bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a Hypoxia Gene Expression Classifier with Predictive Impact for Hypoxic Modification of Radiotherapy in Head and Neck Cancer
Authors: Toustrup Kasper , Sørensen Brita Singers , Nordsmark Marianne , Busk Morten , Wiuf Carsten , Alsner Jan , Overgaard Jens 
Published: August 2011

Abstract
Hypoxia, a common feature of the microenvironment in solid tumors, is associated with resistance to radiotherapy, reduced therapeutic response, and a poorer clinical outcome. In head and neck squamous cell carcinomas (HNSCC), the negative effect of hypoxia on radiotherapy can be counteracted via addition of hypoxic modification to the radiotherapy. To predict which patients harbor hypoxic tumors and would therefore benefit from hypoxic modification, clinically applicable methods for pretherapeutic hypoxic evaluation and categorization are needed. In this study, we developed a hypoxia classifier based on gene expression. Through study of xenograft tumors from human squamous cell carcinoma cell lines, we verified the in vivo relevance of previously identified in vitro derived hypoxia-induced genes. We then evaluated a training set of 58 hypoxia-evaluated HNSCCs to generate a gene expression classifier containing 15 genes. This 15-gene hypoxia classifier was validated in 323 patients with HNSCC randomized for hypoxic modification or placebo in combination with radiotherapy. Tumors categorized as hypoxic on the basis of the classifier were associated with a significantly poorer clinical outcome than nonhypoxic tumors. This outcome was improved and equalized to the nonhypoxic tumors by addition of hypoxic modification. Thus, findings show that the classifier attained both prognostic and predictive impact, and its pretherapeutic use may provide a method to identify those patients who will benefit from hypoxic modification of radiotherapy. Cancer Res; 71(17); 5923–31. ©2011 AACR.
Use of 2‐Octylcyanoacrylate (Dermabond) Tissue Adhesive for Tip Graft Fixation in Open Rhinoplasty
Authors: Min Jin‐Young , Jang Yong Ju 
Published: August 2011

ObjectivesTo describe the use of 2‐octylcyanoacrylate (2‐OCA; Dermabond) for fixation of cartilage grafts in nasal tip surgery via an external approach in Asian patients.Study DesignCase series with chart review.SettingAcademic tertiary care medical center.Subjects and MethodsThis retrospective study analyzed data from 33 Korean patients who underwent open rhinoplasty using 2‐OCA tissue adhesive for fixation of cartilage grafts in tip surgery. Autologous septal, conchal, costal, or homologous costal cartilage was used as graft materials. Layers of cartilages were bonded using 2‐OCA tissue adhesive, and care was taken to prevent the tissue adhesive from spilling and directly contacting surrounding soft tissues. Preoperative and postoperative photographs were reviewed for objective and subjective assessment of aesthetic outcomes.ResultsPostoperative aesthetic outcomes were graded as excellent in 51.5%, fair in 33.3%, and no change/worse in 15.2% of patients. Preoperative and postoperative anthropometric measurements showed that the nasal tip projection increased (0.53 ± 0.03 vs 0.57 ± 0.05; P <. 05) and the nasolabial angle improved (92.54 ± 6.95 vs 96.12 ± 5.20; P <. 05). The overall complication rate was 24.2%, and complications included erythema (9.1%), infection (12.1%), and aesthetic dissatisfaction (3.0%).ConclusionAlthough using 2‐OCA tissue adhesive for tip surgery simplifies the surgical procedures of fixating graft materials, the relatively high complication rate may preclude its use in nasal tip surgery via an external approach for Asian noses.
Demographics and Microbiology of Otorrhea through Patent Tubes Failing Ototopical and/or Oral Antibiotic Therapy
Authors: Fishman Inessa , Sykes Kevin J. , Horvat Rebecca , Selvarangan Rangaraj , Newland Jason , Wei Julie L. 
Published: August 2011

