bluuebunny/crossref_metadata_2025 huggingface dataset:
Qualidade do sono de pacientes com esclerose lateral amiotrófica
Authors: Ghezzi Simone Ribas , Fontes Sissy Veloso , Aguiar Alexandre Santos , Vitali Lígia Masagão , Fukujima Marcia Maiumi , Fukujima Marcia Maiumi , Ortensi Francis Meire Fávero , Silva Helga Cristina Almeida da , Oliveira Acary Souza Bulle de , Prado Gilmar Fernandes do
Published: July 2009

Introdução: A Esclerose Lateral Amiotrófica (ELA) é uma afecção neuromuscular degenerativa de acometimento do Sistema Nervoso Central e Periférico, com acometimento do neurônio motor, na qual os músculos respiratórios são acometidos, dependendo do local de inicio da degeneração neuronal. Como conseqüência desta alteração podem ocorrer distúrbios do sono. As avaliações qualitativas do sono e das manifestações decorrentes dos distúrbios de sono podem ou não ser influenciadas pelas alterações respiratórias. Deve-se levar em conta ainda que a ansiedade pode ser agente desencadeante de distúrbios do sono. Objetivos: Analisar e identificar qual das três escalas de qualidade do sono (Stanford Sleepiness Scale - SSS, Epworth Sleepiness Scale - ESS, Mini-Seep Questionnaire -MSQ) é a mais apropriada para pacientes com ELA e analisar a correlação entre qualidade do sono e duas escalas de avaliação psicológica (Beck Depression Inventory - BDI e State-Trait Anxiety Inventory - STAI I-II). Métodos: Foram avaliados 16 pacientes com ELA (12 homens e 4 mulheres) entre 35 e 77 anos. Todos foram submetidos à aplicação do protocolo de avaliação proposto. Resultados: Houve correlação entre as escalas: SSS e ESS; SSS e MSQ; BDI e SSS e BDI e MSQ. Conclusões: A SSS foi a escala que teve maior índice de correlação com as outras duas escalas de sono; há uma associação entre depressão e distúrbio do sono em pacientes com ELA. O aspecto ansiedade não pode ser considerado como preditor de distúrbio do sono
Ortopedia funcional dos maxilares, respiração bucal e distúrbios respiratórios do sono em crianças
Authors: Oliveira Débora Aparecida Lentini , Carvalho Fernando Rodrigues , Machado Marco Antônio Cardoso , Prado Lucila Bizari Fernandes , Prado Gilmar Fernandes do
Published: July 2009

A relação entre morfologia facial, respiração bucal e distúrbios respiratórios do sono vem sendo discutida, mas ainda não tem suporte científico. Os objetivos desse artigo são: fazer uma atualização do conhecimento sobre a relação entre respiração bucal, distúrbios respiratórios do sono e determinadas más-oclusões; enfatizar a importância da interdisciplinaridade na busca de melhor prognóstico e estabilidade de tratamento, tanto na correção dos distúrbios respiratórios do sono como na correção das más-oclusões
Queixas urinárias em mulheres com infarto cerebral
Authors: Monteiro Ébe Santos dos , Gimenez Márcia Maria , Fontes Sissy Veloso , Fukujima Márcia Maiumi , Prado Gilmar Fernandes do
Published: July 2009

.
Positional effects on citation and readership in arXiv
Authors: Haque Asif‐ul , Ginsparg Paul
Published: July 2009

arXiv.org mediates contact with the literature for entire scholarly communities, providing both archival access and daily email and web announcements of new materials. We confirm and extend a surprising correlation between article position in these initial announcements and later citation impact, due primarily to intentional “self‐promotion” by authors. There is, however, also a pure “visibility” effect: the subset of articles accidentally in early positions fared measurably better in the long‐term citation record. Articles in astrophysics (astro‐ph) and two large subcommunities of theoretical high energy physics (hep‐th and hep‐ph) announced in position 1, for example, respectively received median numbers of citations 83%, 50%, and 100% higher than those lower down, while the subsets there accidentally had 44%, 38%, and 71% visibility boosts. We also consider the positional effects on early readership. The median numbers of early full text downloads for astro‐ph, hep‐th, and hep‐ph articles announced in position 1 were 82%, 61%, and 58% higher than for lower positions, respectively, and those there accidentally had medians visibility‐boosted by 53%, 44%, and 46%. Finally, we correlate a variety of readership features with long‐term citations, using machine learning methods, and conclude with some observations on impact metrics and the dangers of recommender mechanisms.
Exploration of the hydrogen producing potential of Rhodobacter capsulatus chemostat cultures: The application of deceleration‐stat and gradient‐stat methodology
Authors: Hoekema Sebastiaan , van Breukelen Frank R. , Janssen Marcel , Tramper Johannes , Wijffels René H.
Published: July 2009

In this work, the dependency of the volumetric hydrogen production rate of ammonium‐limited Rhodobacter capsulatus chemostat cultures on their imposed biomass concentration and dilution rate was investigated. A deceleration‐stat experiment was performed by lowering the dilution rate from 1.0 d−1 to zero aimed at a constant biomass concentration of 4.0 g L−1 at constant incident light intensity. The results displayed a maximal volumetric hydrogen production rate of 0.6 mmol m−3 s−1, well below model predictions. Possibly the high cell density limited the average light availability, resulting in a sub‐optimal specific hydrogen production rate. To investigate this hypothesis, a gradient‐stat experiment was conducted at constant dilution rate of 0.4 d−1 at constant incident light intensity. The biomass concentration was increased from 0.7 to 4.0 g L−1 by increasing the influent ammonium concentration. Up to a biomass concentration of 1.5 g L−1, the volumetric hydrogen production rate of the system increased according to model predictions, after which it started to decline. The results obtained provide strong evidence that the observed decline in volumetric hydrogen production rate at higher biomass concentrations was at least partly caused by a decrease in light availability. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
Effect of surfactants on separate hydrolysis fermentation and simultaneous saccharification fermentation of pretreated lodgepole pine
Authors: Tu Maobing , Zhang Xiao , Paice Mike , McFarlane Paul , Saddler Jack N.
Published: July 2009

