bluuebunny/crossref_metadata_2025_split huggingface dataset:
A whole genome screen for HIV restriction factors
Authors: Liu Li , Oliveira Nidia MM , Cheney Kelly M , Pade Corinna , Dreja Hanna , Bergin Ann-Marie H , Borgdorff Viola , Beach David H , Bishop Cleo L , Dittmar Matthias T , McKnight Áine 
Published: November 2011

AbstractBackgroundUpon cellular entry retroviruses must avoid innate restriction factors produced by the host cell. For human immunodeficiency virus (HIV) human restriction factors, APOBEC3 (apolipoprotein-B-mRNA-editing-enzyme), p21 and tetherin are well characterised.ResultsTo identify intrinsic resistance factors to HIV-1 replication we screened 19,121 human genes and identified 114 factors with significant inhibition of infection. Those with a known function are involved in a broad spectrum of cellular processes including receptor signalling, vesicle trafficking, transcription, apoptosis, cross-nuclear membrane transport, meiosis, DNA damage repair, ubiquitination and RNA processing. We focused on the PAF1 complex which has been previously implicated in gene transcription, cell cycle control and mRNA surveillance. Knockdown of all members of the PAF1 family of proteins enhanced HIV-1 reverse transcription and integration of provirus. Over-expression of PAF1 in host cells renders them refractory to HIV-1. Simian Immunodeficiency Viruses and HIV-2 are also restricted in PAF1 expressing cells. PAF1 is expressed in primary monocytes, macrophages and T-lymphocytes and we demonstrate strong activity in MonoMac1, a monocyte cell line.ConclusionsWe propose that the PAF1c establishes an anti-viral state to prevent infection by incoming retroviruses. This previously unrecognised mechanism of restriction could have implications for invasion of cells by any pathogen.
Expression of mutant TDP-43 induces neuronal dysfunction in transgenic mice
Authors: Xu Ya-Fei , Zhang Yong-Jie , Lin Wen-Lang , Cao Xiangkun , Stetler Caroline , Dickson Dennis W , Lewis Jada , Petrucelli Leonard 
Published: November 2011

Abstract

Background
Abnormal distribution, modification and aggregation of transactivation response DNA-binding protein 43 (TDP-43) are the hallmarks of multiple neurodegenerative diseases, especially frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS). Researchers have identified 44 mutations in the TARDBP gene that encode TDP-43 as causative for cases of sporadic and familial ALS http://www.molgen.ua.ac.be/FTDMutations/. Certain mutant forms of TDP-43, such as M337V, are associated with increased low molecular weight (LMW) fragments compared to wild-type (WT) TDP-43 and cause neuronal apoptosis and developmental delay in chick embryos. Such findings support a direct link between altered TDP-43 function and neurodegeneration.

Results
To explore the pathogenic properties of the M337V mutation, we generated and characterized two mouse lines expressing human TDP-43 (hTDP-43M337V) carrying this mutation. hTDP-43M337V was expressed primarily in the nuclei of neurons in the brain and spinal cord, and intranuclear and cytoplasmic phosphorylated TDP-43 aggregates were frequently detected. The levels of TDP-43 LMW products of ~25 kDa and ~35 kDa species were also increased in the transgenic mice. Moreover, overexpression of hTDP-43M337V dramatically down regulated the levels of mouse TDP-43 (mTDP-43) protein and RNA, indicating TDP-43 levels are tightly controlled in mammalian systems. TDP-43M337V mice displayed reactive gliosis, widespread ubiquitination, chromatolysis, gait abnormalities, and early lethality. Abnormal cytoplasmic mitochondrial aggregates and abnormal phosphorylated tau were also detected in the mice.

