bluuebunny/crossref_metadata_2025_split huggingface dataset:
Akt Promotes Post-Irradiation Survival of Human Tumor Cells through Initiation, Progression, and Termination of DNA-PKcs–Dependent DNA Double-Strand Break Repair
Authors: Toulany Mahmoud , Lee Kyung-Jong , Fattah Kazi R. , Lin Yu-Fen , Fehrenbacher Brigit , Schaller Martin , Chen Benjamin P. , Chen David J. , Rodemann H. Peter 
Published: May 2012

Abstract
Akt phosphorylation has previously been described to be involved in mediating DNA damage repair through the nonhomologous end-joining (NHEJ) repair pathway. Yet the mechanism how Akt stimulates DNA-protein kinase catalytic subunit (DNA-PKcs)-dependent DNA double-strand break (DNA-DSB) repair has not been described so far. In the present study, we investigated the mechanism by which Akt can interact with DNA-PKcs and promote its function during the NHEJ repair process. The results obtained indicate a prominent role of Akt, especially Akt1 in the regulation of NHEJ mechanism for DNA-DSB repair. As shown by pull-down assay of DNA-PKcs, Akt1 through its C-terminal domain interacts with DNA-PKcs. After exposure of cells to ionizing radiation (IR), Akt1 and DNA-PKcs form a functional complex in a first initiating step of DNA-DSB repair. Thereafter, Akt plays a pivotal role in the recruitment of AKT1/DNA-PKcs complex to DNA duplex ends marked by Ku dimers. Moreover, in the formed complex, Akt1 promotes DNA-PKcs kinase activity, which is the necessary step for progression of DNA-DSB repair. Akt1-dependent DNA-PKcs kinase activity stimulates autophosphorylation of DNA-PKcs at S2056 that is needed for efficient DNA-DSB repair and the release of DNA-PKcs from the damage site. Thus, targeting of Akt results in radiosensitization of DNA-PKcs and Ku80 expressing, but not of cells deficient for, either of these proteins. The data showed indicate for the first time that Akt through an immediate complex formation with DNA-PKcs can stimulate the accumulation of DNA-PKcs at DNA-DSBs and promote DNA-PKcs activity for efficient NHEJ DNA-DSB repair. Mol Cancer Res; 10(7); 945–57. ©2012 AACR.
Prevalence of Kawasaki Disease in Young Adults With Suspected Myocardial Ischemia
Authors: Daniels Lori B. , Tjajadi Matthew S. , Walford Hannah H. , Jimenez-Fernandez Susan , Trofimenko Vera , Fick Daryl B. , Phan Hoang-Anh L. , Linz Peter E. , Nayak Keshav , Kahn Andrew M. , Burns Jane C. , Gordon John B. 
Published: May 2012

Background—
Up to 25% of patients with untreated Kawasaki disease (KD) and 5% of those treated with intravenous immunoglobulin will develop coronary artery aneurysms. Persistent aneurysms may remain silent until later in life when myocardial ischemia can occur. We sought to determine the prevalence of coronary artery aneurysms suggesting a history of KD among young adults undergoing coronary angiography for evaluation of possible myocardial ischemia.

Methods and Results—
We reviewed the medical histories and coronary angiograms of all adults <40 years of age who underwent coronary angiography for evaluation of suspected myocardial ischemia at 4 San Diego hospitals from 2005 to 2009 (n=261). History of KD-compatible illness and cardiac risk factors were obtained by medical record review. Angiograms were independently reviewed for the presence, size, and location of aneurysms and coronary artery disease by 2 cardiologists blinded to the history. Patients were evaluated for number of risk factors, angiographic appearance of their coronary arteries, and known history of KD. Of the 261 young adults who underwent angiography, 16 had coronary aneurysms. After all clinical criteria were assessed, 5.0% had aneurysms definitely (n=4) or presumed (n=9) secondary to KD as the cause of their coronary disease.