The effects of surfactants addition on enzymatic hydrolysis and subsequent fermentation of steam exploded lodgepole pine (SELP) and ethanol pretreated lodgepole pine (EPLP) were investigated in this study. Supplementing Tween 80 during cellulase hydrolysis of SELP resulted in a 32% increase in the cellulose‐to‐glucose yield. However, little improvement was obtained from hydrolyzing EPLP in the presence of the same amount of surfactant. The positive effect of surfactants on SELP hydrolysis led to an increase in final ethanol yield after the fermentation. It was found that the addition of surfactant led to a substantial increase in the amount of free enzymes in the 48 h hydrolysates derived from both substrates. The effect of surfactant addition on final ethanol yield of simultaneous saccharification and fermentation (SSF) was also investigated by using SELP in the presence of additional furfural and hydroxymethylfurfural (HMF). The results showed that the surfactants slightly increased the conversion rates of furfural and HMF during SSF process by Saccharomyces cerevisiae. The presence of furfural and HMF at the experimental concentrations did not affect the final ethanol concentration either. The strategy of applying surfactants in cellulase recycling to reduce enzyme cost is presented. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
Understanding diversity managersõ role in organizational change: Towards a conceptual framework
Authors: Tatlõ Ahu , Özbilgin Mustafa F.
Published: July 2009

The paper presents a conceptual framework charting the agency of diversity managers in organizational change. Evaluating and critiquing the contemporary models of organizational change management, we identify three concepts, which are situatedness, relationality, and praxis, for understanding the diversity managers' agency in the organizational change process. Each orienting concept is explored in the context of current diversity management literature and their combined explanatory power is discussed. Copyright © 2009 ASAC. Published by John Wiley & Sons, Ltd.
Cluster analysis of immunohistochemical markers in leiomyosarcoma delineates specific anatomic and gender subgroups
Authors: Carvalho Jason C. , Thomas Dafydd G. , Lucas David R.
Published: July 2009

BACKGROUND:

Leiomyosarcoma (LMS) can be categorized into uterine, retroperitoneal, nonretroperitoneal soft tissue, cutaneous, visceral, and osseous anatomic subtypes. The differential expression of smooth muscle markers, estrogen receptor (ER), progesterone receptor (PR), and Wilms tumor‐1 protein (WT1) by anatomic subtype and gender was explored.

METHODS:

A total of 78 LMS comprised of 30 uterine and 48 nonuterine tumors were studied. Nonuterine tumors were comprised of 17 soft tissue, 16 retroperitoneal, 7 cutaneous, 5 visceral, and 3 osseous subtypes. Immunohistochemical staining intensity on tissue microarray slides was scored as 0, 1+, or 2+, and cluster analysis was performed on the data.

RESULTS:

Smooth muscle actin was the most sensitive antibody (95%), followed by muscle‐specific actin (91%), calponin (88%), desmin (73%), caldesmon (66%), and myosin (64%). Caldesmon and myosin were usually coexpressed, and were highest in retroperitoneal tumors (94%). There was no discernable correlation noted between histologic differentiation and smooth muscle marker expression. ER was much more common in women, with the highest frequencies noted in female retroperitoneal (86%) and uterine (63%) tumors. Nuclear WT1 was expressed in 11% of all tumors, and was limited to ER‐positive uterine and female retroperitoneal tumors. Cluster analysis segregated 4 groups, most notably 1 driven by ER and PR, with the vast majority being uterine and female retroperitoneal tumors.

CONCLUSIONS:

Smooth muscle markers demonstrated variable sensitivities in LMS, with a tendency for anatomic subtypes to segregate based on expression patterns of these markers. ER defined a subgroup of uterine and female retroperitoneal tumors, and WT1 was limited to such tumors, suggesting a common line of differentiation as well as potential therapeutic targets. Cancer 2009. © 2009 American Cancer Society.
Liver‐intestine cadherin predicts microvascular invasion and poor prognosis of hepatitis B virus‐positive hepatocellular carcinoma
Authors: Ding Zhen‐Bin , Shi Ying‐Hong , Zhou Jian , Shi Guo‐Ming , Ke Ai‐Wu , Qiu Shuang‐Jian , Wang Xiao‐Ying , Dai Zhi , Xu Yang , Fan Jia
Published: July 2009

BACKGROUND:

Liver‐intestine cadherin (LI‐cadherin; CDH‐17) is a new member of the cadherin superfamily with distinct structural and functional features. The study was designed to investigate the role of LI‐cadherin in tumor invasion and prognosis of human hepatitis B virus (HBV)‐positive hepatocellular carcinoma (HCC).

METHODS:

LI‐cadherin expression in HBV‐positive hepatocellular carcinoma cell lines with low‐ and high‐invasive potentials was evaluated by Western‐blot, immunofluorescence, and real‐time polymerase chain reaction (PCR) analyses. The role of LI‐cadherin in tumor invasion was also evaluated in vitro by a small‐interfering ribonucleic acid (siRNA)‐mediated approach. The prognostic significance of LI‐cadherin was validated in a cohort of HBV‐positive HCC patients by immunohistochemistry and Western‐blot.

