induces apoptosis of hepatic cells as measured by the serum levels of CK‐18 fragments. Copyright © 2010 John Wiley & Sons, Ltd.
Proteomics analysis of the temporal changes in axonal proteins during maturation
Authors: Yamatani Hitoshi , Kawasaki Takahiko , Mita Sakura , Inagaki Naoyuki , Hirata Tatsumi
Published: March 2010

After the initial primary projection, axons undergo various structural and functional changes to establish mature neural circuits. The changes in protein expression associated with this maturation were investigated in lateral olfactory tract axons using two‐dimensional gel electrophoresis. The most prominent group upregulated during the period consisted of calcium‐dependent membrane‐binding proteins including VILIP1, neurocalcin δ, copine 6, and annexin A6 from three structurally different families. During maturation of primary cultured neurons, annexin A6 gradually became concentrated on the axon initial segment, and its overexpression significantly enhanced axon branching. On the other hand, overexpression of VILIP1 and neurocalcin δ reduced axon outgrowth and branching. The second group upregulated during axon maturation comprised tubulin‐ and microtubule‐binding proteins including CRMP2, guanine deaminase, MAP1B, and fibronectin type3 SPRY domain‐containing protein. Because the maturation of lateral olfactory axons involves massive extension of secondary collateral branches, the augmentation of these proteins during these stages may underlie the drastic restructuring of the axon cytoskeleton. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70:523–537, 2010
Determination of 13C/12C ratios of urinary excreted boldenone and its main metabolite 5β‐androst‐1‐en‐17β‐ol‐3‐one
Authors: Piper Thomas , Geyer Hans , Gougoulidis Vassilios , Flenker Ulrich , Schänzer Wilhelm
Published: March 2010

Boldenone (androsta–1,4–dien–17β–ol–3–one, Bo) is an anabolic steroid known to have been used in cattle breeding or equine sport as a doping agent for many years. Although not clinically approved for human application, Bo or its main metabolite 5β‐androst‐1‐en‐17β‐ol‐3‐one (BM1) were detected in several doping control samples. For more than 15 years the possibility of endogenous Bo production in human beings has been discussed. This is a challenging issue for doping control laboratories as Bo belongs to the list of prohibited substances of the World Anti‐Doping Agency and therefore the chance for false positive testing is significant. By GC/C/IRMS (gas chromatography/combustion/isotope ratio mass spectrometry) it should be possible to analyze the 13C/12C ratio of either Bo or BM1 and to distinguish whether their source is endogenous or exogenous. Therefore a method was developed to determine the 13C/12C ratios of Bo, BM1, pregnanediol, androsterone, etiocholanolone, and testosterone from a single urine specimen. The validity of the method was ensured by repeated processing of urine fortified with 2–50 ng/mL Bo and BM1. The specificity of the method was ensured by gas chromatography/mass spectrometry determinations. Out of 23 samples investigated throughout the last four years, 11 showed 13C/12C ratios of Bo or BM1 inconsistent with an exogenous origin. Two of these samples were collected from the same athlete within a one‐month interval, strongly indicating the chance of endogenous Bo production by this athlete. Copyright © 2010 John Wiley & Sons, Ltd.
Expanded‐Ring and Backbone‐Functionalised N‐Heterocyclic Carbenes
Authors: Iglesias Manuel , Beetstra Dirk J. , Cavell Kingsley J. , Dervisi Athanasia , Fallis Ian A. , Kariuki Benson , Harrington Ross W. , Clegg William , Horton Peter N. , Coles Simon J. , Hursthouse Michael B.
Published: March 2010

An unsaturated seven‐membered amidinium salt 7 decomposes in the presence of metal salts under basic conditions. However, 7 readily forms a Diels–Alder cycloadduct with CpH from which the RhI complexes may be prepared. Thus, structurally elaborate, sterically crowded carbene ligand complexes bearing peripheral unsaturated functionality are available in a short versatile synthesis.
Non‐Oxido Mixed‐Valence MnII6MnIII4 Cluster with Benzoate, Triethanolamine and Phosphonate Bridging Ligands
Authors: Dendrinou‐Samara Catherine , Muryn Christopher A. , Tuna Floriana , Winpenny Richard E. P.
Published: March 2010

