bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unique DNA Methylation Loci Distinguish Anatomic Site and HPV Status in Head and Neck Squamous Cell Carcinoma
Authors: Lleras Roberto A. , Smith Richard V. , Adrien Leslie R. , Schlecht Nicolas F. , Burk Robert D. , Harris Thomas M. , Childs Geoffrey , Prystowsky Michael B. , Belbin Thomas J. 
Published: July 2013

Abstract
Purpose: We have used a genome-wide approach to identify novel differentially methylated CpG dinucleotides that are seen in different anatomic sites of head and neck squamous cell carcinoma (HNSCC), as well as those that might be related to HPV status in the oropharynx.
Experimental Design: We conducted genome-wide DNA methylation profiling of primary tumor samples and corresponding adjacent mucosa from 118 HNSCC patients undergoing treatment at Montefiore Medical Center, Bronx, NY, using the Illumina HumanMethylation27 beadchip. For each matched tissue set, we measured differentially methylated CpG loci using a change in methylation level (M-value).
Results: When datasets were individually analyzed by anatomic site of the primary tumor, we identified 293 differentially methylated CpG loci in oral cavity squamous cell carcinoma (SCC), 219 differentially methylated CpG loci in laryngeal SCC, and 460 differentially methylated in oropharyngeal SCC. A subset of these differentially methylated CpG loci was common across all anatomic sites of HNSCC. Stratification by HPV status revealed a significantly higher number of differentially methylated CpG loci in HPV+ patients.
Conclusion: Novel epigenetic biomarkers derived from clinical HNSCC specimens can be used as molecular classifiers of this disease, revealing many new avenues of investigation for this disease. Clin Cancer Res; 19(19); 5444–55. ©2013 AACR.
Onartuzumab (MetMAb): Using Nonclinical Pharmacokinetic and Concentration–Effect Data to Support Clinical Development
Authors: Xiang Hong , Bender Brendan C. , Reyes Arthur E. , Merchant Mark , Jumbe Nelson L. ‘Shasha’ , Romero Mally , Davancaze Teresa , Nijem Ihsan , Mai Elaine , Young Judy , Peterson Amy , Damico-Beyer Lisa A. 
Published: July 2013

Abstract
Purpose: We characterized the pharmacokinetics of onartuzumab (MetMAb) in animals and determined a concentration–effect relationship in tumor-bearing mice to enable estimation of clinical pharmacokinetics and target doses.
Experimental Design: A tumor growth inhibition model was used to estimate tumoristatic concentrations (TSC) in mice. Human pharmacokinetic parameters were projected from pharmacokinetics in cynomolgus monkeys by the species-invariant time method. Monte Carlo simulations predicted the percentage of patients achieving steady-state trough serum concentrations (Ctrough ss) ≥TSC for every 3-week (Q3W) dosing.
Results: Onartuzumab clearance (CL) in the linear dose range was 21.1 and 12.2 mL/d/kg in mice and cynomolgus monkeys with elimination half-life at 6.10 and 3.37 days, respectively. The estimated TSC in KP4 pancreatic xenograft tumor-bearing mice was 15 μg/mL. Projected CL for humans in the linear dose range was 5.74 to 9.36 mL/d/kg with scaling exponents of CL at 0.75 to 0.9. Monte Carlo simulations projected a Q3W dose of 10 to 30 mg/kg to achieve Ctrough ss of 15 μg/mL in 95% or more of patients.
Conclusions: Onartuzumab pharmacokinetics differed from typical bivalent glycosylated monoclonal antibodies with approximately 2-times faster CL in the linear dose range. Despite this higher CL, xenograft efficacy data supported dose flexibility with Q1W to Q3W dose regimens in the clinical setting with a TSC of 15 μg/mL as the Ctrough ss target. The projected human efficacious dose of 10 to 30 mg/kg Q3W should achieve the target TSC of 15 μg/mL. These data show effective pharmacokinetic/pharmacodynamic modeling to project doses to be tested in the clinic. Clin Cancer Res; 19(18); 5068–78. ©2013 AACR.
Formation of the Enhanced-V Infrared Cloud-Top Feature from High-Resolution Three-Dimensional Radar Observations
Authors: Homeyer Cameron R. 
Published: July 2013