RESULTS:

Significant high levels of LI‐cadherin mRNA and protein were found in the high‐invasive HCCLM3 as compared with those in low‐invasive PLC/PRF/5 and Hep3B cell line. Cell migration, adhesion to extracellular matrix, and matrigel invasion were significantly reduced after LI‐cadherin knockdown in HCCLM3 cells. Immunohistochemical analysis of 255 HBV‐positive HCC cases showed that overexpression of LI‐cadherin was well correlated with microvascular invasion, which was confirmed by Western‐blot in 32 tumor tissues, and its overexpression was strongly associated with shorter overall survival as well as higher incidence of tumor recurrence.

CONCLUSIONS:

LI‐cadherin is predictive of microvascular invasion and poor prognosis of HBV‐positive HCC, and would be a potential useful intervention target for HCC. Cancer 2009. © 2009 American Cancer Society.
Bevacizumab in association with de Gramont 5‐fluorouracil/folinic acid in patients with oxaliplatin‐, irinotecan‐, and cetuximab‐refractory colorectal cancer
Authors: Vincenzi Bruno , Santini Daniele , Russo Antonio , Spoto Chiara , Venditti Olga , Gasparro Simona , Rizzo Sergio , Zobel Bruno Beomonte , Caricato Marco , Valeri Sergio , Coppola Roberto , Tonini Giuseppe
Published: July 2009

BACKGROUND:

The aim of the current study was the investigation of the value of bevacizumab + 5‐fluorouracil(5–FU)/folinic acid in patients with advanced colorectal cancers who have exhausted standard chemotherapy options.

METHODS:

The authors included 48 heavily pretreated patients (colon:rectum, 33:15; men:women, 23:25; median age, 63 years; range, 27‐79 years) whose disease had progressed during or within an oxaliplatin‐based first‐line chemotherapy, an irinotecan‐based second‐line regimen, and a third‐line treatment with cetuximab plus weekly irinotecan. Bevacizumab was given at a dose of 5 mg/kg. 5‐FU/folinic acid was administered according to the de Gramont schedule.

RESULTS:

The response rate was 6.25%, and 30.4% of patients demonstrated stable disease as the best response. The median time to disease progression was 3.5 months (95% confidence interval [95% CI], 2.3‐6.9 months), and the median survival time was 7.7 months (95% CI, 3.9‐11.9 months). The most common grade 3 to 4 side toxicities (graded according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) were: diarrhea (20.8%), fatigue (14.5%), and stomatitis (12.5%). Grade 3 to 4 hemorrhage occurred in 8 patients (16.6%), including 4 cases of bleeding in the gastrointestinal tract. Other relatively common adverse events such as hypertension, thrombosis, and bowel perforation were reported in 50%, 18.7%, and 4.16%, of patients respectively.

CONCLUSIONS:

The data from the current study suggest a modest but significant clinical benefit of bevacizumab + de Gramont schedule in heavily pretreated colorectal cancer patients. Cancer 2009. © 2009 American Cancer Society.
CMOS current mirror with enhanced input dynamic range
Authors: Wang Hung‐Yu , Jeang Yuan‐Long , Liu Ying‐Chuan , Huang Yu‐Wei
Published: July 2009

A novel CMOS cascode current mirror configuration with enhanced input dynamic range is presented. The proposed mirror circuit combines the advantages of wide input swing, wide output swing and large output resistance capability, which make it attractive for practical application. Based on 0.18 µm MOS model parameters, HSPICE simulation results show that the input current ranges from 1 µA to 1 mA with large bandwidth for the proposed circuit. The simulation results confirm the theoretical prediction. Copyright © 2009 John Wiley & Sons, Ltd.
Dysplastic cells in cytological cervical samples show a high incidence of chromosomal abnormalities
Authors: Song Minghao , Ruth Adam , Policht Frank A. , Bubendorf Lukas , Feichter Georg , Kipp Benjamin R. , Halling Kevin C. , Sokolova Irina A.
Published: July 2009

Chromosomal abnormalities are frequent in most cervical cancers. Amplifications of both the 3q26 (TERC) and 8q24 (MYC) loci have been shown to be prevalent in both high‐grade lesions and invasive cervical carcinoma. Most of these studies have looked at either the histological sample or at the entire cytological population of cells. We have developed a Papanicolaou (Pap) destaining method that allows for the accurate analysis of individual cells that were previously identified by cytopathology as dysplastic. The application of fluorescence in situ hybridization (FISH) was then implemented to determine the chromosomal status of the dysplastic cells in the samples and correlate the two events. Chromosomal abnormality is over a thousand times more frequent in dysplastic cells compared with their morphologically normal counterparts. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.
Evidence‐based guidelines to optimize the selection of antibody panels in cytopathology: Pleural effusions with malignant epithelioid cells
Authors: Westfall Danielle E. , Fan Xuemo , Marchevsky Alberto M.
Published: July 2009

There is no established methodology to help select cost effective antibody panels. We used Bayesian statistics and an evidence‐based pathology (EBP) approach to retrospectively review the use of immunohistochemistry (IHC) in 153 consecutive pleural effusions evaluated in our laboratory from 2005–2007 for the differential diagnosis of malignant mesothelial cells versus carcinoma cells and to estimate the likely site of origin of a carcinoma. The results in this “training” set were used to design antibody panels and test their clinical applicability on a “test set” of 44 pleural effusions collected in early 2008. Cytopathologists had used 6 ± 4.5 IHC tests per case for the diagnosis of malignant mesothelioma (n = 9) and carcinomas of lung (n = 60), breast (n = 47), Müllerian (n = 25), and other origins in the “training set”. The sensitivity and specificity of pleural cytology using all these IHC tests were 32% and 95%, respectively. Sensitivity, specificity and post‐test odds (PTO) of a positive IHC result were calculated for each antibody and by the following classes: malignant mesothelial cells and carcinoma cells by primary site of origin. The antibodies that provided the best PTO to diagnose the most prevalent tumors in our population were included in diagnostic panels for male (calretinin, TTF‐1, PSA and CDX‐2) and female (calretinin, TTF‐1, ER and CA125) patients. These panels provided 100% specificity and 77% and 50% sensitivity, respectively, for the pleural effusions from female and male patients in the “test set.” The use of an EBP approach for test selection in cytopathology is discussed. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.
Update on human polyomavirus BK nephropathy
Authors: Cimbaluk David , Pitelka Lisa , Kluskens Larry , Gattuso Paolo
Published: July 2009

