bluuebunny/crossref_metadata_2025_split huggingface dataset:
Solid‐Phase Synthesis of Structurally Diverse Heterocycles by an Amide–Ketone Condensation/N‐Acyliminium Pictet–Spengler Sequence
Authors: Komnatnyy Vitaly V. , Givskov Michael , Nielsen Thomas E. 
Published: November 2012

AbstractAn efficient approach for the solid‐phase synthesis of structurally diverse heterocyclic compounds is presented. Under acidic reaction conditions, peptidic levulinamides undergo intramolecular ketone–amide condensation reactions to form cyclic N‐acyliminium intermediates. In the presence of a tethered nucleophile, a second cyclization reaction results in the formation of a fused bicyclic ring system. The scope of the methodology was demonstrated by several combinations of substituted ketones and nucleophiles, the latter conveniently originating from amino acids with functionalized side chains, such as tryptophan, substituted phenylalanines, and cysteine. The cyclization sequence provides diastereomerically pure products in high yields. In one extension of the methodology, the resulting relative stereochemistry of the products enables the formation of bridged ring systems by a unique cyclative release mechanism.
Impact of Lesion Length on Functional Significance in Intermediate Coronary Lesions
Authors: Iguchi Tomokazu , Hasegawa Takao , Nishimura Satoshi , Nakata Shinji , Kataoka Toru , Ehara Shoichi , Hanatani Akihisa , Shimada Kenei , Yoshiyama Minoru 
Published: November 2012

AbstractBackground:Myocardial fractional flow reserve (FFR) is useful in the evaluation of coronary lesion ischemia. However, the impact of lesion length on FFR has not been adequately assessed.Hypothesis:We hypothesized that lesion length would influence functional significance in intermediate coronary lesions.Methods:FFR measurements were assessed in 136 patients (163 lesions) with stable angina who had >40% stenotic coronary lesion by quantitative coronary angiography (QCA). One hundred sixty‐three lesions were classified as intermediate (40%–70% stenosis; n=107; group I) or significant (≥70%; n=56; group S) by QCA. We assessed the relationships between lesion length, coronary stenosis, and FFR in these 163 lesions.Results:Regression analysis revealed an inverse correlation between the percentage of diameter stenosis (%DS) and FFR in group S (r = −0.83, P < 0.0001). In group I, no significant correlation was found between %DS and FFR (r = −0.06, P = 0.55), whereas lesion length was significantly inversely correlated with FFR (r = −0.79, P < 0.0001). Receiver operating characteristic curve analysis demonstrated that the best cutoff value for predicting an FFR value <0.80 was a lesion length >16.1 mm in group I (sensitivity, 86%; specificity, 94%).Conclusions:These study findings suggest that lesion length has a physiologically significant impact on intermediate‐grade coronary lesions. Clin. Cardiol. 2011 DOI: 10.1002/clc.22076The authors have no funding, financial relationships, or conflicts of interest to disclose.
Epigenetic silencing of Id4 identifies a glioblastoma subgroup with a better prognosis as a consequence of an inhibition of angiogenesis
Authors: Martini Maurizio , Cenci Tonia , D'Alessandris Giorgio Quintino , Cesarini Valeriana , Cocomazzi Alessandra , Ricci‐Vitiani Lucia , De Maria Ruggero , Pallini Roberto , Larocca Luigi Maria 
Published: November 2012

AbstractBACKGROUND:Inhibitors of DNA binding/differentiation (Id1 to Id4) are a family of helix‐loop‐helix transcription factors, which are highly expressed during embryogenesis and at lower levels in mature tissues. Id4 plays an important role in neuronal stem cell differentiation, and its deregulation has been implicated in glial neoplasia.METHODS:The methylation status of Id4 was analyzed by methylation‐specific polymerase chain reaction (PCR) in 62 glioblastoma (GBM) cases and in 20 normal brain tissues. Methylation status of Id4 was confirmed by sequencing after subcloning and messenger RNA (mRNA) and protein expression. We also evaluated the mRNA expression of MGP (matrix GLA protein), TGF‐β1 (transforming growth factor beta 1), and VEGF (vascular endothelial growth factor) by real‐time PCR analysis. Clinical and histological assessment of tumor angiogenesis was performed by evaluating the relative enhancing tumor ratio on magnetic resonance imaging and microvessel density on von Willebrand factor–stained sections, respectively.RESULTS:The promoter of Id4 was methylated in 23 of 62 (37%) GBMs. In methylated GBMs, Id4 mRNA was significantly reduced, compared with unmethylated GBMs (P = .0002). A significant reduction of protein expression was detected in all hypermethylated cases. GBMs with methylated Id4 showed a significant reduction of MGP, TGF‐β1, and VEGF mRNA expression and had significantly lower relative enhancing tumor ratio (P = .0108) and microvessel density (P = .0241) values with respect to unmethylated GBMs. Finally, Id4 methylation was significantly associated with a favorable clinical outcome (P = .0006).CONCLUSIONS:These data suggest that methylation of Id4 may be involved in the pathogenesis of GBM and in the resistance of this neoplasm to conventional treatment throughout MGP‐mediated neoangiogenesis. Cancer 2013. © 2012 American Cancer Society
Time to adjuvant chemotherapy and survival in non–small cell lung cancer
Authors: Booth Christopher M. , Shepherd Frances A. , Peng Yingwei , Darling Gail , Li Gavin , Kong Weidong , Biagi James J. , Mackillop William J. 
Published: November 2012

