bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low‐Dose D‐Methionine and N‐Acetyl‐L‐Cysteine for Protection from Permanent Noise‐Induced Hearing Loss in Chinchillas
Authors: Clifford Royce E. , Coleman John K. M. , Balough Ben J. , Liu Jianzhong , Kopke Richard D. , Jackson Ronald L. 
Published: July 2011

ObjectiveDespite efforts at public health awareness and stringent industrial standards for hearing protection, noise‐induced hearing loss (NIHL) remains a formidable public health concern. Although many antioxidants have proven to be beneficial in the laboratory for prevention of permanent NIHL, low‐dose combinations of compounds with different biochemical mechanisms of action may allow long‐term administration with fewer side effects and equal efficacy. The mixture of D‐methionine and N‐acetyl‐L‐cysteine administered at levels less than 10% of standard dosing has not been previously reported.Study DesignTwenty‐six female adult Chinchilla laniger were placed in 4 study groups, consisting of (1) a group receiving combination 12.5 mg/kg each D‐methionine and N‐acetyl‐L‐cysteine (DMET/NAC group), (2) a group receiving 12.5 mg/kg D‐methionine (DMET‐only group), (3) a group receiving 12.5 mg/kg N‐acetyl‐L‐cysteine (NAC‐only group), and (4) saline controls.SettingLaboratory.Subjects and MethodsAll groups received twice‐daily intraperitoneal injections 2 days prior to noise exposure, 1 hour before and after exposure on day 3, and for 2 days subsequently, totaling 10 doses of 125 mg/kg for each antioxidant over 5 days.ResultsAlthough NAC‐only animals paralleled saline control recovery during 3 weeks, the DMET‐only group revealed gradual improvement with statistically significant recovery in the middle frequencies. The DMET/NAC group showed significant improvement at most frequencies compared with controls (P <. 001 and P <. 05).ConclusionSignificant recovery of hearing was observed following continuous noise exposure with either DMET only or a combination of low‐dose DMET/NAC, demonstrating a considerably lower dose of antioxidants required than previously reported for hearing recovery following acoustic trauma.
Etiologic Factors in Sialolithiasis
Authors: Huoh Kevin C. , Eisele David W. 
Published: July 2011

ObjectivesThe purpose of this study was to investigate etiologic factors for sialolithiasis in a population of patients from the United States.Study DesignRetrospective, cohort study.SettingTertiary university.Materials and MethodsCharts for all patients diagnosed with sialolithiasis between January 2001 and February 2010 were retrospectively reviewed. Demographic factors, smoking history, comorbid medical conditions, and medication history were recorded. Statistical analyses were then performed on the collected data. Population prevalences of smoking, diuretic usage, cholelithiasis, and nephrolithiasis were obtained through literature review.ResultsA total of 153 patients with sialolithiasis were identified. Of these patients, 125 (82%) had submandibular sialolithiasis, and 28 (18%) had parotid sialolithiasis. Positive smoking histories were present in 67 individuals (44%). Both the current rate of smoking and the rate of a history of smoking were higher in our cohort when compared with the general population, although the differences did not reach statistical significance. Smoking history did not correlate with the size of the primary sialolith. Diuretic usage in the cohort was observed at a rate of 20%, higher than reported population rates of diuretic use of 8.7%. The prevalences of cholelithiasis and nephrolithiasis were not different from observed population rates.ConclusionsSialolithiasis is an uncommon condition of unclear etiology. This study represents an initial attempt to quantify the prevalence of smoking and diuretic therapy in a population of patients with sialolithiasis.
Western Blot Confirmation of the H+/K+‐ATPase Proton Pump in the Human Larynx and Submandibular Gland
Authors: Altman Kenneth W. , Kinoshita Yayoi , Tan Melin , Burstein David , Radosevich James A. 
Published: July 2011