Conclusions—
Coronary sequelae of KD are present in 5% of young adults evaluated by angiography for myocardial ischemia. Cardiologists should be aware of this special subset of patients who may benefit from medical and invasive management strategies that differ from the strategies used to treat atherosclerotic coronary artery disease.
The Leading Pattern of Intraseasonal and Interannual Indian Ocean Precipitation Variability and Its Relationship with Asian Circulation during the Boreal Cold Season
Authors: Hoell Andrew , Barlow Mathew , Saini Roop 
Published: May 2012

The leading pattern of precipitation for the Indian Ocean, one of the most intense areas of rainfall on the globe, is calculated for November–April 1979–2008. The associated regional circulation and thermodynamic forcing of precipitation over Asia are examined at both intraseasonal and interannual time scales. The leading pattern is determined using both empirical orthogonal function analysis of monthly precipitation data and a closely related index of daily outgoing longwave radiation filtered into intraseasonal (33–105 days) and interannual (greater than 105 days) components. The leading pattern has a maximum in the tropical eastern Indian Ocean, and is closely associated with the Madden–Julian oscillation at intraseasonal time scales and related to the El Niño–Southern Oscillation at interannual time scales. Both time scales are associated with baroclinic Gill–Matsuno-like circulation responses extending over southern Asia, but the interannual component also has a strong equivalent barotropic circulation. Thermodynamically, both time scales are associated with cold temperature advection and subsidence over southwest Asia, with advection of the mean temperature by the anomalous wind more important at lower and midlevels and advection of the anomalous temperature by the mean wind more important at upper levels. For individual months, the intraseasonal variability can overwhelm the interannual variability. Enhanced Indian Ocean convection persisted for almost the entire 2007/08 season in association with severe drought over southwest Asia, but a strong intraseasonal signal in January 2008 reversed the pattern, resulting in damaging floods in the midst of drought.
Molecular Basis of Tobacco‐Induced Bacterial Biofilms
Authors: Antunes Marcelo B. , Chi John J. , Liu Zhi , Goldstein‐Daruech Natalia , Palmer James N. , Zhu Jun , Cohen Noam A. 
Published: May 2012

ObjectiveTo evaluate changes in the expression of biofilm‐related genes when exposed to tobacco smoke and oxidative stress.Study DesignExperimental, in vitro.SettingLaboratories of Rhinology and Microbiology, University of Pennsylvania.Subjects and MethodsBacterial biofilm mass was measured using crystal violet staining and measurement of the optical density. Biofilm‐related genes of the Pseudomonas aeruginosa PAO1 strain (pilF, flgK, lasI, lasB, rhlA, and algC) were studied following repetitive exposure to exogenous tobacco smoke and hydrogen peroxide. This was done using a reporter plasmid.ResultsAfter 1 exposure to smoke, there was no change in biofilm formation. However, after 2 and 3 exposures, the biofilm formed had an increased mass (P <. 05). With respect to oxidative stress in the form of H2O2, bacterial cultures demonstrated a dose‐ and time‐dependent induction of biofilm formation compared with control conditions. Gene expression following repetitive smoke exposure demonstrated an increase in expression of pilF, flgK, algC, and lasI genes (P <. 05); a decrease in rhlA (P <. 05); and no significant change in the lasB gene (P = 0.1). Gene expression following H2O2 exposure demonstrated an increase in pilF (P <. 05), whereas the other genes failed to demonstrate a statistical change.ConclusionsRepetitive tobacco smoke exposure leads to molecular changes in biofilm‐related genes, and exposure to oxidative stress in the form of H2O2 induces biofilm growth in PAO1. This could represent adaptative changes due to oxidative stress or chemically mediated through any of the several chemicals encountered in tobacco smoke and may explain increased biofilm formation in microbes isolated from smokers.
Culture of Human Septal Chondrocytes in a Rotary Bioreactor
Authors: Reuther Marsha S. , Wong Van W. , Briggs Kristen K. , Chang Angela A. , Nguyen Quynhhoa T. , Schumacher Barbara L. , Masuda Koichi , Sah Robert L. , Watson Deborah 
Published: May 2012

Objectives(1) To show that extracellular matrix deposition in 3‐dimensional culture of human septal chondrocytes cultured in a rotary bioreactor is comparable to the deposition achieved under static culture conditions. (2) To demonstrate that the biomechanical properties of human septal chondrocytes cultured in a bioreactor are enhanced with time and are analogous to beads cultured under static culture.Study DesignProspective, basic science.SettingResearch laboratory.MethodsHuman septal chondrocytes from 9 donors were expanded in monolayer and seeded in alginate beads. The beads were cultured in a rotary bioreactor for 21 days in media supplemented with growth factors and human serum, using static culture as the control. Biochemical and biomechanical properties of the beads were measured.ResultsGlycosaminoglycan (GAG) accumulation significantly increased during 2 measured time intervals, 0 to 21 days and 10 to 21 days (P <. 01). No significant difference was seen between the static and bioreactor conditions. Substantial type II collagen production was demonstrated in the beads terminated at day 21 of culture in both conditions. In addition, the biomechanical properties of the beads were significantly improved at 21 days in comparison to beads from day 0.ConclusionHuman septal chondrocytes cultured in alginate beads exhibit significant matrix deposition and improved biomechanical properties after 21 days. Alginate bead diameter and stiffness positively correlated with GAG and type II collagen accretion. Matrix production in beads is supported by the use of a rotary bioreactor.
Development, Implementation, and Evaluation of an Institutional Daily Awakening and Spontaneous Breathing Trial Protocol
Authors: Kher Sucharita , Roberts Russel J. , Garpestad Erik , Kunkel Chris , Howard William , Didominico Dorothy , Fergusson Anne , Devlin John W. 
Published: May 2012

