bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Outcome of Critically Ill Pediatric Cancer Patients Admitted to the Pediatric Intensive Care Unit in a Tertiary University Oncology Center in a Developing Country: A 5-Year Experience
Authors: Ali Amany M. , Sayed Heba A. , Elzembely Mahmoud M. 
Published: February 2016

Introduction:
Cancer remains a major cause of death in children, but recent advances in supportive care and progress in the use of chemotherapy have considerably improved the prognosis. The need for intensive care management in pediatric oncology patients is increasing. However, studies demonstrating their outcome in the literature are still deficient, especially in developing countries. Here, we aim to report our experience in managing patients admitted to the pediatric intensive care unit (PICU) at South Egypt Cancer Institute, a tertiary university oncology center in a developing country.

Patients and Methods:
A review of all cancer patients admitted to the PICU at South Egypt Cancer Institute between January 2007 and December 2011 and an evaluation of prognostic factors that may correlate to their short-term outcome were performed.

Results:
A total of 550 pediatric oncology patients were admitted to the PICU on 757 occasions. Hematological malignancies represented 73.6% of the cases. The median duration of PICU stay was 5 days. Sepsis and respiratory failure were the most frequent indications for PICU admission. The overall survival at the time of discharge from the PICU was 60%. Several factors were found to significantly affect the outcome of patients admitted to the PICU, including the underlying disease, the reason for admission, the intervention used, and the number of failing organs at the time of admission to the PICU.

Conclusions:
The prognosis of patients admitted to the PICU in developing countries is still behind those in developed ones. Late referral, especially of patients presenting with respiratory failure, sepsis, and multiorgan failure usually, requires urgent intervention with inotropic support, oxygen therapy, and mechanical ventilation and is significantly associated with poor outcomes, especially in patients with hematological malignancies.
Declaring a tuberculosis outbreak over with genomic epidemiology
Authors: Hatherell Hollie-Ann , Didelot Xavier , Pollock Sue L. , Tang Patrick , Crisan Anamaria , Johnston James C. , Colijn Caroline , Gardy Jennifer 
Published: February 2016

AbstractWe report an updated method for inferring the time at which an infectious disease was transmitted between persons from a time-labelled pathogen genome phylogeny. We applied the method to 48 Mycobacterium tuberculosis genomes as part of a real-time public health outbreak investigation, demonstrating that although active tuberculosis (TB) cases were diagnosed through 2013, no transmission events took place beyond mid-2012. Subsequent cases were the result of progression from latent TB infection to active disease and not recent transmission. This evolutionary genomic approach was used to declare the outbreak over in January 2015.
The non-essentiality of essential genes suggests a loss-of-function therapeutic strategy for loss-of-function human diseases
Authors: Chen Piaopiao , Wang Dandan , Chen Han , Zhou Zhenzhen , He Xionglei 
Published: February 2016

AbstractEssential genes refer to those whose null mutation leads to lethality or sterility. We propose that the fatal effect of inactivating an essential gene can be attributed to either the loss of indispensable core cellular function (type I), or the gain of fatal side effects after losing dispensable periphery function (type II). In principle, inactivation of the type I essential genes can be rescued only by regain of the core functions, whereas inactivation of the type II essential genes could be rescued by a further loss of function of another gene to eliminate the otherwise fatal side effects. Because such loss-of-function rescuing mutations may occur spontaneously, type II essential genes may become non-essential in a few individuals of a large population. We tested this idea in the yeastSacchromyces cerevisiae. Large-scale whole genome sequencing of such essentiality-reversing mutants reveals 14 cases where inactivation of an essential gene is rescued by loss-of-function mutations on another gene. In particular, the essential gene encoding the enzyme adenylosuccinate lyase (ADSL) is shown to be type II, suggesting a loss-of-function therapeutic strategy for the human disorder ADSL deficiency. A proof-of-principle test of this strategy in the nematodeCaenorhabditis elegansshows promising results.
eQTL regulating Transcript Levels Associated with Diverse Biological Processes in Tomato
Authors: Ranjan Aashish , Budke Jessica M. , Rowland Steven D. , Chitwood Daniel H. , Kumar Ravi , Carriedo Leonela , Ichihashi Yasunori , Zumstein Kristina , Maloof Julin N. , Sinha Neelima R. 
Published: February 2016

