bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autism genetics: strategies, challenges, and opportunities
Authors: O'Roak Brian J. , State Matthew W. 
Published: March 2008

AbstractAlthough genes have long been appreciated to play a critical role in determining the risk for pervasive developmental disorders, the specific transcripts contributing to autism spectrum disorders (ASD) have been quite difficult to characterize. However, recent findings are now providing the first insights into the molecular mechanisms underlying these syndromes and have begun to shed light on the allelic architecture of ASD. In this article, we address what is known about the relative contributions of various types of genetic variation to ASD, consider the obstacles facing gene discovery in this complex disorder, and evaluate the common methodologies employed to address these issues, including linkage, molecular and array‐based cytogenetics, and association strategies. We review the current literature, highlighting recent findings implicating both rare mutations and common genetic polymorphisms in the etiology of autism. Finally, we describe key advances in genomic technologies that are transforming all areas of human genetics and consider both the opportunities and challenges for autism research posed by these rapid changes.
Torsionsträgheitsmoment und Schubmittelpunkt von Winkelprofilen
Authors: Kindmann Rolf , Kraus Matthias 
Published: March 2008

AbstractDie genauen Torsionskenngrößen von gewalzten Winkelprofilen, die sich auf Basis von Berechnungen mit der Finite‐Elemente‐Methode (FEM) bestimmen lassen, zeigen teilweise relativ große Abweichungen zu den Näherungslösungen, die im Allgemeinen bei baupraktischen Problemstellungen zur Anwendung kommen. Aus diesem Grund werden die genaue Lage des Schubmittelpunktes sowie genaue Torsionsträgheitsmomente für die Winkelprofile nach DIN EN 10056‐1 zusammengestellt. Darüber hinaus lässt die Kenntnis dieser Größen eine Verbesserung der bekannten Näherungsformeln sowie die Entwicklung neuer Bestimmungsgleichungen für das Torsionsträgheitsmoment zu.
In vivo real-time confocal laser scanning endomicroscopic colonoscopy for the detection and characterization of colorectal neoplasia
Authors: Hurlstone D P , Baraza W , Brown S , Thomson M , Tiffin N , Cross S S 
Published: March 2008

Abstract

Background
Conventional colonoscopy has a significant false-negative rate for intraepithelial neoplasia. Chromoendoscopy increases sensitivity but lacks specificity. The aim was to assess prospectively the clinical applicability and predictive power of the EC3870CIFK confocal laser endomicroscope (CLE) for the in vivo diagnosis of intraepithelial neoplasia during colonoscopy.

Methods
Lesions were identified using chromoscopy followed by CLE imaging and graded according to vascular and cellular changes. CLE imaging of circumscribed lesions and four segmental ‘normal’ colorectal quadrants was performed. Targeted biopsy specimens were then compared with histopathological results.

Results
Forty patients completed the protocol (22 men and 18 women; median age 62 (range 39–82) years). The median duration of ileal intubation and total procedure time were 12 (range 5–26) and 55 (range 28–92) min respectively. Chromoscopic colonoscopy revealed 162 lesions in 39 patients. CLE imaging was obtained on all 162 lesions. Some 5422 confocal images were compared with 802 targeted biopsy specimens. Intraepithelial neoplasia was predicted with an accuracy of 99·1 per cent (sensitivity 97·4 per cent and specificity 99·3 per cent) (P = 0·711).

Conclusion
Confocal laser endomicroscopy permits high-quality cellular, subsurface vascular and stromal imaging, enabling prediction of intraepithelial neoplasia with a high level of accuracy.
Outcome after percutaneous closure of a patent foramen ovale using the Intrasept™ device
Authors: Luermans Justin G.L.M. , Post Martijn C. , Schräder Rainer , Sluysmans Thierry , Vydt Tom , Vermeersch Paul , Chessa Massimo , Onorato Eustaquio , Goy Jean‐Jacques , Budts Werner I.H.L. 
Published: March 2008

