bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interrupting Biosynthesis of O Antigen or the Lipopolysaccharide Core Produces Morphological Defects in Escherichia coli by Sequestering Undecaprenyl Phosphate
Authors: Jorgenson Matthew A. , Young Kevin D. 
Published: August 2016

ABSTRACT

Undecaprenyl phosphate (Und-P) is a member of the family of essential polyprenyl phosphate lipid carriers and in the Gram-negative bacterium
Escherichia coli
is required for synthesizing the peptidoglycan (PG) cell wall, enterobacterial common antigen (ECA), O antigen, and colanic acid. Previously, we found that interruption of ECA biosynthesis indirectly alters PG synthesis by sequestering Und-P via dead-end intermediates, causing morphological defects. To determine if competition for Und-P was a more general phenomenon, we determined if O-antigen intermediates caused similar effects. Indeed, disrupting the synthesis of O antigen or the lipopolysaccharide core oligosaccharide induced cell shape deformities, which were suppressed by preventing the initiation of O-antigen biosynthesis or by manipulating Und-P metabolism. We conclude that accumulation of O-antigen intermediates alters PG synthesis by sequestering Und-P. Importantly, many previous experiments addressed the physiological functions of various oligosaccharides and glycoconjugates, but these studies employed mutants that accumulate deleterious intermediates. Thus, conclusions based on these experiments must be reevaluated to account for possible indirect effects of Und-P sequestration.

IMPORTANCE
Bacteria use long-chain isoprenoids like undecaprenyl phosphate (Und-P) as lipid carriers to assemble numerous glycan polymers that comprise the cell envelope. In any one bacterium, multiple oligosaccharide biosynthetic pathways compete for a common pool of Und-P, which means that disruptions in one pathway may produce secondary consequences that affect the others. Using the Gram-negative bacterium
Escherichia coli
as a model, we demonstrate that interruption of the biogenesis of O antigen, a major outer membrane component, indirectly impairs peptidoglycan synthesis by sequestering Und-P into dead-end intermediates. These results strongly argue that the functions of many Und-P-utilizing pathways must be reevaluated, because much of our current understanding is based on experiments that did not control for these unintended secondary effects.
Growth and nutrition in children with ataxia telangiectasia
Authors: Stewart Emma , Prayle Andrew P , Tooke Alison , Pasalodos Sara , Suri Mohnish , Bush Andy , Bhatt Jayesh M 
Published: August 2016

BackgroundAtaxia telangiectasia (A-T) is a rare multisystem disease with high early mortality from lung disease and cancer. Nutritional failure adversely impacts outcomes in many respiratory diseases. Several factors influence nutrition in children with A-T. We hypothesised that children with A-T have progressive growth failure and that early gastrostomy tube feeding (percutaneous endoscopic gastrostomy, PEG) is a favourable management option with good nutritional outcomes.MethodsData were collected prospectively on weight, height and body mass index (BMI) at the national paediatric A-T clinic. Adequacy and safety of oral intake was assessed. Nutritional advice was given at each multidisciplinary review.Results101 children (51 girls) had 222 measurements (32 once, 32 twice, 24 thrice) between 2009 and 2016. Median (IQR) age was 9.3 (6.4 to 13.1) years. Mean (SD) weight, height and BMI Z-scores were respectively −1 (1.6), −1.2 (1.2) and −0.4 (1.4). 35/101 children had weight Z-scores below −2 on at least one occasion. Weight, height and BMI Z-scores declined over time. Decline was most obvious after 8 years of age. 14/101 (14%) children had a PEG, with longitudinal data available for 12. In a nested case control study, there was a trend for improvement in weight in those with a PEG (p=0.10).ConclusionsPatients with A-T decline in growth over time. There is an urgent need for new strategies, including an understanding of why growth falters. We suggest early proactive consideration of PEG from age 8 years onwards to prevent progressive growth failure.
Establishment of Patient-Derived Tumor Xenograft Models of Epithelial Ovarian Cancer for Preclinical Evaluation of Novel Therapeutics
Authors: Liu Joyce F. , Palakurthi Sangeetha , Zeng Qing , Zhou Shan , Ivanova Elena , Huang Wei , Zervantonakis Ioannis K. , Selfors Laura M. , Shen Yiping , Pritchard Colin C. , Zheng Mei , Adleff Vilmos , Papp Eniko , Piao Huiying , Novak Marian , Fotheringham Susan , Wulf Gerburg M. , English Jessie , Kirschmeier Paul T. , Velculescu Victor E. , Paweletz Cloud , Mills Gordon B. , Livingston David M. , Brugge Joan S. , Matulonis Ursula A. , Drapkin Ronny 
Published: August 2016