The synthesis, structure and magnetic properties of a new non‐oxido mixed‐valence decanuclear heterometallic manganese cluster [K3Mn10(PhCOO)10(PhPO3)2(Htea)6](PhCOO)·6MeCN}n (1), where Htea2– is the dianion of triethanolamine, is reported. Compound 1 can be regarded as an analogue of 24‐metallacrown‐10, acting as a host for three potassium ions. The resulting {Mn10} cage crystallises as a cation; benzoate anions link the cages into a 1D polymer within the crystal. Direct current magnetic susceptibility measurements were collected at temperatures between 1.8 and 300 K and applied magnetic fields of 1 and 10 kG. The room‐temperature value is very close to the spin‐only value of 38.25 cm3 mol–1 K expected for an Mn10‐cage repeat unit comprising six MnII and four MnIII ions. At 2 K and 70 kG the magnetisation reaches a value of 19.5 NμB, suggesting a ground state larger than S = 10.
Efficient Synthesis of Biaryls through the Kumada Reaction Catalyzed by Carbene Adducts of Cyclopalladated Ferrocenylimine
Authors: Ren Gerui , Cui Xiuling , Wu Yangjie
Published: March 2010

A series of carbene adducts of cyclopalladated ferrocenylimine were prepared and evaluated in the cross‐coupling reaction of aryl halides with Grignard reagents (the Kumada reaction). Complex d exhibited high catalytic activity for the coupling of aryl chlorides with sterically hindered Grignard reagents and the reaction tolerated various functional groups. A wide range of biaryls were efficiently obtained in good to excellent yields in the presence of 0.5 mol‐% catalyst under mild reaction conditions.
Continuous Flow Palladium(II)‐Catalyzed Oxidative Heck Reactions with Arylboronic Acids
Authors: Odell Luke R. , Lindh Jonas , Gustafsson Tomas , Larhed Mats
Published: March 2010

Palladium(II)‐catalyzed oxidative Heck reactions were investigated under continuous flow conditions. Selective, fast and convenient protocols for the coupling of arylboronic acids with electron‐rich and electron‐poor olefins were developed by using a commercially available flow reactor.
Overview and rationale for the Systematic Screening and Assessment Method
Authors: Leviton Laura C. , Gutman Marjorie A.
Published: March 2010

This chapter gives the rationale and conceptual defense for the Systematic Screening and Assessment (SSA) Method, a way to identify the most promising innovations in preparation for rigorous evaluation. The SSA Method starts by identifying the innovations that real‐world practitioners have developed and then systematically assesses which innovations will offer the greatest payoff from further evaluation. Through sequential purchase of evaluative information, the SSA Method aims to avoid a variety of problems that evaluators encounter in studying innovations. Besides the identification of promising innovations for evaluation, the benefits include expert technical assistance and feedback to innovators, cross‐site syntheses of trends and common practices, and cost efficiency compared to evaluating innovations that have not been selected or screened for promise. © Wiley Periodicals, Inc., and the American Evaluation Association.
Applying the Systematic Screening and Assessment Method to childhood obesity prevention
Authors: Dawkins Nicola , Wethington Holly , Khan Laura Kettel , Grunbaum Jo Anne , Robin Leah , Barnes Seraphine Pitt , Cotton David , Dunet Diane O. , Leviton Laura C.
Published: March 2010

The authors describe application of the Systematic Screening and Assessment (SSA) Method to an initiative called the Early Assessment of Programs and Policies to Prevent Childhood Obesity. Over a 2‐year period, a national network of practitioners, policy makers, and funders nominated programs and policies across five substantive areas: school district local wellness policies, school‐based comprehensive physical activity programs, day care and after‐school programs, access to healthy foods in low‐income communities, and changes in the built environment to promote physical activity. The role of an expert panel in selecting innovations for evaluability assessment on the basis of the likelihood for a positive health impact is described. © Wiley Periodicals, Inc., and the American Evaluation Association.
Training and support for evaluability assessment methodology
Authors: Osuji Thearis A. , Dawkins Nicola , Rice Starr M.
Published: March 2010

