bluuebunny/crossref_metadata_2025 huggingface dataset:
Organocatalytic Asymmetric Mannich Cyclization of Hydroxylactams with Acetals: Total Syntheses of (−)‐Epilupinine, (−)‐Tashiromine, and (−)‐Trachelanthamidine
Authors: Koley Dipankar , Krishna Yarkali , Srinivas Kyatham , Khan Afsar Ali , Kant Ruchir
Published: September 2014

An asymmetric, organocatalytic, one‐pot Mannich cyclization between a hydroxylactam and acetal is described to provide fused, bicyclic alkaloids bearing a bridgehead N atom. Both aliphatic and aromatic substrates were used in this transformation to furnish chiral pyrrolizidinone, indolizidinone, and quinolizidinone derivatives in up to 89 % yield and 97 % ee. The total syntheses of (−)‐epilupinine, (−)‐tashiromine, and (−)‐trachelanthamidine also achieved to demonstrate the generality of the process.
How to Make 8,1,2‐closo‐MC2B9 Metallacarboranes
Authors: Man Wing Y. , Zlatogorsky Sergey , Tricas Hugo , Ellis David , Rosair Georgina M. , Welch Alan J.
Published: September 2014

Three examples of the rare 8,1,2‐closo‐MC2B9 isomeric form of an icosahedral metallacarborane have been isolated as unexpected trace products in reactions. Seeking to understand how these were formed we considered both the nature of the reactions that were being undertaken and the nature of the coproducts. This led us to propose a mechanism for the formation of the 8,1,2‐closo‐MC2B9 species. The mechanism was then tested, leading to the first deliberate synthesis of an example of this isomer. Thus, deboronation of 4‐(η‐C5H5)‐4,1,8‐closo‐CoC2B10H12 selectively removes the B5 vertex to yield the dianion [nido‐(η‐C5H5)CoC2B9H11]2−, oxidative closure of which affords 8‐(η‐C5H5)‐8,1,2‐closo‐CoC2B9H11 in moderate yield.
Platinum(II)–Gadolinium(III) Complexes as Potential Single‐Molecular Theranostic Agents for Cancer Treatment
Authors: Zhu Zhenzhu , Wang Xiaoyong , Li Tuanjie , Aime Silvio , Sadler Peter J. , Guo Zijian
Published: September 2014

Theranostic agents are emerging multifunctional molecules capable of simultaneous therapy and diagnosis of diseases. We found that platinum(II)–gadolinium(III) complexes with the formula [{Pt(NH3)2Cl}2GdL](NO3)2 possess such properties. The Gd center is stable in solution and the cytoplasm, whereas the Pt centers undergo ligand substitution in cancer cells. The Pt units interact with DNA and significantly promote the cellular uptake of Gd complexes. The cytotoxicity of the Pt–Gd complexes is comparable to that of cisplatin at high concentrations (≥0.1 mM), and their proton relaxivity is higher than that of the commercial magnetic resonance imaging (MRI) contrast agent Gd–DTPA. T1‐weighted MRI on B6 mice demonstrated that these complexes can reveal the accumulation of platinum drugs in vivo. Their cytotoxicity and imaging capabilities make the Pt–Gd complexes promising theranostic agents for cancer treatment.
Restoration of normal left ventricular geometry after percutaneous mitral annuloplasty: Case report and review of literature
Authors: Soofi Muhammad Adil , Alsamadi Faisal
Published: September 2014

Surgical mitral valve intervention is not considered suitable in patients with severe functional mitral regurgitation due to severe dilated cardiomyopathy and severe systolic dysfunction. In such patients percutaneous mitral valve intervention is the next best alternative. We are presenting case report of a patient who presented with severe dyspnea progressing to orthopnea and paroxysmal nocturnal dyspnea. He was found to have severe functional mitral regurgitation and severe left ventricle systolic dysfunction. Surgical mitral intervention was not considered suitable and percutaneous mitral annuloplasty was done. At one month follow‐up significant improvement in symptoms were noted with improvement in severity of mitral regurgitation severity. At 6 months follow‐up further improvement in symptoms were noted along with significant improvement in the severity of mitral regurgitation and normalization of left ventricle geometry. At 1 year follow‐up his symptoms further improved, left ventricle geometry remained normal and mitral regurgitation severity remained mild to moderate. Our case demonstrate that in patient with severe LV systolic dysfunction, severe mitral regurgitation and left bundle branch block percutaneous mitral annuloplasty can obviate the need for CRT‐D due to significant improvement in LV function and geometry along with regression in severity of mitral regurgitation. Improvement in mitral regurgitation severity and LV geometry started early and kept improving with excellent result at 6 and 12 months. © 2014 Wiley Periodicals, Inc.
Stabilization of Palladium Catalysts for the Heck Reaction by Support Functionalization and Solvent Selection
Authors: Oliveira Rafael L. , Hooijmans Jasper B. F. , E. de Jongh Petra , Klein Gebbink Robertus J. M. , P. de Jong Krijn
Published: September 2014