Abstract
Purpose: Ovarian cancer is the leading cause of death from gynecologic malignancy in the United States, with high rates of recurrence and eventual resistance to cytotoxic chemotherapy. Model systems that allow for accurate and reproducible target discovery and validation are needed to support further drug development in this disease.
Experimental Design: Clinically annotated patient-derived xenograft (PDX) models were generated from tumor cells isolated from the ascites or pleural fluid of patients undergoing clinical procedures. Models were characterized by IHC and by molecular analyses. Each PDX was luciferized to allow for reproducible in vivo assessment of intraperitoneal tumor burden by bioluminescence imaging (BLI). Plasma assays for CA125 and human LINE-1 were developed as secondary tests of in vivo disease burden.
Results: Fourteen clinically annotated and molecularly characterized luciferized ovarian PDX models were generated. Luciferized PDX models retain fidelity to both the nonluciferized PDX and the original patient tumor, as demonstrated by IHC, array CGH, and targeted and whole-exome sequencing analyses. Models demonstrated diversity in specific genetic alterations and activation of PI3K signaling pathway members. Response of luciferized PDX models to standard-of-care therapy could be reproducibly monitored by BLI or plasma markers.
Conclusions: We describe the establishment of a collection of 14 clinically annotated and molecularly characterized luciferized ovarian PDX models in which orthotopic tumor burden in the intraperitoneal space can be followed by standard and reproducible methods. This collection is well suited as a platform for proof-of-concept efficacy and biomarker studies and for validation of novel therapeutic strategies in ovarian cancer. Clin Cancer Res; 23(5); 1263–73. ©2016 AACR.
AC0010, an Irreversible EGFR Inhibitor Selectively Targeting Mutated EGFR and Overcoming T790M-Induced Resistance in Animal Models and Lung Cancer Patients
Authors: Xu Xiao , Mao Long , Xu Wanhong , Tang Wei , Zhang Xiaoying , Xi Biao , Xu Rongda , Fang Xin , Liu Jia , Fang Ce , Zhao Li , Wang Xiaobo , Jiang Ji , Hu Pei , Zhao Hongyun , Zhang Li 
Published: August 2016

Abstract
AC0010 is a pyrrolopyrimidine-based irreversible EGFR inhibitor, structurally distinct from previously reported pyrimidine-based irreversible EGFR inhibitors, such as osimertinib and rociletinib. AC0010 selectively inhibits EGFR-active and T790M mutations with up to 298-fold increase in potency compared with wild-type EGFR. In a xenograft model, oral administration of AC0010 at a daily dose of 500 mg/kg resulted in complete remission of tumors with EGFR-active and T790M mutations for over 143 days with no weight loss. Three major metabolites of AC0010 were tested and showed no wild-type EGFR inhibition or off-target effects, such as inhibition of IGF-1R. AC0010 is safe in non–small cell lung cancer (NSCLC) patients at a dose range between 50 and 550 mg once per day, and no hyperglycemia or other severe adverse effects were detected, such as grade 3 QT prolongation. The objective responses were observed in NSCLC patients with EGFR T790M mutation. Mol Cancer Ther; 15(11); 2586–97. ©2016 AACR.
IQGAP1 Scaffold–MAP Kinase Interactions Enhance Multiple Myeloma Clonogenic Growth and Self-Renewal
Authors: Gocke Christian B. , McMillan Ross , Wang Qiuju , Begum Asma , Penchev Vesselin R. , Ali Syed A. , Borrello Ivan , Huff Carol Ann , Matsui William 
Published: August 2016