ObjectiveThe authors have previously demonstrated the H+/K+‐ATPase (proton pump) in human larynx and lung glands via immunohistochemistry (IHC). The present hypothesis is that the proton pump is expressed in other seromucinous glands of the digestive tract that can be confirmed by IHC and Western blot analysis.Study DesignProspective controlled tissue analysis study.SettingAcademic medical institution.MethodsTen anonymous fresh‐frozen donor specimens were obtained, comprising 3 submandibular glands, 4 larynges, and 3 normal stomach specimens for control. Submandibular gland sections were immunostained with 2 monoclonal antibodies selectively reactive with α or β subunits of the H+/K+‐ATPase. Western blot analysis was performed on all specimens.ResultsConsistent IHC staining was observed in the submandibular gland specimens for both α and β subunits. Western blot analysis revealed very strong expression for the stomach at 100 kDa, corresponding to the α protein, and weak but notable banding for all larynx and submandibular gland specimens. Similar findings were noted for the 60‐ to 80‐kDa glycosylated β subunit protein, as well as the 52‐kDa β subunit precursor for all specimens.ConclusionThe H+/K+‐ATPase (proton) pump is present in the human larynx and submandibular gland although in much lower concentrations than in the stomach. Proton pump involvement in human aerodigestive seromucinous glands may have a role in protecting mucosa from acid environments (local or systemic), explain heightened laryngeal sensitivity in those patients with laryngopharyngeal reflux, and be a site of action for proton pump inhibitor pharmacotherapy.
Sentinel Lymph Node Biopsy in Thyroid Cancer
Authors: Amir Alexander , Payne Richard , Richardson Keith , Hier Michael , Mlynarek Alex , Caglar Derin 
Published: July 2011

ObjectiveThe aim of this study is to retrospectively assess the specific perils associated with conducting sentinel lymph node biopsies to determine whether a central compartment neck dissection (CCND) is necessary in well‐differentiated thyroid cancer. The goal was to assess the specific reasons for a false negative in 3 specific patients among a large population of thyroidectomy patients.Study DesignCase series with chart review.SettingThree McGill University teaching hospitals that are part of the McGill University Thyroid Cancer Center in Montreal, Quebec, Canada.SubjectsPatients undergoing thyroidectomy and CCND for nodules suspicious for thyroid cancer (June 2009 to May 2010).MethodsRetrospective analysis of 157 patients who underwent thyroidectomy and analysis of CCND as a function of sentinel lymph node status on frozen section as determined by a pathologist at one of the participating centers.ResultsThree patients were considered true failures or false negatives of the original protocol. These 3 patients were deemed to have benign lymph node status intraoperatively but were found postoperatively to harbor malignancy and therefore should have undergone CCND. The critical reasons for the imperfect false‐negative rate are believed to be secondary to samples falsely deemed benign as well as multinodular disease.ConclusionThe value of sentinel lymph node biopsy in thyroid cancer, although largely debated, appears to be strong. If caution is taken in using dedicated head and neck pathologists for sentinel lymph node cases, as well as properly addressing multinodular malignancy, clinical decision making can be rendered more objective.
Postoperative complications following the Fontan procedure: the role of aprotinin
Authors: Klugman D , Donofrio MT , Zurakowski D , Jonas RA 
Published: July 2011

Objective: To determine how the anti-inflammatory properties of aprotinin impact on postoperative complications in children undergoing the Fontan procedure. Methods: We included all patients between 14 months and 18 years (n=56) undergoing a Fontan operation at our institution between January 2005 and June 2009. The study group (n=29) included patients from January 2005 through December 2007 all of whom received aprotinin. The control group (n=27) included all patients from January 2008 through June 2009 who did not receive aprotinin. We reviewed all medical records and collected preoperative, intraoperative and postoperative data. Duration and volume of chest tube drainage were the primary outcome measures. Results: Of the 20% of patients who had postoperative arrhythmias, multivariate logistic regression analysis demonstrated only aprotinin was associated with significantly decreased postoperative arrhythmias ( P=0.01). Renal function and fenestration or Fontan thrombosis did not differ significantly; there was no statistically significant difference in volume or duration of chest tube drainage. Median duration of chest tube drainage was 7 days in the aprotinin group and 8 days for patients who did not receive aprotinin ( P=0.36). Conclusion: The anti-inflammatory properties of aprotinin may be protective against postoperative arrhythmias. Aprotinin does not confer increased risks of prolonged chest tube drainage, renal dysfunction or thrombosis in patients undergoing the Fontan procedure.
A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic syndromes with del5q
Authors: Fenaux Pierre , Giagounidis Aristoteles , Selleslag Dominik , Beyne-Rauzy Odile , Mufti Ghulam , Mittelman Moshe , Muus Petra , te Boekhorst Peter , Sanz Guillermo , del Cañizo Consuelo , Guerci-Bresler Agnes , Nilsson Lars , Platzbecker Uwe , Lübbert Michael , Quesnel Bruno , Cazzola Mario , Ganser Arnold , Bowen David , Schlegelberger Brigitte , Aul Carlo , Knight Robert , Francis John , Fu Tommy , Hellström-Lindberg Eva ,   for the MDS-004 Lenalidomide del5q Study Group
Published: July 2011