Polyomavirus BK (BKV) has ebeen identified as the main cause of polyomavirus‐associated nephropathy, a major cause of renal allograft failure. Although BKV‐associated nephropathy develops in only 2% to 5% of renal transplant recipients, its prognosis when present is very poor, with irreversible graft failure developing in 45% of affected patients. While the use of urine cytology for the detection of decoy cells has been in use for decades, other diagnostic modalities to detect BKV have emerged, including tissue biopsy, polymerase chain reaction, viral culture, and serology. Currently, there is no consensus regarding the laboratory technique best suited for clinical monitoring. This review article will discuss essential and clinical features of polyomavirus, followed by a discussion pertaining to the various diagnostic modalities that contribute to detecting polyomavirus‐associated nephropathy. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.
Fine needle aspiration biopsy of renal mucinous tubular and spindle cell carcinoma: Report of two cases
Authors: Marks‐Jones Deborah A. , Zynger Debra L. , Parwani Anil V. , Cai Guoping
Published: July 2009

Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare renal tumor. Here we report two cases of MTSCC which were initially evaluated by fine needle aspiration biopsy (FNAB) and followed by surgical resection of the tumors. The cytomorphologic features of MTSCC were characterized by aggregates of relatively uniform, predominantly oval to spindle cells intermixed with abundant metachromatic myxoid matrix. Only rare epithelioid tumor cells with vacuolated cytoplasm were present. Immunohistochemically, the tumor cells were positive for CK7, CK19, CD10, vimentin, E‐cadherin, alpha‐methyl CoA racemase, and negative for CK903 and CK20. EMA and carbonic anhydrase IX immunoreactivity was seen in one of the two cases. Multiple chromosomal losses involving chromosomes 1, 2, 17 and likely chromosome 7 were revealed by fluorescence in situ hybridization (FISH). These cytomorphologic, immunophenotypic, and cytogenetic features were helpful for including this entity in the differential diagnosis of renal cell carcinomas. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.
Effects of therapy in type 1 and type 2 diabetes mellitus with a peptide derived from islet neogenesis associated protein (INGAP)
Authors: Dungan Kathleen M. , Buse John B. , Ratner Robert E.
Published: July 2009

Background

Islet neogenesis associated protein (INGAP) has beta cell regenerating effects in experimental models.

Methods

Subjects with T1DM (N = 63) and T2DM (N = 126) received 300 or 600 mg/day of INGAP peptide in a 90 day, randomized, double‐blind, placebo‐controlled trial.

Results

In T1DM, on‐treatment Arginine‐stimulated C‐peptide (AUC0–30) significantly increased from baseline in the 600 mg group (p = 0.0058 versus placebo); no significant changes were seen in the 300 mg group. In T2DM, stimulated C‐peptide was significantly better preserved in the 600 mg group compared to placebo at day 120, 30 days after washout (p = 0.031 versus placebo), but did not reach statistical significance during treatment or in the 300 mg group. In T2DM, A1C decreased significantly more in the 600 mg group compared to placebo at day 90 (−0.94% versus −0.47%, respectively, p = 0.009) and day 120, 30 days after washout (−0.73% versus −0.24%, respectively, p = 0.013). This was accompanied by significant reductions in mean glucose. No difference from placebo was detected in the 300 mg group or in T1DM. Injection site reactions were the most common adverse event, occurring in 8 (36%) of placebo, 19 (90%) of 300 mg, and 15 (75%) of 600 mg groups (T1DM) and 14 (33%) of placebo, 27 (64%) of 300 mg, and 29 (69%) of 600 mg groups (T2DM).

Conclusions

INGAP peptide increases C‐peptide secretion in T1DM and improves glycaemic control in T2DM. Longer‐term exposure, more frequent dosing, better tolerated formulations or combination with other therapies may be necessary to achieve optimal clinical response. Copyright © 2009 John Wiley & Sons, Ltd.
Back to the roots of modern analytical toxicology: Jean Servais Stas and the Bocarmé murder case
Authors: Wennig Robert
Published: July 2009

In 1850 the Belgian Count Hypolyte Visart de Bocarmé was accused of having killed his brother‐in‐law Gustave Fougnies by poisoning with nicotine. Bocarmé had isolated nicotine from tobacco leaves (Nicotiana tabacum). J. S. Stas (1813–1891) was committed expert and managed to convince the poisoner. He was the first scientist to deproteinize organ tissues by alcohol and could successfully identify nicotine after diethyl ether extraction from the victim's organs. During court trial this identification was challenged by his mentor M. J. B. Orfila from Paris, who had stated 3 years before, that it would never be possible to isolate and identify organic poisons from organ tissues. Copyright © 2009 John Wiley & Sons, Ltd.
A Structural and Magnetic Study of the Series of Double Perovskites Ca2Fe1+xW1–xO6
Authors: Retuerto María , Alonso José Antonio , Martínez‐Lope María Jesús , García‐Hernández Mar , López Carlos A. , Viola María del Carmen , Pedregosa José C. , Fernández‐Díaz María Teresa
Published: July 2009