Conclusion
Our novel TDP-43M337V mouse model indicates that overexpression of hTDP-43M337V alone is toxic in vivo. Because overexpression of hTDP-43 in wild-type TDP-43 and TDP-43M337V mouse models produces similar phenotypes, the mechanisms causing pathogenesis in the mutant model remain unknown. However, our results suggest that overexpression of the hTDP-43M337V can cause neuronal dysfunction due to its effect on a number of cell organelles and proteins, such as mitochondria and TDP-43, that are critical for neuronal activity. The mutant model will serve as a valuable tool in the development of future studies designed to uncover pathways associated with TDP-43 neurotoxicity and the precise roles TDP-43 RNA targets play in neurodegeneration.
Increased 90-kDa ribosomal S6 kinase (Rsk) activity is protective against mutant huntingtin toxicity
Authors: Xifró Xavier , Anglada-Huguet Marta , Rué Laura , Saavedra Ana , Pérez-Navarro Esther , Alberch Jordi 
Published: November 2011

Abstract

Background
The 90-kDa ribosomal S6 kinase (Rsk) family is involved in cell survival. Rsk activation is regulated by sequential phosphorylations controlled by extracellular signal-regulated kinase (ERK) 1/2 and 3-phosphoinositide-dependent protein kinase 1 (PDK1). Altered ERK1/2 and PDK1 phosphorylation have been described in Huntington's disease (HD), characterized by the expression of mutant huntingtin (mhtt) and striatal degeneration. However, the role of Rsk in this neurodegenerative disease remains unknown. Here, we analyzed the protein levels, activity and role of Rsk in in vivo and in vitro HD models.

Results
We observed increased protein levels of Rsk1 and Rsk2 in the striatum of HdhQ111/Q111 and R6/1 mice, STHdhQ111/Q111 cells and striatal cells transfected with full-length mhtt. Analysis of the phosphorylation of Rsk in Hdh mice and STHdh cells showed reduced levels of phospho Ser-380 (dependent on ERK1/2), whereas phosphorylation at Ser-221 (dependent on PDK1) was increased. Moreover, we found that elevated Rsk activity in STHdhQ111/Q111 cells was mainly due to PDK1 activity, as assessed by transfection with Rsk mutant constructs. The increase of Rsk in STHdhQ111/Q111 cells occurred in the cytosol and in the nucleus, which results in enhanced phosphorylation of both cytosolic and nuclear Rsk targets. Finally, pharmacological inhibition of Rsk, knock-down and overexpression experiments indicated that Rsk activity exerts a protective effect against mhtt-induced cell death in STHdhQ7/Q7 cells transfected with mhtt.

Conclusion
The increase of Rsk levels and activity would act as a compensatory mechanism with capacity to prevent mhtt-mediated cell death. We propose Rsk as a good target for neuroprotective therapies in HD.
Evaluating the potential of the sterile insect technique for malaria control: relative fitness and mating compatibility between laboratory colonized and a wild population of Anopheles arabiensis from the Kruger National Park, South Africa
Authors: Munhenga Givemore , Brooke Basil D , Chirwa Tobias F , Hunt Richard H , Coetzee Maureen , Govender Danny , Koekemoer Lizette L 
Published: November 2011

Abstract

Background
The successful suppression of a target insect population using the sterile insect technique (SIT) partly depends on the premise that the laboratory insects used for mass rearing are genetically compatible with the target population, that the mating competitiveness of laboratory reared males is at least comparable to that of their wild counterparts, and that mass rearing and sterilization processes do not in themselves compromise male fitness to a degree that precludes them from successfully competing for mates in the wild. This study investigated the fitness and sexual cross-compatibility between samples of field collected and laboratory reared An. arabiensis under laboratory conditions.

Results
The physiological and reproductive fitness of the MALPAN laboratory strain is not substantially modified with respect to the field population at Malahlapanga. Further, a high degree of mating compatibility between MALPAN and the Malahlapanga population was established based on cross-mating experiments. Lastly, the morphological characteristics of hybrid ovarian polytene chromosomes further support the contention that the MALPAN laboratory colony and the An. arabiensis population at Malahlapanga are genetically homogenous and therefore compatible.