Pd nanoparticles were synthesized on nonfunctionalized and functionalized SBA‐15 grafted with thiol or amine groups. The resulting materials were used as catalysts to study the influence of these functional groups for a similar Pd particle size of approximately 2 nm on the Heck reaction that uses iodide substrates. The nonfunctionalized catalysts lost their activity quickly because of Pd leaching and particle growth. However, if a mixed solvent that consisted of toluene and DMF was used and thiol groups were grafted on SBA‐15, we were able to reduce the Pd leaching and particle growth to thus obtain a more stable catalyst in which an important role of the ligands was to recapture Pd. However, heterogeneity tests, such as a hot filtration test and poisoning experiments, gave a strong indication that Pd still leached from the support and that homogeneous Pd species were mainly responsible for the activity. Pd on S‐functionalized SBA‐15 was able to catalyze the Heck reaction using different substrates to achieve good activity and selectivity in most cases.
Efficient Sensing of Explosives by Using Fluorescent Nonporous Films of Oligophenyleneethynylene Derivatives Thanks to Optimal Structure Orientation and Exciton Migration
Authors: Caron Thomas , Pasquinet Eric , van der Lee Arie , Pansu Robert B. , Rouessac Vincent , Clavaguera Simon , Bouhadid Myriam , Serein‐Spirau Françoise , Lère‐Porte Jean‐Pierre , Montméat Pierre
Published: September 2014

The fluorescence of thin films of a diimine‐substituted phenyleneethynylene compound can be efficiently quenched by nitroaromatic vapors, which is not the case for the unsubstituted parent compound. Thin‐film porosity is usually considered to be an essential factor for efficient quenching, but in the present case the origin of the quenching is completely different, as both films are nonporous and hermetic to 2,4‐dinitrotoluene (DNT) molecules. The molecular organization in the two crystallized thin films offers a low level of π stacking for both compounds, but the orientation of the phenylenethynylene fluorophore differs markedly with respect to the surface of the films. For the substituted compound, the fluorophore is almost parallel to the surface, thus making it readily available to molecules of a nitroaromatic quencher. This rationale is also observed in the case of a related compound bearing methoxy side chains instead of the long octyloxy moieties. Fluorescence‐lifetime experiments show that the efficient quenching process in the nonporous crystallized films of the substituted compound is due to a fast (<70 ps) diffusion of excitons from the bulk of the film toward the surface where they are quenched, thus providing evidence of antenna effects.
Organic–Inorganic Azafullerene‐Gold C59N‐Au Nanohybrid: Synthesis, Characterization, and Properties
Authors: Rotas Georgios , Niemi Marja , Tkachenko Nikolai V. , Zhao Sihan , Shinohara Hisanori , Tagmatarchis Nikos
Published: September 2014

Azafullerene (C59N) was functionalized using a Mannich‐type reaction and then subsequently condensed with lipoic acid to yield dithiolane‐modified C59N. In the following step, the extended dithiolane moiety from the C59N core was utilized to decorate the azafullerene sphere with gold nanoparticles (Au NPs). The latter were initially stabilized with dodecanothiol (DT⋅Au) and then integrated on azafullerene through a ligand exchange reaction with the dithiolane‐functionalized C59N to produce the C59N/DT⋅Au nanohybrid. The nanohybrid was fully characterized by spectroscopy and microscopy, revealing the formation of spherical nanoparticles with a diameter in the range of 2–5 nm, as imaged by HR‐TEM. In the electronic absorption spectrum of C59N/DT⋅Au nanohybrid, the characteristic surface plasmon band (SPB) of Au NPs was observed, however, it was redshifted compared with that of DT⋅Au. The redshift of the SPB is indicative of closer interparticle proximity of Au NPs, in accordance with the formation of aggregated NPs as observed by TEM, in C59N/DT⋅Au nanohybrid. Excited‐state interactions in C59N/DT⋅Au were probed by photoluminescence assays. It was found that the weak emission of C59N at 819 nm was blueshifted by 14 nm in C59N/DT⋅Au, but was stronger in intensity, thus suggesting energy transfer to C59N, within the organic–inorganic C59N/DT⋅Au nanohybrid. Finally, with the aid of pump–probe measurements and transient absorption spectroscopy, the formation of the singlet excited state of C59N was identified.
Photoinduced Electron Transfer within a Zinc Porphyrin–Cyclobis(paraquat‐p‐phenylene) Donor–Acceptor Dyad
Authors: Fathalla Maher , Barnes Jonathan C. , Young Ryan M. , Hartlieb Karel J. , Dyar Scott M. , Eaton Samuel W. , Sarjeant Amy A. , Co Dick T. , Wasielewski Michael R. , Stoddart J. Fraser
Published: September 2014

Understanding the mechanism of efficient photoinduced electron‐transfer processes is essential for developing molecular systems for artificial photosynthesis. Towards this goal, we describe the synthesis of a donor–acceptor dyad comprising a zinc porphyrin donor and a tetracationic cyclobis(paraquat‐p‐phenylene) (CBPQT4+) acceptor. The X‐ray crystal structure of the dyad reveals the formation of a dimeric motif through the intermolecular coordination between the triazole nitrogen and the central Zn metal of two adjacent units of the dyad. Photoinduced electron transfer within the dyad in MeCN was investigated by femtosecond and nanosecond transient absorption spectroscopy, as well as by transient EPR spectroscopy. Photoexcitation of the dyad produced a weakly coupled ZnP+.–CBPQT3+. spin‐correlated radical‐ion pair having a τ=146 ns lifetime and a spin–spin exchange interaction of only 0.23 mT. The long radical‐ion‐pair lifetime results from weak donor–acceptor electronic coupling as a consequence of having nine bonds between the donor and the acceptor, and the reduction in reorganization energy for electron transfer caused by charge dispersal over both paraquat units within CBPQT3+..
Potent Anticancer Activity and Possible Low Toxicity of Platinum(II) Complexes with Functionalized 1,1‐Cyclobutanedicarboxylate as a Leaving Ligand
Authors: Zhao Jian , Gou Shaohua , Liu Fengfan
Published: September 2014