AbstractObjectives: This multi‐centre study reports safety and efficacy of percutaneous patent foramen ovale (PFO) closure, using the fourth generation Intrasept™ device. Background: PFO has been associated with paradoxical embolism and cryptogenic stroke. Percutaneous PFO closure seems to reduce the risk for recurrent paradoxical thrombo‐embolism. Currently, different devices are used for PFO closure. Methods: Patients, who underwent a PFO closure with the Intrasept device (Cardia, Eagan, MN) between July 2002 and September 2006, were included in the study. The primary endpoint was defined as reoccurrence of stroke, transient ischemic attack (TIA), or peripheral thrombo‐embolism. Peri‐procedural and mid‐term complications were reported. Results: Four‐hundred thirty patients (mean age 50.7 ± 13.0 years, 231 men) underwent closure. The indications were cryptogenic stroke (69.8%), TIA (23.5%), peripheral embolism (3.3%), and other (3.5%). The median follow‐up time was 0.8 years, range 3.9 years. The primary endpoint occurred in 0.5% for stroke, in 2.5% for TIA, and in none for peripheral embolism. Peri‐procedural complications were reported in 11.5% of cases, from which 0.2% was defined as major. No severe complications occurred during mid‐term follow‐up. A residual shunt was present in 12.5% of patients who did not suffer from a recurrent event, compared to 36.4% of patients who reached the primary endpoint (P = 0.04). Conclusion: This multi‐centre study suggests that percutaneous closure of a symptomatic PFO with the fourth generation Intrasept device is safe and might be effective to prevent the recurrence of paradoxical thrombo‐embolic events. © 2008 Wiley‐Liss, Inc.
Addressing the hemodynamic dilemma of combined mitral and aortic stenosis
Authors: Suh William M. , Kern Morton J. 
Published: March 2008

AbstractAccurate assessment of valvular hemodynamics is essential in the decision‐making process when referring a patient for cardiac surgery who has suspected coexistent aortic and mitral valve disease. Often times, one valvular lesion is worse than the other, and the question of “prophylactically” replacing the less severe valve at the time of surgery is controversial. In these situations and because of uncertainty regarding noninvasive assessment, hemodynamic evaluation in the cardiac catheterization laboratory provides critical information in guiding therapy. © 2008 Wiley‐Liss, Inc.
Methods to reduce patients' maximum skin dose during percutaneous coronary intervention for chronic total occlusion
Authors: Suzuki Shigeru , Furui Shigeru , Isshiki Takaaki , Kozuma Ken , Koyama Yutaka , Ochiai Masahiko , Asakura Yasushi 
Published: March 2008

AbstractObjectives: The purpose of this research is to assess the patient's entrance skin dose (ESD) during percutaneous coronary intervention (PCI) for chronic total occlusion (CTO), and discuss methods to reduce the maximum ESDs. Background: Only a few reports are available on the methods to reduce patients' maximum ESD during the procedures. Methods: This study included consecutive 30 patients who underwent PCI procedures for CTO in the three institutions. Pearson correlation test was employed to determine the relationship between total fluoroscopic time (TFT) and the maximum ESD, dose area product (DAP) value, and the maximum ESD in each institution. Results: There were significant correlations between the TFT and maximum ESD (Institution 1: P = 0.000410, Institution 2: P = 0.000525), and between the DAP and the maximum ESD (Institution 2: P < 0.0001). In Institution 1, TFT of 60 min was set as the upper limit, and the maximum ESDs were controlled within 7 Gy. In Institution 2, the angiographic unit was a biplane system, and two skin sites were exposed, corresponding to the angulation of each X‐ray tube. In Institution 3, the interventionalist changed the beam angulations frequently by several degrees during the procedures, and the maximum ESD was controlled within 3 Gy even during procedures with a TFT of more than 1 hr. Conclusions: The TFT and DAP, the latter of which is preferable, are useful to estimate the maximum ESD. Limiting the TFT or DAP, or changing the beam angulations is important to control ESD during prolonged procedures. © 2008 Wiley‐Liss, Inc.
Progress in the retrograde approach for chronic total coronary artery occlusion
Authors: Matsumi Jyunya , Saito Shigeru 
Published: March 2008