Abstract
Despite improved outcomes in newly diagnosed multiple myeloma, virtually all patients relapse and ultimately develop drug-resistant disease. Aberrant RAS/MAPK signaling is activated in the majority of relapsed/refractory multiple myeloma patients, but its biological consequences are not fully understood. Self-renewal, as defined by the long-term maintenance of clonogenic growth, is essential for disease relapse, and we examined the role of RAS/MAPK activation on multiple myeloma self-renewal by targeting IQ motif–containing GTPase-activating protein 1 (IQGAP1), an intracellular scaffold protein required for mutant RAS signaling. We found that loss of IQGAP1 expression decreased MAPK signaling, cell-cycle progression, and tumor colony formation. Similarly, a peptide mimicking the WW domain of IQGAP1 that interacts with ERK inhibited the clonogenic growth and self-renewal of multiple myeloma cell lines and primary clinical specimens in vitro as well as tumor-initiating cell frequency in immunodeficient mice. During multiple myeloma progression, self-renewal may be enhanced by aberrant RAS/MAPK signaling and inhibited by targeting IQGAP1. Mol Cancer Ther; 15(11); 2733–9. ©2016 AACR.
Optical Coherence Tomography to Optimize Results of Percutaneous Coronary Intervention in Patients with Non–ST-Elevation Acute Coronary Syndrome
Authors: Meneveau Nicolas , Souteyrand Geraud , Motreff Pascal , Caussin Christophe , Amabile Nicolas , Ohlmann Patrick , Morel Olivier , Lefrançois Yoann , Descotes-Genon Vincent , Silvain Johanne , Braik Nassim , Chopard Romain , Chatot Marion , Ecarnot Fiona , Tauzin Hélène , Van Belle Eric , Belle Loïc , Schiele François 
Published: August 2016

Background:
No randomized study has investigated the value of optical coherence tomography (OCT) in optimizing the results of percutaneous coronary intervention (PCI) for non–ST-segment elevation acute coronary syndromes.

Methods:
We conducted a multicenter, randomized study involving 240 patients with non–ST-segment elevation acute coronary syndromes to compare OCT-guided PCI (use of OCT pre- and post-PCI; OCT-guided group) to fluoroscopy-guided PCI (angiography-guided group). The primary end point was the functional result of PCI assessed by the measure of post PCI fractional flow reserve. Secondary end points included procedural complications and type 4a periprocedural myocardial infarction. Safety was assessed by the rate of acute kidney injury.

Results:

OCT use led to a change in procedural strategy in 50% of the patients in the OCT-guided group. The primary end point was improved in the OCT-guided group, with a significantly higher fractional flow reserve value (0.94±0.04 versus 0.92±0.05,
P
=0.005) compared with the angiography-guided group. There was no significant difference in the rate of type 4a myocardial infarction (33% in the OCT-group versus 40% in the angiography-guided group,
P
=0.28). The rates of procedural complications (5.8%) and acute kidney injury (1.6%) were identical in each group despite longer procedure time and use of more contrast medium in the OCT-guided group. Post-PCI OCT revealed stent underexpansion in 42% of patients, stent malapposition in 32%, incomplete lesion coverage in 20%, and edge dissection in 37.5%. This led to the more frequent use of poststent overdilation in the OCT-guided group versus the angiography-guided group (43% versus 12.5%,
P
<0.0001) with lower residual stenosis (7.0±4.3% versus 8.7±6.3%,
P
=0.01).

Conclusions:
In patients with non–ST-segment elevation acute coronary syndromes, OCT-guided PCI is associated with higher postprocedure fractional flow reserve than PCI guided by angiography alone. OCT did not increase periprocedural complications, type 4a myocardial infarction, or acute kidney injury.

Clinical Trial Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT01743274.
Ten-Year Outcomes After Coronary Artery Bypass Grafting According to Age in Patients With Heart Failure and Left Ventricular Systolic Dysfunction
Authors: Petrie Mark C. , Jhund Pardeep S. , She Lilin , Adlbrecht Christopher , Doenst Torsten , Panza Julio A. , Hill James A. , Lee Kerry L. , Rouleau Jean L. , Prior David L. , Ali Imtiaz S. , Maddury Jyotsna , Golba Krzysztof S. , White Harvey D. , Carson Peter , Chrzanowski Lukasz , Romanov Alexander , Miller Alan B. , Velazquez Eric J. 
Published: August 2016

Background:
Advancing age is associated with a greater prevalence of coronary artery disease in heart failure with reduced ejection fraction and with a higher risk of complications after coronary artery bypass grafting (CABG). Whether the efficacy of CABG compared with medical therapy (MED) in patients with heart failure caused by ischemic cardiomyopathy is the same in patients of different ages is unknown.