ObjectivesPosttympanostomy tube otorrhea (PTTO) results in significant health care cost and decreased satisfaction with care. The authors reviewed PTTO failing initial ototopical and/or oral antibiotic therapy and microbiology/susceptibility data from cultures.Study DesignCase series with chart review.SettingA community university satellite ambulatory clinic and the outpatient clinic of a children’s hospital.MethodsReview of 202 patients with 228 discrete episodes of culture‐positive otorrhea from January 2004 to January 2009.ResultsPTTO occurred an average of 13 months after tube placement. Median otorrhea duration was 21 days (mean, 42 days). A mean of 1.6 visits (range, 1‐6) to the pediatric otolaryngology office was required for PTTO resolution. Ototopical therapy was reported used in 198 of 228 (87%) episodes of otorrhea prior to pediatric otolaryngology visit. Nearly 50% of patients were prescribed at least 1 or more courses of systemic antibiotics. Staphylococcus aureus accounted for 52% of the organisms cultured, with 57% methicillin‐resistant S aureus (MRSA). S aureus resistance to clindamycin was high (49%) and resistance to levofloxacin was low (1.8%). MRSA was 68% clindamycin resistant, much higher than both ours and the children’s hospital’s clindamycin resistance rate of MRSA cultured from all other body sites.ConclusionsPTTO that presents as having failed ototopical and/or oral antibiotics most commonly consists of S aureus, Streptococcus pneumoniae, and Pseudomonas aeruginosa. MRSA is highly prevalent in this population. It is not necessary to culture PTTO that presents to an otolaryngology office, as resistance to levofloxacin was only 1.8%. It is unclear why the same fluoroquinolone ototopical therapy that failed initially is often successful in treating PTTO after otolaryngologist visit.
The effects of rivastigmine on processing speed and brain activation in patients with multiple sclerosis and subjective cognitive fatigue
Authors: Huolman S , Hämäläinen P , Vorobyev V , Ruutiainen J , Parkkola R , Laine T , Hämäläinen H 
Published: August 2011

Background: Cognitive decline and fatigue are typical in multiple sclerosis (MS). However, there is no official medication for either of these symptoms. Objective: The purpose of this study was to estimate the effects of a single dose of rivastigmine on processing speed and associated brain activity in patients with MS and subjective cognitive fatigue. Methods: Fifteen patients with MS and subjective cognitive fatigue and 13 healthy controls (HCs) matched for age, gender and education performed a neuropsychological assessment and functional (f)MRI. A modified version of the Paced Visual Serial Addition Test (mPVSAT) was used as the behavioural task during fMRIs. After the first scanning session, both groups were randomly divided into two subgroups receiving either rivastigmine or placebo. A single dose of rivastigmine or placebo was administrated double-blindly and 2.5 hours later the scanning was repeated. Results: At baseline, the patients with MS showed slower processing speed in mPVSAT compared with the HCs. They also demonstrated stronger bilateral frontal activation after sustained cognitive effort than the HCs. Performance improvement and a further activation increase in the left anterior frontal cortex and additional activation in the right cerebellum were observed in patients who received rivastigmine but not in patients on placebo, or in HCs with placebo or rivastigmine. Conclusion: These preliminary findings suggest that rivastigmine may improve cognitive processing speed by enhancing compensatory brain activation in patients with MS.
A qualitative study of families of a child with a nut allergy
Authors: Pitchforth Emma , Weaver Simon , Willars Janet , Wawrzkowicz Emilia , Luyt David , Dixon-Woods Mary 
Published: August 2011

Objectives: The aim of this study was to explore, using qualitative methods, the experiences of children and their parents living with nut allergy. Methods: Children with a confirmed diagnosis of peanut allergy were identified from a database of patients maintained at an allergy clinic at a large teaching hospital. Interviews with 26 families were conducted involving 11 children, 25 mothers and 12 fathers. Results: The diagnosis of nut allergy signalled a critical transition—or biographical disruption—in the life of the family. Parents took on the role of ‘alert assistant’ and sought to create ‘safe places’ where nuts were not permitted, but often struggled when outside the home environment. The option of ‘passing as normal’, often used by people with a chronic illness to avoid stigma, was not available to them. Consequently, parents often reported being treated as faddy, demanding, and neurotic, and children suffered from teasing and exclusion. The social consequences of nut allergy were worsened by poor labelling and control of foods and products containing nuts. Discussion: In many ways, nut allergy may be considered a form of disability, because it imposes social barriers on participating fully in society.
A Comprehensive Histological Assessment of Osteoarthritis Lesions in Mice
Authors: McNulty Margaret A. , Loeser Richard F. , Davey Cynthia , Callahan Michael F. , Ferguson Cristin M. , Carlson Cathy S. 
Published: August 2011