Two platinum(II) complexes, DN603 and DN604, were designed and prepared by using 3‐oxocyclobutane‐1,1‐dicarboxylate as a ligand. The compounds were prepared according to the concept that incorporation of a functionalized moiety in the leaving ligand that did not affect its coordination bonding to the metal atom would play a key role in the anticancer activity of the resulting platinum complex. The newly prepared compounds were found to show potent in vitro anticancer activity comparable to cisplatin and oxaliplatin; especially DN604, which exhibited low acute toxicity similar to carboplatin, and presented acceptable solubility and stability in water. Chemical and biological results indicated that the functionalized moiety, uncoordinated, led to potent anticancer activity and low apparent toxicity of the platinum complexes by affecting the kinetic properties of the compounds.
Impact of Clinical and Therapeutic Factors on Incident Cardiovascular and Cerebrovascular Events in a Population‐Based Cohort of HIV‐Infected and Non–HIV‐Infected Adults
Authors: Tripathi Avnish , Liese Angela D. , Winniford Michael D. , Jerrell Jeanette M. , Albrecht Helmut , Rizvi Ali A. , Zhang Jiajia , Duffus Wayne A.
Published: September 2014

Background

Cardiovascular and cerebrovascular (CVD) events/diseases are a common cause of non–acquired immunodeficiency syndrome (AIDS)‐related mortality in the aging human immunodeficiency virus (HIV)‐infected population. The incidence rate and clinical correlates of CVD in people living with HIV/AIDS compared to the general population warrants further investigation.

Hypothesis

HIV/AIDS is associated with increased risk CVD compared to general population.

Methods

CVD events in a matched cohort of HIV‐infected and non–HIV‐infected adults, ≥18 years old, served through the South Carolina Medicaid program during 1994 to 2011 were examined using time‐dependent proportional hazards regression and marginal structural modeling.

Results

A retrospective cohort of 13 632 adults was followed longitudinally for an average of 51 months. The adjusted hazard ratio (aHR) of incident CVD events was higher among HIV‐infected individuals exposed to combination antiretroviral therapy (cART) (aHR = 1.15) compared to the non–HIV‐infected group, but did not differ from the subgroup of cART‐naïve HIV‐infected adults. A higher aHR of incident CVD was associated with comorbid hypertension (aHR = 2.18), diabetes (aHR = 1.38), obesity (aHR = 1.30), tobacco use (aHR = 1.47), and hepatitis C coinfection (aHR = 1.32), and older age (aHR = 1.26), but with a lower risk among females (aHR = 0.86). A higher risk of incident CVD events was also apparent in HIV‐infected individuals with exposure to both protease inhibitors (adjusted risk ratio [aRR] = 1.99) and non‐nucleoside reverse transcriptase inhibitors (aRR = 2.19) compared to those with no exposure. Sustained viral load suppression was associated with a lower risk of incident CVD events (aRR = 0.74).

Conclusions

After adjusting for traditional risk factors and sociodemographic differences, there is higher risk of incident cardiovascular events among HIV‐infected individuals exposed to combined antiretroviral medications compared to the general population.
Synthesis and Crystal Structures of Gold Nanowires with Gemini Surfactants as Directing Agents
Authors: Xu Feng , Hou Hao , Gao Zhinong
Published: September 2014

The preparation of crystalline gold nanowires (NWs) by using gemini surfactants as directing agents through a three‐step seed‐mediated method is reported. Unlike the nanorods with relatively low aspect ratios (typically below 20) obtained by using cetyltrimethylammonium bromide as a directing agent, the NWs obtained in this investigation can reach up to 4.4 μm, and the largest aspect ratio is calculated to be 210. For this, each of seven different gemini surfactants are utilized as directing agents, and the length and/or aspect ratio of the NWs can be tuned by varying the hydrocarbon chain lengths of the gemini surfactants. Both single and twinned crystalline structures are elucidated by selected‐area electron diffraction and high‐resolution transmission electron microscopy studies. The use of gemini surfactants not only advances the synthesis of gold nanostructures, but improves the understanding of the growth mechanism for seed‐mediated growth.
Integrating environmental, molecular, and morphological data to unravel an ice‐age radiation of arctic‐alpine Campanula in western North America
Authors: DeChaine Eric G. , Wendling Barry M. , Forester Brenna R.
Published: September 2014

Many arctic‐alpine plant genera have undergone speciation during the Quaternary. The bases for these radiations have been ascribed to geographic isolation, abiotic and biotic differences between populations, and/or hybridization and polyploidization. The Cordilleran Campanula L. (Campanulaceae Juss.), a monophyletic clade of mostly endemic arctic‐alpine taxa from western North America, experienced a recent and rapid radiation. We set out to unravel the factors that likely influenced speciation in this group. To do so, we integrated environmental, genetic, and morphological datasets, tested biogeographic hypotheses, and analyzed the potential consequences of the various factors on the evolutionary history of the clade. We created paleodistribution models to identify potential Pleistocene refugia for the clade and estimated niche space for individual taxa using geographic and climatic data. Using 11 nuclear loci, we reconstructed a species tree and tested biogeographic hypotheses derived from the paleodistribution models. Finally, we tested 28 morphological characters, including floral, vegetative, and seed characteristics, for their capacity to differentiate taxa. Our results show that the combined effect of Quaternary climatic variation, isolation among differing environments in the mountains in western North America, and biotic factors influencing floral morphology contributed to speciation in this group during the mid‐Pleistocene. Furthermore, our biogeographic analyses uncovered asynchronous consequences of interglacial and glacial periods for the timing of refugial isolation within the southern and northwestern mountains, respectively. These findings have broad implications for understanding the processes promoting speciation in arctic‐alpine plants and the rise of numerous endemic taxa across the region.
Desert salt flats as oases for the spider Saltonia incerta Banks (Araneae: Dictynidae)
Authors: Crews Sarah C. , Gillespie Rosemary G.
Published: September 2014

