bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contiguous gene syndrome due to a maternally inherited 8.41 Mb distal deletion of chromosome band Xp22.3 in a boy with short stature, ichthyosis, epilepsy, mental retardation, cerebral cortical heterotopias and Dandy–Walker malformation
Authors: van Steensel M.A.M. , Vreeburg M. , Engelen J. , Ghesquiere S. , Stegmann A.P.A. , Herbergs J. , van Lent J. , Smeets B. , Vles J.H. 
Published: October 2008

AbstractMicrodeletions of Xp22.3 are associated with contiguous gene syndromes, the extent and nature of which depend on the genes encompassed by the deletion. Common symptoms include ichthyosis, mental retardation and hypogonadism. We report on a boy with short stature, ichthyosis, severe mental retardation, cortical heterotopias and Dandy–Walker malformation. The latter two abnormalities have so far not been reported in terminal Xp deletions. MLPA showed deletion of SHOX and subsequent analysis using FISH and SNP‐arrays revealed that the patient had an 8.41 Mb distal deletion of chromosome region Xp22.31 → Xpter. This interval contains several genes whose deletion can partly explain our patient's phenotype. His cortical heterotopias and DWM suggest that a gene involved in brain development may be in the deleted interval, but we found no immediately obvious candidates. Interestingly, further analysis of the family revealed that the patient had inherited his deletion from his mother, who has a mos 46,X,del(X)(p22)/45,X/46, XX karyotype. © 2008 Wiley‐Liss, Inc.
Microcephaly, malformation of brain development and intracranial calcification in sibs: Pseudo‐TORCH or a new syndrome
Authors: Abdel‐Salam Ghada M.H. , Zaki Maha S. , Saleem Sahar N. , Gaber Khaled R. 
Published: October 2008

AbstractWe report on five sibs affected by congenital microcephaly, growth retardation, sloping forehead, bitemporal grooving and micrognathia. Generalized tonic‐clonic seizures started very early in life. Postnatal brain computerized tomography (CT) presented cortical band‐like calcification, calcification of basal ganglia and brain stem while brain magnetic resonance imaging (MRI) revealed abnormal gyral pattern, marked loss of white matter, dysplastic ventricles, polymicrogyria, hypogenesis of corpus callosum and cerebellar hypoplasia. No abnormalities of the internal organs, eye, or skeleton were found to be associated with this syndrome. Fetal Magnetic resonance imaging helped reaching the diagnosis in utero in one patient. Three patients died in the first years of life while the others within days after birth preceded by high fever and status epilepticus. These patients present many overlapping features with pseudo TORCH syndrome, however, the imaging findings are quite different. We propose that the distinct pattern in these sibs constitutes genetic disorder of microcephaly, developmental brain malformation and intracranial calcification of likely autosomal recessive inheritance. © 2008 Wiley‐Liss, Inc.
Safety and efficacy of 22 weeks of treatment with sapropterin dihydrochloride in patients with phenylketonuria
Authors: Lee Phillip , Treacy Eileen P. , Crombez Eric , Wasserstein Melissa , Waber Lewis , Wolff Jon , Wendel Udo , Dorenbaum Alex , Bebchuk Judith , Christ‐Schmidt Heidi , Seashore Margretta , Giovannini Marcello , Burton Barbara K. , Morris Andrew A. ,   the Sapropterin Research Group
Published: October 2008

AbstractPhenylketonuria (PKU) is an inherited metabolic disease characterized by phenylalanine (Phe) accumulation, which can lead to neurocognitive and neuromotor impairment. Sapropterin dihydrochloride, an FDA‐approved synthetic formulation of tetrahydrobiopterin (6R‐BH4, herein referred to as sapropterin) is effective in reducing plasma Phe concentrations in patients with hyperphenylalaninemia due to tetrahydrobiopterin (BH4)‐responsive PKU, offering potential for improved metabolic control. Eighty patients, ≥8 years old, who had participated in a 6‐week, randomized, placebo‐controlled study of sapropterin, were enrolled in this 22‐week, multicenter, open‐label extension study comprising a 6‐week forced dose‐titration phase (5, 20, and 10 mg/kg/day of study drug consecutively for 2 weeks each), a 4‐week dose‐analysis phase (10 mg/kg/day), and a 12‐week fixed‐dose phase (patients received doses of 5, 10, or 20 mg/kg/day based on their plasma Phe concentrations during the dose titration). Dose‐dependent reductions in plasma Phe concentrations were observed in the forced dose‐titration phase. Mean (SD) plasma Phe concentration decreased from 844.0 (398.0) µmol/L (week 0) to 645.2 (393.4) µmol/L (week 10); the mean was maintained at this level during the study's final 12 weeks (652.2 [382.5] µmol/L at week 22). Sixty‐eight (85%) patients had at least one adverse event (AE). All AEs, except one, were mild or moderate in severity. Neither the severe AE nor any of the three serious AEs was considered related to sapropterin. No AE led to treatment discontinuation. Sapropterin is effective in reducing plasma Phe concentrations in a dose‐dependent manner and is well tolerated at doses of 5–20 mg/kg/day over 22 weeks in BH4‐responsive patients with PKU. © 2008 Wiley‐Liss, Inc.
Cognitive‐behavioral features of children with Wolf–Hirschhorn syndrome: Preliminary report of 12 cases
Authors: Fisch Gene S. , Battaglia Agatino , Parrini Barbara , Youngblom Janey , Simensen Richard 
Published: October 2008

