bluuebunny/crossref_metadata_2025_split huggingface dataset:
Present and future of antisense therapy for splicing modulation in inherited metabolic disease
Authors: Pérez Belen , Rodríguez‐Pascau Laura , Vilageliu Luisa , Grinberg Daniel , Ugarte Magdalena , Desviat Lourdes R. 
Published: June 2010

AbstractThe number of mutations identified deep in introns which activate or create novel splice sites resulting in pathogenic pseudoexon inclusion in mRNA continues to grow for inherited metabolic disease (IMD) and other human genetic diseases. A common characteristic is that the native splice sites remain intact thus retaining the potential for normal splicing. Antisense oligonucleotides (AO) have been shown to modulate the splicing pattern by steric hindrance of the recognition and binding of the splicing apparatus to the selected sequences. In the case of pseudoexons, AO force the use of the natural splice sites, recovering normally spliced transcripts encoding functional protein. This review summarizes the present knowledge of antisense splicing modulation as a molecular therapy approach for pseudoexon‐activating mutations, with a focus in IMD. Although the feasibility of treatment for patients with IMD has yet to be proven, it appears to be clinically promising, as positive results have been reported in cellular and animal models of disease, and antisense therapy for splicing modulation is currently in the clinical trials phase for Duchenne muscular dystrophy patients. Here, we review the most recent advances in AO stability, targeting and delivery, and other issues to be considered for an effective treatment in the clinical setting. Although the number of patients who can be potentially treated is low for each IMD, it represents an excellent therapeutical option as a type of personalized molecular medicine which is especially relevant for diseases for which there is, to date, no efficient treatment.
Preparation of Diacid 1,3‐Diacylglycerols
Authors: Craven R. John , Lencki Robert W. 
Published: June 2010

AbstractA complete methodology (including synthesis, purification and analysis) for the preparation of 1,3‐DAG is described. For a successful synthesis project, the strengths and weaknesses of each particular process should be taken into account and measures taken to offset or balance potential weaknesses. To this end, we describe some of the challenges associated with: chemically and enzymatically catalyzed acylglycerol syntheses; recrystallization and flash chromatography for purification of partial acylglycerols; and thin‐layer chromatography (TLC) separation of DAG. For this work, 1‐MAG intermediates and subsequent diacid 1,3‐DAG were prepared using non‐enzymatic methods, whereas, monoacid 1,3‐DAG were prepared by enzymatic methods. It was not always possible to obtain pure samples of target compounds—in recrystallizations this is due to solid solution formation and co‐crystallization and in chromatographic separations it is due to co‐elution of components with similar Rf. Furthermore, TLC Rf of DAG is determined by two main factors: acyl chain length and positional isomerism. Interestingly, while the role of positional isomerism is well‐known, the role of acyl chain length in these separations has only recently come to light.
Reproducibility of Peripheral Quantitative Computed Tomography Measurements at the Radius and Tibia in Healthy Pre- and Postmenopausal Women
Authors: Szabo Kristina A. , Webber Colin E. , Gordon Christopher , Adachi Jonathan D. , Tozer Richard , Papaioannou Alexandra 
Published: June 2010

Purpose The objectives of this study were to utilise the XCT-2000 pQCT scanner to determine the mean values and the reproducibility of in vivo total, trabecular, and cortical volumetric bone measurements at distal and diaphyseal sites of the radius and the tibia, as well as calf muscle and subcutaneous fat areas, in healthy pre- and postmenopausal women. Methods Twenty-nine women (14 premenopausal and 15 postmenopausal) were recruited to participate in this study. Distal and diaphyseal sites of the radius (at 4% and 20% of the length of the radius) and tibia (at 4%, 38%, and 66% of the length of the tibia) were examined. Results The root mean square coefficient of variation for measurements at the distal tibia gave the most favorable reproducibility values for total (1.5%) and trabecular (1.6%) density, whereas the diaphyseal tibia showed the most favorable reproducibility value for cortical density (0.3%). The root mean square coefficients of variation for measurements of muscle and fat cross-sectional areas at the calf were 0.6% and 0.7%, respectively. At the distal tibia, the mean values for total ( P < .05) and trabecular ( P < .01) density were significantly lower in postmenopausal women than in premenopausal women. Conclusions The data presented here indicate that XCT-2000 pQCT scans at the tibia provide highly reproducible measurements of total, cortical, and trabecular bone as well as muscle and fat cross-sectional areas. Furthermore, significant differences in volumetric bone measurements between healthy pre- and postmenopausal women were evident only at the distal tibia, suggesting that this site warrants further study.
Novel approaches to global mining of aberrantly methylated promoter sites in squamous head and neck cancer
Authors: Worsham Maria J. , Chen Kang Mei , Stephen Josena K. , Havard Shaleta , Benninger Michael S. 
Published: June 2010