The deserts of southwestern North America have undergone dramatic changes over their recent geological history including large changes in size and connectivity during the Pleistocene glaciopluvial cycles. This study examines the population history of the rare spider Saltonia incerta, once thought to be extinct, to determine the role of past climatological events in shaping the structure of the species. This species is restricted to salt crusts of intermittent or dry lakes, streams or rivers in the desert southwest, a region that was much wetter during glacial periods. We examine the distribution and genetic variability of populations to test whether there is recent dispersal throughout the range of the species. Analyses of mitochondrial and nuclear DNA indicate significant population structure, with one major clade comprising New Mexico localities and one comprising California‐northern Baja California localities. Finer‐scale structure is evident within the California clade, although not all of the subclades are reciprocally monophyletic. However, isolation with migration analysis suggests that migration is very low to non‐existent. These results extend the known distribution of Saltonia, provide genetic evidence of strong isolation among localities within drainage basins and between drainage basins and provide a mechanistic understanding of population connectivity after the aridification of the American southwest. The implication is that although the species' distribution has been fragmented, populations have persisted throughout this area, suggesting that desert salt flats may have served as refugia for at least some terrestrial species.
Assembly of a 1H‐Pyrrol‐2(5H)‐one Core through a Cascade Ugi Reaction/5‐endo‐dig Carbocyclization/Retro‐Claisen Fragmentation Process
Authors: Peshkov Anatoly A. , Peshkov Vsevolod A. , Li Zhenghua , Pereshivko Olga P. , Van der Eycken Erik V.
Published: September 2014

A cascade transformation involving the Ugi reaction followed by 5‐endo‐dig carbocyclization and retro‐Claisen fragmentation providing access to a 1H‐pyrrol‐2(5H)‐one core is described. The operating protocol is very similar to the typical Ugi reaction settings, while the overall outcome results from the application of a 3‐substituted propiolic acid and a phenylglyoxal as acid and aldehyde components, respectively. The utility of process is demonstrated through the synthesis of a small library of 5‐oxo‐2,5‐dihydro‐1H‐pyrrole‐2‐carboxamides.
Voltammetric Determination of Pb(II) and Cd(II) Ions in Well Water Using a Sputtered Bismuth Screen‐Printed Electrode
Authors: Sosa Velia , Serrano Núria , Ariño Cristina , Díaz‐Cruz José Manuel , Esteban Miquel
Published: September 2014

A method using commercially available sputtered bismuth screen‐printed electrodes (BispSPE), as substitute to mercury electrodes, for the determination of trace Pb(II) and Cd(II) ions in drinking well water samples collected in a contaminated area in The Republic of El Salvador by means of differential pulse anodic stripping voltammetry (DPASV) has been proposed. The comparable detection and quantification limits obtained for both BispSPE and hanging mercury drop electrode (HMDE), together with the similar results with a high reproducibility obtained in these water samples analyses recommend the applicability of BispSPE for the determination of low level of metal concentrations in natural samples.
Redox Mechanism and Evaluation of Kinetic and Thermodynamic Parameters of 1,3‐Dioxolo[4,5‐g]pyrido[2,3‐b]quinoxaline Using Electrochemical Techniques
Authors: Shah Aamir Hassan , Shah Afzal , Rana Usman Ali , Khan Salah Ud‐Din , Hussain Hidayat , Khan Sher Bahadar , Qureshi Rumana , Badshah Amin
Published: September 2014

The electrochemical behavior of a biologically important heterocyclic compound, 1,3‐dioxolo[4,5‐g]pyrido[2,3‐b]quinoxaline was investigated by cyclic, square wave and differential pulse voltammetry in solutions of different pH. Kinetic and thermodynamic parameters like standard rate constant, diffusion coefficient, apparent energy of activation, standard Gibbs free energy and enthalpy and entropy changes were evaluated. Limits of detection and quantification were determined by square wave voltammetry. The redox mechanism of the compound was proposed on the basis of experimental results. Computational chemistry was used as a tool for the verification of experimental outcomes and assessment of different theoretical parameters
Development of Graphene/CdSe Quantum Dots‐Co Phthalocyanine Nanocomposite for Oxygen Reduction Reaction
Authors: Nyoni Stephen , Nyokong Tebello
Published: September 2014

Nanocomposites containing CdSe quantum dots, tetra(4‐(4,6‐diaminopyrimidin‐2‐ylthio) phthalocyaninatocobalt(II)) (CoPyPc) and reduced graphene nanosheets (rGNS) were devoloped and used for the modification of a glassy carbon electrode. Characterization of the nanocomposites was done by transmission electron microscopy (TEM) and X‐ray diffraction (XRD) analyses. Cyclic voltammetry (CV) was used for electrochemical characterization of the prepared nanocomposite for oxygen reduction reaction. The oxygen reduction activity for rGNS/CdSe‐CoPyPc nanocomposite was found to be superior over the individual nanomaterials in this study. The activity of the nanocomposite towards oxygen reduction was also tested for tolerance to methanol crossover effect using chronoamperometry (CA) and electrochemical impedance spectroscopy (EIS) studies.
Radiation‐induced epithelial‐myoepithelial carcinoma in a patient previously treated with mantle‐field radiation therapy for Hodgkin lymphoma
Authors: Mann Justin M. , Kellman Robert M. , Hahn Seung S. , de la Roza Gustavo L. , Gajra Ajeet
Published: September 2014

Background

Radiation‐induced salivary gland tumors are well described in the literature, with mucoepidermoid cancer being the most common histologic entity. Epithelial‐myoepithelial carcinoma is a rare tumor accounting for <1% of all tumors in the salivary glands.

