bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strategies to identify future shortages due to interruptions in the health care procurement supply chain and their impact on health services: a method from the English National Health Service
Authors: Grose Jane , Richardson Janet 
Published: August 2013

Objectives The uninterrupted supply of essential items for patient care is crucial for organizations that deliver health care. Many products central to health care are derived from natural resources such as oil and cotton, supplies of which are vulnerable to climate change and increasing global demand. The purpose of this study was to identify which items would have the greatest effect on service delivery and patient outcomes should they no longer be available. Methods Using a consensus development approach, all items bought by one hospital, over one year, were subjected to a filtering process. Criteria were developed to identify at-risk products and assess them against specific risks and opportunities. Seventy-two items were identified for assessment against a range of potential impacts on service delivery and patient outcomes, from no impact to significant impact. Clinical and non-clinical participants rated the items. Results In the category of significant impact, consensus was achieved for 20 items out of 72. There were differences of opinion between clinical and non-clinical participants in terms of significant impact in relation to 18 items, suggesting that priority over purchasing decisions may create areas of conflict. Reducing reliance on critically scarce resources and reducing demand were seen as the most important criteria in developing sustainable procurement. Conclusion The method was successful in identifying items vulnerable to supply chain interruption and should be repeated in other areas to test its ability to adapt to local priorities, and to assess how it functions in a variety of public and private settings.
A Good Living Versus A Good Life
Authors: Chalofsky Neal , Cavallaro Liz 
Published: August 2013

The Problem The expectation for meaningful work and work–life integration is firmly entrenched in the minds of the GenerationY/Millennial generations in the workplace. Yet, in updating the literature and rethinking the impact on Chalofsky’s (2003) construct for meaningful work, the question arose as to whether meaningful work can and should exist in a vacuum or should it be viewed as part of a meaningful life. If so, what are the implications for the construct and for human resource development (HRD). How far can and should HRD go to help ensure a meaningful and purposeful life for present and future generations in the workplace? The Solution This article provides a sketch of the current research and thinking about meaningful work and a basis for the rest of the articles in this issue. The tightness of the “fit” between self and work can determine how meaningful one’s work is perceived. How work fits within a meaningful life, and how one’s life fits within the context of the organization, the community, the society, and the planet can shape a meaningful existence. The Stakeholders The intended audience for this article includes HRD scholars, scholar-practitioners, consultants, and students interested in the construct of meaningful work, and the implications of reframing HRD around meaning and purpose.
Cellular mechanisms underlying failed beta cell regeneration in offspring of protein-restricted pregnant mice
Authors: Cox Aaron R , Beamish Christine A , Carter David E , Arany Edith J , Hill David J 
Published: August 2013

Low birth weight and poor foetal growth following low protein (LP) exposure are associated with altered islet development and glucose intolerance in adulthood. Additionally, LP-fed offspring fail to regenerate their β-cells following depletion with streptozotocin (STZ) in contrast to control-fed offspring that restore β-cell mass. Our objective was to identify signalling pathways and cellular functions that may be critically altered in LP offspring rendering them susceptible to developing long-term glucose intolerance and decreased β-cell plasticity. Pregnant Balb/c mice were fed a control (C; 20% protein) or an isocaloric LP (8% protein) diet throughout gestation and C diet thereafter. Female offspring were injected intraperitoneally with 35 mg/kg STZ or vehicle on days 1 to 5 for each dietary treatment. At 30 days of age, total RNA was extracted from pancreatic tissue for microarray analysis using the Affymetrix GeneChip Mouse Genome 430 2.0. Gene and protein expression were quantified from isolated islets. Finally, β-cell proliferation was determined in vitro following REG1α treatment. The microarray data and GO enrichment analysis indicated that foetal protein restriction alters the early expression of genes necessary for many cell functions, such as oxidative phosphorylation and free radical scavenging. Expression of Reg1 was upregulated following STZ, whereas protein content was decreased in LP + STZ islets. Furthermore, REG1α failed to stimulate β-cell proliferation in vitro in LP + STZ islets. Therefore, early nutritional insults may programme the Reg1 pathway resulting in a limited ability to increase β-cell mass during metabolic stress. In conclusion, this study implicates the Reg1 pathway in β-cell regeneration and describes altered programming of gene expression in LP offspring, which underlies later development of cell dysfunction and glucose intolerance in adulthood.
Core Stabilization Exercise Prescription, Part I
Authors: Brumitt Jason , Matheson J. W. , Meira Erik P. 
Published: August 2013