The authors describe training of a network of professionals to conduct evaluability assessments for the Early Assessment of Programs and Policies on Childhood Obesity Initiative (Early Assessment Initiative). We learned that (1) the professionals trained had a diverse set of skills and expertise, (2) a training refresher session solidified methods and concepts, (3) evaluability assessments were improved when training included content on qualitative interviewing and development and application of logic models, and (4) comprehensive and consistent training methods helped to ensure consistency and methodological integrity. © Wiley Periodicals, Inc., and the American Evaluation Association.
Impact, insights, and implications of the Systematic Screening and Assessment Method
Authors: Khan Laura Kettel , Dawkins Nicola , Leviton Laura C.
Published: March 2010

The authors present both impressions and evidence about early impacts of the Systematic Screening and Assessment (SSA) Method as applied to childhood obesity prevention. They describe how the approach has rapidly identified policy and environmental interventions that are promising and worthy of further study, contributed to field knowledge about childhood obesity prevention, and encouraged further development of specific policies and environmental interventions. The SSA Method presents a new way of identifying promising interventions from the field. By stimulating discussion of real‐world application among prevention researchers, it has contributed to developing a research agenda for policy and environmental approaches to prevention. By identifying real‐world applications for formal evaluation, SSA facilitates a process parallel to translation of research to practice: that is, translation of practice to research. © Wiley Periodicals, Inc., and the American Evaluation Association.
fMRI study of mesial temporal lobe epilepsy using amplitude of low‐frequency fluctuation analysis
Authors: Zhang Zhiqiang , Lu Guangming , Zhong Yuan , Tan Qifu , Chen Huafu , Liao Wei , Tian Lei , Li Zhihao , Shi Jixin , Liu Yijun
Published: March 2010

Various functional imaging tools have been used to detect epileptic activity in the neural network underlying mesial temporal lobe epilepsy (mTLE). In the present fMRI study, a data‐driven approach was employed to map interictal epileptic activity in mTLE patients by measuring the amplitude of low‐frequency fluctuation (ALFF) of the blood oxygen level‐dependent (BOLD) signal. Twenty‐four left mTLE patients and 26 right mTLE patients were investigated by comparing with 25 healthy subjects. In the patients, the regions showing increased ALFF were consistently distributed in the mesial temporal lobe, thalamus, and a few of other cortical and subcortical structures composing a mesial temporal epilepsy network proposed previously, while the regions showing decreased ALFF were mostly located in the areas of so‐called default‐mode network. Data of simultaneous EEG‐fMRI from a portion of the patients suggested that the increases in ALFF might be associated with the interictal epileptic activity. Individual analyses based on statistic parametric mapping revealed a moderate sensitivity and a fairly high specificity for the lateralization of unilateral mTLE. We conclude that the ALFF analysis may provide a useful tool in fMRI study of epilepsy. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.
Overall brain connectivity maps show cortico‐subcortical abnormalities in schizophrenia
Authors: Salvador Raymond , Sarró Salvador , Gomar Jesús J. , Ortiz‐Gil Jordi , Vila Fidel , Capdevila Antoni , Bullmore Ed , McKenna Peter J. , Pomarol‐Clotet Edith
Published: March 2010

Abnormal interactions between areas of the brain have been pointed as possible causes for schizophrenia. However, the nature of these disturbances and the anatomical location of the regions involved are still unclear. Here, we describe a method to estimate maps of net levels of connectivity in the resting brain, and we apply it to look for differential patterns of connectivity in schizophrenia. This method uses partial coherences as a basic measure of covariability, and it minimises the effect of major physiological noise. When overall (net) connectivity maps of a sample of 40 patients with schizophrenia were compared with the maps from a matched sample of 40 controls, a single area of abnormality was found. It is an area of patient hyper‐connectivity and is located frontally, in medial and orbital structures, clearly overlapping the anterior node of the default mode network (DMN). When this area is used as a region of interest in a second‐level analysis, it shows functional hyper‐connections with several cortical and subcortical structures. Interestingly, the most significant abnormality is found with the caudate, which has a bilateral pattern of abnormality, pointing to a possible DMN–striatum deviant relation in schizophrenia. However, hyper‐connectivity observed with other regions (right hippocampus and amygdala, and other cortical structures) suggests a more pervasive alteration of brain connectivity in this disease. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.
Two New Indole Alkaloids from Tabernaemontana hystrixSteud. (Apocynaceae)
Authors: de Souza Jucimar J. , Mathias Leda , Braz‐Filho Raimundo , Vieira Ivo J. Curcino
Published: March 2010