The synthesis of the Ca2Fe1+xW1–xO6 perovskite solid solution in the range x = 0.13–0.33 by a soft‐chemistry procedure followed by annealing at different temperatures under different reducing atmospheres, and its characterization by X‐ray and neutron diffraction together with magnetic measurements, is reported. The average Fe oxidation state in this series varies smoothly from Fe2.46+ in Ca2Fe1.13W0.87O6 to Fe3+ in Ca2Fe1.33W0.67O6. A detailed description of the crystal structure of four selected members of this series (x = 0.2, 0.23, 0.30, 0.33) is provided. All these compounds crystallize in the space group P21/n, with a ≈ b ≈ √2a0 and c ≈ 2a0, although they show different levels of long‐range ordering between the two different cations placed at the B positions of the A2B′B″O6 perovskite structure. The driving force for this B′/B″ ordering is the charge difference between both kinds of cations, whereby the earlier members of the series, which contain a large proportion of Fe2+, are fully ordered whereas a strong antisite disorder effect is observed for the later members. The evolution of this antisite disordering has a dramatic influence on the magnetic properties across the series. Thus, for x = 0.20, the ferrimagnetic Curie temperature is above 400 K, although the saturation magnetization is very low, since there is a poor coherence between the antiferromagnetic patches formed by Fe–O–Fe interactions between the B′ and B″ positions of the perovskite, whereas the x = 0.33 compound, which has a lower TC of 310 K, shows a considerable saturation magnetization and a surprisingly strong magnetic neutron scattering for such a structurally disordered sample. The observed scattering can be ascribed to the good coherence obtained via Fe–O–Fe superexchange interactions among the Fe‐rich, antiferromagnetically ordered patches that occur naturally thorughout the crystal. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
gem‐Bisphosphonate‐Ended Group Dendrimers: Design and Gadolinium Complexing Properties
Authors: Franc Grégory , Turrin Cédric‐Olivier , Cavero Emma , Costes Jean‐Pierre , Duhayon Carine , Caminade Anne‐Marie , Majoral Jean‐Pierre
Published: July 2009

The synthesis of the first gem‐bisphosphonate‐ended group dendrimers is described using nucleophilic substitution of terminal P(S)Cl2 units of phosphorus dendrimers of generation 1 to 3 with protected aminophenols followed by deprotection of amino groups and Michael addition with vinylidene tetraisopropyl bisphosphonate. These dendrimers were found to act as chelating agents towards Gd ions.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Efficient Synthesis of Modular Amino Acid Derivatives Containing Selenium with Pronounced GPx‐Like Activity
Authors: Alberto Eduardo E. , Soares Letiére C. , Sudati Jéssie H. , Borges Antonio C. A. , Rocha João B. T. , Braga Antonio L.
Published: July 2009

New chiral selenide‐ and diselenide amino acid derivatives have been synthesized. By a simple and efficient two‐step route, these new compounds were obtained from inexpensive and commercially available L‐amino acids. The products, with a highly modular character, were obtained in good to excellent yields. Selected examples were also efficiently used as GPx mimics, catalyzing the reduction of H2O2 to water at the expense of PhSH. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Synthesis and Properties of Oligonucleotides Containing Novel Fluorescent Biaryl Units
Authors: Ueno Yoshihito , Komatsuzaki Shinji , Takasu Keiji , Kawai Satoru , Kitamura Yoshiaki , Kitade Yukio
Published: July 2009

We describe the synthesis and properties of oligonucleotides (ONs) containing biaryl units, which are composed of a bis(hydroxymethyl)benzene residue and a naphthalene or pyrene moiety. We found that by introducing the biaryl units into the ONs, the aromatic chromophores were suitably arrayed in the DNAs. Further, we succeeded in the detection of a single‐base mismatch in RNA by using the ON containing the biaryl unit as a molecular beacon. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Selective elimination of amplified CDK4 sequences correlates with spontaneous adipocytic differentiation in liposarcoma
Authors: Hélias‐Rodzewicz Zofia , Pédeutour Florence , Coindre Jean‐Michel , Terrier Philippe , Aurias Alain
Published: July 2009

Well‐differentiated and undifferentiated liposarcomas are characterized by high‐level amplifications of chromosome 12 regions including the CDK4 and MDM2 genes. These amplicons are either localized, in well‐differentiated liposarcoma (WDLPS), on extrachromosomal structures (ring or rod chromosomes), or integrated into chromosome arms in undifferentiated tumors. Our results reveal that extrachromosomal amplicons are unstable, and frequently lost by micronucleation. This loss correlates with hypermethylation of eliminated sequences and changes of their replication time. Treatment of cells with demethylating agents during early S‐phase significantly decreases the rate of micronuclei positive for CDK4. We also demonstrate that, in our model, micronuclei are generated during anaphase as a consequence of anaphase abnormalities (chromosome lagging and anaphase bridges). Finally, a dramatic increase of adipocytic differentiation was noted in cells that have eliminated copies of CDK4 gene in micronuclei. These findings provide evidence that, in WDLPS, adipocytic differentiation could be the consequence of CDK4 loss, an event occurring rarely in undifferentiated tumors in which the amplified sequences are integrated into chromosome arms. © 2009 Wiley‐Liss, Inc.
Were genome‐wide linkage studies a waste of time? Exploiting candidate regions within genome‐wide association studies
Authors: Yoo Yun J. , Bull Shelley B. , Paterson Andrew D. , Waggott Daryl , Sun Lei
Published: July 2009