Context: Injury to the low back can cause significant pain and dysfunction, which can affect an athlete’s performance and result in time lost from sport. A common conservative treatment is therapeutic core stabilization exercises, which can address pain and musculoskeletal dysfunction in patients with low back pathology. Evidence Acquisition: MEDLINE and CINAHL were searched (from 1966 to March 2013) to identify relevant research. Keywords and keyword combinations searched included motor control exercise, segmental stabilization, core stabilization, transversus abdominis, multifidi, and low back pain. Results: There are 2 popular rehabilitation strategies to assess core function and promote core stabilization. Each has been developed based on biomechanical models of lumbar segmental stability and observed motor control dysfunction in patients with low back pain. Conclusion: Controversy exists among clinical and research groups as to the optimal strategy for an athlete with low back pain.
Feasibility of the Nintendo WiiFit™ for improving walking in individuals with a lower limb amputation
Authors: Imam Bita , Miller William C , McLaren Linda , Chapman Paul , Finlayson Heather 
Published: August 2013

Objectives: To evaluate the feasibility of the Nintendo WiiFit™ as an adjunct to usual therapy in individuals with a lower limb amputation. Methods: The study was a Multiple Baseline (AB) Single Subject Research Design. Subjects were ≥19 years old, had their first unilateral transtibial or transfemoral amputation  ≤12 months ago, and were participating in prosthetic training. WiiFit training was provided for 30 min, 5 times a week, for a minimum of 2 and a maximum of 6 weeks in addition to usual therapy. Feasibility indicators were safety, post-intervention fatigue and pain levels, adherence, and subject’s acceptability of the program as measured by the Short Feedback Questionnaire–modified (SFQ-M). The primary clinical outcome was walking capacity assessed by the 2 Minute Walk Test (2MWT). The secondary clinical outcomes were the Short Physical Performance Battery, L-test, and Activities-Specific Balance Confidence. Results: Subjects (4 transtibial; 2 transfemoral) had a median age of 48.5 years (range = 45–59 years). No adverse events associated with the intervention occurred. Median pain and fatigue levels were 1.3 (range = 0.5–3.5) and 3.1 (range = 1.4–4.1), respectively. Median adherence was 80%. Subjects found the WiiFit enjoyable and acceptable (median SFQ-M = 35). Five subjects showed statistical improvement on the 2MWT and four on the secondary outcomes ( p < 0.05). Conclusion: The WiiFit intervention was found to be feasible in individuals with unilateral lower limb amputation. This research provides the foundation for future clinical research investigating the use of the WiiFit as a viable adjunctive therapy to improve outcomes in individuals with unilateral lower limb amputation who are participating in prosthetic training.
Axl, a prognostic and therapeutic target in acute myeloid leukemia mediates paracrine crosstalk of leukemia cells with bone marrow stroma
Authors: Ben-Batalla Isabel , Schultze Alexander , Wroblewski Mark , Erdmann Robert , Heuser Michael , Waizenegger Jonas S. , Riecken Kristoffer , Binder Mascha , Schewe Denis , Sawall Stefanie , Witzke Victoria , Cubas-Cordova Miguel , Janning Melanie , Wellbrock Jasmin , Fehse Boris , Hagel Christian , Krauter Jürgen , Ganser Arnold , Lorens James B. , Fiedler Walter , Carmeliet Peter , Pantel Klaus , Bokemeyer Carsten , Loges Sonja 
Published: August 2013

Key PointsAxl inhibition by BGB324 is active in FLT3-mutated and FLT3 wild-type AML, and presence of Axl and Gas6 are required for therapeutic efficacy. AML cells educate BMDSCs to secrete Gas6, which mediates leukemia cell proliferation and therapy resistance.
Composite schemes for variational inequalities over equilibrium problems and variational inclusions
Authors: Yao Yonghong , Kang Jung Im , Cho Yeol Je , Liou Yeong-Cheng 
Published: August 2013

Abstract
Let C be a nonempty closed convex subset of a Hilbert space H, and let

T
:
H
→
H

be a nonlinear mapping. It is well known that the following classical variational inequality has been applied in many areas of applied mathematics, modern physical sciences, computerized tomography and many others. Find a point

x
∗

∈
C

such that

〈
T

x
∗

,
x
−

x
∗

〉

≥
0
,

∀
x
∈
C
.