Two new monoterpene indole alkaloids named ibogamine‐7,8‐dione (1) and 12‐methoxyvoachalotine (2), and eight known ones, coronaridine (3), coronaridine hydroxyindolenine (4), 5‐oxocoronaridine (5), 3‐oxocoronaridine hydroxyindolenine (6), 3‐oxocoronaridine (7), vobasine (8), ibogamine (9), and olivacine (10), were isolated from a CH2Cl2 extract of the root bark from Tabernaemontana hystrix. The structures of the compounds were elucidated on the basis of spectroscopic data analyses, mainly 1H‐ and 13C‐NMR, including 2D experiments (1H,1H‐COSY, HMBC, and HMQC).
Five New C19‐Diterpenoid Alkaloids from Aconitum hemsleyanum
Authors: Shen Yong , Zuo Ai‐Xue , Jiang Zhi‐Yong , Zhang Xue‐Mei , Wang Hong‐Ling , Chen Ji‐Jun
Published: March 2010

Five new C19‐diterpenoid alkaloids, named hemsleyaconitines A–E (1–5, resp.), were isolated from Aconitum hemsleyanum Pritz. By UV, IR, MS, 1D‐ and 2D‐NMR analyses, their structures were elucidated as 18‐dehydroxygeniculatine D (1), 6‐hydroxy‐14‐O‐veratroylneoline (2), 14‐O‐acetyl‐8‐ethoxysachaconitine (3), 18‐veratroylkaracoline (4) and 8‐O‐ethylaustroconitine B (5).
Three New Terpenoids from Pinus yunnanensis
Authors: Wang Bin , Ju Jing , He Xiu‐Feng , Yuan Tao , Yue Jian‐Min
Published: March 2010

A new abietatrienoid, 15‐methoxydidehydroabietic acid (1), a new ring B‐seco abietatrienoid, 10‐hydroxy‐9,10‐secoabieta‐8,11,13‐trien‐18‐oic acid (2), and a new tetracyclic triterpenoid, pinusyunnanol (3), together with five known compounds, were obtained from the twigs and needles of Pinus yunnanensis. The structures of the new compounds were elucidated by means of extensive spectroscopic analyses.
An Environmentally Benign Catalytic Method for Efficient and Selective Nucleophilic Ring Opening of Oxiranes by Zirconium Tetrakis(dodecyl Sulfate)
Authors: Jafarpour Maasoumeh , Rezaeifard Abdolreza , Aliabadi Marzieh
Published: March 2010

An operationally simple and environmentally benign protocol for a highly regio‐ and chemoselective preparation of β‐substituted alcohols by means of ring‐opening reactions of oxiranes with various aliphatic alcohols, H2O, NaN3, and NaCN as nucleophiles in the presence of catalytic amounts of zirconium tetrakis(dodecyl sulfate) as Lewis acid/surfactant‐combined catalysts (LASCs) was developed. The high efficiency of the catalyst was confirmed by the high product yields obtained within desired times and, in particularly by the reusability of the ZrIV complex.
Three New Dimeric Orcinol Glucosides from Curculigo orchioides
Authors: Zuo Ai‐Xue , Shen Yong , Jiang Zhi‐Yong , Zhang Xue‐Mei , Zhou Jun , Lü Jun , Chen Ji‐Jun
Published: March 2010

