bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequent Alterations and Epigenetic Silencing of Differentiation Pathway Genes in Structurally Rearranged Liposarcomas
Authors: Taylor Barry S. , DeCarolis Penelope L. , Angeles Christina V. , Brenet Fabienne , Schultz Nikolaus , Antonescu Cristina R. , Scandura Joseph M. , Sander Chris , Viale Agnes J. , Socci Nicholas D. , Singer Samuel 
Published: October 2011

Abstract
We explored diverse alterations contributing to liposarcomagenesis by sequencing the genome, exome, transcriptome, and cytosine methylome of a primary and recurrent dedifferentiated liposarcoma (DLPS) from distinct chemotherapy/radiotherapy-naïve patients. The liposarcoma genomes had complex structural rearrangements, but in different patterns, and with varied effects on the structure and expression of affected genes. While the point mutation rate was modest, integrative analyses and additional screening identified somatic mutations in HDAC1 in 8.3% of DLPS. Liposarcoma methylomes revealed alterations in differentiation pathway genes, including CEBPA methylation in 24% of DLPS. Treatment with demethylating agents, which restored CEBPA expression in DLPS cells, was antiproliferative and proapoptotic in vitro and reduced tumor growth in vivo. Both genetic and epigenetic abnormalities established a role for small RNAs in liposarcomagenesis, typified by methylation-induced silencing of microRNA-193b in DLPS but not its well-differentiated counterpart. These findings reveal an unanticipated role for epigenetic abnormalities in DLPS tumors and suggest demethylating agents as potential therapeutics.
Significance: Multimodality sequence analysis of DLPS revealed recurrent mutations and epigenetic abnormalities critical to liposarcomagenesis and to the suppression of adipocyte differentiation. Pharmacologic inhibition of DNA methylation promoted apoptosis and differentiated DLPS cells in vitro and inhibited tumor growth in vivo, providing a rationale for investigating methylation inhibitors in this disease. Cancer Discovery; 1(7); 587–97. ©2011 AACR.
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Understanding the Effect of Workload on Automation Use for Younger and Older Adults
Authors: McBride Sara E. , Rogers Wendy A. , Fisk Arthur D. 
Published: October 2011

Objective: This study examined how individuals, younger and older, interacted with an imperfect automated system. The impact of workload on performance and automation use was also investigated. Background: Automation is used in situations characterized by varying levels of workload. As automated systems spread to domains such as transportation and the home, a diverse population of users will interact with automation. Research is needed to understand how different segments of the population use automation. Method: Workload was systematically manipulated to create three levels (low, moderate, high) in a dual-task scenario in which participants interacted with a 70% reliable automated aid. Two experiments were conducted to assess automation use for younger and older adults. Results: Both younger and older adults relied on the automation more than they complied with it. Among younger adults, high workload led to poorer performance and higher compliance, even when that compliance was detrimental. Older adults’ performance was negatively affected by workload, but their compliance and reliance were unaffected. Conclusion: Younger and older adults were both able to use and double-check an imperfect automated system. Workload affected how younger adults complied with automation, particularly with regard to detecting automation false alarms. Older adults tended to comply and rely at fairly high rates overall, and this did not change with increased workload. Application: Training programs for imperfect automated systems should vary workload and provide feedback about error types, and strategies for identifying errors. The ability to identify automation errors varies across individuals, thereby necessitating training.
Role of the Sphenoidal Process of the Septal Cartilage in the Development of Septal Deviation
Authors: Kim Joohwan , Kim Sung Won , Kim Soo Whan , Cho Jin Hee , Park Yong Jin 
Published: October 2011