Objective: Accurate histological assessment of osteoarthritis (OA) is critical in studies evaluating the effects of interventions on disease severity. The purpose of the present study was to develop a histological grading scheme that comprehensively and quantitatively assesses changes in multiple tissues that are associated with OA of the stifle joint in mice. Design: Two representative midcoronal sections from 158 stifle joints, including naturally occurring and surgically induced OA, were stained with H&E and Safranin-O stains. All slides were evaluated to characterize the changes present. A grading scheme that includes both measurements and semiquantitative scores was developed, and principal components analysis (PCA) was applied to the resulting data from the medial tibial plateaus. A subset of 30 tibial plateaus representing a wide range of severity was then evaluated by 4 observers. Reliability of the results was evaluated using intraclass correlation coefficients (ICCs) and area under the receiver operating characteristic (ROC) curve. Results: Five factors were retained by PCA, accounting for 74% of the total variance. Interobserver and intraobserver reproducibilities for evaluations of articular cartilage and subchondral bone were acceptable. The articular cartilage integrity and chondrocyte viability factor scores were able to distinguish severe OA from normal, minimal, mild, and moderate disease. Conclusion: This newly developed grading scheme and resulting factors characterize a range of joint changes in mouse stifle joints that are associated with OA. Overall, the newly developed scheme is reliable and reproducible, characterizes changes in multiple tissues, and provides comprehensive information regarding a specific site in the stifle joint.
Alternative activation of macrophages by IL-4 enhances the proteolytic capacity of their phagosomes through synergistic mechanisms
Authors: Balce Dale R. , Li Baoquan , Allan Euan R. O. , Rybicka Joanna M. , Krohn Regina M. , Yates Robin M. 
Published: August 2011

AbstractAlternatively activated macrophages, generated in a T-helper 2 environment, have demonstrated roles in wound repair and tissue remodeling in addition to being charged with immune tasks. Because the hydrolytic chemistries of the phagosomal lumen are central to many of these functions, we investigated their modification after alternative activation with IL-4 and IL-13. Most significantly, we found striking up-regulation of the proteolytic levels within the phagosome of IL-4–activated macrophages. Two synergistic mechanisms were determined to underlie this up-regulation. First, IL-4–activated macrophages displayed increased expression of cathepsin S and L, providing greater proteolytic machinery to the phagosome despite unchanged rates of lysosomal contribution. Secondly, decreased phagosomal NADPH oxidase (NOX2) activity, at least partially resulting from decreased expression of the NOX2 subunit gp91phox, resulted in a more reductive lumenal microenvironment, which in turn, enhanced activities of local cysteine cathepsins. Decreased NOX2 activity additionally increased the phagosome's ability to reduce disulfides, further enhancing the efficiency of the macrophage to degrade proteins containing disulfide bonds. Together, these changes initiated by IL-4 act synergistically to rapidly and dramatically enhance the macrophage's ability to degrade phagocytosed protein, which, we reason, better equips this cell for its roles in wound repair and tissue remodeling.
ProbPS: A new model for peak selection based on quantifying the dependence of the existence of derivative peaks on primary ion intensity
Authors: Zhang Shenghui , Wang Yaojun , Bu Dongbo , Zhang Hong , Sun Shiwei 
Published: August 2011

Abstract

Background
The analysis of mass spectra suggests that the existence of derivative peaks is strongly dependent on the intensity of the primary peaks. Peak selection from tandem mass spectrum is used to filter out noise and contaminant peaks. It is widely accepted that a valid primary peak tends to have high intensity and is accompanied by derivative peaks, including isotopic peaks, neutral loss peaks, and complementary peaks. Existing models for peak selection ignore the dependence between the existence of the derivative peaks and the intensity of the primary peaks. Simple models for peak selection assume that these two attributes are independent; however, this assumption is contrary to real data and prone to error.

Results
In this paper, we present a statistical model to quantitatively measure the dependence of the derivative peak's existence on the primary peak's intensity. Here, we propose a statistical model, named ProbPS, to capture the dependence in a quantitative manner and describe a statistical model for peak selection. Our results show that the quantitative understanding can successfully guide the peak selection process. By comparing ProbPS with AuDeNS we demonstrate the advantages of our method in both filtering out noise peaks and in improving de novo identification. In addition, we present a tag identification approach based on our peak selection method. Our results, using a test data set, suggest that our tag identification method (876 correct tags in 1000 spectra) outperforms PepNovoTag (790 correct tags in 1000 spectra).