Methods and Results

We describe the first case of radiation‐induced epithelial‐myoepithelial carcinoma in the English‐language medical literature. A 48‐year‐old man presented with right‐sided mandibular pain and trismus, 25 years after mantle‐field radiation therapy (RT) for Hodgkin lymphoma. He underwent excision of a right submandibular mass, which revealed a diagnosis of epithelial‐myoepithelial carcinoma. Although typically a low‐grade tumor, the histology revealed extensive necrosis and high mitotic activity. The patient required multiple resections and adjuvant therapy after multiple recurrences over a 4‐year period.

Conclusion

Reports of epithelial‐myoepithelial carcinoma are relatively rare and this case highlights the importance of long‐term follow‐up and increased awareness of the risks of salivary gland tumors in this population. © 2014 Wiley Periodicals, Inc. Head Neck 37: E96–E98, 2015
Dental implants in irradiated versus nonirradiated patients: A meta‐analysis
Authors: Chrcanovic Bruno Ramos , Albrektsson Tomas , Wennerberg Ann
Published: September 2014

The purpose of the present meta‐analysis was to test the null hypothesis of no difference in dental implant failure rates, postoperative infection, and marginal bone loss for patients being rehabilitated by dental implants and being previously irradiated in the head and neck region versus nonirradiated patients against the alternative hypothesis of a difference. The study suggests that irradiation negatively affects the survival of implants, as well as the difference in implant location (maxilla vs mandible), but there is no statistically significant difference in survival when implants are inserted before or after 12 months after radiotherapy. The study failed to support the effectiveness of hyperbaric oxygen therapy in irradiated patients. It was observed that there was a tendency of lower survival rates of implants inserted in the patients submitted to higher irradiation doses. The results should be interpreted with caution because of the presence of uncontrolled confounding factors in the included studies. © 2015 Wiley Periodicals, Inc. Head Neck 38: 448–481, 2016
Potent antitumor activity of cabozantinib, a c‐MET and VEGFR2 inhibitor, in a colorectal cancer patient‐derived tumor explant model
Authors: Song Eun‐Kee , Tai WM , Messersmith Wells A. , Bagby Stacey , Purkey Alicia , Quackenbush Kevin S. , Pitts Todd M. , Wang Guoliang , Blatchford Patrick , Yahn Rachel , Kaplan Jeffrey , Tan Aik Choon , Atreya Chloe E. , Eckhardt Gail , Kelley Robin K. , Venook Alan , Kwak Eunice L. , Ryan David , Arcaroli John J.
Published: September 2014

Antiangiogenic therapy is commonly used for the treatment of colorectal cancer (CRC). Although patients derive some clinical benefit, treatment resistance inevitably occurs. The MET signaling pathway has been proposed to be a major contributor of resistance to antiangiogenic therapy. MET is upregulated in response to vascular endothelial growth factor pathway inhibition and plays an essential role in tumorigenesis and progression of tumors. In this study, we set out to determine the efficacy of cabozantinib in a preclinical CRC patient‐derived tumor xenograft model. We demonstrate potent inhibitory effects on tumor growth in 80% of tumors treated. The greatest antitumor effects were observed in tumors that possess a mutation in the PIK3CA gene. The underlying antitumor mechanisms of cabozantinib consisted of inhibition of angiogenesis and Akt activation and significantly decreased expression of genes involved in the PI3K pathway. These findings support further evaluation of cabozantinib in patients with CRC. PIK3CA mutation as a predictive biomarker of sensitivity is intriguing and warrants further elucidation. A clinical trial of cabozantinib in refractory metastatic CRC is being activated.
USP33 mediates Slit‐Robo signaling in inhibiting colorectal cancer cell migration
Authors: Huang Zhaohui , Wen Pushuai , Kong Ruirui , Cheng Haipeng , Zhang Binbin , Quan Cao , Bian Zehua , Chen Mengmeng , Zhang Zhenfeng , Chen Xiaoping , Du Xiang , Liu Jianghong , Zhu Li , Fushimi Kazuo , Hua Dong , Wu Jane Y.
Published: September 2014