AbstractAfter the introduction of the retrograde approach in percutaneous coronary intervention for chronic total occlusion (CTO), different kinds of strategies and techniques have been developed in order to achieve final success. However, it has not been fully demonstrated whether these strategies and techniques can really improve the final result. We observed one case, for which the initial attempt of the retrograde approach for a CTO lesion was unsuccessful despite the successful approach of a retrograde guidewire to the lesion, and with the second retrograde approach 3 years later being eventually successful by using various kinds of strategies and techniques. This case clearly demonstrates how the final success through the retrograde approach can be achieved by using a combination of the improved strategies and techniques for CTO lesions. © 2008 Wiley‐Liss, Inc.
Enhancing Fluorescence Brightness: Effect of Reverse Intersystem Crossing Studied by Fluorescence Fluctuation Spectroscopy
Authors: Ringemann Christian , Schönle Andreas , Giske Arnold , von Middendorff Claas , Hell Stefan W. , Eggeling Christian 
Published: March 2008

AbstractExperiments based on fluorescence detection are limited by the population of the fluorescence marker’s long‐lived dark triplet state, leading to pronounced photobleaching reactions and blinking which reduces the average fluorescence signal obtained per time interval. By irradiation with a second, red‐shifted laser line, we initiate reverse intersystem crossing (ReISC) which enhances the fluorescence signal of common fluorophores up to a factor of 14. The reverse intersystem crossing from the triplet state back to the singlet system is achieved by photoexcitation to higher‐excited triplet states, which are, however, prone to photobleaching. We gain insights into the competing pathways of ReISC and photobleaching. The relative efficiencies of these two pathways and the triplet lifetime determine the achievable fluorescence enhancement, which varies strongly with the choice of dye, excitation irradiance and wavelength, and with environmental conditions. The study of ReISC not only results in a better understanding of a fluorescent label’s photophysics, but the method is a possible approach to optimize fluorescence emission in experiments, where signal strength is a critical parameter.
Retina development in zebrafish requires the heparan sulfate proteoglycan agrin
Authors: Liu I‐Hsuan , Zhang Chengjin , Kim Min Jung , Cole Gregory J. 
Published: March 2008

AbstractRecent studies from our laboratory have begun to elucidate the role of agrin in zebrafish development. One agrin morphant phenotype that results from agrin knockdown is microphthalmia (reduced eye size). To begin to understand the mechanisms underlying the role of agrin in eye development, we have analyzed retina development in agrin morphants. Retinal differentiation is impaired in agrin morphants, with retinal lamination being disrupted following agrin morpholino treatment. Pax 6.1 and Mbx1 gene expression, markers of eye development, are markedly reduced in agrin morphants. Formation of the optic fiber layer of the zebrafish retina is also impaired, exhibited as both reduced size of the optic fiber layer, and disruption of retinal ganglion cell axon growth to the optic tectum. The retinotectal topographic projection to the optic tectum is perturbed in agrin morphants in association with a marked loss of heparan sulfate expression in the retinotectal pathway, with this phenotype resembling retinotectal phenotypes observed in mutant zebrafish lacking enzymes for heparan sulfate synthesis. Treatment of agrin morphants with a fibroblast growth factor (Fgf) receptor inhibitor, rescue of the retinal lamination phenotype by transplantation of Fgf8‐coated beads, and disruption of both the expression of Fgf‐dependent genes and activation of ERK in agrin morphants provides evidence that agrin modulation of Fgf function contributes to retina development. Collectively, these agrin morphant phenotypes provide support for a crucial role of agrin in retina development and formation of an ordered retinotectal topographic map in the optic tectum of zebrafish. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008.
Low‐level defective processing of non‐verbal sounds in dyslexic children
Authors: Uclés Paulino , Méndez Mario , Garay José 
Published: March 2008

AbstractWe compared processing of non‐verbal auditory stimuli by dyslexic and non‐dyslexic children using electrophysiological methods. The study included 39 children (17 with dyslexia plus 22 controls) assessed via frontal, central, parietal, and temporal electrodes. As an extension of previous P300 event‐related potential studies, we analysed variations in the power values of 40‐Hz oscillations (gamma‐band oscillations involved in cognitive processing) during a specific time window in response to the auditory ‘oddball’ paradigm that entail target (random 2 kHz) and standard (frequent 1 kHz) stimuli. Dyslexic children differed significantly from controls (P<0.001) in the mean power of the wavelet‐transformed 40‐Hz oscillation in a time interval starting at 25 ms after stimulus onset up to 50 ms. This means defective processing of sounds. Within groups, standard and target tones elicited significantly different power values (P<0.001). Correlations of values between standard and target responses at each electrode position were not significant within either group, although dyslexics showed a lower correlation than controls. Significant differences in the mean power of these oscillations detected at very early stages of auditory processing in dyslexic children and the wide range of mean values reveal impairment in processing non‐verbal sounds in dyslexia. Our results also support recent findings using behavioural and electrophysiological methods suggesting that dyslexia is a general auditory deficit instead of a speech‐specific deficit. Copyright © 2008 John Wiley & Sons, Ltd.
Selective enzymatic synthesis of lower acylglycerols rich in polyunsaturated fatty acids
Authors: Hernández‐Martín Estela , Otero Cristina 
Published: March 2008