Introduction: While one controlled trial found that a daily awakening and spontaneous breathing trial (DA-SBT) decreases time on mechanical ventilation (MV), there is a paucity of real-world data surrounding the development, implementation, and impact of DA-SBT protocols. We describe a multidisciplinary process improvement effort in 2, 10-bed medical intensive care units (MICUs) at a 330-bed academic medical center that focused on the development, implementation, and evaluation of a new DA-SBT protocol. Methods: A DA-SBT protocol, developed using results from a nursing survey literature and available institutional resources, was implemented after extensive clinician education and institution of quality reminders to boost use. Postprotocol compliance was evaluated. Use of sedation, DA and SBT practices, and clinical outcomes were retrospectively compared between the before and after DA-SBT protocol groups (ie, consecutive MICU patients requiring a continuously infused sedative [CIS] ≥24 hours). Results: In the after group (n = 32), the DA and SBT compliances were 44% and 84%, respectively. Compared with the before group (n = 33), after group patients received CIS on fewer days of MV (100% vs 67%, P = .003) and had their CIS down-titrated by ≥25% on more days of CIS (40% vs 71%, P = .006). Neither total CIS dose ( P = .49), total MV days ( P = .75), days of MV where a SBT occurred ( P = .38), nor episodes of self-extubation (15% vs 6%, P = .43) differed between the 2 groups. Conclusion: Despite the implementation of a DA-SBT protocol that was individualized to clinician preferences and institutional resources and accompanied by substantial education and reminders for use, compliance to the DA component of this protocol was low and duration of MV remained unchanged. Additional quality improvement strategies are needed to overcome barriers to DA-SBT protocol use that may not exist in controlled clinical trials.
Process modelling for contingency tables with ordered categories
Authors: Heaton Matthew J , Gray Simone C , Gelfand Alan E 
Published: May 2012

We consider the setting of a multi-way contingency table with ordinal classifications. The contribution of this paper is to propose a joint probability model for the uncensored variables that is apart from the imposed categorization. Specifically, for an m-way table, we assume that the cell counts arise as a binned point pattern over a bounded set in m-dimensional Euclidean space where the point pattern is a realization of a non-homogeneous Poisson process. The intensity which drives the point pattern is itself viewed as a realization of a log Gaussian process over the set. With such an approach we achieve full inference regarding the underlying joint distribution, in particular, inference for familiar associations between the ordinal variables in the absence of interval censoring. Additionally, inference can be provided for any newly created cells where such creation is achieved through redefinition of the ordinal classifications. That is, rather than ad hoc reallocation, we achieve a fully model-based reallocation enabling quantification of uncertainty. For a contingency table with nominal classifications as well, our approach creates an intensity for the ordinal variables for each level of the nominal variables. The methodology is detailed within a hierarchical framework, showing associated computation and convenient dimension reduction techniques to facilitate model fitting. We illustrate with both simulated data and a real census dataset.
WHIM syndrome caused by a single amino acid substitution in the carboxy-tail of chemokine receptor CXCR4
Authors: Liu Qian , Chen Haoqian , Ojode Teresa , Gao Xiangxi , Anaya-O'Brien Sandra , Turner Nicholas A. , Ulrick Jean , DeCastro Rosamma , Kelly Corin , Cardones Adela R. , Gold Stuart H. , Hwang Eugene I. , Wechsler Daniel S. , Malech Harry L. , Murphy Philip M. , McDermott David H. 
Published: May 2012