Originally discovered in neuronal guidance, the Slit‐Robo pathway is emerging as an important player in human cancers. However, its involvement and mechanism in colorectal cancer (CRC) remains to be elucidated. Here, we report that Slit2 expression is reduced in CRC tissues compared with adjacent noncancerous tissues. Extensive promoter hypermethylation of the Slit2 gene has been observed in CRC cells, which provides a mechanistic explanation for the Slit2 downregulation in CRC. Functional studies showed that Slit2 inhibits CRC cell migration in a Robo‐dependent manner. Robo‐interacting ubiquitin‐specific protease 33 (USP33) is required for the inhibitory function of Slit2 on CRC cell migration by deubiquitinating and stabilizing Robo1. USP33 expression is downregulated in CRC samples, and reduced USP33 mRNA levels are correlated with increased tumor grade, lymph node metastasis and poor patient survival. Taken together, our data reveal USP33 as a previously unknown tumor‐suppressing gene for CRC by mediating the inhibitory function of Slit‐Robo signaling on CRC cell migration. Our work suggests the potential value of USP33 as an independent prognostic marker of CRC.
Cancer survival in China, 2003–2005: A population‐based study
Authors: Zeng Hongmei , Zheng Rongshou , Guo Yuming , Zhang Siwei , Zou Xiaonong , Wang Ning , Zhang Limei , Tang Jingao , Chen Jianguo , Wei Kuangrong , Huang Suqin , Wang Jian , Yu Liang , Zhao Deli , Song Guohui , Chen Jianshun , Shen Yongzhou , Yang Xiaoping , Gu Xiaoping , Jin Feng , Li Qilong , Li Yanhua , Ge Hengming , Zhu Fengdong , Dong Jianmei , Guo Guoping , Wu Ming , Du Lingbin , Sun Xibin , He Yutong , Coleman Michel P , Baade Peter , Chen Wanqing , Yu Xue Qin
Published: September 2014

Limited population‐based cancer registry data available in China until now has hampered efforts to inform cancer control policy. Following extensive efforts to improve the systematic cancer surveillance in this country, we report on the largest pooled analysis of cancer survival data in China to date. Of 21 population‐based cancer registries, data from 17 registries (n = 138,852 cancer records) were included in the final analysis. Cases were diagnosed in 2003–2005 and followed until the end of 2010. Age‐standardized relative survival was calculated using region‐specific life tables for all cancers combined and 26 individual cancers. Estimates were further stratified by sex and geographical area. The age‐standardized 5‐year relative survival for all cancers was 30.9% (95% confidence intervals: 30.6%‐31.2%). Female breast cancer had high survival (73.0%) followed by cancers of the colorectum (47.2%), stomach (27.4%), esophagus (20.9%), with lung and liver cancer having poor survival (16.1% and 10.1%), respectively. Survival for women was generally higher than for men. Survival for rural patients was about half that of their urban counterparts for all cancers combined (21.8% vs. 39.5%); the pattern was similar for individual major cancers except esophageal cancer. The poor population survival rates in China emphasize the urgent need for government policy changes and investment to improve health services. While the causes for the striking urban‐rural disparities observed are not fully understood, increasing access of health service in rural areas and providing basic health‐care to the disadvantaged populations will be essential for reducing this disparity in the future.
Intrauterine devices and endometrial cancer risk: A pooled analysis of the Epidemiology of Endometrial Cancer Consortium
Authors: Felix Ashley S. , Gaudet Mia M. , Vecchia Carlo La , Nagle Christina M. , Shu Xiao Ou , Weiderpass Elisabete , Adami Hans Olov , Beresford Shirley , Bernstein Leslie , Chen Chu , Cook Linda S. , Vivo Immaculata De , Doherty Jennifer A. , Friedenreich Christine M. , Gapstur Susan M. , Hill Dierdre , Horn‐Ross Pamela L. , Lacey James V. , Levi Fabio , Liang Xiaolin , Lu Lingeng , Magliocco Anthony , McCann Susan E. , Negri Eva , Olson Sara H. , Palmer Julie R. , Patel Alpa V. , Petruzella Stacey , Prescott Jennifer , Risch Harvey A. , Rosenberg Lynn , Sherman Mark E. , Spurdle Amanda B. , Webb Penelope M. , Wise Lauren A. , Xiang Yong‐Bing , Xu Wanghong , Yang Hannah P. , Yu Herbert , Zeleniuch‐Jacquotte Anne , Brinton Louise A.
Published: September 2014

Intrauterine devices (IUDs), long‐acting and reversible contraceptives, induce a number of immunological and biochemical changes in the uterine environment that could affect endometrial cancer (EC) risk. We addressed this relationship through a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We combined individual‐level data from 4 cohort and 14 case‐control studies, in total 8,801 EC cases and 15,357 controls. Using multivariable logistic regression, we estimated pooled odds ratios (pooled‐ORs) and 95% confidence intervals (CIs) for EC risk associated with ever use, type of device, ages at first and last use, duration of use and time since last use, stratified by study and adjusted for confounders. Ever use of IUDs was inversely related to EC risk (pooled‐OR = 0.81, 95% CI = 0.74–0.90). Compared with never use, reduced risk of EC was observed for inert IUDs (pooled‐OR = 0.69, 95% CI = 0.58–0.82), older age at first use (≥35 years pooled‐OR = 0.53, 95% CI = 0.43–0.67), older age at last use (≥45 years pooled‐OR = 0.60, 95% CI = 0.50–0.72), longer duration of use (≥10 years pooled‐OR = 0.61, 95% CI = 0.52–0.71) and recent use (within 1 year of study entry pooled‐OR = 0.39, 95% CI = 0.30–0.49). Future studies are needed to assess the respective roles of detection biases and biologic effects related to foreign body responses in the endometrium, heavier bleeding (and increased clearance of carcinogenic cells) and localized hormonal changes.
CAST: A retrospective analysis of cabazitaxel and abiraterone acetate sequential treatment in patients with metastatic castrate‐resistant prostate cancer previously treated with docetaxel
Authors: Wissing Michel D. , Coenen Jules L.L.M. , van den Berg Pieter , Westgeest Hans M. , van den Eertwegh Alfons J.M. , van Oort Inge M. , Bos Monique M. , Bergman André M. , Hamberg Paul , ten Tije Albert J. , Los Maartje , Lolkema Martijn P.J.K. , de Wit Ronald , Gelderblom Hans
Published: September 2014