ObjectivePromoter hypermethylation is emerging as a promising molecular strategy for early detection of cancer. We examined promoter methylation status of 1143 cancer‐associated genes to perform a global but unbiased inspection of methylated regions in head and neck squamous cell carcinoma (HNSCC).Study DesignLaboratory‐based study.SettingIntegrated health care system.Subjects and MethodsFive samples, two frozen primary HNSCC biopsies and three HNSCC cell lines, were examined. Whole genomic DNA was interrogated using a combination of DNA immunoprecipitation (IP) and Affymetrix whole‐genome tiling arrays.ResultsOf the 1143 unique cancer genes on the array, 265 were recorded across five samples. Of the 265 genes, 55 were present in all five samples, and 36 were common to four of five samples, 46 to three of five, 56 to two of five, and 72 to one of five samples. Hypermethylated genes in the five samples were cross‐examined against those in PubMeth, a cancer methylation database combining text mining and expert annotation (http://www.pubmeth.org). Of the 441 genes in PubMeth, only 33 are referenced to HNSCC. We matched 34 genes in our samples to the 441 genes in the PubMeth database. Of the 34 genes, eight are reported in PubMeth as HNSCC associated.ConclusionThis pilot study examined the contribution of global DNA hypermethylation to the pathogenesis of HNSCC. The whole‐genome methylation approach indicated 231 new genes with methylated promoter regions not yet reported in HNSCC. Examination of this comprehensive gene panel in a larger HNSCC cohort should advance selection of HNSCC‐specific candidate genes for further validation as biomarkers in HNSCC.
Survival in oral cavity minor salivary gland carcinoma
Authors: Kakarala Kiran , Bhattacharyya Neil 
Published: June 2010

ObjectiveTo describe the epidemiology and comparative survival for minor salivary gland cancer of the oral cavity.Study DesignHistorical cohort study.SettingAcademic medical center.Subjects and MethodsCases of minor salivary gland cancer of the oral cavity were extracted from the Surveillance, Epidemiology, and End Results database (1988‐2005) and staged. Kaplan‐Meier survivals were compared according to histology as well as T stage and N stage. A Cox proportional hazards model incorporating histology, T stage, N stage, age, and sex was analyzed.ResultsA total of 639 salivary gland cancers of the oral cavity (55% female; mean age, 56 years) were identified with complete staging information, consisting of 318 mucoepidermoid, 169 adenoid cystic, 139 adenocarcinoma, and 14 acinic cell cancers. The hard palate and gums were the most common subsites involved (87.6%), followed by lip (7.2%) and tongue (5.2%). At presentation, T1 and T4 tumors predominated (42.6% and 35.2%, respectively); 93.4 percent were N0. Overall mean survival (months) was 157.9 and was similar across histologic subtypes: mucoepidermoid (172.4), adenoid cystic (141.4), acinic cell (138.7), and adenocarcinoma (147.2). Survival for low‐ and intermediate‐grade mucoepidermoid carcinoma (171.0 and 182.3, respectively) was better than survival for high‐grade mucoepidermoid carcinoma (50.3, P < 0.001). On multivariate analysis, N stage (P < 0.001) was the most powerful predictor of survival, along with T stage (P = 0.013), age (P < 0.001), and sex (P < 0.001).ConclusionT stage and N stage are the most powerful predictors of survival in minor salivary gland carcinoma of the oral cavity. With the exception of high‐grade mucoepidermoid carcinoma, survival for these lesions is generally favorable.
Cochlear implantations in young children with cochlear nerve deficiency diagnosed by MRI
Authors: Kang Woo Seok , Lee Jeong Hyun , Lee Ha Na , Lee Kwang‐Sun 
Published: June 2010