AbstractAs a subset of genetic abnormalities, subtelomeric deletions have been found in 7–10% of individuals with mental retardation (MR). One subtelomeric deletion, Wolf‐Hirschhorn syndrome (WHS), causes mild to severe MR, but the cognitive‐behavioral features of individuals with WHS have not been studied systematically. To that end, we administered a comprehensive cognitive‐behavioral battery to 12 children with WHS, ages 4–17 years, who also had some expressive language. Using the Stanford‐Binet (4th Edition), we found cognitive deficits ranged from mild to severe, with mean IQ = 44.1. Interviewing parents with the Vineland Adaptive Behavior Scales, we found mean adaptive behavior score (DQ) = 37.3, with females exhibiting slightly higher scores than males. Cognitive profiles indicated relative strengths in Verbal and Quantitative Reasoning. Adaptive behavior profiles noted significant relative strengths in the Socialization Domain. These cognitive‐behavioral profiles differed from children with other subtelomeric deletion syndromes, 2q37 or 8p23. Attention deficits and hyperactivity (ADHD) were observed in 7/12 (58%) of the children we tested. One child attained a score on the Child Autism Rating Scale (CARS) suggestive of mild autism. We conclude that different genetic disorders, which cause MR, produce diverse cognitive‐behavioral profiles. Consequently, cognitive‐behavioral profiles of children with MR need to be assessed more comprehensively. © 2008 Wiley‐Liss, Inc.
Rheology of 1‐butyl‐3‐methylimidazolium chloride cellulose solutions. II. Solution character and preparation
Authors: Collier J. R. , Watson J. L. , Collier B. J. , Petrovan S. 
Published: October 2008

AbstractThe focus of this article of a three part series is the effects of preparation and composition on the shear rheology of cellulose in the ionic liquid 1‐butyl‐3‐methylimidazolium chloride ([Bmim]Cl). Included are the effects of three different degrees of polymerization, (i.e., average molecular weight), manual versus high shear mixing, a range of cellulose concentrations, and the effects of controlled amounts of lignin and a hemicellulose. The rheology implies that a gel phase develops at higher degrees of polymerization, higher concentration, and at lower temperatures. The first article focused primarily on shear rheology of cellulose in [Bmim]Cl with a high shear preparation technique, one degree of polymerization, a narrow range of cellulose concentrations, and temperature. The third article focuses on elongational rheology of cellulose in [Bmim]Cl. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Rheological properties of recycled chlorinated polyethylene/natural rubber blends vulcanized by sulfur
Authors: Prasopnatra Preeyanuch , Saeoui Pongdhorn , Sirisinha Chakrit 
Published: October 2008

AbstractBlends of elastomeric chlorinated polyethylene (CPE) and natural rubber (NR) with a blend composition ratio of 80/20 were prepared and recycled. Viscoelastic properties of the blends as a function of the recycling cycle were monitored. The results obtained revealed that, with an increase in the number of recycling cycles, a noticeable change in the viscoelastic properties of blends could be observed; that is, a decrease in the elastic contribution associated with a noticeable shift in the glass‐transition temperature of the NR phase of the blends was observed, implying a molecular change in the NR phase via a thermal chain‐scission mechanism. The influence of magnesium oxide (MgO) as an acid acceptor for CPE on the viscoelasticity of the blends was also investigated. Through a reduction of the amount of MgO, the molecular change was found to be more pronounced in NR than in CPE phases in a manner similar to the increase in the recycling cycles. An explanation of the changes in the viscoelastic properties of the blends with various MgO loadings and recycling cycles is proposed in terms of thermal degradation via a molecular chain‐scission mechanism taking place mainly in the NR phase. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
A Comparison of Methods for Adaptive Treatment Selection
Authors: Friede Tim , Stallard Nigel 
Published: October 2008