ObjectiveThe sphenoidal process of the septal cartilage (SP) is a small strip of cartilage between the perpendicular plate of ethmoid bone and vomer. The present study was performed to evaluate the clinical significance of the SP in the development of nasal septal deviation.Study DesignProspective, controlled.SettingAcademic rhinologic practice.Subjects and MethodsThe authors examined 136 patients with nasal septal deviation. The length of SP was measured during septal surgery, and values were compared with the deviation angle. The distance between the anterior nasal spine (ANS) and the breakpoint of the suture line between the septal cartilage and the perpendicular plate of the ethmoid bone (ANS‐PPE) and that from the ANS to the point where the choana meets the sphenoid sinus (ANS‐CS) were determined and compared according to the age.ResultsThe mean length of SP in patients with a deviated nasal septum was 25.90 ± 7.82 mm and decreased with age. The average deviation angles at the level of the ostiomeatal unit and nasal valve area were 8.28° ± 3.50° and 10.37° ± 4.38°, respectively. These angles increased with the length of SP (P <. 01). The mean length of ANS‐PPE showed a significant negative correlation with age. The mean length of ANS‐CS had no correlation with age.ConclusionSP was longer with increasing deviation angle in patients with nasal septal deviation. A long SP, a remnant cartilaginous tail of the nasal septum resulting from delayed ossification of the nasal septum, contributes to the exacerbation of septal deviation.
Acute Mediastinitis Associated with Foreign Body Erosion from the Hypopharynx and Esophagus
Authors: Liu Jiajia , Zhang Xiaoli , Xie Dinghua , Peng Anquan , Yang Xinming , Yu Fenglei , Liu Deliang 
Published: October 2011

ObjectiveMediastinitis secondary to hypopharyngeal and esophageal foreign bodies is a rare but lethal complication. So far, no literature on a large scale has been reported. This investigation reviewed cases of mediastinitis associated with foreign body ingestion during the past 40 years.Study DesignCase series with chart review.SettingSecond Xiangya Hospital, Central South University.Subjects and MethodsOf 2981 patients with hypopharyngeal and esophageal foreign body impaction included between 1969 and 2010, 93 had complications of acute mediastinitis. Four patients were dead within 4 hours after admission. The rest of the 89 patients underwent surgical drainage. Thirteen underwent primary repair (7 cases with suture, 6 cases with omentum onlay graft), and 9 patients underwent endoscopic stent placement at the same time.ResultsThe mean (SD) time between ingestion and initial treatment of patients who developed mediastinitis was 7.72 (1.93) days, compared with 1.92 (1.41) days for those who did not (P <. 05). Morbidity was 3.1% and mortality was 30.1% (28/93), but the mortality of every decade has decreased from 38.7% in the 1970s to 8.3% today. Nine cases with local stent were all recovered.ConclusionsDelay in initiating treatment and intrathoracic esophageal foreign bodies are the main risk factors of mediastinitis secondary to foreign body ingestion. Computed tomography plays an important role in diagnosis and guiding treatments. In conjunction with aggressive surgical debridement and drainage, endoscopic stent placement could be the optimal management for most patients.
Assessing Laryngopharyngeal Reflux Symptoms with the Reflux Symptom Index
Authors: Printza Athanasia , Kyrgidis Athanassios , Oikonomidou Eirini , Triaridis Stefanos 
Published: October 2011

ObjectiveTo validate the Reflux Symptom Index (RSI) in Greek patients and estimate the prevalence of laryngopharyngeal reflux (LPR) symptoms in the Greek population.Study DesignProspective, controlled validation study.SettingTertiary referral hospital and primary care.Subjects and MethodsFor validation purposes, the instrument was administered to 53 patients with confirmed LPR. Sex‐ and age‐matched controls with no LPR or gastroesophageal reflux disease (GERD) symptoms presenting in a primary care setting composed the control group. Reliability and construct validity were statistically appraised. Using the RSI, the authors estimated the prevalence of LPR in a randomly selected sample of the Greek adult population.ResultsThe mean (SD) RSI score of the 172 sex‐ and age‐matched controls was 3.2 (3.5). The mean (SD) RSI score of the 53 confirmed LPR patients was 19.9 (6.8). Cronbach α was 0.865. Factor analysis verified that the RSI instrument consists of 2 principal factors. To estimate the prevalence of LPR, a representative sample of the Greek adult population (188 subjects) completed the RSI questionnaire: 36.3% were male, and 29.6% were smokers. Mean (SD) age was 53.4 (17.7) years. The instrument was able to discriminate 16 patients with LPR symptoms with a mean (SD) score of 18.91 (6.39).ConclusionThe authors evaluated the internal consistency, reliability, and construct validity of the RSI for the Greek population. Factor analysis of the Greek translation of the RSI demonstrated that it can be a reliable tool in the diagnostic approach of LPR patients. Using the RSI, the authors recorded that the prevalence of LPR in a representative sample of the Greek population is 8.5%.
Identification of Hearing Loss in Pediatric Patients with Down Syndrome
Authors: Park Albert H. , Wilson Matt A. , Stevens Paul T. , Harward Richard , Hohler Nancy 
Published: October 2011