AbstractThis phase 3, randomized, double-blind study assessed the efficacy and safety of lenalidomide in 205 red blood cell (RBC) transfusion-dependent patients with International Prognostic Scoring System Low-/Intermediate-1-risk del5q31 myelodysplastic syndromes. Patients received lenalidomide 10 mg/day on days 1-21 (n = 69) or 5 mg/day on days 1-28 (n = 69) of 28-day cycles; or placebo (n = 67). Crossover to lenalidomide or higher dose was allowed after 16 weeks. More patients in the lenalidomide 10- and 5-mg groups achieved RBC-transfusion independence (TI) for ≥ 26 weeks (primary endpoint) versus placebo (56.1% and 42.6% vs 5.9%; both P < .001). Median duration of RBC-TI was not reached (median follow-up, 1.55 years), with 60% to 67% of responses ongoing in patients without progression to acute myeloid leukemia (AML). Cytogenetic response rates were 50.0% (10 mg) versus 25.0% (5 mg; P = .066). For the lenalidomide groups combined, 3-year overall survival and AML risk were 56.5% and 25.1%, respectively. RBC-TI for ≥ 8 weeks was associated with 47% and 42% reductions in the relative risks of death and AML progression or death, respectively (P = .021 and .048). The safety profile was consistent with previous reports. Lenalidomide is beneficial and has an acceptable safety profile in transfusion-dependent patients with Low-/Intermediate-1-risk del5q myelodysplastic syndrome. This trial was registered at www.clinicaltrials.gov as #NCT00179621.
The Hbo1-Brd1/Brpf2 complex is responsible for global acetylation of H3K14 and required for fetal liver erythropoiesis
Authors: Mishima Yuta , Miyagi Satoru , Saraya Atsunori , Negishi Masamitsu , Endoh Mitsuhiro , Endo Takaho A. , Toyoda Tetsuro , Shinga Jun , Katsumoto Takuo , Chiba Tetsuhiro , Yamaguchi Naoto , Kitabayashi Issay , Koseki Haruhiko , Iwama Atsushi 
Published: July 2011

Abstract
The histone acetyltransferases (HATs) of the MYST family include TIP60, HBO1, MOZ/MORF, and MOF and function in multisubunit protein complexes. Bromodomain-containing protein 1 (BRD1), also known as BRPF2, has been considered a subunit of the MOZ/MORF H3 HAT complex based on analogy with BRPF1 and BRPF3. However, its physiologic function remains obscure. Here we show that BRD1 forms a novel HAT complex with HBO1 and regulates erythropoiesis. Brd1-deficient embryos showed severe anemia because of impaired fetal liver erythropoiesis. Biochemical analyses revealed that BRD1 bridges HBO1 and its activator protein, ING4. Genome-wide mapping in erythroblasts demonstrated that BRD1 and HBO1 largely colocalize in the genome and target key developmental regulator genes. Of note, levels of global acetylation of histone H3 at lysine 14 (H3K14) were profoundly decreased in Brd1-deficient erythroblasts and depletion of Hbo1 similarly affected H3K14 acetylation. Impaired erythropoiesis in the absence of Brd1 accompanied reduced expression of key erythroid regulator genes, including Gata1, and was partially restored by forced expression of Gata1. Our findings suggest that the Hbo1-Brd1 complex is the major H3K14 HAT required for transcriptional activation of erythroid developmental regulator genes.
Bronchoscopic techniques in diagnosis and staging of lung cancer
Authors: Herth F.J.F. 
Published: July 2011