A central issue in genome‐wide association (GWA) studies is assessing statistical significance while adjusting for multiple hypothesis testing. An equally important question is the statistical efficiency of the GWA design as compared to the traditional sequential approach in which genome‐wide linkage analysis is followed by region‐wise association mapping. Nevertheless, GWA is becoming more popular due in part to cost efficiency: commercially available 1M chips are nearly as inexpensive as a custom‐designed 10 K chip. It is becoming apparent, however, that most of the on‐going GWA studies with 2,000–5,000 samples are in fact underpowered. As a means to improve power, we emphasize the importance of utilizing prior information such as results of previous linkage studies via a stratified false discovery rate (FDR) control. The essence of the stratified FDR control is to prioritize the genome and maintain power to interrogate candidate regions within the GWA study. These candidate regions can be defined as, but are by no means limited to, linkage‐peak regions. Furthermore, we theoretically unify the stratified FDR approach and the weighted P‐value method, and we show that stratified FDR can be formulated as a robust version of weighted FDR. Finally, we demonstrate the utility of the methods in two GWA datasets: Type 2 diabetes (FUSION) and an on‐going study of long‐term diabetic complications (DCCT/EDIC). The methods are implemented as a user‐friendly software package, SFDR. The same stratification framework can be readily applied to other type of studies, for example, using GWA results to improve the power of sequencing data analyses. Genet. Epidemiol. 34: 107–118, 2010. © 2009 Wiley‐Liss, Inc.
Reliability and validity of the Vanderbilt Head and Neck Symptom Survey: A tool to assess symptom burden in patients treated with chemoradiation
Authors: Murphy Barbara A. , Dietrich Mary S. , Wells Nancy , Dwyer Kathleen , Ridner Sheila H. , Silver Heidi J. , Gilbert Jill , Chung Christine H. , Cmelak Anthony , Burkey Brian , Yarbrough Wendell G. , Sinard Robert , Netterville James
Published: July 2009

Background.

We describe the development and validation of the Vanderbilt Head and Neck Symptom Survey (VHNSS), which was designed to screen for tumor‐ and treatment‐specific symptoms in patients with head and neck cancer undergoing concurrent chemoradiation (CCR).

Methods.

Using a 2‐step card sort method, we identified high‐impact and high‐frequency toxicities in patients with head and neck cancer treated with CCR. This resulted in a 28‐item questionnaire which scores symptoms on a 0 to 10 scale (none to severe). The tool was validated using data collected from 5 supportive care studies comprising a total sample of 332 patients with head and neck cancer.

Results.

Responses to the VHNSS items demonstrated a very consistent pattern (Cronbach's alpha = 0.943) with each item contributing substantially to the global index. Five symptom subscales were identified including “Nutrition,” “Pain,” “Voice,” “Swallow,” and “Mucous/Dry Mouth.” Each of the cluster scores demonstrated good internal consistency. The pattern of associations between the VHNSS and established tools indicated appropriate convergence and divergence. Comparison of global and subscale scores and objective measure were also in the expected direction providing further evidence of validity.

Conclusions.

The findings provide support that the VHNSS is a valid and reliable tool to assess head and neck–specific symptom burden and function loss. Further research to evaluate this screening tool as a part of a systems approach to supportive care is warranted. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
Metastases to level IIb in squamous cell carcinoma of the oral cavity: A systematic review and meta‐analysis
Authors: Lea Jane , Bachar Gideon , Sawka Anna M. , Lakra Deepak C. , Gilbert Ralph W. , Irish Jonathan C. , Brown Dale H. , Gullane Patrick J. , Goldstein David P.
Published: July 2009

Background.

In this study, a meta‐analysis of level IIb metastases in squamous cell carcinoma (SCC) of the oral cavity was conducted.

Methods.

Two independent reviewers screened abstracts and full text papers deemed potentially relevant. Data were pooled using a random intercept model.

Results.

In this analysis, 729 abstracts and 177 full text papers were screened (Kappa statistic 0.8 and 1.0, respectively). A total of 332 patients in 9 papers were included in the analysis. Twenty patients had level IIb metastases (mean, 6%; range, 0% to 10.4%). The pooled percentage of level IIb metastases was 6.0% (95% CI: 3.5–8.6). Only 3 patients with level IIb metastases had isolated nodal disease. Eighty‐five percent of those with level IIb metastases had additional nodal disease (95% CI: 64.0–94.8), with IIa being a common denominator among all.

Conclusion.

Level IIb nodal metastases are relatively uncommon in previously untreated SCC of the oral cavity (6%). Furthermore, isolated level IIb nodal disease is uncommon. However, given the quality of evidence to date, it is recommended that dissection of level IIb remain the standard of care in oral cavity squamous cell cancer. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
Nutrition impact symptoms: Key determinants of reduced dietary intake, weight loss, and reduced functional capacity of patients with head and neck cancer before treatment
Authors: Kubrak Catherine , Olson Kärin , Jha Naresh , Jensen Louise , McCargar Linda , Seikaly Hadi , Harris Jeffery , Scrimger Rufus , Parliament Matthew , Baracos Vickie E.
Published: July 2009

Background.

Our aim was to evaluate the prevalence and relationship of symptoms with reduced dietary intake, weight, and functional capacity in patients with head and neck cancer.

Methods.

Three hundred forty‐one patients were prospectively screened with the patient‐generated subjective global assessment before treatment. Logistic analysis was used to relate symptoms to reduced dietary intake, weight, and functional capacity. Cumulative hazard analysis was performed to determine the time and risk of weight loss of each symptom. Survival analysis was performed with Cox proportional hazards model.

Results.

Anorexia, dysphagia, mouth sores, and others were significant predictors of reduced dietary intake and weight. Symptom presence accelerated the time and probability of weight loss. Body mass index ≤18.5 related to overall survival (p value = .001).

Conclusions.