AbstractWHIM syndrome is a rare, autosomal dominant, immunodeficiency disorder so-named because it is characterized by warts, hypogammaglobulinemia, infections, and myelokathexis (defective neutrophil egress from the BM). Gain-of-function mutations that truncate the C-terminus of the chemokine receptor CXCR4 by 10-19 amino acids cause WHIM syndrome. We have identified a family with autosomal dominant inheritance of WHIM syndrome that is caused by a missense mutation in CXCR4, E343K (1027G → A). This mutation is also located in the C-terminal domain, a region responsible for negative regulation of the receptor. Accordingly, like CXCR4R334X, the most common truncation mutation in WHIM syndrome, CXCR4E343K mediated approximately 2-fold increased signaling in calcium flux and chemotaxis assays relative to wild-type CXCR4; however, CXCR4E343K had a reduced effect on blocking normal receptor down-regulation from the cell surface. Therefore, in addition to truncating mutations in the C-terminal domain of CXCR4, WHIM syndrome may be caused by a single charge-changing amino acid substitution in this domain, E343K, that results in increased receptor signaling.
Bronchoalveolar lavage neuregulin-1 is elevated in acute lung injury and correlates with inflammation
Authors: Finigan James H. , Mishra Rangnath , Vasu Vihas T. , Silveira Lori J. , Nethery David E. , Standiford Theodore J. , Burnham Ellen L. , Moss Marc , Kern Jeffrey A. 
Published: May 2012

Shedding of neuregulin (NRG)-1 from the pulmonary epithelium leads to activation of the epithelial human epidermal growth factor receptor (HER)2 receptor, increased pulmonary epithelial permeability and acute lung injury (ALI). We sought to determine whether NRG-1 was detectable and elevated in bronchoalveolar lavage (BAL) and plasma from patients with ALI compared with controls and to determine whether a correlation exists between NRG-1 and inflammation and outcome in ALI.Matched BAL and plasma samples were obtained from 23 ALI patients requiring intubation and mechanical ventilation. Control patients (n=5) included healthy volunteers. NRG-1 and indices of inflammation were measured in BAL and plasmaviaELISA.The mean±sdBAL NRG-1 concentration in ALI patients was 187.0±21.35 pg·mL−1compared with 85.50±9.2 pg·mL−1in controls (p=0.001). Increased BAL NRG-1 was associated with markers of inflammation, and inversely correlated with ventilator-free days (VFDs; r= -0.51, p=0.015). Plasma NRG-1 was elevated in ALI patients compared with controls (611.7±354.2versus25.17±19.33 pg·mL−1, p<0.001) and inversely correlated with VFDs (r= -0.51, p=0.04).These results confirm shedding of NRG-1 in ALI and suggest that the NRG-1–HER2 pathway is active in patients with ALI.
Targeted hypoglossal neurostimulation for obstructive sleep apnoea: a 1-year pilot study
Authors: Mwenge Gimbada B. , Rombaux Philippe , Dury Myriam , Lengelé Benoît , Rodenstein Daniel 
Published: May 2012

Continuous positive airway pressure (CPAP) is an effective but cumbersome treatment for obstructive sleep apnoea (OSA). Noncompliant patients need alternative therapies.We studied a tongue neurostimulation approach: targeted hypoglossal neurostimulation (THN) therapy with the aura6000™ System. A multi-contact electrode positioned around the main trunk of the twelfth nerve connected to an implanted pulse generator stimulates segments of the nerve, activating dilator muscles. The primary objective was to improve the polysomnographically determined apnoea/hypopnoea index (AHI) at 3 months, and maintain the improvement after 12 months of treatment. 13 out of 14 operated patients were successfully implanted.At 12 months, the AHI decreased from 45±18 to 21±17, a 53% reduction (p<0.001). The 4% oxygen desaturation index fell from 29±20 to 15±16 and the arousal index from 37±13 to 25±14, both p<0.001. The Epworth sleepiness scale decreased from 11±7 to 8±4 (p=0.09). THN was neither painful nor awakened patients, who all complied with therapy. There were two transient tongue paresis.The present study represents the longest study of any hypoglossal neurostimulation reported to date. We conclude that THN is safe and effective to treat OSA in patients not compliant with CPAP.
A new double-tracer gas single-breath washout to assess early cystic fibrosis lung disease
Authors: Singer Florian , Stern Georgette , Thamrin Cindy , Abbas Chiara , Casaulta Carmen , Frey Urs , Latzin Philipp 
Published: May 2012