Cabazitaxel and abiraterone have both received approval for treating metastatic castrate‐resistant prostate cancer (mCRPC) patients after first‐line docetaxel therapy. In the cabazitaxel and abiraterone sequential treatment (CAST) study, the clinical outcome of docetaxel‐treated mCRPC patients treated sequentially with both cabazitaxel and abiraterone was studied. Data were collected retrospectively from mCRPC patients at 12 hospitals across the Netherlands who initiated cabazitaxel and/or abiraterone before December 2012. Primary outcome measure was overall survival (OS); secondary measures were progression‐free survival (PFS), biochemical PFS, and best clinical and PSA response. Hospital admission data during treatment were collected, as well as toxicities resulting in treatment discontinuation or patient death. Sixty‐three and 69 patients received Cab→Abi (cabazitaxel prior to abiraterone) and Abi→Cab before July 10th, 2013, respectively. Median OS was 19.1 months and 17.0 months in Cab→Abi and Abi→Cab treated patients, respectively (p = 0.369). Median PFS and biochemical PFS were significantly longer in Cab→Abi treated patients: 8.1 versus 6.5 (p = 0.050) and 9.5 versus 7.7 months (p = 0.024), respectively. Although partial responses to cabazitaxel occurred in both groups, Abi→Cab treated patients had a significantly decreased antitumor response from cabazitaxel than Cab→Abi treated patients (median PFS 5.0 versus 2.6 months, p < 0.001). Minor differences in toxicities were observed based on therapy sequence; generally, toxicity from cabazitaxel could be severe, while abiraterone toxicity was milder. This retrospective analysis indicates that primary progression on cabazitaxel or abiraterone did not preclude a response to the other agent in mCRPC patients. However, tumor response of both agents, particularly cabazitaxel, was lower when administered as higher‐line therapy in the selected study population.
SOCIAL POLICIES TOWARD CHILDREN OF DIVERSE ETHNIC, RACIAL, AND LANGUAGE GROUPS IN THE UNITED STATES
Authors: Laosa Luis M.
Published: September 2014

In every era in the history of U.S. public policies toward children, certain groups of children have been identified as being “at risk” and hence of social concern and responsibility. These groups consist of the physically handicapped and those with serious diseases; the emotionally disturbed; the mentally retarded; orphans; children whose mothers or fathers are permanently or temporarily absent; illegitimate, destitute, indigent, neglected, abused, and anti‐social or delinquent children. Only very recently have the children belonging to specified ethnic, racial, and language groups been added as major “risk” categories and thus become a major focus of social concern and public responsibility.

The source of the social concern about all the groups listed above is the alleged inability of the family (when it exists) to cope with the problems implied by membership in the group, or the public danger that follows from leaving these problems untreated. This social concern does not mean that American society has always accepted full responsibility for children in these risk categories. It has not always provided care, treatment, or rehabilitation, nor has it always sought to prevent their misfortunes. Since colonial times, however, it has at least shown concern for certain categories of children.

My principal purpose in this monograph is to trace major trends in the evolution of those aspects of social policies toward children that bear directly on issues of ethnic, racial, and language diversity in our society. I also seek to examine the public attitudes, the intellectual assumptions, and the sociodemographic trends that have accompanied these policy developments. In addition, I pay some attention to the roles that the social and behavioral sciences have played with regard to such policies.
STANDARD ERRORS OF MEASUREMENT AT DIFFERENT ABILITY LEVELS
Authors: Lord Frederic M.
Published: September 2014

Four methods are outlined for estimating or approximating from a single test administration the standard error of measurement of number‐right test score at specified ability levels or cutting scores. The methods are illustrated and compared on one set of real test data.
THE TEST PERFORMANCE OF HANDICAPPED PEOPLE
Authors: Bennett Randy Elliot , Ragosta Marjorie , Stricker Lawrence J.
Published: September 2014

This paper is the second in a series of reports emanating from a four‐year research program meant to further knowledge of college and graduate admissions testing and handicapped people. The purpose of this paper is to document existing research on the test performance of handicapped people with respect to admissions and other similar tests. In addition, the psychometric characteristics of these tests when used with handicapped people are reported.

Though much more data need to be collected, several observations are made. Handicapped students as a general group perform appreciably lower than national norms on the SAT and ACT Assessment (by about .5 standard deviations). Of the four specific disability groups discussed, the admissions test performance of physically handicapped and of visually impaired examinees is most similar to the nondisabled population. The admissions test performance of learning disabled individuals ranks third among the specific disability groups. With limited exceptions, the performance of this group is appreciably lower than national norms (generally by at least .5 standard deviations). Hearing impaired students perform the least we 11 of all disabled groups on admissions tests.

The limited data on the reliability of cognitive tests for handicapped examinees show no trustworthy differences in measurement precision between disabled and nondisabled populations. The results of the small number of validity investigations that have been conducted also show no dependable differences across populations. Data on the ACT Assessment and the SAT generally support the validity of these measures as equivalent predictors of col lege performance in selected disabled student groups and the nonhandicapped population.