AbstractBACKGROUND:The time interval between surgery and initiation of adjuvant chemotherapy (ACT) may impact survival in colorectal and breast cancers. This is the first report describing the association between time to adjuvant chemotherapy (TTAC) and survival in non–small cell lung cancer (NSCLC).METHODS:All cases of NSCLC diagnosed in Ontario, Canada, from 2004 to 2006 who underwent surgical resection (n = 3354) were identified using the Ontario Cancer Registry. TTAC was defined as the interval between dates of surgery and initiation of ACT. Factors associated with TTAC greater than 10 weeks were evaluated by logistic regression. The Cox proportional hazards model was used to describe the effect of delayed TTAC (analyzed as a continuous variable) on overall survival.RESULTS:Among the 1032 cases treated with ACT, the median TTAC was 8 weeks (range, 1‐16 weeks); 35% of cases initiated ACT more than 10 weeks after surgery. Rates of TTAC greater than 10 weeks varied widely across regions (11%‐50%, P = .001). There was no significant association between increased comorbidity and delayed TTAC; there was a trend toward greater delay in TTAC with longer postoperative hospital stay (P = .054) and postoperative readmission to hospital (P = .056). Male sex, higher stage of disease, greater comorbidity, and more extensive surgery were independently associated with inferior survival. TTAC was not associated with overall survival (odds ratio = 1.00, 95% confidence interval = 0.99‐1.00).CONCLUSIONS:One‐third of NSCLC patients treated with ACT in the general population start ACT beyond 10 weeks after surgery. Delayed TTAC does not appear to be associated with inferior survival in NSCLC. Cancer 2013. © 2012 American Cancer Society.
Attrition rates, reasons, and predictive factors in supportive care and palliative oncology clinical trials
Authors: Hui David , Glitza Isabella , Chisholm Gary , Yennu Sriram , Bruera Eduardo 
Published: November 2012

AbstractBACKGROUND:Attrition is common among supportive care/palliative oncology clinical trials. However, to the authors' knowledge, few studies to date have documented the reasons and predictors for dropout. In the current study, the authors' objective was to determine the rate, reasons, and factors associated with attrition both before reaching the primary endpoint and at the end of the study.METHODS:A review of all prospective interventional supportive care/palliative oncology trials conducted in the Department of Palliative Care and Rehabilitation Medicine at The University of Texas MD Anderson Cancer Center in Houston between 1999 and 2011 was performed. Patient and study characteristics and attrition data were extracted.RESULTS:A total of 1214 patients were included in 18 clinical trials. The median age of the patients was 60 years. Approximately 41% had an Eastern Cooperative Oncology Group performance status of ≥ 3, a median Edmonton Symptom Assessment Scale (ESAS) for fatigue of 7 of 10, and a median ESAS for dyspnea of 2 of 10. The attrition rate was 26% (95% confidence interval [95% CI], 23%‐28%) for the primary endpoint and 44% (95% CI, 41%‐47%) for the end of the study. Common reasons for primary endpoint dropout were symptom burden (21%), patient preference (15%), hospitalization (10%), and death (6%). Primary endpoint attrition was associated with a higher baseline intensity of fatigue (odds ratio [OR], 1.10 per point; P = .01) and a longer study duration (P = .04). End‐of‐study attrition was associated with higher baseline levels of dyspnea (OR, 1.06; P = .01), fatigue (OR, 1.08; P = .01), Hispanic race (OR, 1.87; P = .002), higher level of education (P = .02), longer study duration (P = .01), and outpatient studies (P = 0.05).CONCLUSIONS:The attrition rate was high in supportive care/palliative oncology clinical trials, and was associated with various patient characteristics and a high baseline symptom burden. These findings have implications for future clinical trial design including eligibility criteria and sample size calculation. Cancer 2013. © 2012 American Cancer Society.
Phase 2 trial of concurrent bevacizumab and transhepatic arterial chemoembolization in patients with unresectable hepatocellular carcinoma
Authors: Buijs Manon , Reyes Diane K. , Pawlik Timothy M. , Blackford Amanda L. , Salem Riad , Messersmith Wells A. , Weekes Colin D. , Mulcahy Mary , Kamel Ihab R. , Geschwind Jean‐Francois H. 
Published: November 2012