In cystic fibrosis (CF), tests for ventilation inhomogeneity are sensitive but not established for clinical routine. We assessed feasibility of a new double-tracer gas single-breath washout (SBW) in school-aged children with CF and control subjects, and compared SBW between groups and with multiple-breath nitrogen washout (MBNW).Three SBW and MBNW were performed in 118 children (66 with CF) using a side-stream ultrasonic flowmeter setup. The double-tracer gas containing 5% sulfur hexafluoride and 26.3% helium was applied during one tidal breath. Outcomes were SBW phase III slope (SIIIDTG), MBNW-derived lung clearance index (LCI), and indices of acinar (Sacin) and conductive (Scond) ventilation inhomogeneity.SBW took significantly less time to perform than MBNW. SBW and MBNW were feasible in 109 (92.4%) and 98 (83.0%) children, respectively. SIIIDTGdiffered between children with CF and controls, mean±sdwas -456.7±492.8 and -88.4±129.1 mg·mol·L−1, respectively. Abnormal SIIIDTGwas present in 36 (59%) children with CF. SIIIDTGwas associated with LCI (r= -0.58) andSacin(r= -0.58), but not withScond.In CF, steeply sloping SIIIDTGpotentially reflects ventilation inhomogeneity near the acinus entrance. This tidal SBW is a promising test to assess ventilation inhomogeneity in an easy and fast way.
Clinical characteristics and corticosteroid treatment of acute eosinophilic pneumonia
Authors: Rhee Chin Kook , Min Kyung Hoon , Yim Nam Yeol , Lee Ji Eun , Lee Na Rae , Chung Man Pyo , Jeon Kyeongman 
Published: May 2012

The clinical characteristics and optimal duration of corticosteroid treatment for acute eosinophilic pneumonia (AEP) have not been fully evaluated. This was a retrospective study of prospectively collected data from 137 patients with AEP, treated with standardised protocol, to clarify the clinical characteristics and compare the efficacies of 2 weeks
versus
4 weeks of corticosteroid treatment for AEP.
The majority of the patients altered their smoking habits within a median (interquartile range) of 17 (13-26) days prior to development of AEP. 80 (58%) patients presented with acute respiratory failure. A total of 127 (92%) patients were treated with corticosteroids: 4 weeks, n=42; 2 weeks, n=85. Major symptoms were resolved in 3 days and the severity of respiratory failure was inversely correlated with clinical outcomes. After adjusting for differences in baseline characteristics between the groups, the differences in adjusted mean (95% confidence interval) for resolution of dyspnoea and disappearance of all symptoms were 0.57 (-0.71-1.86) and -0.04 (-1.91-1.83) days, respectively. The difference in adjusted proportion of resolution of radiological abnormalities was 6.92% (-8.19-22.02).
In conclusion, the duration of corticosteroid treatment could be shortened to 2 weeks, even in patients with respiratory failure.
Genetic divergence and the genetic architecture of complex traits in chromosome substitution strains of mice
Authors: Spiezio Sabrina H , Takada Toyoyuki , Shiroishi Toshihiko , Nadeau Joseph H 
Published: May 2012

Abstract

Background
The genetic architecture of complex traits strongly influences the consequences of inherited mutations, genetic engineering, environmental and genetic perturbations, and natural and artificial selection. But because most studies are under-powered, the picture of complex traits is often incomplete. Chromosome substitution strains (CSSs) are a unique paradigm for these genome surveys because they enable statistically independent, powerful tests for the phenotypic effects of each chromosome on a uniform inbred genetic background. A previous CSS survey in mice and rats revealed many complex trait genes (QTLs), large phenotypic effects, extensive epistasis, as well as systems properties such as strongly directional phenotypic changes and genetically-determined limits on the range of phenotypic variation. However, the unusually close genetic relation between the CSS progenitor strains in that study raised questions about the impact of genetic divergence: would greater divergence between progenitor strains, with the corresponding changes in gene regulation and protein function, lead to significantly more distinctive phenotypic features, or alternatively would epistasis and systems constraints, which are pervasive in CSSs, limit the range of phenotypic variation regardless of the extent of DNA sequence variation?

Results
We analyzed results for an extensive survey of traits in two new panels of CSSs where the donor strains were derived from inbred strains with more distant origins and discovered a strong similarity in genetic and systems properties among the three CSS panels, regardless of divergence time.

Conclusion
Our results argue that DNA sequence differences between host and donor strains did not substantially affect the architecture of complex traits, and suggest instead that strong epistasis buffered the phenotypic effects of genetic divergence, thereby constraining the range of phenotypic variation.