AbstractVariation in gene expression, in addition to sequence polymorphisms, is known to influence developmental, physiological and metabolic traits in plants. Genetic mapping populations have facilitated identification of expression Quantitative Trait Loci (eQTL), the genetic determinants of variation in gene expression patterns. We used an introgression population developed from the wild desert-adaptedSolanum pennelliiand domesticated tomatoSolanum lycopersicumto identify the genetic basis of transcript level variation. We established the effect of each introgression on the transcriptome, and identified ~7,200 eQTL regulating the steady state transcript levels of 5,300 genes. Barnes-Hutt-distributed stochastic neighbor embedding clustering identified 42 modules revealing novel associations between transcript level patterns and biological processes. The results showed a complex genetic architecture of global transcript abundance pattern in tomato. Several genetic hotspots regulating a large number of transcript level patterns relating to diverse biological processes such as plant defense and photosynthesis were identified. Important eQTL regulating transcript level patterns were related to leaf number and complexity, and hypocotyl length. Genes associated with leaf development showed an inverse correlation with photosynthetic gene expression but eQTL regulating genes associated with leaf development and photosynthesis were dispersed across the genome. This comprehensive expression QTL analysis details the influence of these loci on plant phenotypes, and will be a valuable community resource for investigations on the genetic effects of eQTL on phenotypic traits in tomato.
Analytical results for directional and quadratic selection gradients for log-linear models of fitness functions
Authors: Morrissey Michael B. , Goudie I. B. J. 
Published: February 2016

AbstractEstablished methods for inference about selection gradients involve least-squares regression of fitness on phenotype. While these methods are simple and may generally be quite robust, they do not account well for distributions of fitness.Some progress has previously been made in relating inferences about trait-fitness relationships from generalised linear models to selection gradients in the formal quantitative genetic sense. These approaches involve numerical calculation of average derivatives of relative fitness with respect to phenotype.We present analytical results expressing selection gradients as functions of the coefficients of generalised linear models for fitness in terms of traits. The analytical results allow calculation of univariate and multivariate directional, quadratic, and correlational selection gradients from log-linear and log-quadratic models.The results should be quite generally applicable in selection analysis. They apply to any generalised linear model with a log link function. Furthermore, we show how they apply to some situations including inference of selection from (molecular) paternity data, capture-mark-recapture analysis, and survival analysis. Finally, the results may bridge some gaps between typical approaches in empirical and theoretical studies of natural selection.
Boiler: Lossy compression of RNA-seq alignments using coverage vectors
Authors: Pritt Jacob , Langmead Ben 
Published: February 2016

AbstractWe describe Boiler, a new software tool for compressing and querying large collections of RNA-seq alignments. Boiler discards most per-read data, keeping only a genomic coverage vector plus a few empirical distributions summarizing the alignments. Since most per-read data is discarded, storage footprint is often much smaller than that achieved by other compression tools. Despite this, the most relevant per-read data can be recovered; we show that Boiler compression has only a slight negative impact on results given by downstream tools for isoform assembly and quantification. Boiler also allows the user to pose fast and useful queries without decompressing the entire file. Boiler is free open source software available fromgithub.com/jpritt/boiler.
A framework to study vendors’ contribution in a client vendor relationship in information technology service outsourcing in India
Authors: Jain Daisy Mathur , Khurana Reema 
Published: February 2016