AbstractBACKGROUND:Vascular endothelial growth factor is up‐regulated in hepatocellular carcinoma (HCC) and is further up‐regulated after transhepatic arterial chemoembolization. The authors of this report conducted a phase 2 trial to evaluate the safety and efficacy of bevacizumab combined with chemoembolization in patients with unresectable HCC.METHODS:Patients who had an Eastern Cooperative Oncology Group performance of status 0 to 2, a Child‐Pugh score of A or B, and Barcelona Clinic Liver Cancer stage B or C HCC were eligible. Treatment consisted of bevacizumab every 2 weeks and chemoembolization during the third week of a 6‐week cycle for up to 3 cycles over 6 months. The primary endpoints were safety and efficacy.RESULTS:Twenty‐five patients received chemoembolization and bevacizumab. The most common grade 3 and 4 events after the first treatment cycle were leukocytopenia (12%), fatigue (12%), and hyponatremia (12%). Serious toxicities that had a known association with bevacizumab were observed in 4 patients. Thirty‐day mortality was 0%. The median time to tumor progression for the targeted lesions was not reached, and overall survival was 10.8 months. The objective response rate was 60% using enhancement response evaluation criteria, and the disease control rate was 100%.CONCLUSIONS:Concurrent treatment with bevacizumab and chemoembolization was safe in carefully selected patients and demonstrated antitumor activity in patients with unresectable HCC. These results support the further development of bevacizumab combined with chemoembolization as a treatment for unresectable HCC. Cancer 2013. © 2012 American Cancer Society.
Prospective analysis of atypical epithelial cells as a high‐risk cytologic feature for malignancy in pancreatic cysts
Authors: Pitman Martha B. , Yaeger Kurt A. , Brugge William R. , Mino‐Kenudson Mari 
Published: November 2012

AbstractBACKGROUND:Pancreatic cysts are aspirated to assess whether a cyst is mucinous on one hand and malignant on the other. The authors' retrospective data have indicated that high‐grade atypical epithelial cells (AECs) identified on cytology are a high‐risk feature and a better threshold than “positive” for detecting malignancy. The objective of the current study was to assess the accuracy of AECs in predicting malignancy in pancreatic cysts.METHODS:Cysts aspirated by endoscopic ultrasound (EUS)‐guided fine‐needle aspiration (EUS‐FNAs) obtained between January 2006 and June 2011 were evaluated. Cytologic, histologic, imaging, and cyst fluid analysis data were recorded. AECs were defined as cells that had an increased nuclear‐to‐cytoplasmic ratio and nuclear hyperchromasia with or without membrane abnormalities and with or without cytoplasmic vacuoles, but of insufficient quality and quantity for a “positive” interpretation. Malignancy included mucinous cysts with high‐grade dysplasia and invasive carcinoma. Performance characteristics of cytology with AECs or worse (high‐grade atypia [HGA]) for predicting malignancy were assessed.RESULTS:There were 70 FNAs that had histologic confirmation from 404 EUS‐FNAs in 352 patients. Excluding 4 nondiagnostic FNAs, the study cohort consisted of 66 FNAs for analysis. There were 24 malignant cysts with 20 true‐positive, 4 false‐negative, 36 true‐negative, and 6 false‐positive results. For the detection of malignancy, HGA had 83% sensitivity, 86% specificity, a positive predictive value of 77%, a negative predictive value of 90%, and 85% overall accuracy. The lower threshold for malignancy with AECs resulted in a 12% increase in the detection of malignancy.CONCLUSIONS:A finding of AECs on cytology is a high‐risk feature for malignancy and is an accurate triage threshold for resection. Cancer (Cancer Cytopathol) 2013;121:29–36 © 2012 American Cancer Society.
The addition of RPMI significantly improves the cellularity of cerebrospinal fluid cytology specimens over time
Authors: Renshaw Scott A. , Gupta Suresh , Campos Michael , Hodes Lori , Renshaw Andrew A. , Gould Edwin W. 
Published: November 2012