The lack of data on test performance, reliability, and validity prohibits drawing definitive conclusions at this time. Further research is necessary before the fairness of the admissions testing process for handicapped examinees can be soundly evaluated.
FOREIGN NATIONALS TAKING THE GRE GENERAL TEST DURING 1981–82: SELECTED CHARACTERISTICS AND TEST PERFORMANCE
Authors: Wilson Kenneth M.
Published: September 2014

During the 1981–82 testing year, foreign nationals representing over 140 countries or territories made up approximately 17 percent of all GRE General Test takers. However, they were heavily concentrated in scientific‐technical fields–for example, almost one‐half of all examinees in engineering and one‐third of those in math‐science fields were foreign nationals. Most of these examinees were non‐native speakers of English for whom average scores on the verbal and analytical measures were considerably lower than those of native English speakers (both U.S. and foreign) in similar fields of study. However, the quantitative mean profile, by field, of foreign examinees did not vary according to English language background and was quite similar to that of U.S. examinees.

Detailed comparative profiles of GRE performance data are provided for the general foreign and U.S. examinee populations, and for foreign examinees classified by country of citizenship. In addition, the study analyzes GRE performance of groups of foreign and U.S. examinees defined in terms of age, sex, reported English language communication status, intended graduate field, U.S. vs other undergraduate origin, repeater vs nonrepeater status, and other personal, academic, and testing‐related characteristics.

Study findings suggest that GRE General Test data (especially verbal and analytical test data) generated by non‐U.S. citizens from non‐native English speaking societies should not be treated as comparable to test data for U.S. examinees or examinees from other native‐English speaking societies.
ASYMPTOTIC PROPERTIES OF THE ROBUSTIFIED JACKKNIFED ESTIMATOR
Authors: Jones Douglas H.
Published: September 2014

This article describes several properties of Wainer and Wright's (1980) jackknifed ability estimator. These properties are as follows: the first order asymptotic behavior of the standard jackknife, including consistency properties; the first order asymptotic behavior of the general M‐type robustified jackknife including consistency properties and formulas for the standard error; and a small sample distribution‐free formula for the standard error of the standard jackknife.
A PROFILE OF PREPARATION IN MATHEMATICS
Authors: Hale Gordon A. , Whittington Beverly
Published: September 2014

A self‐evaluation instrument entitled the Mathematics Inventory was developed whose purpose is to generate a profile of a student's preparation in core areas of secondary school mathematics. This report discusses pilot research using a draft version of the inventory. Appended to the report are the inventory along with prototypes of reports to students and to schools that could be generated from the students' inventory responses.
INFERENCES ABOUT LATENT POPULATIONS FROM COMPLEX SAMPLES*
Authors: Mislevy Robert J.
Published: September 2014

Standard procedures for drawing inferences from complex samples do not apply when the variables of interest z are not observed directly, but must be inferred from secondary random variables x that depend on z stochastically. Employing Rubin's (1977) approach to missing data in survey research, we present a procedure by which reasonable inferences can be made in such situations. The key is to represent knowledge about latent variables in the form of a predictive distribution, conditional on manifest variables. It is then possible to obtain the expectations of statistics that would have been computed if the values of the latent variables corresponding to sampled units were known, along with variance estimators that account for uncertainty due to both subject sampling and the latency of z.
NOTES ON THE USE OF LOG‐LINEAR MODELS FOR FITTING DISCRETE PROBABILITY DISTRIBUTIONS
Authors: Holland Paul W. , Thayer Dorothy T.
Published: September 2014

The theory of log‐linear models is developed for multinomially distributed data – i.e., frequency distributions and discrete multivariate distributions. Such models have applications to data smoothing and can be used in test equating. Attention is given to the computations used to find maximum likelihood estimates using Newton's method and to the computation of asymptotic standard errors for the fitted frequencies. Two examples, using real data, are used to illustrate the output of a computer program that implements these ideas.
TRENDS IN THE SELECTION OF SCIENCE, MATHEMATICS, OR ENGINEERING AS MAJOR FIELDS OF STUDY AMONG TOP‐SCORING SAT TAKERS
Authors: Grandy Jerilee
Published: September 2014

The study explored the major field preferences of top‐scoring SAT examinees over the past decade, focussing especially on the numbers choosing to major in math, science, and engineering. The major findings were the following:

The proportion of top‐scoring examinees planning to major in math, science, and engineering is greater than the proportion of the rest of the examinee population planning to major in any of those fields.

The proportion of top‐scoring examinees planning to major in math, science, and engineering increased until 1982 and then declined slightly. The decline reflects an overall decline in interest in mathematics and the physical sciences. Engineering seems to have leveled off after 1982, but it is not clear how the trend will continue.

There is a considerable difference in the major field selections of males and females. In 1986, 55 percent of the top‐scoring males and only 34 percent of the top‐scoring females selected a major within math, science, and engineering. Only about 15 percent of the white females having the highest mathematical aptitude (scoring above the 90th percentile on Math) plan to major in a highly quantitative field, namely, mathematics, physical sciences, or engineering.

The percentage of top‐scoring females planning to major in math, science, and engineering rose until 1982 and then declined, following much the same pattern as the trend for males.

There has been a shift in the proportions of top‐scoring examinees planning to study different fields within math, science, and engineering. Over the past decade, the proportion planning to study engineering has risen from 33 percent to 47 percent.

Over the past decade, there has been a clear increase in the number of top‐scoring examinees planning to study engineering and business, and there have been declines particularly in the more quantitative sciences and in the health fields other than pre‐medicine. Business has proved to attract more white females and blacks of both sexes than white males.