Purpose– The information technology (IT) industry has been continuously expanding. This has resulted in promoting outsourcing of work by clients to vendors. Most of the published research has focussed on when clients should start outsourcing, what to outsource, criteria for vendor selection, etc., however the vendor side of the relationship has been mostly ignored. The purpose of this paper is to delve deep into the vendors’ side and what aspects a vendor needs to consider in order to maintain a good relationship with the clients.Design/methodology/approach– The research design of the paper is to use literature survey to define the components of the client vendor relationship (CVR), identify the parameters impacting the relationship, establish correlation between the independent variables and the dependent variable; subsequently to propose a framework for the CVR.Findings– The findings have been that – communication, technical value addition, knowledge sharing and client vendor adaptability are vital to any outsourcing engagement and if the vendor is able to get good knowledge transfer of the application at hand and the business domain, it can perform better. Vendors, which proactively resolve issues, ensure stable deliveries before time and identify improvements in the software outside the work assigned maintain better relationship. Further a vendor must be adaptable to clients, cultural, time zone differences, should provide a good project manager and be ready to change tools, resources as per client needs. As long as the vendor is able to ensure the above, the stability of the client country and need for information security is not as important to vendors.Research limitations/implications– The study has limitations as it focusses on the vendors’ side and is inclined toward Indian vendors’ perspectives. Future research can include client as well and can be conducted for a different geography.Originality/value– The research work is original and adds value to the IT service outsourcing industry by identifying the parameters which need to be monitored for a sustainable CVR.
Development and implementation of product sustainment simulator utilizing fuzzy cognitive map (FCM)
Authors: Uzochukwu Benedict M. , Udoka Silvanus J. , Balogun Femi 
Published: February 2016

Purpose
– Managing product life cycle data is important for achieving design excellence, product continued operational performance, customer satisfaction and sustainment. As a result, it is important to develop a sustainment simulator to transform life cycle data into actionable design metrics. Currently, there is apparent lack of technologies and tools to synthesize product life time data. The purpose of this paper is to provide a description of how a product sustainment simulator was developed using fuzzy cognitive map (FCM). As a proof of concept, and to demonstrate the utility of the simulator, an implementation example utilizing product life time data as input was demonstrated.

Design/methodology/approach
– The sustainment simulator was developed using visual basic. The simulation experiment was accomplished using a FCM. The Statistical Analytical Software tool was used to run structural equation model programs that provided the initial input into the FCM and the simulator. Product life data were used as input to the simulator.

Findings
– There is an apparent lack of technologies and tools to synthesize product life time data. This constitutes an impediment to designing the next generation of sustainable products. Modern tools, technologies and techniques must be used if the goal of removing product design and sustainment disablers is to be achieved. Product sustainment can, therefore, be achieved using the simulator.

Research limitations/implications
– The sustainment simulator is a tool that demonstrates in a practical way how a product life time generated data can be transformed into actionable design parameters. This paper includes analysis of a sample generated using random numbers. The lack of actual data set is primarily due to reluctance of organizations to avail the public of actual product life time data. However, this paper provides a good demonstration of how product life time data can be transformed to ensure product sustainment.

Practical implications
– The technique used in this research paper would be very useful to product designers, engineers and research and development teams in developing data manipulation tools to improve product operational and sustainable life cycle performance. Sustainment conscious organizations will, no doubt, benefit from a strong comparative and competitive advantage over rivals.

Originality/value
– Utilizing the simulator to transform product life time data into actionable design metrics through the help of an efficient decision support tool like the FCM constitutes a step in supporting product life cycle management. The outcome of this paper alerts product designers on parameters which should be taken into account when designing a new generation of a given product(s).
New drivers and challenges in a multi-polar world
Authors: Caiazza Rosa 
Published: February 2016

Purpose– The purpose of this paper is to explore current trends in multi-polar world with the aim of assessing new drivers and challenges in cross-border M & A.Design/methodology/approach– A case study analysis of cross-border M & A is described and discussed.Findings– The paper indicates strategic motivations and implementation challenges of cross-border M & A under current pressures of a world characterized by multiple centers of economic power.Originality/value– This paper evidence new direction in cross-border M & A research for reinterpreting existing paradigms and developing new ones.
Differential
In Vitro
and
In Vivo
Toxicities of Antimicrobial Peptide Prodrugs for Potential Use in Cystic Fibrosis
Authors: Forde Éanna , Schütte André , Reeves Emer , Greene Catherine , Humphreys Hilary , Mall Marcus , Fitzgerald-Hughes Deirdre , Devocelle Marc 
Published: February 2016