Conclusions
We have shown that ProbPS improves the accuracy of peak selection which further enhances the performance of de novo sequencing and tag identification. Thus, our model saves valuable computation time and improving the accuracy of the results.
Tight associations between transcription promoter type and epigenetic variation in histone positioning and modification
Authors: Nozaki Tadasu , Yachie Nozomu , Ogawa Ryu , Kratz Anton , Saito Rintaro , Tomita Masaru 
Published: August 2011

Abstract

Background
Transcription promoters are fundamental genomic cis-elements controlling gene expression. They can be classified into two types by the degree of imprecision of their transcription start sites: peak promoters, which initiate transcription from a narrow genomic region; and broad promoters, which initiate transcription from a wide-ranging region. Eukaryotic transcription initiation is suggested to be associated with the genomic positions and modifications of nucleosomes. For instance, it has been recently shown that histone with H3K9 acetylation (H3K9ac) is more likely to be distributed around broad promoters rather than peak promoters; it can thus be inferred that there is an association between histone H3K9 and promoter architecture.

Results
Here, we performed a systematic analysis of transcription promoters and gene expression, as well as of epigenetic histone behaviors, including genomic position, stability within the chromatin, and several modifications. We found that, in humans, broad promoters, but not peak promoters, generally had significant associations with nucleosome positioning and modification. Specifically, around broad promoters histones were highly distributed and aligned in an orderly fashion. This feature was more evident with histones that were methylated or acetylated; moreover, the nucleosome positions around the broad promoters were more stable than those around the peak ones. More strikingly, the overall expression levels of genes associated with broad promoters (but not peak promoters) with modified histones were significantly higher than the levels of genes associated with broad promoters with unmodified histones.

Conclusion
These results shed light on how epigenetic regulatory networks of histone modifications are associated with promoter architecture.
LeukoCatch, a quick and efficient tool for the preparation of leukocyte extracts from blood
Authors: Okuzaki Daisuke , Kimura Shoichi , Yabuta Norikazu , Ohmine Toshinari , Nojima Hiroshi 
Published: August 2011

Abstract

Background
Whole-protein extracts from peripheral blood leukocytes are ideal for basic and clinical research. However, lack of a simple preparation technique has limited the use of such extracts. The aim of this study is to develop a simple and easy system that can selectively obtain leukocyte extracts without hemoglobin.

Methods
A filter that captures the leukocytes but not RBCs was set at the bottom of a 10-mL medical syringe by sandwiching it between plastic stoppers. The capturing efficiency of leukocytes with this tool, called LeukoCatch, was examined using human macrophage cells (MONO-MAC-6). The abilities of LeukoCatch system to capture the leukocyte proteins and to remove the hemoglobin from RBCs were tested by western blot analysis using human blood samples.

Results
This study presents the development of LeukoCatch, a novel tool that allows the preparation of leukocyte extracts from blood samples within 3 min without centrifugation. Tissue-cultured human macrophage cells were tested to determine the optimal filter numbers and pass-through frequencies of LeukoCatch, which was then applied to 2-mL blood samples. Samples were passed 2~5 times through a LeukoCatch equipped with 5 filters, washed twice with phosphate-buffered saline for red cell removal, and leukocyte proteins were extracted with 0.5 mL of elution buffer. Western blot analysis of the purified extract indicated that more than 90% of hemoglobin was removed by the LeukoCatch and that the protein recovery rate of leukocytes was at least 4 times better than that of the conventional centrifugation method.

Conclusion
We conclude that LeukoCatch is useful not only for diagnosis at the bedside but also for basic research using blood samples or tissue culture cells.
Feasibility and acceptability of ACT for the community case management of malaria in urban settings in five African sites
Authors: Akweongo Patricia , Agyei-Baffour Peter , Sudhakar Morankar , Simwaka Bertha N , Konaté Amadou T , Adongo Philip B , Browne Edmund NL , Tegegn Ayalew , Ali Doreen , Traoré Abdoulaye , Amuyunzu-Nyamongo Mary , Pagnoni Franco , Barnish Guy 
Published: August 2011

Abstract

Background
The community case management of malaria (CCMm) is now an established route for distribution of artemisinin-based combination therapy (ACT) in rural areas, but the feasibility and acceptability of the approach through community medicine distributors (CMD) in urban areas has not been explored. It is estimated that in 15 years time 50% of the African population will live in urban areas and transmission of the malaria parasite occurs in these densely populated areas.