Methods:
A total of 1212 patients (median follow-up, 9.8 years) with ejection fraction ≤35% and coronary disease amenable to CABG were randomized to CABG or MED in the STICH trial (Surgical Treatment for Ischemic Heart Failure).

Results:

Mean age at trial entry was 60 years; 12% were women; 36% were nonwhite; and the baseline ejection fraction was 28%. For the present analyses, patients were categorized by age quartiles: quartile 1, ≤54 years; quartile, 2 >54 and ≤60 years; quartile 3, >60 and ≤67 years; and quartile 4, >67 years. Older versus younger patients had more comorbidities. All-cause mortality was higher in older compared with younger patients assigned to MED (79% versus 60% for quartiles 4 and 1, respectively; log-rank
P
=0.005) and CABG (68% versus 48% for quartiles 4 and 1, respectively; log-rank
P
<0.001). In contrast, cardiovascular mortality was not statistically significantly different across the spectrum of age in the MED group (53% versus 49% for quartiles 4 and 1, respectively; log-rank
P
=0.388) or CABG group (39% versus 35% for quartiles 4 and 1, respectively; log-rank
P
=0.103). Cardiovascular deaths accounted for a greater proportion of deaths in the youngest versus oldest quartile (79% versus 62%). The effect of CABG versus MED on all-cause mortality tended to diminish with increasing age (
P
interaction
=0.062), whereas the benefit of CABG on cardiovascular mortality was consistent over all ages (
P
interaction
=0.307). There was a greater reduction in all-cause mortality or cardiovascular hospitalization with CABG versus MED in younger compared with older patients (
P
interaction
=0.004). In the CABG group, cardiopulmonary bypass time or days in intensive care did not differ for older versus younger patients.

Conclusions:
CABG added to MED has a more substantial benefit on all-cause mortality and the combination of all-cause mortality and cardiovascular hospitalization in younger compared with older patients. CABG added to MED has a consistent beneficial effect on cardiovascular mortality regardless of age.

Clinical Trial Registration:

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00023595.
The metallothionein gene from the Oriental river prawn Macrobrachium nipponense (De Haan, 1849): characterization and expression in response to hypoxia and reoxygenation
Authors: Sun Shengming , Gu Zhimin , Fu Hongtuo , Zhu Jian 
Published: August 2016

Since mammals make use of metallothioneins (MTs) to protect against hypoxia-generated reactive oxygen species (ROS), here we investigate whether MTs have the same effect in the Oriental river prawnMacrobrachium nipponense(De Haan, 1849). Levels ofM. nipponenseMT (MnMT) mRNA in different tissues were analysed using a real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). We found that MnMT is differentially expressed in the haemocytes, intestine, gills, heart, hepatopancreas and muscle. The highest levels of expression occurred in the hepatopancreas and heart. The results of the qRT-PCR and Western blot indicated that MnMT mRNA and protein expression in the hepatopancreas increased significantly in response to hypoxia 24 h and followed by 1 h reoxygenation compared to normoxia. Similarly, there were also significant increases in respiratory bursts and ROS production in the hepatopancreas. The MT protein possibly has a protective effect against ROS generated during hypoxia and reoxygenation stimuli.
A review of the genus Alpheopsis (Decapoda, Caridea, Alpheidae) from the seas of China
Authors: Wang Yanrong , Sha Zhongli 
Published: August 2016