Abstract
The responsible mechanism for the formation of the enhanced-V infrared cloud-top feature observed above tropopause-penetrating thunderstorms is not well understood. A new method for the combination of volumetric radar reflectivity from individual radars into three-dimensional composites with high vertical resolution (1 km) is introduced and used to test various formation mechanisms proposed in the literature. For analysis, a set of 89 enhanced-V storms over the eastern continental United States are identified in the 10-yr period from 2001 to 2010 using geostationary satellite data. The background atmospheric state from each storm is determined using the Interim ECMWF Re-Analysis (ERA-Interim) and radiosonde observations. In conjunction with the infrared temperature fields, analysis of the radar data in a coordinate relative to the location of the overshooting convective top and in altitudes relative to the tropopause suggests that above-anvil (stratospheric) cirrus clouds are the most likely mechanism for the formation of the enhanced V.
Shear at the Base of the Oceanic Mixed Layer Generated by Wind Shear Alignment
Authors: Brannigan Liam , Lenn Yueng-Djern , Rippeth Tom P. , McDonagh Elaine , Chereskin Teresa K. , Sprintall Janet 
Published: July 2013

AbstractObservations are used to evaluate a simple theoretical model for the generation of near-inertial shear spikes at the base of the open ocean mixed layer when the upper ocean displays a two-layer structure. The model predicts that large changes in shear squared can be produced by the alignment of the wind and shear vectors. A climatology of stratification and shear variance in Drake Passage is presented, which shows that these assumptions are most applicable to summer, fall, and spring but are not highly applicable to winter. Temperature, salinity, and velocity data from a high spatial resolution cruise in Drake Passage show that the model does not predict all large changes in shear variance; the model is most effective at predicting changes in shear squared when it arises owing to near-inertial wind-driven currents without requiring a rotating resonant wind stress. The model is also more effective where there is a uniform mixed layer above a strongly stratified transition layer. Rotary spectral and statistical analysis of an additional 242 Drake Passage transects from 1999 to 2011 confirmed the presence of this shear-spiking mechanism, particularly in summer, spring, and fall when stratification is stronger.
The Effects of Variations in Buffer Gas Mixing Ratios on Commercial Carbon Dioxide Cavity Ring-Down Spectroscopy Sensors
Authors: Long D. A. , Gameson L. , Truong G.-W. , Bielska K. , Cygan A. , Hodges J. T. , Whetstone J. R. , van Zee R. D. 
Published: July 2013

Abstract
Primary gas standards, gas chromatography, and frequency-stabilized cavity ring-down spectroscopy measurements have been used to assess the effect of variations in the argon mixing ratio on the CO2 mixing ratios reported by commercial cavity ring-down spectroscopy sensors. Supporting calculations demonstrate that the use of argon-free, synthetic air standards can lead to a bias of ≈0.7 μmol mol−1 at atmospheric concentration levels of CO2 as a result of pressure-broadening effects. This bias is an order of magnitude greater than the precision of the best commercial sensors and significantly exceeds the World Meteorological Organization's target compatibility goal.
Cytochrome P450-isoenzyme 1A1 in susceptibility to tobacco-related lung cancer
Authors: Sadeck Nabil El , Ibrahim Bedir M , Alassal Mohamed A 
Published: July 2013

Background Tobacco smoke contains many carcinogens that may mediate susceptibility to lung cancer. Cytochrome P450 isoenzyme 1A1 activity and expression increases several fold in lung cancer due to smoking. Finding the role of cytochrome P450 1A1 in susceptibility to tobacco-related lung cancer may be important to predict the outcome in early stage cancer, and may result in an improved survival rate. Patients and methods This study was carried on 2 groups of patients: group A was 20 patients with operable smoking-related lung cancer, who underwent surgery at the time of diagnosis; group B was 20 nonsmokers without lung cancer who underwent chest exploration following road traffic accidents. Specimens were obtained from tumor tissue and surrounding healthy tissue in group A patients, and from healthy lung tissue in group B patients. These specimens were sent for measurement of protein content and cytochrome P450 1A1 activity. Results There was significantly greater tissue cytochrome P450 1A1 activity in group A compared to group B. Patients with stage II cancer showed significantly higher levels of tissue cytochrome P450 1A1 activity than those with stage I. There was also a significant difference in tissue cytochrome P450 1A1 activity between the tumor tissue and the tissue surrounding the tumor. Conclusion Carcinogens in smoke increase cytochrome P450 1A1 activity, which might be considered to play a role in cigarette smoking-induced lung cancer.
Detection of prostate cancer in peripheral zone: comparison of MR diffusion tensor imaging, quantitative dynamic contrast-enhanced MRI, and the two techniques combined at 3.0 T
Authors: Li Chunmei , Chen Min , Li Saying , Zhao Xuna , Zhang Chen , Luo Xiaojie , Zhou Cheng 
Published: July 2013