SummaryTechnologic advances in bronchoscopy continue to improve our ability to perform minimally invasive, accurate evaluations of the tracheobronchial tree and to perform an ever-increasing array of diagnostic, therapeutic, and palliative interventions. The role of both “old” and “new” diagnostic bronchoscopy will continue to evolve as further improvements are made in bronchoscopes, accessory equipment, and imaging technologies. The major challenge in the adoption of the many new bronchoscopic techniques into routine clinical practice is the need for well-designed studies to delineate the appropriate use of these interventions and to better define their limitations.
Antioxidant components of naturally-occurring oils exhibit marked anti-inflammatory activity in epithelial cells of the human upper respiratory system
Authors: Gao Meixia , Singh Anju , Macri Kristin , Reynolds Curt , Singhal Vandana , Biswal Shyam , Spannhake Ernst W 
Published: July 2011

Abstract

Background
The upper respiratory tract functions to protect lower respiratory structures from chemical and biological agents in inspired air. Cellular oxidative stress leading to acute and chronic inflammation contributes to the resultant pathology in many of these exposures and is typical of allergic disease, chronic sinusitis, pollutant exposure, and bacterial and viral infections. Little is known about the effective means by which topical treatment of the nose can strengthen its antioxidant and anti-inflammatory defenses. The present study was undertaken to determine if naturally-occurring plant oils with reported antioxidant activity can provide mechanisms through which upper respiratory protection might occur.

Methods
Controlled exposure of the upper respiratory system to ozone and nasal biopsy were carried out in healthy human subjects to assess mitigation of the ozone-induced inflammatory response and to assess gene expression in the nasal mucosa induced by a mixture of five naturally-occurring antioxidant oils - aloe, coconut, orange, peppermint and vitamin E. Cells of the BEAS-2B and NCI-H23 epithelial cell lines were used to investigate the source and potential intracellular mechanisms of action responsible for oil-induced anti-inflammatory activity.

Results
Aerosolized pretreatment with the mixed oil preparation significantly attenuated ozone-induced nasal inflammation. Although most oil components may reduce oxidant stress by undergoing reduction, orange oil was demonstrated to have the ability to induce long-lasting gene expression of several antioxidant enzymes linked to Nrf2, including HO-1, NQO1, GCLm and GCLc, and to mitigate the pro-inflammatory signaling of endotoxin in cell culture systems. Nrf2 activation was demonstrated. Treatment with the aerosolized oil preparation increased baseline levels of nasal mucosal HO-1 expression in 9 of 12 subjects.

Conclusions
These data indicate that selected oil-based antioxidant preparations can effectively reduce inflammation associated with oxidant stress-related challenge to the nasal mucosa. The potential for some oils to activate intracellular antioxidant pathways may provide a powerful mechanism through which effective and persistent cytoprotection against airborne environmental exposures can be provided in the upper respiratory mucosa.
Modeling measurement error in tumor characterization studies
Authors: Rakovski Cyril , Weisenberger Daniel J , Marjoram Paul , Laird Peter W , Siegmund Kimberly D 
Published: July 2011

Abstract

Background
Etiologic studies of cancer increasingly use molecular features such as gene expression, DNA methylation and sequence mutation to subclassify the cancer type. In large population-based studies, the tumor tissues available for study are archival specimens that provide variable amounts of amplifiable DNA for molecular analysis. As molecular features measured from small amounts of tumor DNA are inherently noisy, we propose a novel approach to improve statistical efficiency when comparing groups of samples. We illustrate the phenomenon using the MethyLight technology, applying our proposed analysis to compare MLH1 DNA methylation levels in males and females studied in the Colon Cancer Family Registry.

Results
We introduce two methods for computing empirical weights to model heteroscedasticity that is caused by sampling variable quantities of DNA for molecular analysis. In a simulation study, we show that using these weights in a linear regression model is more powerful for identifying differentially methylated loci than standard regression analysis. The increase in power depends on the underlying relationship between variation in outcome measure and input DNA quantity in the study samples.