Three new phenolic glucosides named orcinosides A, B, and C (1, 2, and 3, resp.) were isolated in low yields (4.0×10−6, 11.5×10−6, 4.5×10−6%, resp.) from the rhizomes of Curculigo orchioides. Their structures were elucidated by comprehensive spectroscopic analyses including FAB‐MS, HR‐ESI‐MS, IR, and 1D‐ and 2D‐NMR (HSQC, HMBC) data. Compounds 1–3 contained two orcinol‐glucoside moieties linked through a CH2 group.
Synthesis of Racemic Δ3‐2‐Hydroxybakuchiol and Its Analogues
Authors: Shi Lei , Lei Xinsheng , Zhang Jiange , Lin Guoqiang
Published: March 2010

The first synthetic approach to (±)‐Δ3‐2‐hydroxybakuchiol (=4‐[(1E,5E)‐3‐ethenyl‐7‐hydroxy‐3,7‐dimethylocta‐1,5‐dien‐1‐yl]phenol; 14) and its analogues 13a–13f was developed by 12 steps (Schemes 2 and 3). The key features of the approach are the construction of the quaternary C‐center bearing the ethenyl group by a Johnson–Claisen rearrangement (→6); and of an (E)‐alkenyl iodide via a Takai–Utimoto reaction (→11); and an arylation via a Negishi cross‐coupling reaction (→12e–12f).
Specific Deuteration in Patuletin and Related Flavonoids via Keto–Enol Tautomerism: Solvent‐ and Temperature‐Dependent 1H‐NMR Studies
Authors: Faizi Shaheen , Siddiqi Humaira , Naz Aneela , Bano Samina , Lubna
Published: March 2010

An H/D exchange process in patuletin (1) and its derivatives in D‐donor solvents (e.g., CF3COOD), which occurs regioselectively at C(8) was observed for the first time during NMR studies. The effect of substituents and temperature on the deuteration of various flavonoids (see Fig. 1) which include apigenin, chrysin, galangin, kaempferol, luteolin, morin, myricetin, patuletin, patulitrin, and quercetin, as well as derivatives of patuletin was examined extensively under NMR conditions. The rate constant of deuteration at C(8) of patuletin (1) and two flavones, luteolin (3) and apigenin (12), was also determined in CF3COOD. The D‐atom was introduced into the flavonoids via a keto–enol tautomerism (Scheme 1). During these studies, monodeuterated patuletin was also obtained as a new compound. The examined flavonoids have been reported to possess significant pharmacological activities, and their deuterated derivatives would be of importance for the identification and quantification of these compounds in biological matrices.
Medicinal Flowers. Part 29. Acylated Oleanane‐Type Triterpene Bisdesmosides: Perennisaponins G, H, I, J, K, L, and M with Pancreatic Lipase Inhibitory Activity from the Flowers of Bellis perennis
Authors: Morikawa Toshio , Li Xuezheng , Nishida Eriko , Nakamura Seikou , Ninomiya Kiyofumi , Matsuda Hisashi , Oda Yoshimi , Muraoka Osamu , Yoshikawa Masayuki
Published: March 2010

The MeOH extract from the flowers of Bellis perennis was found to show pancreatic‐lipase inhibitory activity (IC50 455 μg/ml). From the extract, seven new triterpene saponins named perennisaponins G (1; IC50 163 μM), H (2; 137 μM), I (3; 147 μM), J (4; 148 μM), K (5; 223 μM), L (6; 81.4 μM), and M (7; 195 μM) were isolated as pancreatic lipase inhibitors. The stereostructures of 1–7 were elucidated on the basis of chemical and spectroscopic evidence.
Structural Characterization of an Artefact and Simultaneous Quantification of Two Monoterpenes and Their Artefacts of Isolation in White‐Peony Root
Authors: Cheng Yushan , Peng Cheng , Zhang Hao , Liu Xianbo
Published: March 2010

Sodium benzoylpaeoniflorinsulfonate (3), a new artefact, was isolated from sulfur‐fumigated white‐peony root and characterized by mass and NMR spectroscopy. A HPLC method was developed for the simultaneous determination of sodium paeoniflorinsulfonate (1), paeoniflorin (2), sodium benzoylpaeoniflorinsulfonate (3), and benzoylpaeoniflorin (4). The method developed was successfully applied to quantify the four compounds in 14 white‐peony‐root samples. The quantity of four constituents in sulfur‐fumigated white‐peony root may be regarded as an index for the quality assessment of this Chinese medicine.
Three New Kaempferol Glycosides from Cardamine leucantha
Authors: Yang Fan , Su Yan‐Fang , Bi Yan‐Ping , Xu Jing , Zhu Zhi‐Qiang , Tu Guang‐Zhong , Gao Xiu‐Mei
Published: March 2010