The genusAlpheopsis(Decapoda, Alpheidae) from the seas of China is reviewed. Two species belonging to the genus are described, including one newly recorded species,Alpheopsis yaldwyniBanner & Banner, 1973. In this study the mouthparts of the two species were dissected and illustrated for the first time. The differences between the Chinese material and previous descriptions are reported. A key to all species of the genusAlpheopsisis provided.
Tolerability and Efficacy of Eltrombopag in Chronic Immune Thrombocytopenia: Meta-Analysis of Randomized Controlled Trials
Authors: Elgebaly Ahmed Saber , Ashal Gehad El , Elfil Mohamed , Menshawy Ahmed 
Published: August 2016

Background: Eltrombopag is an oral thrombopoietin receptor agonist that stimulates the production of normally functioning platelets. The aim of this meta-analysis is to synthesize evidence about the safety and efficacy of eltrombopag for both adult and children with primary immune thrombocytopenia (ITP). Methods: A computer literature search of PubMed, Scopus, Web of Science, and Cochrane Central was conducted. Records were screened for eligible studies, and data were extracted and synthesized using Review Manager for Windows. Subgroup analysis and sensitivity analysis were conducted to investigate whether treatment effect varies significantly between adults and children. Results: Six randomized controlled trials (N = 611 patients) were included in the final analysis. The overall effect estimates favored eltrombopag group in terms of overall platelet response (relative risk [RR]: 3.42; 95% confidence interval [CI]: 2.51-4.65; P < .0001), incidence of significant bleeding (RR: 0.56; 95% CI: 0.41-0.77; P = .0004), and number of cases needed to rescue treatment (RR: 0.45; 95% CI: 0.32-0.65; P < .0001). The efficacy of eltrombopag did not differ significantly between children and adults except for incidence of any bleeding (RR: 0.83 vs 0.51; P = .008). Conclusion: Eltrombopag is a tolerable and effective drug for the management of chronic ITP in children and adults.
Evaluation of electronic health record implementation on pharmacist interventions related to oral chemotherapy management
Authors: Finn Anastasia , Bondarenka Carolyn , Edwards Kathy , Hartwell Rebekah , Letton Cathy , Perez Andy 
Published: August 2016

Background With the ever growing arsenal of oral chemotherapy agents now available, cancer treatment is being increasingly managed in the outpatient setting. However, oral chemotherapy use is often associated with several potential obstacles and complications. In order to provide optimal patient safety and oral chemotherapy monitoring, our institution implemented an oral chemotherapy program managed by clinical pharmacists electronically through Epic Beacon. Objective To describe implementation of a novel pharmacist-managed oral chemotherapy program and evaluate pharmacist interventions before and after implementation of an oral chemotherapy program. Methods This was a single-center retrospective chart review of documented pharmacy interventions for oral chemotherapy prescriptions during three months prior to as well as three months following Epic Beacon implementation. Time periods for data inclusion were October–December 2013 (pre-Beacon) and October–December 2014 (post-Beacon). Patients included in the study had one or more oral chemotherapy orders during the pre-Beacon period, the post-Beacon period, or both pre- and post-Beacon. Our analysis did not include oral chemotherapy orders that were placed outside of a treatment plan in the post-Beacon period. Results A total of 240 patients with 450 total oral chemotherapy orders were assessed over the duration of the study. Beacon implementation allowed a greater number of oral chemotherapy orders to be reviewed, with 134 oral chemotherapy orders reviewed in the study period prior to Beacon implementation and 316 orders reviewed in the post-Beacon period. Additionally, there were 660% more pharmacist interventions (89 interventions pre-Beacon versus 681 interventions post-Beacon), with an increased focus on coordination of care, chemotherapy calendar coordination, and assistance with treatment plans. Furthermore, implementation of Epic Beacon allowed identification of over 500% more chemotherapy order errors (41 total errors identified pre-Beacon versus 250 total errors identified post-Beacon). Pharmacists were also able to identify more significant, serious, or potentially lethal errors following implementation. The time associated with oral chemotherapy review and intervention also increased accordingly with number of orders reviewed. Conclusion Implementation of an electronic workflow for oral chemotherapy dramatically increased pharmacist review of orders, resulting in improved documentation of interventions and errors, decreased need for clarification of orders, as well as increased volume of prescriptions at our on-site pharmacy. This study demonstrates a comprehensive approach to maximize safety when oral chemotherapy is utilized as a component of the treatment regimen.