Conclusions
Tumor characteristics measured from small amounts of tumor DNA are inherently noisy. We propose a statistical analysis that accounts for the measurement error due to sampling variation of the molecular feature and show how it can improve the power to detect differential characteristics between patient groups.
Statistical Mutation Calling from Sequenced Overlapping DNA Pools in TILLING Experiments
Authors: Missirian Victor , Comai Luca , Filkov Vladimir 
Published: July 2011

Abstract

Background
TILLING (Targeting induced local lesions IN genomes) is an efficient reverse genetics approach for detecting induced mutations in pools of individuals. Combined with the high-throughput of next-generation sequencing technologies, and the resolving power of overlapping pool design, TILLING provides an efficient and economical platform for functional genomics across thousands of organisms.

Results
We propose a probabilistic method for calling TILLING-induced mutations, and their carriers, from high throughput sequencing data of overlapping population pools, where each individual occurs in two pools. We assign a probability score to each sequence position by applying Bayes' Theorem to a simplified binomial model of sequencing error and expected mutations, taking into account the coverage level. We test the performance of our method on variable quality, high-throughput sequences from wheat and rice mutagenized populations.

Conclusions
We show that our method effectively discovers mutations in large populations with sensitivity of 92.5% and specificity of 99.8%. It also outperforms existing SNP detection methods in detecting real mutations, especially at higher levels of coverage variability across sequenced pools, and in lower quality short reads sequence data. The implementation of our method is available from: http://www.cs.ucdavis.edu/~filkov/CAMBa/.
Cellular Expression of Smarca4 (Brg1)-regulated Genes in Zebrafish Retinas
Authors: Hensley Monica R , Emran Farida , Bonilla Sylvia , Zhang Liyun , Zhong Wenxuan , Grosu Paul , Dowling John E , Leung Yuk Fai 
Published: July 2011

AbstractBackgroundIn a recent genomic study, Leung et al. used a factorial microarray analysis to identify Smarca4 (Brg1)-regulated genes in micro-dissected zebrafish retinas. Two hundred and fifty nine genes were grouped in three-way ANOVA models which carried the most specific retinal change. To validate the microarray results and to elucidate cellular expression patterns of the significant genes for further characterization, 32 known genes were randomly selected from this group.In situhybridization of these genes was performed on the same types of samples (wild-type (WT) andsmarca4a50/a50(yng) mutant) at the same stages (36 and 52 hours post-fertilization (hpf)) as in the microarray study.ResultsThirty out of 32 riboprobes showed a positivein situstaining signal. Twenty seven out of these 30 genes were originally further classified as Smarca4-regulated retinal genes, while the remaining three as retinal-specific expression independent of Smarca4 regulation. It was found that 90.32% of the significant microarray comparisons that were used to identify Smarca4-regulated retinal genes had a corresponding qualitative expression change in thein situhybridization comparisons. This is highly concordant with the theoretical true discovery rate of 95%. Hierarchical clustering was used to investigate the similarity of the cellular expression patterns of 25 out of the 27 Smarca4-regulated retinal genes that had a sufficiently high expression signal for an unambiguous identification of retinal expression domains. Three broad groups of expression pattern were identified; including 1) photoreceptor layer/outer nuclear layer specific expression at 52 hpf, 2) ganglion cell layer (GCL) and/or inner nuclear layer (INL) specific expression at both 36 & 52 hpf, and 3) GCL and/or INL specific expression at 52 hpf only. Some of these genes have recently been demonstrated to play key roles in retinal cell-type specification, differentiation and lamination. For the remaining three retinal-specific genes that are independent of Smarca4 regulation, they all had a subtle expression difference between WT andsmarca4a50/a50retinas as detected byin situhybridization. This subtle expression difference was also detected by the original microarray analysis. However, the difference was lower than the fold change cut-off used in that study and hence these genes were not inferred as Smarca4-regulated retinal genes.ConclusionsThis study has successfully investigated the expression pattern of 32 genes identified from the original factorial microarray analysis. The results have demonstrated that the true discovery rate for identifying Smarca4-regulated retinal genes is 90.3%. Hence, the significant genes from the microarray study are good candidates for cell-type specific markers and will aid further investigation of retinal differentiation.