ObjectiveTo determine the type of hearing loss, incidence of the lost to follow‐up rate, and the time to diagnose sensorineural hearing loss (SNHL) in children with Down syndrome (DS) identified from a statewide database.Study DesignCase series with chart review.SettingPediatric referral center.Subjects and MethodsThree hundred forty‐four patients with DS born in Utah between January 2002 and December 2006 were identified using the Utah Department of Health’s Newborn Hearing Screening database and birth defects registry.ResultsThree hundred thirty‐two patients were included in the study. Eighty‐seven infants (26.2%) did not pass their newborn hearing screening (NBS). Thirty‐three of these children (37.9%) had a conductive hearing loss attributed to serous otitis media. Five infants had SNHL; 3 children were diagnosed with a mixed hearing loss (MHL). The average time to diagnose a sensorineural hearing loss was 485 ± 601 days. One child who passed his NBS was subsequently found to have an SNHL. More than 43% of the newborns with DS who passed their NBS developed a conductive hearing loss requiring insertion of ventilation tubes. Eighty‐four percent of newborns with DS who did not undergo NBS did not have any apparent subsequent audiologic testing.ConclusionPatients with DS present with a relatively high incidence of conductive hearing loss, MHL, and SNHL and a higher lost to follow‐up rate compared to patients without DS. The authors were not able to diagnose SNHL within the 90‐day period recommended by the Joint Committee on Infant Hearing.
Loss of Normal Knee Motion After Anterior Cruciate Ligament Reconstruction Is Associated With Radiographic Arthritic Changes After Surgery
Authors: Shelbourne K. Donald , Urch Scott E. , Gray Tinker , Freeman Heather 
Published: October 2011

Background: Meniscectomy and articular cartilage damage have been found to increase the prevalence of osteoarthritis after anterior cruciate ligament reconstruction, but the effect of knee range of motion has not been extensively studied. Hypothesis: The prevalence of osteoarthritis as observed on radiographs would be higher in patients who had abnormal knee range of motion compared with patients with normal knee motion, even when grouped for like meniscal or articular cartilage lesions. Study Design: Cohort study; Level of evidence, 3. Methods: We prospectively followed patients at a minimum of 5 years after surgery. The constant goal of rehabilitation was to obtain full knee range of motion as quickly as possible after surgery and maintain it in the long term. Range of motion and radiographs were evaluated at the time of initial return to full activities (early follow-up) and final follow-up according to International Knee Documentation Committee (IKDC) objective criteria. A patient was considered to have normal range of motion if extension was within 2° of the opposite knee including hyperextension and knee flexion was within 5°. Radiograph findings were rated as abnormal if any signs of joint space narrowing, sclerosis, or osteophytes were present. Results: Follow-up was obtained for 780 patients at a mean of 10.5 ± 4.2 years after surgery. Of these, 539 had either normal or abnormal motion at both early and final follow-up. In 479 patients who had normal extension and flexion at both early and final follow-up, 188 (39%) had radiographic evidence of osteoarthritis versus 32 of 60 (53%) patients who had less than normal extension or flexion at early and final follow-up ( P = .036). In subgroups of patients with like meniscal status, the prevalence of normal radiograph findings was significantly higher in patients with normal motion at final follow-up versus patients with motion deficits. Multivariate logistic regression analysis of categorical variables showed that abnormal knee flexion at early follow-up, abnormal knee extension at final follow-up, abnormal knee flexion at final follow-up, partial medial meniscectomy, and articular cartilage damage were significant factors related to the presence of osteoarthritis on radiographs. Abnormal knee extension at early follow-up showed a trend toward statistical significance ( P = .0544). Logistic regression showed the odds of having osteoarthritis were 2 times more for patients with abnormal range of motion at final follow-up; these odds were similar for those with partial medial meniscectomy and articular cartilage damage. Conclusion: The prevalence of osteoarthritis on radiographs in the long term after anterior cruciate ligament reconstruction is lower in patients who achieve and maintain normal knee motion, regardless of the status of the meniscus.
TNF-α/Fas-RIP-1–induced cell death signaling separates murine hematopoietic stem cells/progenitors into 2 distinct populations
Authors: Xiao Yechen , Li Hongling , Zhang Jun , Volk Andrew , Zhang Shubin , Wei Wei , Zhang Shanshan , Breslin Peter , Zhang Jiwang 
Published: October 2011