ABSTRACT

There has been considerable interest in the use of antimicrobial peptides (AMPs) as antimicrobial agents for the treatment of many conditions, including cystic fibrosis (CF). The challenging conditions of the CF patient lung require robust AMPs that are active in an environment of high proteolytic activity but that also have low cytotoxicity and immunogenicity. Previously, we developed prodrugs of AMPs that limited the cytotoxic effects of AMP treatment by rendering the antimicrobial activity dependent on the host enzyme neutrophil elastase (NE). However, cytotoxicity remained an issue. Here, we describe the further optimization of the AMP prodrug (pro-AMP) model for CF to produce pro-WMR, a peptide with greatly reduced cytotoxicity (50% inhibitory concentration against CFBE41o- cells, >300 μM) compared to that of the previous group of pro-AMPs. The bactericidal activity of pro-WMR was increased in NE-rich bronchoalveolar lavage (BAL) fluid from CF patients (range, 8.4% ± 6.9% alone to 91.5% ± 5.8% with BAL fluid;
P
= 0.0004), an activity differential greater than that of previous pro-AMPs. In a murine model of lung delivery, the pro-AMP modification reduced host toxicity, with pro-WMR being less toxic than the active peptide. Previously, host toxicity issues have hampered the clinical application of AMPs. However, the development of application-specific AMPs with modifications that minimize toxicity similar to those described here can significantly advance their potential use in patients. The combination of this prodrug strategy with a highly active AMP has the potential to produce new therapeutics for the challenging conditions of the CF patient lung.
The Central Hinge Link Truncation of the Antimicrobial Peptide Fowlicidin-3 Enhances Its Cell Selectivity without Antibacterial Activity Loss
Authors: Qu Pei , Gao Wei , Chen Huixian , Li Dan , Yang Na , Zhu Jian , Feng Xingjun , Liu Chunlong , Li Zhongqiu 
Published: February 2016

ABSTRACT
Antimicrobial peptides (AMPs) have been paid considerable attention because of their broad-spectrum antimicrobial activity and a reduced possibility of the development of bacterial drug resistance. Fowlicidin-3 (Fow-3) is an identified type of chicken cathelicidin AMP that has exhibited considerable antimicrobial activity and cytotoxicity. To reduce cell toxicity and improve cell selectivity, several truncated peptides of fowlicidin-3, Fow-3(1-15), Fow-3(1-19), Fow-3(1-15-20-27), and Fow-3(20-27), were synthesized. Our results indicated that neither the N- nor C-terminal segment alone [Fow-3(1-15), Fow-3(1-19), Fow-3(20-27)] was sufficient to confer antibacterial activity. However, Fow-3(1-19) with the inclusion of the central hinge link (-AGIN-) retained substantial cell toxicity, which other analogs lost. Fow-3(1-15-20-27) displayed potent antimicrobial activity for a wide range of Gram-negative and Gram-positive bacteria and no obvious hemolytic activity or cytotoxicity. The central link region was shown to be critically important in the function of cell toxicity but was not relevant to antibacterial activity. Fow-3(1-15-20-27) maintained antibacterial activity in the presence of physiological concentrations of salts. The results from fluorescence spectroscopy, scanning electron microcopy, and transmission electron microcopy showed that Fow-3(1-15-20-27) as well as fowlicidin-3 killed bacterial cells by increasing membrane permeability and damaging the membrane envelope integrity. Fow-3(1-15-20-27) could be a promising antimicrobial agent for clinical application.
Model-Based Phase 3 Dose Selection for HIV-1 Attachment Inhibitor Prodrug BMS-663068 in HIV-1-Infected Patients: Population Pharmacokinetics/Pharmacodynamics of the Active Moiety, BMS-626529
Authors: Landry Ishani , Zhu Li , Abu Tarif Malaz , Hruska Matthew , Sadler Brian M. , Pitsiu Maria , Joshi Samit , Hanna George J. , Lataillade Max , Boulton David W. , Bertz Richard J. 
Published: February 2016

ABSTRACT

BMS-663068 is an oral prodrug of the HIV-1 attachment inhibitor BMS-626529, which prevents viral attachment to host CD4
+
T cells by binding to HIV-1 gp120. To guide dose selection for the phase 3 program, pharmacokinetic/pharmacodynamic modeling was performed using data from two phase 2 studies with HIV-1-infected subjects (
n
= 244). BMS-626529 population pharmacokinetics were described by a two-compartment model with first-order elimination from the central compartment, zero-order release of prodrug from the extended-release formulation into a hypothetical absorption compartment, and first-order absorption into the central compartment. The covariates of BMS-663068 formulation type, lean body mass, baseline CD8
+
T-cell percentage, and ritonavir coadministration were found to be significant contributors to intersubject variability. Exposure-response analyses showed a relationship between the log