AbstractTraditionally drug development is generally divided into three phases which have different aims and objectives. Recently so‐called adaptive seamless designs that allow combination of the objectives of different development phases into a single trial have gained much interest. Adaptive trials combining treatment selection typical for Phase II and confirmation of efficacy as in Phase III are referred to as adaptive seamless Phase II/III designs and are considered in this paper. We compared four methods for adaptive treatment selection, namely the classical Dunnett test, an adaptive version of the Dunnett test based on the conditional error approach, the combination test approach, and an approach within the classical group‐sequential framework. The latter two approaches have only recently been published. In a simulation study we found that no one method dominates the others in terms of power apart from the adaptive Dunnett test that dominates the classical Dunnett by construction. Furthermore, scenarios under which one approach outperforms others are described. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
On Identification of the Number of Best Treatments Using the Newman‐Keuls Test
Authors: Wu Samuel S. , Wang Weizhen , Annis David H. 
Published: October 2008

AbstractIn this paper, we provide a stochastic ordering of the Studentized range statistics under a balanced one‐way ANOVA model. Based on this result we show that, when restricted to the multiple comparisons with the best, the Newman–Keuls (NK) procedure strongly controls experimentwise error rate for a sequence of null hypotheses regarding the number of largest treatment means. In other words, the NK procedure provides an upper confidence bound for the number of best treatments. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Aesthetics and Power Considerations in Multiple Testing – A Contradiction?
Authors: Hommel Gerhard , Bretz Frank 
Published: October 2008

AbstractIn this paper we discuss aesthetical concepts and requirements for reasonable multiple test procedures. Aesthetical considerations lead to logical decision patterns which are conceivable and, if possible, simple to use and to communicate. Such considerations are sometimes contradictory to the ubiquitous requirement of maximizing power for a multiple test procedure. We illustrate the necessary trade‐offs with several examples. We start by considering important logical properties and then discuss three different concepts of monotonicity. Afterwards we have a closer look at the recently proposed “fallback procedure” and show that it has some less appealing properties. Finally, we investigate the distribution of the numbers of significant results with respect to both expectation and variance. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Detecting Potential Safety Issues in Clinical Trials by Bayesian Screening
Authors: Gould A. Lawrence 
Published: October 2008

AbstractPatients in large clinical trials report many different adverse events, most of which will not have been anticipated in the protocol. Conventional hypothesis testing of between group differences for each adverse event can be problematic: Lack of significance does not mean lack of risk, the tests usually are not adjusted for multiplicity, and the data determine which hypotheses are tested. This paper describes a Bayesian screening approach that does not test hypotheses, is self‐adjusting for multiplicity, provides a direct assessment of the likelihood of no material drug‐event association, and quantifies the strength of the observed association. The approach directly incorporates clinical judgment by having the criteria for treatment association determined by the investigator(s). Diagnostic properties can be evaluated analytically. Application of the method to findings from a vaccine trial yield results similar to those found by methods using a false discovery rate argument and using a hierarchical Bayes approach. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
General Solutions to Multiple Testing Problems
Authors: Sonnemann Eckart 
Published: October 2008

AbstractThe introduction of sequentially rejective multiple test procedures (Einot and Gabriel, 1975; Naik, 1975; Holm, 1977; Holm, 1979) has caused considerable progress in the theory of multiple comparisons. Emphasizing the closure of multiple tests we give a survey of the general theory and its recent results in applications. Some new applications are given including a discussion of the connection with the theory of confidence regions. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Isofagomine Induced Stabilization of Glucocerebrosidase
Authors: Kornhaber Gregory J. , Tropak Michael B. , Maegawa Gustavo H. , Tuske Steven J. , Coales Stephen J. , Mahuran Don J. , Hamuro Yoshitomo 
Published: October 2008