ObjectiveTo investigate postoperative outcomes after cochlear implantation in young children with cochlear nerve deficiency and compare the results with those of cochlear implantation in patients with normal cochlear nerve.Study DesignHistorical cohort study.SettingTertiary referral center.Subjects and MethodsSix children under the age of 36 months with cochlear nerve deficiency, as determined by magnetic resonance imaging (MRI), received cochlear implantation between July 2006 and March 2008. Fifteen children under the age of 36 months with normal cochlear nerve in the implanted ear underwent cochlear implantation during the same period and were selected as the control group. Medical records, imaging studies, and speech evaluations were reviewed.ResultsOur study group scored lower in the Infant‐Toddler Meaningful Auditory Integration Scale compared to the control group. Our study group produced categories of auditory performance scores not less than 4 except for one patient. Speech intelligibility rating scores in the control group gradually increased after cochlear implantation, but for the study group, the score remained zero 12 months after the implantation. In open‐set one‐syllable tests, five patients with cochlear nerve deficiency showed no response at the latest follow‐up, whereas patient 6 began to show delayed improvement after 18 months. The results of the open‐set two‐syllable test were similar to those of the open‐set one‐syllable test.ConclusionYoung children with nonvisualized cochlear nerve on MRI showed worse outcomes compared to the children with normal cochlear nerve. Cochlear nerve deficiency on MRI is a marker of very poor outcome with cochlear implantations.
Fractal quantitative endoscopic evaluation of the upper airway in patients with obstructive sleep apnea syndrome
Authors: Delides Alexander , Viskos Alexandros 
Published: June 2010

ObjectiveTo analyze computer‐assisted quantitative measurements of endoscopic images taken during fiberoptic nasopharyngoscopy with Müller's maneuver that were processed with the use of fractal geometry and correlate them with the apnea‐hypopnea index of patients with obstructive sleep apnea syndrome as well as habitual snorers.Study DesignDiagnostic test assessment for the analysis of images acquired through fiberoptic nasopharyngoscopy with Müller's maneuver and processed with the use of fractal geometry.SettingSleep laboratory in a tertiary care private hospital in Athens, Greece.Subjects and MethodsA total of 42 subjects (25 patients, 17 control subjects) underwent fiberoptic endoscopic nasopharyngoscopy with Müller's maneuver and polysomnographic overnight testing. Endoscopic images were digitally analyzed, and fractal analysis software was used to determine fractal dimensions of postpalatal airway contour during quiet inspiration and Müller's maneuver. Findings were correlated with the apnea‐hypopnea index.ResultsFractal dimension of collapsed airway and airway collapsibility was shown to be correlated with the apnea‐hypopnea index (r = −0.481 and 0.518). We used 9.5 percent airway collapsibility on the basis of fractal dimensions as a cutoff (decided according to a receiver operating characteristic curve) and found that the predictability of obstructive sleep apnea had a sensitivity of 92.0 percent (95% confidence interval 75.03‐97.78) and a specificity of 82.4 percent (95% confidence interval 58.97‐93.8), with a positive predictive value of 88.5 percent and a negative predictive value of 87.5 percent (P < 0.0001).ConclusionFractal analysis provides an additional measure of objectivity for the interpretation of computer‐assisted quantitative endoscopic evaluation of patients with obstructive sleep apnea. Nevertheless, as confidence intervals show, some uncertainty remains regarding the real population estimate, and therefore additional studies involving larger population groups are encouraged.
Otolaryngology office‐based treatment of obstructive sleep apnea‐hypopnea syndrome with titratable and nontitratable thermoplastic mandibular advancement devices
Authors: Friedman Michael , Pulver Tanya , Wilson Meghan N. , Golbin Dina , Leesman Christopher , Lee George , Joseph Ninos J. 
Published: June 2010