Three new kaempferol glycosides, kaempferol 3‐O‐β‐D‐glucopyranosyl‐(1→6)‐β‐D‐galactopyranosyl‐7‐O‐α‐L‐rhamnopyranoside (1), kaempferol 3‐O‐β‐D‐galactopyranosyl‐7‐O‐β‐D‐glucopyranosyl‐(1→3)‐α‐L‐rhamnopyranoside (2), and kaempferol 3‐O‐β‐D‐glucopyranosyl‐(1→6)‐β‐D‐galactopyranosyl‐7‐O‐β‐D‐glucopyranosyl‐(1→3)‐α‐L‐rhamnopyranoside (3), were isolated from the whole herbs of Cardamine leucantha, along with three known kaempferol glycosides, kaempferol 7‐O‐α‐L‐rhamnopyranoside, kaempferitrin, and kaempferol 3‐O‐β‐D‐galactopyranosyl‐7‐O‐α‐L‐rhamnopyranoside. Their structures were elucidated on the basis of spectroscopic methods.
11‐ and 4′‐Epimers of Chaetomugilin A, Novel Cytostatic Metabolites from Marine Fish‐Derived Fungus Chaetomium globosum
Authors: Muroga Yasuhide , Yamada Takeshi , Numata Atsushi , Tanaka Reiko
Published: March 2010

11‐ and 4′‐epichaetomugilin A were isolated from a strain of Chaetomium globosum that was originally isolated from the marine fish Mugil cephalus. 11‐Epichaetomugilin A is the first compound to have an opposite absolute configuration at C(11) to that of other azaphilones isolated to date. Their absolute configurations were elucidated on the basis of spectroscopic analyses, including 1D‐ and 2D‐NMR techniques, and some chemical transformations. 11‐Epichaetomugilin A weakly inhibited the growth of cultured P388 cells and HL‐60 cells (IC50 88.9 and 66.7 μM, resp.).
Correction of a Reported Xanthone Synthesis: The Preparation of a Benzo[c]coumarin
Authors: Benn Michael H. , Parvez Masood , Perry Nigel B. , Rauk Arvi , van Klink John W.
Published: March 2010

Reinvestigation of a reported synthesis of 5,8‐dihydroxy‐1,3‐dimethoxyxanthone from the reaction of 3,5‐dimethoxyphenol with 2‐(methoxycarbonyl)‐1,4‐benzoquinone resulted in the identification of the product as the isomer of benzo[c]coumarin, i.e., 7,10‐dihydroxy‐1,3‐dimethoxy‐6H‐dibenzo[b,d]pyran‐6‐one, established by X‐ray crystallography. This requires the revision of the structures of the derivatives that were reported.
Synthesis of 1,3‐Selenazol‐2(3H)‐imines
Authors: Atanassov Plamen K. , Linden Anthony , Heimgartner Heinz
Published: March 2010

The reaction of N,N′‐diarylselenoureas 16 with phenacyl bromide in EtOH under reflux, followed by treatment with NH3, gave N,3‐diaryl‐4‐phenyl‐1,3‐selenazol‐2(3H)‐imines 13 in high yields (Scheme 2). A reaction mechanism via formation of the corresponding Se‐(benzoylmethyl)isoselenoureas 18 and subsequent cyclocondensation is proposed (Scheme 3). The N,N′‐diarylselenoureas 16 were conveniently prepared by the reaction of aryl isoselenocyanates 15 with 4‐substituted anilines. The structures of 13a and 13c were established by X‐ray crystallography.
Disclaiming onerous property in insolvency: A comparative study
Authors: Omar Paul J.
Published: March 2010