AbstractSelective elimination of saturated fatty acid (FA) residues from vegetable oils (sesame, borage, olive, and sunflower) produces lower acylglycerols rich in unsaturated and polyunsaturated FA residues. Novozym® 435 releases greater amounts of saturated FA residues than unsaturated residues relative to other biocatalysts. Highest selectivity is obtained for 50 wt‐% Novozym® 435 with respect to the oil and [ethanol]/[FA] = 25. Under these conditions, 88–90% of saturated residues are released versus only 44–45% of unsaturated residues. Product acylglycerols have ratios of unsaturated to saturated residues of 21.5–23.0 relative to 5.22–4.73 for the precursor oils. Ethanolysis is faster with Novozym® 435. This biocatalyst is much less susceptible to inactivation by ethanol than other biocatalysts. However, in excess ethanol ([EtOH]/[FA] = 4.5–25), the rate and conversion both increased when the ethanol concentration decreased. The best combination of conversion and selectivity is obtained with 50 wt‐% Novozym® 435 and [ethanol]/[FA] = 4.5. Under these conditions, the product obtained in 1 h contains ca. 48% triacylglycerols, 24% diacylglycerols and 28% monoacylglycerols; the mol percentage of unsaturated FA residues is 12.3 times greater than that of saturated residues. The sn‐2 position is essentially free of saturated FA residues. After use for ten reaction cycles, Novozym® 435 retains 80% of its initial activity.
Identification of new regional marker proteins to map mouse brain by 2‐D difference gel electrophoresis screening
Authors: Jacobs Sandy , Van de Plas Babs , Van der Gucht Estel , Clerens Stefan , Cnops Lieselotte , Van den Bergh Gert , Arckens Lutgarde 
Published: March 2008

AbstractTo screen for new region‐specific protein markers we compared the proteome maps of the primary visual and somatosensory areas V1 and S1 in mouse brain using 2‐D difference gel electrophoresis (2‐D DIGE). Twenty‐three protein spots showed a statistically significant difference in expression level between V1 and S1, with 52% appearing more abundantly in V1. Twenty‐six proteins were mass spectrometrically identified in 22 spots. To assess the validity of this list of potential areal markers generated by 2‐D DIGE, the effective area‐specific distribution profile of creatine kinase brain subtype (CKB), a protein with a clearly higher expression level in S1, was monitored with in situ hybridization. The mRNA expression profile of CKB displayed a clear area‐specific distribution, which allowed demarcation of S1 and its topographical borders with neighboring neocortical areas. This proteomic study demonstrates the innovative application of 2‐D DIGE and MS to select new regional markers for neuroscience research.
Protein‐aptamer binding studies using microchip affinity capillary electrophoresis
Authors: Gong Maojun , Nikcevic Irena , Wehmeyer Kenneth R. , Limbach Patrick A. , Heineman William R. 
Published: March 2008

AbstractThe use of traditional CE to detect weak binding complexes is problematic due to the fast‐off rate resulting in the dissociation of the complex during the separation process. Additionally, proteins involved in binding interactions often nonspecifically stick to the bare‐silica capillary walls, which further complicates the binding analysis. Microchip CE allows flexibly positioning the detector along the separation channel and conveniently adjusting the separation length. A short separation length plus a high electric field enables rapid separations thus reducing both the dissociation of the complex and the amount of protein loss due to nonspecific adsorption during the separation process. Thrombin and a selective thrombin‐binding aptamer were used to demonstrate the capability of microchip CE for the study of relatively weak binding systems that have inherent limitations when using the migration shift method or other CE methods. The rapid separation of the thrombin–aptamer complex from the free aptamer was achieved in less than 10 s on a single‐cross glass microchip with a relatively short detection length (1.0 cm) and a high electric field (670 V/cm). The dissociation constant was determined to be 43 nM, consistent with reported results. In addition, aptamer probes were used for the quantitation of standard thrombin samples by constructing a calibration curve, which showed good linearity over two orders of magnitude with an LOD for thrombin of 5 nM at a three‐fold S/N.
Transoral laser surgery for supraglottic cancer
Authors: Rodrigo Juan P. , Suárez Carlos , Silver Carl E. , Rinaldo Alessandra , Ambrosch Petra , Fagan Johannes J. , Genden Eric M. , Ferlito Alfio 
Published: March 2008