AbstractWe studied the effects of TNF-α and Fas-induced death signaling in hematopoietic stem and progenitor cells (HSPCs) by examining their contributions to the development of bone marrow failure syndromes in Tak1-knockout mice (Tak1−/−). We found that complete inactivation of TNF-α signaling by deleting both of its receptors, 1 and 2 (Tnfr1−/−r2−/−), can prevent the death of 30% to 40% of Tak1−/− HSPCs and partially repress the bone marrow failure phenotype of Tak1−/− mice. Fas deletion can prevent the death of 5% to 10% of Tak1−/− HSPCs but fails to further improve the survival of Tak1−/−Tnfr1−/−r2−/− HSPCs, suggesting that Fas might induce death within a subset of TNF-α-sensitive HSPCs. This TNF-α/Fas-induced cell death is a type of receptor-interacting protein-1 (RIP-1)–dependent programmed necrosis called necroptosis, which can be prevented by necrostatin-1, a specific RIP-1 inhibitor. In addition, we found that the remaining Tak1−/− HSPCs died of apoptosis mediated by the caspase-8–dependent extrinsic apoptotic pathway. This apoptosis can be converted into necroptosis by the inhibition of caspase-8 and prevented by inhibiting both caspase-8 and RIP-1 activities. We concluded that HSPCs are heterogeneous populations in response to death signaling stimulation. Tak1 mediates a critical survival signal, which protects against both TNF-α/Fas-RIP-1–dependent necroptosis and TNF-α/Fas-independent apoptosis in HSPCs.
Analysis of conserved microRNAs in floral tissues of sexual and apomictic Boechera species
Authors: Amiteye Samuel , Corral José M , Vogel Heiko , Sharbel Timothy F 
Published: October 2011

Abstract

Background
Apomixis or asexual seed formation represents a potentially important agronomic trait whose introduction into crop plants could be an effective way to fix and perpetuate a desirable genotype through successive seed generations. However, the gene regulatory pathways underlying apomixis remain unknown. In particular, the potential function of microRNAs, which are known to play crucial roles in many aspects of plant growth and development, remains to be determined with regards to the switch from sexual to apomictic reproduction.

Results
Using bioinformatics and microarray validation procedures, 51 miRNA families conserved among angiosperms were identified in Boechera. Microarray assay confirmed 15 of the miRNA families that were identified by bioinformatics techniques. 30 cDNA sequences representing 26 miRNAs could fold back into stable pre-miRNAs. 19 of these pre-miRNAs had miRNAs with Boechera-specific nucleotide substitutions (NSs). Analysis of the Gibbs free energy (ΔG) of these pre-miRNA stem-loops with NSs showed that the Boechera-specific miRNA NSs significantly (p ≤ 0.05) enhance the stability of stem-loops. Furthermore, six transcription factors, the Squamosa promoter binding protein like SPL6, SPL11 and SPL15, Myb domain protein 120 (MYB120), RELATED TO AP2.7 DNA binding (RAP2.7, TOE1 RAP2.7) and TCP family transcription factor 10 (TCP10) were found to be expressed in sexual or apomictic ovules. However, only SPL11 showed differential expression with significant (p ≤ 0.05) up-regulation at the megaspore mother cell (MMC) stage of ovule development in apomictic genotypes.

Conclusions
This study constitutes the first extensive insight into the conservation and expression of microRNAs in Boechera sexual and apomictic species. The miR156/157 target squamosa promoter binding protein-like 11 (SPL11) was found differentially expressed with significant (p ≤ 0.05) up-regulation at the MMC stage of ovule development in apomictic genotypes. The results also demonstrate that nucleotide changes in mature miRNAs significantly (p ≤ 0.05) enhance the thermodynamic stability of pre-miRNA stem-loops.
CcpA represses the expression of the divergent cit operons of Enterococcus faecalis through multiple cresites
Authors: Suárez Cristian A , Blancato Víctor S , Poncet Sandrine , Deutscher Josef , Magni Christian 
Published: October 2011

Abstract

Background
In Enterococcus faecalis the genes encoding the enzymes involved in citrate metabolism are organized in two divergent operons, citHO and oadHDB-citCDEFX-oadA-citMG (citCL locus). Expression of both operons is specifically activated by adding citrate to the medium. This activation is mediated by binding of the GntR-like transcriptional regulator (CitO) to the cis-acting sequences located in the cit intergenic region. Early studies indicated that citrate and glucose could not be co-metabolized suggesting some form of catabolite repression, however the molecular mechanism remained unknown.