AbstractStructurally destabilizing mutations in acid β‐glucosidase (GCase) can result in Gaucher disease (GD). The iminosugar isofagomine (IFG), a competitive inhibitor and a potential pharmacological chaperone of GCase, is currently undergoing clinical evaluation for the treatment of GD. An X‐ray crystallographic study of the GCase‐IFG complex revealed a hydrogen bonding network between IFG and certain active site residues. It was suggested that this network may translate into greater global stability. Here it is demonstrated that IFG does increase the global stability of wild‐type GCase, shifting its melting curve by ∼15 °C and that it enhances mutant GCase activity in pre‐treated N370S/N370S and F213I/L444P patient fibroblasts. Additionally, amide hydrogen/deuterium exchange mass spectroscopy (H/D‐Ex) was employed to identify regions within GCase that undergo stabilization upon IFG‐binding. H/D‐Ex data indicate that the binding of IFG not only restricts the local protein dynamics of the active site, but also propagates this effect into surrounding regions.
Impact of opening an acute palliative care unit on administrative outcomes for a general oncology ward
Authors: Rigby Andrew , Krzyzanowska Monika , Le Lisa W. , Swami Nadia , Coe Gary , Rodin Gary , Moore Malcolm , Zimmermann Camilla 
Published: October 2008

AbstractBACKGROUND.Acute palliative care units (APCUs) are gaining popularity in tertiary care centers. In this study, the authors examined the impact of opening an APCU on administrative outcomes for a general oncology ward (GOW) at a comprehensive cancer center.METHODS.The GOW database was reviewed for 3 periods: June 2000 through May 2002 (before the APCU opened), June 2002 through May 2004 (transitional period, including APCU opening in a temporary location), and June 2004 through May 2006 (after opening of the APCU). Data were extracted on demographics, reasons for admission, admission type, waiting time for admission, length of stay (LOS), overstay (>2 days over expected LOS), death rate, and discharge destination. Linear regression analysis and the Cochran‐Armitage test were used for data analysis.RESULTS.There were 5340 admissions: The median patient age was 60 years, and 55% of patients were women. The most common primary cancers were head and neck (22%), gynecologic (21%), gastrointestinal (13%), and lung (12%). There were significant trends on the GOW in decreased admissions for palliative care (12.2%, 9.6%, and 7.9%, respectively, for the 3 periods; P < .0001), fewer inpatient deaths (11.4%, 8.6%, and 6.1%, respectively; P < .0001), and fewer patients with prolonged waits for a bed on a palliative care unit (3.4%, 3%, and 1.7%, respectively; P = .002). Admissions increased for interventions (10.4%, 17.3%, and 22.5%, respectively, for the 3 periods; P < .0001) and for chemotherapy (6.8%, 6.6%, and 9.7%, respectively; P = .001).CONCLUSIONS.After the opening of an APCU at the authors' cancer center, the GOW experienced a decrease in administrative endpoints related to palliative and end‐of‐life care and an increase in endpoints related to cancer‐directed interventions. Prospective studies with clinical endpoints will be required to determine whether this specialization of inpatient care improves quality of life, quality of death, and psychosocial well being. Cancer 2008. © 2008 American Cancer Society.
The American Cancer Society guidelines for breast screening with magnetic resonance imaging
Authors: Murphy Colleen D. , Lee Janie M. , Drohan Brian , Euhus David M. , Kopans Daniel B. , Gadd Michele A. , Rafferty Elizabeth A. , Specht Michelle C. , Smith Barbara L. , Hughes Kevin S. 
Published: October 2008

AbstractBACKGROUND.The American Cancer Society (ACS) guidelines for screening with breast magnetic resonance imaging (MRI) recommend MRI for women who have a lifetime risk ≥20% of developing breast cancer. Genetic testing for breast cancer gene (BRCA) mutations is offered to women who have a risk ≥10% of carrying a mutation. The objectives of the current study were 1) to identify the number of women in a breast cancer screening population who had ≥20% lifetime breast cancer risk and, thus, were candidates for screening MRI; and 2) to determine the number of women who had ≥10% risk of BRCA mutation yet had <20% lifetime risk of breast cancer and, thus, may not have been identified as candidates for MRI screening.METHODS.From 2003 to 2005, women who underwent screening mammography completed a self‐administered questionnaire regarding breast cancer risk factors. For each patient, the lifetime breast cancer risk and the risk of BRCA mutation was determined by using the computerized BRCAPRO breast cancer risk‐assessment model.RESULTS.Of 18,190 women, 78 (0.43%) had ≥20% lifetime risk of breast cancer, all of whom had ≥10% risk of carrying a BRCA mutation. An additional 374 women (2.06%) had <20% lifetime breast cancer risk but ≥10% risk of mutation. Overall, there were 183 (1%) predicted mutation carriers, 27 women (0.15%) who had ≥20% lifetime risk of breast cancer, and 62 women (0.34%) who had ≥10% risk of mutation but <20% lifetime breast cancer risk.CONCLUSIONS.The ACS guidelines for breast MRI screening may systematically exclude MRI screening for many women who have a substantial risk for BRCA mutation. The current results demonstrated a need for greater awareness of breast cancer risk factors in the screening mammography population, so that high‐risk women can be identified and given access to genetic testing and counseling regarding all risk‐reducing interventions. Cancer 2008. © 2008 American Cancer Society.
Reversed mutation rates of KRAS and EGFR genes in adenocarcinoma of the lung in Taiwan and their implications
Authors: Wu Chun‐Chieh , Hsu Hui‐Yu , Liu Hui‐Ping , Chang John Wen‐Cheng , Chen Ya‐Ting , Hsieh Wen‐Yu , Hsieh Jia‐Juan , Hsieh Meng‐Shu , Chen Yi‐Rong , Huang Shiu‐Feng 
Published: October 2008