Conclusions
It is concluded that the presence of a perennial and isolated population of An. arabiensis at Malahlapanga presents a unique opportunity for assessing the feasibility of SIT as a malaria vector control option. The MALPAN laboratory colony has retained sufficient enough measures of reproductive and physiological fitness to present as a suitable candidate for male sterilization, mass rearing and subsequent mass release of sterile males at Malahlapanga in order to further assess the feasibility of SIT in a field setting.
Team behaviors in emergency care: a qualitative study using behavior analysis of what makes team work
Authors: Mazzocato Pamela , Hvitfeldt Forsberg Helena , von Thiele Schwarz Ulrica 
Published: November 2011

Abstract

Objective
Teamwork has been suggested as a promising approach to improving care processes in emergency departments (ED). However, for teamwork to yield expected results, implementation must involve behavior changes. The aim of this study is to use behavior analysis to qualitatively examine how teamwork plays out in practice and to understand eventual discrepancies between planned and actual behaviors.

Methods
The study was set in a Swedish university hospital ED during the initial phase of implementation of teamwork. The intervention focused on changing the environment and redesigning the work process to enable teamwork. Each team was responsible for entire care episodes, i.e. from patient arrival to discharge from the ED. Data was collected through 3 days of observations structured around an observation scheme. Behavior analysis was used to pinpoint key teamwork behaviors for consistent implementation of teamwork and to analyze the contingencies that decreased or increased the likelihood of these behaviors.

Results
We found a great discrepancy between the planned and the observed teamwork processes. 60% of the 44 team patients observed were handled solely by the appointed team members. Only 36% of the observed patient care processes started according to the description in the planned teamwork process, that is, with taking patient history together. Beside this behavior, meeting in a defined team room and communicating with team members were shown to be essential for the consistent implementation of teamwork. Factors that decreased the likelihood of these key behaviors included waiting for other team members or having trouble locating each other. Getting work done without delay and having an overview of the patient care process increased team behaviors. Moreover, explicit instructions on when team members should interact and communicate increased adherence to the planned process.

Conclusions
This study illustrates how behavior analysis can be used to understand discrepancies between planned and observed behaviors. By examining the contextual conditions that may influence behaviors, improvements in implementation strategies can be suggested. Thereby, the adherence to a planned intervention can be improved, and/or revisions of the intervention be suggested.
Duration of antibiotic therapy for bacteremia: a systematic review and meta-analysis
Authors: Havey Thomas C , Fowler Robert A , Daneman Nick 
Published: November 2011

Abstract
Introduction
The optimal duration of antibiotic therapy for bloodstream infections is unknown. Shorter durations of therapy have been demonstrated to be as effective as longer durations for many common infections; similar findings in bacteremia could enable hospitals to reduce antibiotic utilization, adverse events, resistance and costs.

Methods
A search of the MEDLINE, EMBASE and COCHRANE databases was conducted for the years 1947-2010. Controlled trials were identified that randomized patients to shorter versus longer durations of treatment for bacteremia, or the infectious foci most commonly causing bacteremia in critically ill patients (catheter-related bloodstream infections (CRBSI), intra-abdominal infections, pneumonia, pyelonephritis and skin and soft-tissue infections (SSTI)).

Results
Twenty-four eligible trials were identified, including one trial focusing exclusively on bacteremia, zero in catheter related bloodstream infection, three in intra-abdominal infection, six in pyelonephritis, thirteen in pneumonia and one in skin and soft tissue infection. Thirteen studies reported on 227 patients with bacteremia allocated to 'shorter' or 'longer' durations of treatment. Outcome data were available for 155 bacteremic patients: neonatal bacteremia (n = 66); intra-abdominal infection (40); pyelonephritis (9); and pneumonia (40). Among bacteremic patients receiving shorter (5-7 days) versus longer (7-21 days) antibiotic therapy, no significant difference was detected with respect to rates of clinical cure (45/52 versus 47/49, risk ratio 0.88, 95% confidence interval [CI] 0.77-1.01), microbiologic cure (28/28 versus 30/32, risk ratio 1.05, 95% CI 0.91-1.21), and survival (15/17 versus 26/29, risk ratio 0.97, 95% CI 0.76-1.23).