e

-transformed concentration at the end of a dosing interval (
C
tau
) normalized for the protein binding-adjusted BMS-626529 half-maximal (50%) inhibitory concentration (PBAIC
50
) and the change in the HIV-1 RNA level from the baseline level after 7 days of BMS-663068 monotherapy. The probability of achieving a decline in HIV-1 RNA level of >0.5 or >1.0 log
10
copies/ml as a function of the log

e

-transformed PBAIC
50
-adjusted
C
tau
after 7 days of monotherapy was 99 to 100% and 57 to 73%, respectively, for proposed BMS-663068 doses of 400 mg twice daily (BID), 600 mg BID (not studied in the phase 2b study), 800 mg BID, 600 mg once daily (QD), and 1,200 mg QD. On the basis of a slight advantage in efficacy of BID dosing over QD dosing, similar responses for the 600- and 800-mg BID doses, and prior clinical observations, BMS-663068 at 600 mg BID was predicted to have the optimal benefit-risk profile and selected for further clinical investigation. (The phase 2a proof-of-concept study AI438006 and the phase 2b study AI438011 are registered at ClinicalTrials.gov under numbers NCT01009814 and NCT01384734, respectively.)
Complete Nucleotide Sequence of pKOI-34, an IncL/M Plasmid Carrying
bla
IMP-34
in Klebsiella oxytoca Isolated in Japan
Authors: Shimada Norimitsu , Kayama Shizuo , Shigemoto Norifumi , Hisatsune Junzo , Kuwahara Ryuichi , Nishio Hisaaki , Yamasaki Katsutoshi , Wada Yasunao , Sueda Taijiro , Ohge Hiroki , Sugai Motoyuki 
Published: February 2016

ABSTRACT

We determined the complete nucleotide sequence of a self-transmissible IncL/M plasmid, pKOI-34, from a
Klebsiella oxytoca
isolate. pKOI-34 possessed the core structure of an IncL/M plasmid found in
Erwinia amylovora
, pEL60, with two mobile elements inserted, a transposon carrying the arsenic resistance operon and a Tn
21
-like core module (
tnp
and
mer
modules) piggybacking
bla
IMP-34
as a class 1 integron, In
808
, where
bla
IMP-34
confers a resistance to carbapenems in
K. oxytoca
and
Klebsiella pneumoniae
.
Pseudomonas aeruginosa and Its Bacterial Components Influence the Cytokine Response in Thymocytes and Splenocytes
Authors: Weber Andreas , Zimmermann Corinna , Mausberg Anne K. , Dehmel Thomas , Kieseier Bernd C. , Hartung Hans-Peter , Hofstetter Harald H. 
Published: February 2016

ABSTRACT

Infections with
Pseudomonas aeruginosa
may cause many different diseases. The spectrum of such infections in general includes inflammation and bacterial sepsis. Hospital-acquired pneumonia, naturally resistant to a wide range of antibiotics, is associated with a particularly high mortality rate in mechanically ventilated patients. The pathogenesis of
P. aeruginosa
is complex and mediated by several virulence factors, as well as cell-associated factors. We have previously demonstrated that stimulation with different bacteria triggers the cytokine response of thymocytes. In this study, we investigated the effect of
P. aeruginosa
and its different components on the cytokine production of immature and mature immune cells. We found that the induced cytokine pattern in the thymus and the spleen after infections with
P. aeruginosa
is primarily mediated by lipopolysaccharide (LPS) of the outer cell membrane, but other components of the bacterium can influence the cytokine secretion as well. Stimulation with heat-killed
P. aeruginosa
and LPS does not influence the amount of cytokine-producing CD4
+
T cells but instead suppresses the emergence of Th17 cells. However, stimulation with
P. aeruginosa
or its components triggers the interleukin-17 (IL-17) response both in thymocytes and in splenocytes. We conclude that infections with
P. aeruginosa
affect the cytokine secretion of immature and mature cells and that IL-17 and Th17 cells play only a minor role in the development of pathological systemic inflammatory disease conditions during
P. aeruginosa
infections. Therefore, other inflammatory immune responses must be responsible for septic reactions of the host.