BACKGROUNDCytology specimens of cerebrospinal fluid (CSF) may be hypocellular, and the cells in CSF specimens degrade rapidly.METHODSIn the current study, the authors attempted to determine whether the addition of RPMI media to CSF specimens at the time of their receipt in the laboratory could improve the cellularity of specimens that would be processed 24 hours and 48 hours later.RESULTSCompared with the initial specimen that was processed at the time of receipt in the laboratory, specimens with RPMI added preserved at least 90% of their cellularity. In contrast, specimens that were processed without RPMI lost 70% and 94% of their cellularity at 24 hours and 48 hours, respectively, even with refrigeration.CONCLUSIONSFor CSF specimens that cannot be immediately processed, the addition of RPMI appears to significantly improve cellularity at 24 hours to 48 hours after their receipt in the laboratory. Cancer (Cancer Cytopathol) 2013;121:271–4. © 2012 American Cancer Society.
Frequency Shift in Graphene‐Enhanced Raman Signal of Molecules
Authors: Yaghobian Fatemeh , Korn Tobias , Schüller Christian 
Published: November 2012

AbstractGraphene‐enhanced Raman scattering (GERS) is emerging as an important method due to the need for highly reproducible, quantifiable, and biocompatible active substrates. As a result of its unique two‐dimensional carbon structure, graphene provides particularly large enhanced Raman signals for molecules adsorbed on its surface. In this work, the GERS signals of a test molecule, 4‐mercaptobenzoic acid (4‐MBA), with reproducible enhancement factors are discussed and compared with surface‐enhanced Raman scattering (SERS) signals from highly active substrates, covered with spherical silver nanoparticles. It is shown that chemical interactions between the molecule and graphene can result in a frequency shift in the graphene‐enhanced Raman signal of the molecule.
Self‐Assembled Polymeric Chelate Nanoparticles as Potential Theranostic Agents
Authors: Škodová M. , Černoch P. , Štěpánek P. , Chánová E. , Kučka J. , Kálalová Z. , Kaňková D. , Hrubý M. 
Published: November 2012

AbstractImprovements in cancer diagnostics and therapy have recently attracted the interest of many different branches of science. This study presents one of the new possible approaches in the diagnostics and therapy of cancer by using polymeric chelates as carriers. Graft copolymers with a backbone containing 8‐hydroxyquinoline‐5‐sulfonic acid chelating groups and poly(ethylene oxide) hydrophilic grafts are synthesized and characterized. The polymers assemble and form particles after the addition of a biometal cation, such as iron or copper. The obtained nanoparticles exhibit a hydrodynamic diameter of around 25 nm and a stability of at least several hours, which are counted as essential parameters for biomedical purposes. To prove their biodegradability, a model degradation with deferoxamine is performed and, together with high radiolabeling efficiency with copper‐64, their possible use for nuclear medicine purposes is demonstrated.
Controlled Synthesis of Monodisperse SiO2TiO2Microspheres with a Yolk–Shell Structure as Effective Photocatalysts
Authors: Yoo Jung Bo , Yoo Hyo Jin , Lim Byung Wook , Lee Kang Hyuk , Kim Mi Hyun , Kang Donghyeon , Hur Nam Hwi 
Published: November 2012

AbstractMonodisperse yolk–shell SiO2–TiO2microspheres were synthesized using core–shell silica microspheres as templates. In the absence of prior surface modifications, a uniform coating of the TiO2layer on the core–shell silica was achieved through a sol–gel route. Mesoporous silica shells between the outer TiO2shell and the SiO2core were selectively removed by using a weak base, yielding yolk–shell SiO2–TiO2microspheres (ys‐SiO2@TiO2). Using the same templates, we synthesized Pt‐encased microspheres (SiO2@Pt‐TiO2), in which Pt nanoparticles are embedded between the SiO2core and the TiO2shell. Selective etching of the silica shells in SiO2@Pt‐TiO2yields Pt‐encased yolk–shell SiO2–TiO2microspheres (ys‐SiO2@${ \char60 {\rm{Pt}} \char62 }$TiO2), which contain void spaces suitable for use as nanoreactors. The ys‐SiO2@${ \char60 {\rm{Pt}} \char62 }$TiO2catalyst shows enhanced hydrogen production from water under UV‐light irradiation presumably as a result of multiple reflections within the void spaces and can be reused without losing their activity. Moreover, this core–shell template method is effective for the synthesis of other yolk–shell microspheres with different metal oxides.
Commentary on ‘Probiotics for prevention of necrotizing enterocolitis in preterm infants’
Authors: Caplan Michael 
Published: November 2012