Background Previous studies have shown that the diagnostic accuracy for prostate cancer improved with diffusion tensor imaging (DTI) or quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) only. However, the efficacy of combined DTI and quantitative DCE-MRI in detecting prostate cancer at 3.0 T is still indeterminate. Purpose To investigate the utility of diffusion tensor imaging (DTI), quantitative DCE-MRI, and the two techniques combined at 3.0 T in detecting prostate cancer of the peripheral zone (PZ). Material and Methods: DTI and DCE-MRI of 33 patients was acquired prior to prostate biopsy. Regions of interest (ROIs) were drawn according to biopsy zones which were apex, mid-gland, and base on each side of the PZ. Apparent diffusion coefficient (ADC), fractional anisotropy (FA), volume transfer constant (Ktrans), and rate constant (kep) values of cancerous sextants and non-cancerous sextants in PZ were calculated. Logistic regression models were generated for DTI, DCE-MRI, and DTI + DCE-MRI. Receiver-operating characteristic (ROC) curves were used to compare the ability of these models to differentiate cancerous sextants from non-cancerous sextants of PZ. Results There were significant differences in the ADC, FA, Ktrans, and kep values between cancerous sextants and non-cancerous sextants in PZ ( P < 0.0001, P < 0.0001, P < 0.0001, and P < 0.0001, respectively). The area under curve (AUC) for DTI + DCE-MRI was significantly greater than that for either DTI (0.93 vs. 0.86, P = 0.0017) or DCE-MRI (0.93 vs. 0.84, P = 0.0034) alone. Conclusion The combination of DTI and quantitative DCE-MRI has better diagnostic performance in detecting prostate cancer of the PZ than either technique alone.
Assessing Child Care Providers’ Knowledge and Attitudes Regarding Support of Breastfeeding in a Region with Low Breastfeeding Prevalence
Authors: Lucas Ashley , McMahon Pamela M. , Asling Marci Brewer , Knobloch Annette , Kosh Emily , Sims Kacie 
Published: July 2013

Background: Working mothers who place their infants into out-of-home child care face many challenges to sustaining breastfeeding. Child care providers, who are in frequent close contact with young families, may be potential resources for promoting breastfeeding. Objectives: This study focused on identifying child care providers’ attitudes toward and knowledge about breastfeeding as well as providers’ perceptions about strategies to increase breastfeeding rates among mothers of infants in child care centers. Methods: Seventy-five providers from 11 child care centers in the Baton Rouge, Louisiana, area were surveyed using paper and pencil questionnaires. Self-reported demographics, attitudes, knowledge, and perceptions about breastfeeding were collected. Results: Responses demonstrated a generally positive attitude toward breastfeeding among child care providers but a knowledge deficit in terms of the health impacts and proper handling of breast milk. A minority of providers reported that their center’s staff currently receives breastfeeding education, but most providers believed that measures to promote the use of breast milk in their center should target parents rather than the center staff. Conclusion: Child care providers need resources about the benefits of human milk, proper handling of expressed milk, and ways to make centers more breastfeeding friendly. Many providers feel ineffective in supporting breastfeeding and are unaware of the role they may play in mothers’ infant feeding decisions. Though child care providers do not appear to believe they can influence parents’ decisions about breastfeeding, educating and empowering them could play an important role in increasing breastfeeding rates.
Acute hydrofluoric acid exposure reported to Taiwan Poison Control Center, 1991–2010
Authors: Wu M-L , Yang C-C , Ger J , Tsai W-J , Deng J-F 
Published: July 2013

Background: Hydrofluoric acid (HF) is a dangerous chemical that can cause severe cutaneous burns as well as possible systemic toxicity. Methods: We retrospectively analyzed all human HF exposure cases reported to the National Poison Control Center of Taiwan between 1991 and 2010. Results: In this 20-year survey, 324 calls were identified, with a majority of dermal exposure (84%). Occupational exposure accounted for 80% of all cases, with workers in semiconductor industry (61%), cleaning industry (15%), chemical or metal industry (13%), and other industries (11%). Electrolyte imbalances were uncommon, hypocalcemia, hypomagnesemia, and hypokalemia were recorded in 8.6%, 1.2%, and 1.5% of all cases, respectively. Most cases (64%) of dermal exposure received antidotal treatment. Treatment modalities of dermal exposure included calcium gluconate soaking, 49.8%; intravenous calcium, 20.6%; and topical use of calcium gluconate gel, 13.9%. Twenty patients (7%) received surgery. Following HF exposure, the majority of patients presented with mild (56.5%) or moderate (36.7%) toxic effects. However, four patients were severely intoxicated; two patients died of HF-related dysrhythmia and shock. Conclusions: Significant symptomology may occur following HF exposure, and most of the HF exposure required hospitals evaluation. Calcium gluconate soaks appear to be effective in reducing local pain and tissue damage. Hyperkalemia should not be overemphasized as a common finding in HF exposure, hypokalemia tends to occur in cases of severe HF poisoning.
‘You have to be mindful of whose story it is’: The challenges of undertaking life story work with people with dementia and their family carers
Authors: McKeown Jane , Ryan Tony , Ingleton Christine , Clarke Amanda 
Published: July 2013