In this paper, we consider the following variational inequality. Find a point

x
∗

∈
C

such that

〈
(
F
−
γ
f
)

x
∗

,
x
−

x
∗

〉

≥
0
,

∀
x
∈
C
,

and, for solutions of the variational inequality (B) with the feasibility set C, which is the intersection of the set of solutions of an equilibrium problem and the set of a solutions of a variational inclusion, construct the two composite schemes, that is, the implicit and explicit schemes to converge strongly to the unique solution of the variational inequality (B).
Recently, many authors introduced some kinds of algorithms for solving the variational inequality problems, but, in fact, our two schemes are more simple for finding solutions of the variational inequality (B) than others.

MSC:49J30, 47H10, 47H17, 49M05.
Geological and climatic changes in quaternary shaped the evolutionary history of Calibrachoa heterophylla, an endemic South-Atlantic species of petunia
Authors: Mäder Geraldo , Fregonezi Jéferson N , Lorenz-Lemke Aline P , Bonatto Sandro L , Freitas Loreta B 
Published: August 2013

AbstractBackgroundThe glacial and interglacial cycles that characterized the Quaternary greatly affected the distribution and genetic diversity of plants. In the Neotropics, few phylogeographic studies have focused on coastal species outside of the Atlantic Rainforest. Climatic and sea level changes during the Quaternary played an important role in the evolutionary history of many organisms found in coastal regions. To contribute to a better understanding of plant evolution in this environment in Southern South America, we focused onCalibrachoa heterophylla(Solanaceae), an endemic and vulnerable wild petunia species from the South Atlantic Coastal Plain (SACP).ResultsWe assessed DNA sequences from two cpDNA intergenic spacers and analyzed them using a phylogeographic approach. The present phylogeographic study reveals the influence of complex geologic and climatic events on patterns of genetic diversification. The results indicate thatC. heterophyllaoriginated inland and subsequently colonized the SACP; the data show that the inland haplogroup is more ancient than the coastal one and that the inland was not affected by sea level changes in the Quaternary. The major diversification ofC.heterophyllathat occurred after 0.4 Myr was linked to sea level oscillations in the Quaternary, and any diversification that occurred before this time was obscured by marine transgressions that occurred before the coastal sand barrier’s formation. Results of the Bayesian skyline plot showed a recent population expansion detected inC. heterophyllaseems to be related to an increase in temperature and humidity that occurred at the beginning of the Holocene.ConclusionsThe geographic clades have been formed when the coastal plain was deeply dissected by paleochannels and these correlate very well with the distributional limits of the clades. The four major sea transgressions formed a series of four sand barriers parallel to the coast that progressively increased the availability of coastal areas after the regressions and that may have promoted the geographic structuring of genetic diversity observed today. The recent population expansion for the entire species may be linked with the event of marine regression after the most recent sea transgression at ~5 kya.
Identification of differential expression genes associated with host selection and adaptation between two sibling insect species by transcriptional profile analysis
Authors: Li Haichao , Zhang Hao , Guan Ruobing , Miao Xuexia 
Published: August 2013

Abstract

Background
Cotton bollworm (Helicoverpa armigera) and oriental tobacco budworm (Helicoverpa assulta) are noctuid sibling species. Under artificial manipulation, they can mate and produce fertile offspring. As serious agricultural insect pests, cotton bollworms are euryphagous insects, but oriental tobacco budworms are oligophagous insects. To identify the differentially expressed genes that affect host recognition and host adaptation between the two species, we constructed digital gene expression tag profiles for four developmental stages of the two species. High-throughput sequencing results indicated that we have got more than 23 million 17nt clean tags from both species, respectively. The number of unique clean tags was nearly same in both species (approximately 357,000).

Results
According to the gene annotation results, we identified 83 and 68 olfaction related transcripts from H. armigera and H. assulta, respectively. At the same time, 1137 and 1138 transcripts of digestion enzymes were identified from the two species. Among the olfaction related transcripts, more odorant binding protein and G protein-coupled receptor were identified in H. armigera than in H. assulta. Among the digestion enzymes, there are more detoxification enzyme, e.g. P450, carboxypeptidase and ATPase in H. assulta than in H. armigera. These differences partially explain that because of the narrow host plant range of H. assulta, more detoxification enzymes would help them increase the food detoxification and utilization efficiency.