Objective1) Share our experiences treating patients with obstructive sleep apnea‐hypopnea syndrome (OSAHS) with titratable and nontitratable thermoplastic mandibular advancement devices (MADs) fitted in our otolaryngology clinic. 2) Compare these devices in terms of objective response (OR), as defined by a ≥ 50 percent decrease in baseline apnea‐hypopnea index (AHI) and an AHI < 20, and subjective parameters, including adherence. 3) Determine overall success, as defined by OR plus adherence at two months follow‐up.Study DesignCohort study.SettingTertiary care center.Subjects and MethodsPatients with OSAHS who tried and failed or refused both continuous positive airway pressure (CPAP) and surgical therapy were fitted with a nontitratable Snore Guard (n = 38), nontitratable SomnoGuard 2.0 (n = 8), or titratable SomnoGuard AP (n = 41). Pre‐ and post‐treatment assessment included: 1) Epworth Sleepiness Scale, 2) snoring level, 3) polysomnogram. Patients were contacted at two months follow‐up to assess adherence and subjective parameters.ResultsOR was achieved in 62.1 percent of patients. Overall mean reduction in AHI was from 39.96 ± 23.70 to 14.86 ± 13.46 (P = 0.000). Adherence at two months was 58.5 percent. No significant differences were observed in OR or adherence according to MAD type, though improvements in AHI and minimum oxygen saturation were significantly better for the SomnoGuard AP than for the nontitratable devices. Overall success was 38.6 percent.ConclusionThermoplastic MADs are a relatively inexpensive treatment alternative for patients with OSAHS who fail/refuse CPAP and upper airway surgery. They can be easily fitted in the otolaryngology clinic. Long‐term compliance, efficacy, and safety are unknown at this time.
Bipolar radiofrequency tonsillotomy compared with traditional cold dissection tonsillectomy in adults with recurrent tonsillitis
Authors: Nemati Shadman , Banan Rahmatollah , Kousha Abdorrahim 
Published: June 2010

ObjectiveTo compare short‐ and long‐term results of radiofrequency tonsillotomy and traditional cold dissection tonsillectomy in adult patients with recurrent tonsillitis.Study DesignA randomized clinical trial.SettingA tertiary referral university hospital.Subjects and MethodsOf 62 adults with recurrent tonsillitis, 24 patients were treated with cold dissection tonsillectomy, while radiofrequency tonsillotomy (RF) by use of radiofrequency induced thermotherapy probes was performed in the remaining 38 patients. Duration of surgery, amount of intraoperative bleeding, recovery time, postsurgical pain (measured by use of visual analogue scale on days 1, 3, 5, and 10 after surgery), dysphagia, weight loss, and time of return to normal diet and activity were measured. All the patients were followed for 12 to 24 months for recurrence of tonsillitis episodes.ResultsComparing the radiofrequency tonsillotomy group to the cold dissection tonsillectomy group, mean duration of surgery was 16.89 versus 45.04 minutes, recovery time was 14.32 minutes versus 17.08 minutes, and amount of intraoperative bleeding was 15 to 20 cc versus 250 to 300 cc, respectively (P < 0.005). There was no difference between the two groups in the recurrence of tonsillitis episodes after 24 months.ConclusionTonsillotomy with radiofrequency is a simple, rapid, and effective method in adult patients with recurrent tonsillitis.
Wrong‐site sinus surgery in otolaryngology
Authors: Shah Rahul K. , Nussenbaum Brian , Kienstra Matthew , Glenn Michael , Brereton Jean , Patel Milesh M. , Nielsen David , Roberson David W. 
Published: June 2010

ObjectiveTo determine the scope of wrong‐site sinus surgery.Study DesignElectronic mail survey.SettingE‐mailed via the American Academy of Otolaryngology–Head and Neck Surgery's weekly newsletter.Subjects and MethodsMembers were asked about wrong‐site sinus surgery in an 11‐item survey.ResultsA total of 455 members responded (response rate 19.8%). Forty‐two (9.3%) have heard of a case of wrong‐site sinus surgery occurring. Twenty‐one cases were analyzed; of these, 10 (48%) implicated radiographic error, and the Universal Protocol was followed in one third. In seventeen reports (81%), there was disclosure to the family, one case with delayed disclosure; there was no disclosure in three cases. Sixty‐one percent (n = 266) are concerned about operating on the wrong sinus or side. Forty‐nine percent (n = 216) routinely use a checklist preoperatively. There is large variation in site marking for sinus surgery. Sixty‐five percent (n = 282) routinely review the computed tomography scan prior to surgery.ConclusionApproximately 10 percent of survey respondents know of a case of wrong‐site sinus surgery occurring; the majority of respondents are concerned about a wrong‐sinus or wrong‐sided surgery occurring in their practice. Otolaryngologists should be vigilant regarding the potential for inverted computed tomography images; there should be national efforts to address this latent systems defect. Surgeons should be trained in understanding the role of and engaging in disclosure and in other techniques that are of greatest support to the patient. Consideration of sinus‐specific checklists should be led by the societies representing sinus surgeons.
Evaluating the diagnosis of chronic rhinosinusitis based on clinical guidelines and endoscopy
Authors: Bhattacharyya Neil , Lee Linda N. 
Published: June 2010