Methods
Pre- and post-implementation studies were conducted in five African cities: Ghana, Burkina Faso, Ethiopia and Malawi. CMDs were trained to educate caregivers, diagnose and treat malaria cases in < 5-year olds with ACT. Household surveys, focus group discussions and in-depth interviews were used to evaluate impact.

Results
Qualitative findings: In all sites, interviews revealed that caregivers' knowledge of malaria signs and symptoms improved after the intervention. Preference for CMDs as preferred providers for malaria increased in all sites.
Quantitative findings: 9001 children with an episode of fever were treated by 199 CMDs in the five study sites. Results from the CHWs registers show that of these, 6974 were treated with an ACT and 6933 (99%) were prescribed the correct dose for their age. Fifty-four percent of the 3,025 children for which information about the promptness of treatment was available were treated within 24 hours from the onset of symptoms.
From the household survey 3700 children were identified who had an episode of fever during the preceding two weeks. 1480 (40%) of them sought treatment from a CMD and 1213 of them (82%) had received an ACT. Of these, 1123 (92.6%) were administered the ACT for the correct number of doses and days; 773 of the 1118 (69.1%) children for which information about the promptness of treatment was available were treated within 24 hours from onset of symptoms, and 768 (68.7%) were treated promptly and correctly.

Conclusions
The concept of CCMm in an urban environment was positive, and caregivers were generally satisfied with the services. Quality of services delivered by CMDs and adherence by caregivers are similar to those seen in rural CCMm settings. The proportion of cases seen by CMDs, however, tended to be lower than was generally seen in rural CCMm. Urban CCMm is feasible, but it struggles against other sources of established healthcare providers. Innovation is required by everyone to make it viable.
Biodistribution and blood clearance of plasmid DNA administered in arginine peptide complexes
Authors: Woo Jung Gyu , Kim Na Young , Yang Jai Myung , Shin Sungho 
Published: August 2011

Abstract

Background
Peptide/DNA complexes have great potential as non-viral methods for gene delivery. Despite promising results for peptide-mediated gene delivery technology, an effective systemic peptide-based gene delivery system has not yet been developed.

Methods
This study used pCMV-Luc as a model gene to investigate the biodistribution and the in vivo efficacy of arginine peptide-mediated gene delivery by polymerase chain reaction (PCR).

Results
Plasmid DNA was detected in all organs tested 1 h after intraperitoneal administration of arginine/DNA complexes, indicating that the arginine/DNA complexes disseminated widely through the body. The plasmid was primarily detected in the spleen, kidney, and diaphragm 24 h post administration. The mRNA expression of plasmid DNA was noted in the spleen, kidney, and diaphragm for up to 2 weeks, and in the other major organs, for at least 1 week. Blood clearance studies showed that injected DNA was found in the blood as long as 6 h after injection.

Conclusions
Taken together, our results demonstrated that arginine/DNA complexes are stable in blood and are effective for in vivo gene delivery. These findings suggest that intraperitoneal administration of arginine/DNA complexes is a promising tool in gene therapy.
Optical properties of as-grown and annealed InAs quantum dots on InGaAs cross-hatch patterns
Authors: Himwas Chalermchai , Panyakeow Somsak , Kanjanachuchai Songphol 
Published: August 2011

AbstractInAs quantum dots (QDs) grown on InGaAs cross-hatch pattern (CHP) by molecular beam epitaxy are characterized by photoluminescence (PL) at 20 K. In contrast to QDs grown on flat GaAs substrates, those grown on CHPs exhibit rich optical features which comprise as many as five ground-state emissions from [1-10]- and [110]-aligned QDs, two wetting layers (WLs), and the CHP. When subject to in situ annealing at 700°C, the PL signals rapidly degrades due to the deterioration of the CHP which sets the upper limit of overgrowth temperature. Ex situ hydrogen annealing at a much lower temperature of 350°C, however, results in an overall PL intensity increase with a significant narrowing and a small blueshift of the high-energy WL emission due to hydrogen bonding which neutralizes defects and relieves associated strains.