Symptoms present before treatment may adversely affect the dietary intake, weight, and functional capacity of patients. Symptom treatment and management is critical to weight loss prevention. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
18F‐FDG‐PET/CT versus panendoscopy for the detection of synchronous second primary tumors in patients with head and neck squamous cell carcinoma
Authors: Haerle Stephan K. , Strobel Klaus , Hany Thomas F. , Sidler Daniel , Stoeckli Sandro J.
Published: July 2009

Background.

This study assesses the additional value of 18F‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography/CT (18F‐FDG‐PET/CT) with respect to synchronous primaries in patients undergoing panendoscopy for staging of head and neck squamous cell carcinoma.

Methods.

In all, 311 patients underwent both modalities. Cytology, histology, and/or clinical/imaging follow‐up served as reference standard.

Results.

The prevalence of second primary tumors detected by panendoscopy was 4.5%, compared with 6.1% detected by 18F‐FDG‐PET/CT. The sensitivity for panendoscopy was 74%, the specificity was 99.7%, the positive predictive value (PPV) was 93%, and the negative predictive value (NPV) was 98%. The sensitivity for 18F‐FDG‐PET/CT was 100%, the specificity was 95.7%, the PPV was 59%, and the NPV was 100%.

Conclusions.

18F‐FDG‐PET/CT is superior to panendoscopy. With a negative 18F‐FDG‐PET/CT, the extent of endoscopy can be reduced to the area of the primary tumor. Due to the costs, 18F‐FDG‐PET/CT is recommended only in advanced disease to assess potential distant disease. In early‐stage cancer, panendoscopy is accurate enough to rule out secondary tumors. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
Ex vivo gene therapy using autologous dermal fibroblasts expressing hLMP3 for rat mandibular bone regeneration
Authors: Parrilla Claudio , Lattanzi Wanda , Rita Fetoni Anna , Bussu Francesco , Pola Enrico , Paludetti Gaetano
Published: July 2009

Background.

Implantation of autologous skin fibroblasts transduced ex vivo with a replication‐defective adenoviral vector, carrying the LIM mineralization protein‐3 (Ad‐LMP‐3), and adsorbed on a hydroxyapatite/collagen (HA/COL) scaffold.

Methods.

Twenty‐seven Wistar rats were used. A 5‐ × 5‐mm full‐thickness defect was created in the exposed mandible. All animals were randomized into 3 experimental groups: (1) autologous dermal fibroblasts transduced with Ad‐LMP‐3 and adsorbed on the HA/COL; (2) nontransduced dermal fibroblasts adsorbed on the HA/COL scaffold; and (3) HA/COL scaffold without cells. Three‐dimensional micro‐CT (3DmicroCT or 3DμCT) and histological analysis were performed.

Results.

Efficient neoosteogenesis was observed in animals treated with LMP‐3–expressing cells (group 1) as soon as 4 weeks after surgery. Conversely, nonsignificant bone formation was detected in control animals (groups 2 and 3) at all time points tested.

Conclusion.

These results suggest that the experimental approach based on transplantation of genetically modified autologous cells could provide an alternative treatment for cranio‐maxillo‐facial defects. Nonetheless, additional data from the study on larger bone defects must follow to foresee a clinical application in the near future. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
Down‐regulation of BiP/GRP78 sensitizes resistant prostate cancer cells to gene‐therapeutic overexpression of REIC/Dkk‐3
Authors: Tanimoto Ryuta , Sakaguchi Masakiyo , Abarzua Fernando , Kataoka Ken , Kurose Kaoru , Murata Hitoshi , Nasu Yasutomo , Kumon Hiromi , Huh Nam‐Ho
Published: July 2009

We have recently shown that an adenovirus carrying REIC/Dkk‐3 (Ad‐REIC) exhibits a potent tumor‐specific cell‐killing function for various human cancers. It has also become evident that some human cancers are resistant to Ad‐REIC‐induced apoptosis. The aim of the present study was to determine the molecular mechanisms of resistance to Ad‐REIC. First, we isolated resistant clones from a human prostate cancer cell line, PC3, after repeated exposure to Ad‐REIC. Infection efficiency of the adenovirus vector and expression level of REIC/Dkk‐3 in the resistant clones were similar to those in the parental PC3 cells. By screening for alteration in levels and functional status of proteins involved in Ad‐REIC‐induced apoptosis, we found that BiP/GRP78, an ER‐residing chaperone protein, was expressed at higher levels consistently among resistant cells. Expression levels of BiP and rates of apoptosis induced by Ad‐REIC were inversely correlated. Down‐regulation of BiP with siRNA sensitized the resistant cells to Ad‐REIC in vivo as well as in culture. These results indicate that BiP is a major determinant of resistance to Ad‐REIC‐induced apoptosis. Thus BiP is useful for diagnosis of inherent and acquired resistance of cancers and also as a target molecule to overcome resistance to the gene therapeutic Ad‐REIC.
Prevalence and risk factors of human papillomavirus infection by penile site in uncircumcised Kenyan men
Authors: Smith Jennifer S. , Backes Danielle M. , Hudgens Michael G. , Bailey Robert C. , Veronesi Giovanni , Bogaarts Martijn , Agot Kawango , Ndinya‐Achola J.O. , Maclean Ian , Agingu Walter , Meijer Chris J.L.M. , Moses Stephen , Snijders Peter J.F.
Published: July 2009