AbstractBACKGROUND.In western countries, the Kirsten ras oncogene homolog gene (KRAS) mutation rate is high in patients with nonsmall cell lung cancer (NSCLC), especially in those with adenocarcinoma (30%‐50%), but the epidermal growth factor receptor gene (EGFR) mutation rate is very low (3%‐8%). In addition, KRAS mutations reportedly were associated with EGFR tyrosine kinase inhibitor (EGFR‐TKI) resistance. In Taiwan, high EGFR mutation rates associated with high EGFR‐TKI response rates in patients with NSCLC have been reported; however, KRAS mutation data are limited and have not been correlated with TKI response.METHODS.KRAS mutation analysis was performed on 237 NSCLC specimens, and the results were correlated with clinicopathologic features. All but 2 tumors also underwent EGFR mutation analysis.RESULTS.KRAS mutations were identified in only 9 of 237 patients (3.80%). Five patients were women who were nonsmokers, and 4 patients were men who were ever‐smokers. The mutation rate was 5.03% in patients with adenocarcinoma (8 of 159 patients) and 1.56% in patients with squamous cell carcinoma (1 of 64 patients). Four mutations were G12V, 3 mutations were G12D, 1 mutation was L19F, and 1 was the duplication insertion mutation dupT50_M72. In contrast, EGFR mutations were detected in 96 of 235 patients (40.8%) and in 90 of 157 adenocarcinomas (57.3%). None of the KRAS mutations coexisted with EGFR mutations. KRAS mutations were not associated significantly with any clinicopathologic characteristics, including smoking status. Among the 53 patients who had received TKI monotreatment, only 1 patient had a KRAS mutation and had progressive disease.CONCLUSIONS.The KRAS mutation rate was too low to play a significant role in TKI resistance or tumorigenesis among Taiwanese patients with NSCLC, which was the complete reverse of the results reported in western countries. Cancer 2008. © 2008 American Cancer Society.
Head and neck squamous cell carcinoma in patients aged ≥80 years
Authors: Italiano Antoine , Ortholan Cecile , Dassonville Olivier , Poissonnet Gilles , Thariat Juliette , Benezery Karen , Vallicioni Jacques , Peyrade Frédéric , Marcy Pierre‐Yves , Bensadoun René‐Jean 
Published: October 2008

AbstractBACKGROUND.Scarce data exist concerning the outcome of very elderly patients with head and neck squamous cell carcinoma (HNSCC).METHODS.The clinical files of 316 patients aged ≥80 years with HNSCC who were included in the authors' hospital database between 1987 and 2006 were reviewed retrospectively.RESULTS.Approximately 88% of patients received locoregional treatment, 31% of patients underwent surgery, and 57% of patients received definitive radiotherapy. The median disease‐specific survival (DSS) was 21.3 months, and a plateau was observed after 5 years. The median overall survival (OS) was 13.0 months. Both the median DSS and the median OS were longer for patients with stage I/II HNSCC than for patients with stage III/IV HNSCC (median DSS, not reached vs 11.4 months; P < .001; median OS, 41.9 months vs 7.9 months; P < .001). On multivariate analysis, stage I/II disease, treatment with curative intent, and evidence of locoregional control were independent predictors of improved survival.CONCLUSIONS.The outcome of patients with stage I/II HNSCC aged ≥80 years was similar to that of younger patients, and the current results indicated that age should not be used to deny them optimal treatment. Elderly patients with stage III/IV HNSCC had poor survival. Geriatric tools should be used to identify elderly patients who are eligible for optimal locoregional treatment. Cancer 2008. © 2008 American Cancer Society.