Introduction Life story work is increasingly being used with people with dementia; this work offers a critical appraisal of some challenges that may be faced in practice. Design and methods An in-depth case study analysis was undertaken to understand the experiences of people with dementia, family carers and care staff in using life story work in an NHS Mental Health and Social Care Trust. Data collection included semi-structured interviews, observation, conversations and field notes. Findings Private memories were sometimes recalled by the person with dementia that were not for inclusion in any written product; enabling the person with dementia to tell their own life story could be a challenge; quality of the life story books was variable and; at times, life story work may be overused with the person with dementia. Conclusion Services should not be deterred from undertaking life story work with people with dementia, but there is a need to adopt a planned approach to its implementation that includes facilitation, education and supervision.
Hif-2α is not essential for cell-autonomous hematopoietic stem cell maintenance
Authors: Guitart Amelie V. , Subramani Chithra , Armesilla-Diaz Alejandro , Smith Gillian , Sepulveda Catarina , Gezer Deniz , Vukovic Milica , Dunn Karen , Pollard Patrick , Holyoake Tessa L. , Enver Tariq , Ratcliffe Peter J. , Kranc Kamil R. 
Published: July 2013

Key Points
Hif-2α–dependent signaling is dispensable for steady-state multilineage hematopoiesis. Hif-2α is not essential for HSC self-renewal.
Both a traditional and modified Daniel Fast improve the cardio-metabolic profile in men and women
Authors: Alleman Rick J. , Harvey Innocence C. , Farney Tyler M. , Bloomer Richard J. 
Published: July 2013

Abstract

Background
The Daniel Fast involves dietary modification similar to a purified vegan diet. Although improvements in several health-specific biomarkers have been noted with this plan, the removal of animal products results in a significant reduction in both dietary protein and saturated fatty acid intake, which results in a loss of lean body mass and a reduction in HDL-cholesterol.

Methods
We assigned 29 men and women to either a traditional or modified Daniel Fast for 21 days and measured anthropometric and biochemical markers of health pre and post intervention. The modified Daniel Fast was otherwise identical to the traditional plan but included one serving per day of lean meat and dairy (skim milk), providing approximately 30 grams per day of additional protein.

Results
Compared to baseline, both plans resulted in similar and significant improvements in blood lipids, as well as a reduction in inflammation.

Conclusions
Modification of dietary intake in accordance with either a traditional or modified Daniel Fast may improve risk factors for cardiovascular and metabolic disease.
Autologous transplantation of adipose-derived stromal cells ameliorates ventilator-induced lung injury in rats
Authors: Liang Zuo Di , Yin Xiu Ru , Cai Da Sheng , Zhou Heng , Pei Ling 
Published: July 2013

Abstract

Background
Adipose-derived stromal cells (ADSCs) are a good alternative to multipotent stem cells for regenerative medicine. Low tidal volume (LVT) has proved to be an effective ventilation strategy. However, it is not known if ADSCs and LVT can protect against ventilator-induced lung injury (VILI). This study was aimed to determine the potential of ADSCs and LVT to repair following VILI and to elucidate the mechanisms responsible for this section.

Methods
A total of 72 rats were randomly assigned into group I (sham group, n = 18), group II (1 h of high tidal volume-ventilated (HVT) 40 mL/kg to peak airway pressures of approximately 35 cm H2O and 100% oxygen, n = 18), group III (1 h of HVT followed by 6 h LVT 6 mL/kg to peak airway pressures of approximately 6 cm H2O and 100% oxygen, n = 18) and group IV (1 h of HVT followed by intravenous injection of 5 × 106 ADSCs, n = 18). All animals were sacrificed 7 after the experiments lasted for 7 hours. Bronchoalveolar lavage fluid (BALF) was collected and lungs were harvested for analysis.