Results
In this study, we observed that the citHO promoter is repressed in the presence of sugars transported by the Phosphoenolpyruvate:carbohydrate Phosphotranserase System (PTS sugars). This result strongly suggested that Carbon Catabolic Repression (CCR) impedes the expression of the activator CitO and the subsequent induction of the cit pathway. In fact, we demonstrate that CCR is acting on both promoters. It is partially relieved in a ccpA-deficient E. faecalis strain indicating that a CcpA-independent mechanism is also involved in regulation of the two operons. Furthermore, sequence analysis of the citH/oadH intergenic region revealed the presence of three putative catabolite responsive elements (cre). We found that they are all active and able to bind the CcpA/P-Ser-HPr complex, which downregulates the expression of the cit operons. Systematic mutation of the CcpA/P-Ser-HPr binding sites revealed that cre1 and cre2 contribute to citHO repression, while cre3 is involved in CCR of citCL

Conclusion
In conclusion, our study establishes that expression of the cit operons in E. faecalis is controlled by CCR via CcpA-dependent and -independent mechanisms.
From RNA-seq to large-scale genotyping - genomics resources for rye (Secale cereale L.)
Authors: Haseneyer Grit , Schmutzer Thomas , Seidel Michael , Zhou Ruonan , Mascher Martin , Schön Chris-Carolin , Taudien Stefan , Scholz Uwe , Stein Nils , Mayer Klaus FX , Bauer Eva 
Published: October 2011

Abstract

Background
The improvement of agricultural crops with regard to yield, resistance and environmental adaptation is a perpetual challenge for both breeding and research. Exploration of the genetic potential and implementation of genome-based breeding strategies for efficient rye (Secale cereale L.) cultivar improvement have been hampered by the lack of genome sequence information. To overcome this limitation we sequenced the transcriptomes of five winter rye inbred lines using Roche/454 GS FLX technology.

Results
More than 2.5 million reads were assembled into 115,400 contigs representing a comprehensive rye expressed sequence tag (EST) resource. From sequence comparisons 5,234 single nucleotide polymorphisms (SNPs) were identified to develop the Rye5K high-throughput SNP genotyping array. Performance of the Rye5K SNP array was investigated by genotyping 59 rye inbred lines including the five lines used for sequencing, and five barley, three wheat, and two triticale accessions. A balanced distribution of allele frequencies ranging from 0.1 to 0.9 was observed. Residual heterozygosity of the rye inbred lines varied from 4.0 to 20.4% with higher average heterozygosity in the pollen compared to the seed parent pool.

Conclusions
The established sequence and molecular marker resources will improve and promote genetic and genomic research as well as genome-based breeding in rye.
A conformation ensemble approach to protein residue-residue contact
Authors: Eickholt Jesse , Wang Zheng , Cheng Jianlin 
Published: October 2011

Abstract

Background
Protein residue-residue contact prediction is important for protein model generation and model evaluation. Here we develop a conformation ensemble approach to improve residue-residue contact prediction. We collect a number of structural models stemming from a variety of methods and implementations. The various models capture slightly different conformations and contain complementary information which can be pooled together to capture recurrent, and therefore more likely, residue-residue contacts.

Results
We applied our conformation ensemble approach to free modeling targets from both CASP8 and CASP9. Given a diverse ensemble of models, the method is able to achieve accuracies of. 48 for the top L/5 medium range contacts and. 36 for the top L/5 long range contacts for CASP8 targets (L being the target domain length). When applied to targets from CASP9, the accuracies of the top L/5 medium and long range contact predictions were. 34 and. 30 respectively.

Conclusions
When operating on a moderately diverse ensemble of models, the conformation ensemble approach is an effective means to identify medium and long range residue-residue contacts. An immediate benefit of the method is that when tied with a scoring scheme, it can be used to successfully rank models.