ObjectiveTo validate the diagnosis of chronic rhinosinusitis (CRS) according to recent clinical practice guidelines and determine the added utility of nasal endoscopy.Study DesignProspective diagnostic cohort study.SettingAcademic medical center.Subjects and MethodsA consecutive series of adult patients presenting for evaluation of CRS were prospectively studied with the use of the rhinosinusitis symptom inventory (RSI), nasal endoscopy, and sinus computed tomography (CT). Symptom scores were tabulated from the RSI. Nasal endoscopy was performed to evaluate for purulence or polyps. Sinus CT scans were scored with the Lund system, with the reviewers blinded to the RSI scores and endoscopic findings. The clinical diagnosis of CRS was determined on the basis of the published adult sinusitis guideline criteria and compared with the diagnostic gold standard, CT.ResultsA total of 202 patients were studied. The prevalence of CRS was 39.6 percent, as defined by CT (Lund score ≥ 4). For symptom criteria alone, the sensitivity, specificity, positive predictive value, and negative predictive value were 88.7, 12.3, 39.9, and 62.5 percent, respectively, for CRS (P = 0.82). The addition of endoscopic findings to symptom criteria significantly improved the specificity, predictive value, and negative predictive value to 84.1, 66.0, and 70.3 percent (P < 0.0001). The odds ratio of a true diagnosis of CRS improved from 1.1 to 4.6 (95% confidence interval, 2.3‐9.2). Sensitivity analysis adjusting symptom severity did not significantly alter diagnostic accuracy.ConclusionIn patients meeting current guideline symptom criteria for CRS, the addition of nasal endoscopy improves diagnostic accuracy and should be emphasized as an early diagnostic tool. Diagnostic endoscopy may help reduce the use of CT, reducing costs and radiation exposure.
Nasal septum to columella attachment: A major tip support?
Authors: Ordóñez‐Ordóñez Leonardo Elías , Navarro‐García Usmaila S. , Angulo‐Martínez Esther Sofía 
Published: June 2010

ObjectiveTo determine whether surgical section of attachment of the medial crural footplates to the quadrangular cartilage produces loosening of the nasal tip.Study DesignProspective, observational, before‐and‐after study.SettingTertiary care center.Subjects and MethodsHispanic patients undergoing septoplasty who required a transfixion incision were included. A six‐month postoperative assessment of the nasal tip support was compared with preoperative values. As measures of the nasal tip support, we included tip recoil test, nasolabial angle, tip rotation angle, nasofacial angle, and the Goode method for determining tip projection.ResultsTwenty‐seven patients completed the follow‐up, and their results are reported. There were no statistically significant differences after septoplasty in any of the five measurements used to assess the nasal tip support (P > 0.05).ConclusionIn this preliminary cohort of Hispanic patients, surgical section of the attachment of the medial crural footplates to the quadrangular cartilage does not produce significant changes in nasal tip support.
KERNELS OF MORPHISMS BETWEEN INDECOMPOSABLE INJECTIVE MODULES
Authors: FACCHINI ALBERTO , ECEVIT ŞULE , KOŞAN M. TAMER 
Published: June 2010

AbstractWe show that the endomorphism rings of kernels ker ϕ of non-injective morphisms ϕ between indecomposable injective modules are either local or have two maximal ideals, the module ker ϕ is determined up to isomorphism by two invariants called monogeny class and upper part, and a weak form of the Krull–Schmidt theorem holds for direct sums of these kernels. We prove with an example that our pathological decompositions actually take place. We show that a direct sum ofnkernels of morphisms between injective indecomposable modules can have exactlyn! pairwise non-isomorphic direct-sum decompositions into kernels of morphisms of the same type. IfERis an injective indecomposable module andSis its endomorphism ring, the duality Hom(−,ER) transforms kernels of morphismsER→ERinto cyclically presented left modules over the local ringS, sending the monogeny class into the epigeny class and the upper part into the lower part.
Task-priority motion planning of underactuated systems: an endogenous configuration space approach – ERRATUM
Authors: Ratajczak Adam , Karpińska Joanna , Tchoń Krzysztof 
Published: June 2010

Figures 2 and 5 were incorrectly reproduced in the above publication (Ratajczak et al. 2009). The figures are reproduced below in their correct form.
Fig. 2.Task-priority algorithm (both S1 and S2).Fig. 5.Single-task algorithm (only S1).