Results
High tidal volume-ventilated (HVT) rats exhibited typical VILI features compared with sham rats. Lung edema, histological lung injury index, concentrations of total protein, total cell counts, number of neutrophils in bronchoalveolar lavage fluid (BALF), tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-10 and transforming growth factor-β1 in BALF were significantly increased in HVT rats. Additionally, gene and protein levels of Na+ channel subunits, Na-K-ATPase pump activity and alveolar fluid clearance were significantly decreased in HVT rats. All these indices of VILI were significantly improved in rats treated with ADSCs. However, compared with ADSCs treatment, LVT strategy had little therapeutic effect in the present study.

Conclusion
These results may provide valuable insights into the effects of ADSCs in acute lung injury.
New players in the same old game: a system level in silico study to predict type III secretion system and effector proteins in bacterial genomes reveals common themes in T3SS mediated pathogenesis
Authors: Sadarangani Vineet , Datta Sunando , Arunachalam Manonmani 
Published: July 2013

Abstract

Background
Type III secretion system (T3SS) plays an important role in virulence or symbiosis of many pathogenic or symbiotic bacteria [CHM 2:291–294, 2007; Physiology (Bethesda) 20:326–339, 2005]. T3SS acts like a tunnel between a bacterium and its host through which the bacterium injects ‘effector’ proteins into the latter [Nature 444:567–573, 2006; COSB 18:258–266, 2008]. The effectors spatially and temporally modify the host signalling pathways [FEMS Microbiol Rev 35:1100–1125, 2011; Cell Host Microbe5:571–579, 2009]. In spite its crucial role in host-pathogen interaction, the study of T3SS and the associated effectors has been limited to a few bacteria [Cell Microbiol 13:1858–1869, 2011; Nat Rev Microbiol 6:11–16, 2008; Mol Microbiol 80:1420–1438, 2011]. Before one set out to perform systematic experimental studies on an unknown set of bacteria it would be beneficial to identify the potential candidates by developing an in silico screening algorithm. A system level study would also be advantageous over traditional laboratory methods to extract an overriding theme for host-pathogen interaction, if any, from the vast resources of data generated by sequencing multiple bacterial genomes.

Results
We have developed an in silico protocol in which the most conserved set of T3SS proteins was used as the query against the entire bacterial database with increasingly stringent search parameters. It enabled us to identify several uncharacterized T3SS positive bacteria. We adopted a similar strategy to predict the presence of the already known effectors in the newly identified T3SS positive bacteria. The huge resources of biochemical data [FEMS Microbiol Rev 35:1100–1125, 2011; Cell Host Microbe 5:571–579, 2009; BMC Bioinformatics 7(11):S4, 2010] on the T3SS effectors enabled us to search for the common theme in T3SS mediated pathogenesis. We identified few cellular signalling networks in the host, which are manipulated by most of the T3SS containing pathogens. We went on to look for correlation, if any, between the biological quirks of a particular class of bacteria with the effectors they harbour. We could pin point few effectors, which were enriched in certain classes of bacteria.

Conclusion
The current study would open up new avenues to explore many uncharacterized T3SS positive bacteria. The experimental validation of the predictions from this study will unravel a generalized mechanism for T3SS positive bacterial infection into host cell.
Engineered Pichia pastoris for enhanced production of S-adenosylmethionine
Authors: Kamarthapu Venu , Ragampeta Srinivas , Rao Khareedu Venkateswara , Reddy Vudem Dashavantha 
Published: July 2013

Abstract
A genetically engineered strain of Pichia pastoris expressing S-adenosylmethionine synthetase gene from Saccharomyces cerevisiae under the control of AOX 1 promoter was developed. Induction of recombinant strain with 1% methanol resulted in the expression of SAM2 protein of ~ 42 kDa, whereas control GS115 showed no such band. Further, the recombinant strain showed 17-fold higher enzyme activity over control. Shake flask cultivation of engineered P. pastoris in BMGY medium supplemented with 1% L-methionine yielded 28 g/L wet cell weight and 0.6 g/L S-adenosylmethionine, whereas control (transformants with vector alone) with similar wet cell weight under identical conditions accumulated 0.018 g/L. The clone cultured in the bioreactor containing enriched methionine medium showed increased WCW (117 g/L) as compared to shake flask cultures and yielded 2.4 g/L S-adenosylmethionine. In spite of expression of SAM 2 gene up to 90 h, S-adenosylmethionine accumulation tended to plateau after 72 h, presumably because of the limited ATP available in the cells at stationery phase. The recombinant P pastoris seems promising as potential source for industrial production of S-adenosylmethionine.