Conclusions
No significant differences in clinical cure, microbiologic cure and survival were detected among bacteremic patients receiving shorter versus longer duration antibiotic therapy. An adequately powered randomized trial of bacteremic patients is needed to confirm these findings.
Discovery of active enhancers through bidirectional expression of short transcripts
Authors: Melgar Michael F , Collins Francis S , Sethupathy Praveen 
Published: November 2011

Abstract
Background
Long-range regulatory elements, such as enhancers, exert substantial control over tissue-specific gene expression patterns. Genome-wide discovery of functional enhancers in different cell types is important for our understanding of genome function as well as human disease etiology.

Results
In this study, we developed an in silico approach to model the previously reported phenomenon of transcriptional pausing, accompanied by divergent transcription, at active promoters. We then used this model for large-scale prediction of non-promoter-associated bidirectional expression of short transcripts. Our predictions were significantly enriched for DNase hypersensitive sites, histone H3 lysine 27 acetylation (H3K27ac), and other chromatin marks associated with active rather than poised or repressed enhancers. We also detected modest bidirectional expression at binding sites of the CCCTC-factor (CTCF) genome-wide, particularly those that overlap H3K27ac.

Conclusions
Our findings indicate that the signature of bidirectional expression of short transcripts, learned from promoter-proximal transcriptional pausing, can be used to predict active long-range regulatory elements genome-wide, likely due in part to specific association of RNA polymerase with enhancer regions.
Optimisation of whole blood and plasma manganese assay by ICP-MS without use of a collision cell
Authors: Richardson Claire , Roberts Edward , Nelms Simon , Roberts Norman B. 
Published: November 2011

AbstractManganese (Mn) toxicity has been reported in patients receiving total parenteral nutrition. To avoid unnecessary exposure it is recommended by NICE (National Institute for Clinical Excellence) that blood Mn concentrations are monitored. The aim of the study was to develop a method using inductively coupled plasma mass spectrometry (ICP-MS) for the reliable determination of Mn in plasma and whole blood, as indices of acute and chronic exposure.Whole blood and plasma samples were prepared by appropriate dilution (diluent containing 0.005% Triton X-100, 0.2% propan-2-ol, 0.2% butan-1-ol and 1% nitric acid) addition of an internal standard gallium, followed by centrifugation to remove cell debris. Thermo Fisher Scientific ExCell and X Series ICP-MS instruments were used to define and correct for polyatomic interference on Mn assay.Mn was quantified at mass 55 using aqueous calibration and the polyatomic interference from FeH was successfully eliminated by modified (Xt) skimmer cones but not with the collision cell (collision gas 7% HA method has been developed using ICP-MS for the analysis of whole blood and plasma Mn incorporating a novel method of eliminating interference by utilizing the different geometries of the Xt interface cones. The procedure is simple and robust with good precision and recovery over a wide dynamic range.
A Comparison of the Light- Reduction Capacity of Commonly Used Incubator Covers
Authors: Lee Yi-Hui , Malakooti Nima , Lotas Marilyn 
Published: November 2011

Purpose:The use of incubator covers to enhance preterm infants’ rest and recovery is common in the NICU. However, the kinds of covers used vary extensively among and within nurseries. Few data exist on the effectiveness of different types of covers in reducing light levels to the infant. This study compared several types of commonly used incubator covers as to efficacy of light reduction.Design:A descriptive, comparative design was used in this study.Sample:Twenty-three incubator covers were tested, including professional, receiving blanket, hand-crocheted, three-layer quilt, and flannel.Main Outcome Variable:The percentage of light level reduction of different incubator covers under various ambient light level settings.Results:The amount of light reduction provided by incubator covers varies depending on type of fabric as well as percentage of incubator surface shielded by the cover. Dark-colored covers provided greater light reduction than bright/light-colored covers when covers identical in fabric type were compared. The light-reduction efficiency of the covers varied depending on the level of ambient light. Covers provided less light reduction in higher ambient light levels.
Putting Babies “Back to Sleep”: Can We Do Better?
Authors: Levy Raydo Linda , Reu-Donlon Christine 
Published: November 2011