Insolvency practitioners in charge of certain insolvency procedures have a facility open to them to disclaim property deemed to be onerous and whose retention as part of the debtor's estate may affect the mass of creditors. This article takes a comparative survey of a number of jurisdictions in the common‐law and civil‐law worlds. Its purpose is to assess whether work carried out at international level seeking to benchmark insolvency procedures generally should be revised to take into account enviornmental concerns in relation to such disclaimed property. Copyright © 2010 John Wiley & Sons, Ltd.
Binding of anti‐Parkinson's disease drugs to human serum albumin is allosterically modulated
Authors: Fanali Gabriella , Rampoldi Viviana , Masi Alessandra di , Bolli Alessandro , Lopiano Leonardo , Ascenzi Paolo , Fasano Mauro
Published: March 2010

Binding of drugs to plasma proteins is an important determinant for their efficacy because it modulates drug availability to the intended target. Co‐administered drugs may bind to the same protein site or to different functionally linked clefts following competitive and allosteric mechanisms. Here, we report a thermodynamic and computational characterization of the binding mode of apomorphine and benserazide, two therapeutic agents co‐administered in the treatment of Parkinson's disease, to human serum albumin (HSA). Apomorphine binds to HSA with a simple equilibrium (Kd= 3.1 × 10−6M). Conversely, benserazide binds to HSA with two independent equilibria (Kd1≤ 10−6M andKd2= 5.0 × 10−5M). Values ofKdandKd2increase to 1.5 × 10−5M and 5.0 × 10−4M, respectively, in the presence of heme. Accordingly, theKdvalue for heme binding to HSA increases from 5.0 × 10−7M to 4.8 × 10−6M and 9.2 × 10−7M, in the presence of saturating amounts of apomorphine and benserazide, respectively. TheKd1value for benserazide binding to HSA is not affected by heme binding, whereas apomorphine and benserazide inhibit warfarin binding to HSA, and vice versa. Therefore, apomorphine and the second benserazide molecule bind to the warfarin site, allosterically linked to the heme site. Simulated docking of apomorphine and benserazide into the warfarin site provides favorable values of intermolecular energy (−23.0 kJ mol−1and −15.2 kJ mol−1, respectively). Considering the apomorphine, benserazide, and HSA‐heme plasma levels and the possible co‐administration of warfarin, these results appear relevant in the management of patients affected by Parkinson's disease. © 2010 IUBMB IUBMB Life, 62(5): 371–376, 2010
Dichloroacetate‐ and trichloroacetate‐induced oxidative stress in the hepatic tissues of mice after long‐term exposure
Authors: Hassoun Ezdihar A. , Cearfoss Jacquelyn , Spildener Jessica
Published: March 2010

Dichoroacetate (DCA) and trichloroacetate (TCA) were found to be hepatotoxic and hepatocarcinogenic in rodents. To investigate the role of oxidative stress in the long‐term hepatotoxicity of the compounds, groups of mice were administered 7.7, 77, 154 and 410 mg kg−1 per day, of either DCA or TCA, by gavage, for 4 weeks (4‐W) and 13 weeks (13‐W), and superoxide anion (SA), lipid peroxidation (LP) and DNA‐single strand breaks (SSBs) were determined in the hepatic tissues. Significant increases in all of the biomarkers were observed in response to the tested doses of both compounds in the two test periods, with significantly greater increases observed in the 13‐W, as compared with the 4‐W, period. Hepatomegaly was only observed with a DCA dose of 410 mg kg−1 per day in the 13‐W treatment period, and that was associated with significant declines in the biomarkers, when compared with the immediately lower dose. With the exception of LP production in the 13‐W treatment period that was similarly induced by the two compounds, the DCA‐induced increases in all of the biomarkers were significantly greater than those of TCA. Since those biomarkers were significantly induced by the compounds' doses that were shown to be carcinogenic but at earlier periods than those demonstrating hepatotoxicity/haptocarcinogencity, they can be considered as initial events that may lead to later production of those long‐term effects. The results also suggest LP to be a more significant contributing mechanism than SA and DNA damage to the long‐term hepatotoxicity of TCA. Copyright © 2010 John Wiley & Sons, Ltd.