AbstractThe goal of treatment for supraglottic cancer is to achieve cure and to preserve laryngeal function. Organ preservation strategies include both endoscopic and open surgical approaches as well as radiation and chemotherapy. The challenge is to select the correct modalities for each patient. Endoscopic procedures should be limited to tumors that can be completely visualized during diagnostic microlaryngoscopy. If complete resection can be achieved, the oncologic results of transoral laser surgery appear to be comparable to those of classic supraglottic laryngectomy. In addition, functional results of transoral laser resection are superior to those of the conventional open approach, in terms of the time required to restore swallowing, tracheotomy rate, incidence of pharyngocutaneous fistulae, and shorter hospital stay. The management of the neck remains of paramount importance, as survival of patients with supraglottic cancer depends more on cervical metastasis than on the primary tumor. Most authors advocate bilateral elective neck dissection. However, in selected cases (T1,T2 clinically negative [N0] lateral supraglottic cancers), ipsilateral selective neck dissection could be performed without compromising survival. The authors conclude that with careful selection of patients, laser supraglottic laryngectomy is a suitable, and often the preferred, treatment option for supraglottic cancer. © 2008 Wiley Periodicals, Inc. Head Neck, 2008
The therapeutic potential of the proteasome in leukaemia
Authors: McCloskey Scott Marshall , McMullin Mary Frances , Walker Brian , Irvine Alexandra E 
Published: March 2008

AbstractMany cellular processes converge on the proteasome, and its key regulatory role is increasingly being recognized. Proteasome inhibition allows the manipulation of many cellular pathways including apoptotic and cell cycle mechanisms. The proteasome inhibitor bortezomib has enhanced responses in newly diagnosed patients with myeloma and provides a new line of therapy in relapsed and refractory patients. Malignant cells are more sensitive to proteasome inhibition than normal haematopoietic cells. Proteasome inhibition enhances many conventional therapies and its role in leukaemia is promising. Copyright © 2008 John Wiley & Sons, Ltd.
Childhood cancers in Chennai, India, 1990–2001: Incidence and survival
Authors: Swaminathan Rajaraman , Rama Ranganathan , Shanta Viswanathan 
Published: March 2008

AbstractChildhood cancers (age at diagnosis: 0–14 years) comprise a variety of malignancies, with incidence varying worldwide by age, sex, ethnicity and geography, that provide insights into cancer etiology. A total of 1,334 childhood cancers registered in population‐based cancer registry, Chennai, India, during 1990–2001 and categorized by International Classification of Childhood Cancer norms formed the study material. Cases included for survival analysis were 1,274 (95.5%). Absolute survival was calculated by actuarial method. Cox proportional hazard model was used to elicit the prognostic factors for survival. The age‐standardized rates for all childhood cancers together were 127 per million boys and 88 per million girls. A decreasing trend in incidence rates with increasing 5‐year age groups was observed in both sexes. The top 5 childhood cancers were the same among boys and girls: leukemias, lymphomas, central nervous system neoplasms, retinoblastomas and renal tumors. The highest 5‐year absolute survival was observed in Hodgkin's disease (65%) followed by Wilm's tumor (64%), retinoblastomas (48%), non‐Hodgkin's lymphomas (47%), osteosarcomas (44%), acute lymphoid leukemia and astrocytoma (39%). Multifactorial analysis of age at diagnosis and sex showed no differences in the risk of dying for all childhood cancers. Completeness of treatment and type of hospital combination emerged as a prognostic factor for survival for all childhood cancers together (p< 0.001), acute lymphoid leukemia (p< 0.001) and non‐Hodgkin's lymphoma (p= 0.04). A Childhood Cancer Registry with high‐resolution data collection is advocated for in‐depth analysis of variation in incidence and survival. © 2008 Wiley‐Liss, Inc.