The American Academy of Pediatrics first recommended in 1992 that infants be placed on their backs for sleep to reduce the risk for sudden infant death syndrome (SIDS). Since that time, there has been a national drop in the incidence of SIDS of more than 40 percent. Unfortunately, many parents and other caregivers are still receiving inconsistent information and observing varying practices regarding infant sleep position.This article emphasizes the role of the health care professional in both teaching and modeling these potentially lifesaving practices consistently and unambiguously. Available literature is reviewed regarding attitudes and beliefs about infant sleep positioning, and specific concerns are addressed in order to allow for better tailoring of educational programs.
Neonatal Intravenous Extravasation Injuries: Evaluation of a Wound Care Protocol
Authors: Sawatzky-Dickson Doris , Bodnaryk Karen 
Published: November 2011

Purpose:To evaluate an evidence-based wound protocol for intravenous extravasation injuries in neonates.Sample:Nine newborns with intravenous extravasation injuries. Birth weight: 582–4,404 gm, gestational age: 24–40 weeks.Results:Five wounds were colonized with coagulase-negative Staphylococcus species, two with diphtheroids, three with Enterococcus. There was no evidence of wound infection or systemic infection. Rates of wound healing ranged from one to six weeks.
Midline Catheter Use in the Intensive Care Nursery
Authors: Leick-Rude Mary Kay , Haney Barbara 
Published: November 2011

Purpose: To describe the use of midline catheters in a Level IV, 48-bed NICU over a four-and-a-half-year period.Design: Nonrandomized prospective review of data obtained for quality assurance monitoring.Sample: 1,130 catheters inserted in 858 patients ranging in age at insertion from 1 to 249 days, 360–8,000 gm in weight, and 23–42 weeks gestational age at birth.Outcome Variables: Catheter outcome data related to dwell times; patient characteristics; insertion site; and reason for removal, including failure related to infiltration, leaking, occlusion, dislodgment, infection, phlebitis, or malposition.Results: There was no significant statistical difference in median catheter survival times related to weight or postconceptional age. Overall mean catheter dwell time was 8.7 days. Scalp was the most common insertion site (49 percent), and the site with the longest dwell time was the saphenous vein at the knee, which lasted a mean of 12.9 days. Elective removal represented 43 percent of all removals. Incidence of positive blood culture was 3.5 percent (0.41/1,000 catheter days), with the risk significantly higher if a central line was also in place.
Administration of Comfort Medication at End of Life in Neonates: Effects of Weight
Authors: Matthews Angela Lee , O’Conner-Von Susan 
Published: November 2011

Purpose:To examine whether a relationship exists between a neonate’s weight and the neonate’s receipt of comfort medication between four hours prior to elective ventilator withdrawal and death. It was hypothesized that the greater the neonate’s weight, the more likely the neonate was to receive comfort medication at end of life.Design:A retrospective chart review.Sample:One hundred seventy-one neonates in a midwestern Level III NICU who died after withdrawal of ventilatory support.Results:Of the 171 neonates in the sample, 27.5 percent (n = 47) did not receive comfort medication within the designated time frame; neonates who weighed <800 g were significantly less likely to receive comfort medication than were their heavier cohorts.Conclusion:In this sample, smaller neonates were given comfort medication less often while they were dying than were their larger counterparts.
Discharge Teaching in the NICU: Are Parents Prepared? An Integrative Review of Parents’ Perceptions
Authors: Sneath Nicole 
Published: November 2011

Background:At the end of their infant’s NICU stay, parents are expected to assume full responsibility for their infant’s care. It is important to look at discharge practices from the parents’ points of view to see whether our strategies are effective.Objectives:Review the literature for studies that give insight into parents’ perceptions of the discharge process in order to assist health care providers in evaluating the available research and to identify any gaps in the literature.Method:A literature search was performed to identify published studies that discuss parental perceptions related to their preparedness for their infant’s discharge home from the NICU.Results:Data from the parents’ perspective were lacking. There are limitations in the data that are available. Parents are not prepared for discharge and have unanswered questions. Parental perceptions are different from health care professionals’ perceptions.Discussion:The studies that have been done need to be repeated in different centers, with greater sample sizes, and with subjects of different cultures, ethnicities, and socioeconomic status. There is a need for more research into parental perceptions of preparedness for their infant’s discharge and ways to increase parental preparedness for discharge home from the NICU.