AbstractThis is a commentary on a Cochrane review, published in this issue of EBCH, first published as: Alfaleh K, Anabrees J, Bassler D, Al‐Kharfi T. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database of Systematic Reviews 2011, Issue 3. Art. No.: CD005496. DOI: 10.1002/14651858.CD005496.pub3.Further information for this Cochrane review is available in this issue of EBCH in the accompanying Summary article. Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Deoxythiosugar Derivatives with Furano, Pyrano, and Septano Motifs from L‐Gulono‐1,4‐lactone and D‐Glycero‐D‐gulo‐heptono‐1,4‐lactone
Authors: Gunasundari Thanikachalam , Chandrasekaran Srinivasan 
Published: November 2012

AbstractA short synthesis of thiosugar derivatives mimicking furanose, pyranose, and septanose structures has been achieved starting from L‐gulono‐1,4‐lactone and D‐glucoheptono‐1,4‐lactone. Different strategies used in the synthesis are: (1) a nucleophilic displacement and Michael addition; (2) epoxide ring opening and Michael addition; (3) epoxide ring opening and nucleophilic displacement process; and (4) double nucleophilic displacement. All of these reactions used benzyltriethylammonium tetrathiomolybdate, (BnEt3N)2MoS4 as the sulfur‐transfer reagent.
Intramolecular Carbolithiation Reactions in the Construction of Medium‐Sized Rings. Synthesis of Pyrroloisoquinolines, Benzazepines, and Benzazocines
Authors: García‐Calvo Oihane , Coya Estíbaliz , Lage Sergio , Coldham Iain , Sotomayor Nuria , Lete Esther 
Published: November 2012

AbstractMesityllithium (MesLi) was found to be superior to butyllithium for the formation of aryllithium intermediates by iodine–lithium exchange. Subsequent intramolecular carbolithiation of the 2‐alkenyl‐substituted ortho‐lithiated N‐benzylpyrroles proceeded efficiently when the alkene was substituted with an electron‐withdrawing group. The procedure is applicable to the construction of six‐, seven‐, and eight‐membered rings, thus, opening new routes to pyrroloisoquinolines, benzazepines, and benzazocines. Although the use of (–)‐sparteine as a chiral ligand led to low levels of enantioselection, enantiomerically pure isoquinolines could be synthesized by applying this protocol to the related pyrrolidines derived from proline, as the reactions proceeded with complete diastereoselectivity.
Effects of hydrophobicity on splash erosion of model soil particles by a single water drop impact
Authors: Ahn Sujung , Doerr Stefan H. , Douglas Peter , Bryant Robert , Hamlett Christopher A.E. , McHale Glen , Newton Michael I. , Shirtcliffe Neil J. 
Published: November 2012

ABSTRACTRaindrop impact can be a major contributor to particle mobilization for soils and other granular materials. In previous work, water repellent soils, comprised of hydrophobic particles, have been shown to exhibit greater splash erosion losses under multiple drop impact. However, the underlying principle differences in splash behavior between hydrophobic and hydrophilic granular surfaces have not been studied to date. In this study the effects of particle hydrophobicity on splash behaviour by a single water drop impact were examined using high‐speed videography. Water drops (4 mm in diameter) were dropped on beds of hydrophilic and hydrophobic glass beads (sieved range: 350–400 µm), serving as model soil particles. The drop velocity on impact was 2.67 m s‐1, which corresponds to ~30% of the terminal velocity of a raindrop of similar size. The resulting impact behaviour was measured in terms of the trajectories of particles ejected from the beds and their final resting positions. The response to the impacting water drop was significantly different between hydrophilic and hydrophobic particles in terms of the distance distribution, the median distance travelled by the particles and number of ejected particles. The greater ejection distances of hydrophobic particles were mainly the result of the higher initial velocities rather than differences in ejecting angles. The higher and longer ejection trajectories for hydrophobic particles, compared with hydrophilic particles, indicate that particle hydrophobicity affects splash erosion from the initial stage of rainfall erosion before a water layer may be formed by accumulating drops. The ~10% increase in average splash distance for hydrophobic particles compared with hydrophilic particles suggests that particle hydrophobicity can result in greater net erosion rate, which would be amplified on sloping surfaces, for example, by ridges in ploughed agricultural soils or hillslopes following vegetation loss by clearing or wildfire. Copyright © 2012 John Wiley & Sons, Ltd.