Human papillomavirus (HPV) prevalence was estimated from 2,705 sexually active, uncircumcised, human immunodeficiency virus seronegative men aged 17–28 years in Kisumu, Kenya. HPV prevalence was 51.1% (95% confidence interval: 49.2–53.0%) in penile cells from the glans/coronal sulcus and/or shaft. HPV prevalence varied by anatomical site, with 46.5% positivity in the glans/coronal sulcus compared with 19.1% in the shaft (p < 0.0001). High‐risk HPV was detected in 31.2% of glans and 12.3% of shaft samples (p < 0.0001). HPV16 was the most common type and 29.2% of men were infected with more than one HPV type. Risk factors for HPV infection included presence of C. trachomatis, N. gonorrhea, self‐reported sexually transmitted infections, and less frequent bathing. Lifetime number of sexual partners and herpes simplex virus type‐2 seropositivity were also marginally associated with HPV infection.
Elevated lung cancer risk is associated with deficiencies in cell cycle checkpoints: genotype and phenotype analyses from a case‐control study
Authors: Zheng Yun‐Ling , Kosti Ourania , Loffredo Christopher A. , Bowman Elise , Mechanic Leah , Perlmutter Donna , Jones Raymond , Shields Peter G. , Harris Curtis C.
Published: July 2009

Cell cycle checkpoints play critical roles in the maintenance of genomic integrity and inactivation of checkpoint genes are frequently perturbed in most cancers. In a case‐control study of 299 non‐small cell lung cancer cases and 550 controls in Baltimore, we investigated the association between γ‐radiation‐induced G2/M arrest in cultured blood lymphocytes and lung cancer risk, and examined genotype‐phenotype correlations between genetic polymorphisms of 20 genes involving in DNA repair and cell cycle control and γ‐radiation‐induced G2/M arrest. The study was specifically designed to examine race and gender differences in risk factors. Our data indicated that a less efficient DNA damage‐induced G2/M checkpoint was associated with an increased risk of lung cancer in African American women with an adjusted odds ratio (OR) of 2.63 (95% CI = 1.01–7.26); there were no statistically significant associations for Caucasians, or African American men. When the African American women were categorized into quartiles, a significant reverse trend of decreased G2/M checkpoint function and increased lung cancer risk was present, with lowest‐vs.‐highest quartile OR of 13.72 (95% CI = 2.30–81.92, ptrend < 0.01). Genotype‐phenotype correlation analysis indicated that polymorphisms in ATM, CDC25C, CDKN1A, BRCA2, ERCC6, TP53, and TP53BP1 genes were significantly associated with the γ‐radiation‐induced G2/M arrest phenotype. This study provides evidence that a less efficient G2/M checkpoint is significantly associated with lung cancer risk in African American women. The data also suggested that the function of G2/M checkpoint is modulated by genetic polymorphisms in genes involved in DNA repair and cell cycle control.
Polymorphisms in TNF and HSP‐70 show a significant association with gastric cancer and duodenal ulcer
Authors: Partida‐Rodríguez Oswaldo , Torres Javier , Flores‐Luna Lourdes , Camorlinga Margarita , Nieves‐Ramírez Miriam , Lazcano Eduardo , Perez‐Rodríguez Martha
Published: July 2009

Tumour Necrosis Factor (TNF) and Heat Shock Protein 70 (HSP70) are important molecules in inflammatory, infectious and tumoral processes. The genes codifying these molecules are polymorphic and certain alleles have been associated with susceptibility to disease. Gastric cancer is associated with an Helicobacter pylori‐induced chronic inflammatory response. The aim of this work was to analyze whether polymorphisms in inflammation‐related genes are associated with the development of gastric cancer. We studied 447 Mexican adult patients including 228 with non‐atrophic gastritis, 98 with intestinal metaplasia, 63 with gastric cancer and 58 with duodenal ulcer, and 132 asymptomatic individuals as well. DNA from peripheral white blood cells was typed for the Single Nucleotide Polymorphisms (SNPs) −308 of TNF‐α, +252 of TNF‐β, +190 of HSP70‐1, +1267 of HSP70‐2 and +2437 of HSP70‐HOM. Compared with the asymptomatic group, we found a significant association of TNF‐β*A and HSP70‐1*C alleles with gastric cancer (OR 5.69 and 3.76, respectively) and HSP70‐1*C with duodenal ulcer (OR 3.08). Genotype TNF‐β G/G showed a significant gene‐dose effect with gastric cancer (OR 0.09); whereas HSP70‐1 C/G showed significant association with both, gastric cancer (OR 13.31) and duodenal ulcer (OR 16.19). Polymorphisms in TNF and HSP70 showed a significant severity‐dose‐response as risk markers from preneoplastic lesions to gastric cancer in Mexican population, probably because of their association with an intense and sustained inflammatory response.
How to evaluate emerging technologies in cervical cancer screening?
Authors: Arbyn Marc , Ronco Guglielmo , Cuzick Jack , Wentzensen Nicolas , Castle Philip E.
Published: July 2009

Excellent recommendations exist for studying therapeutic and diagnostic questions. We observe that good guidelines on assessment of evidence for screening questions are currently lacking. Guidelines for diagnostic research (STARD), involving systematic application of the reference test (gold standard) to all subjects of large study populations, are not pertinent in situations of screening for disease that is currently not yet present. A five‐step framework is proposed for assessing the potential use of a biomarker as a screening tool for cervical cancer:i) correlation studies establishing a trend between the rate of biomarker expression and severity of neoplasia;ii) diagnostic studies in a clinical setting where all women are submitted to verification by the reference standard;iii) biobank‐based studies with assessment in archived cytology samples of the biomarker in cervical cancer cases and controls;iv) prospective cohort studies with baseline assessment of the biomarker and monitoring of disease;v) randomised intervention trials aiming to observe reduced incidence of cancer (or its surrogate, severe dysplasia) in the experimental arm at subsequent screening rounds. The 5‐phases framework should guide researchers and test developers in planning assessment of new biomarkers and protect clinicians and stakeholders against premature claims for insufficiently evaluated products. © 2009 UICC.