Conclusions
This study supplied some differentially expressed genes affecting host selection and adaptation between the two sibling species. These genes will be useful information for studying on the evolution of host plant selection. It also provides some important target genes for insect species-specific control by RNAi technology.
Comprehensive characterization of erythroid-specific enhancers in the genomic regions of human Krüppel-like factors
Authors: Xiong Qian , Zhang Zhaojun , Chang Kai-Hsin , Qu Hongzhu , Wang Hai , Qi Heyuan , Li Yajuan , Ruan Xiuyan , Yang Yaran , Yang Yadong , Li Yanming , Sandstrom Richard , Sabo Peter J , Li Qiliang , Stamatoyannopoulos George , Stamatoyannopoulos John A , Fang Xiangdong 
Published: August 2013

Abstract

Background
Mapping of DNase I hypersensitive sites (DHSs) is a powerful tool to experimentally identify cis-regulatory elements (CREs). Among CREs, enhancers are abundant and predominantly act in driving cell-specific gene expression. Krüppel-like factors (KLFs) are a family of eukaryotic transcription factors. Several KLFs have been demonstrated to play important roles in hematopoiesis. However, transcriptional regulation of KLFs via CREs, particularly enhancers, in erythroid cells has been poorly understood.

Results
In this study, 23 erythroid-specific or putative erythroid-specific DHSs were identified by DNase-seq in the genomic regions of 17 human KLFs, and their enhancer activities were evaluated using dual-luciferase reporter (DLR) assay. Of the 23 erythroid-specific DHSs, the enhancer activities of 15 DHSs were comparable to that of the classical enhancer HS2 in driving minimal promoter (minP). Fifteen DHSs, some overlapping those that increased minP activities, acted as enhancers when driving the corresponding KLF promoters (KLF-Ps) in erythroid cells; of these, 10 DHSs were finally characterized as erythroid-specific KLF enhancers. These 10 erythroid-specific KLF enhancers were further confirmed using chromatin immunoprecipitation coupled to sequencing (ChIP-seq) data-based bioinformatic and biochemical analyses.

Conclusion
Our present findings provide a feasible strategy to extensively identify gene- and cell-specific enhancers from DHSs obtained by high-throughput sequencing, which will help reveal the transcriptional regulation and biological functions of genes in some specific cells.
Identification of a novel infection-enhancing epitope on dengue prM using a dengue cross-reacting monoclonal antibody
Authors: Luo Ya-Yan , Feng Jun-Jie , Zhou Jun-Mei , Yu Zhi-Zhun , Fang Dan-Yun , Yan Hui-Jun , Zeng Gu-Cheng , Jiang Li-Fang 
Published: August 2013

Abstract

Background
Dengue virus (DENV) infection is the most important arthropod- borne viral disease in human, but antiviral therapy and approved vaccines remain unavailable due to antibody-dependent enhancement (ADE) phenomenon. Many studies showed that pre-membrane (prM)-specific antibodies do not efficiently neutralize DENV infection but potently promote ADE infection. However, most of the binding epitopes of these antibodies remain unknown.

Results
In the present study, we characterized a DENV cross-reactive monoclonal antibody (mAb), 4D10, that neutralized poorly but potently enhanced infection of four standard DENV serotypes and immature DENV (imDENV) over a broad range of concentration. In addition, the epitope of 4D10 was successfully mapped to amino acid residues 14 to18 of DENV1-4 prM protein using a phage-displayed peptide library and comprehensive bioinformatics analysis. We found that the epitope was DENV serocomplex cross-reactive and showed to be highly immunogenic in Balb/c mice. Furthermore, antibody against epitope peptide PL10, like 4D10, showed broad cross-reactivity and weak neutralizing activtity with four standard DENV serotypes and imDENV but significantly promoted ADE infection. These results suggested 4D10 and anti-PL10 sera were infection-enhancing antibodies and PL10 was infection-enhancing epitope.

Conclusions
We mapped the epitope of 4D10 to amino acid residues 14 to18 of DENV1-4 prM and found that this epitope was infection-enhancing. These findings may provide significant implications for future vaccine design and facilitate understanding the pathogenesis of DENV infection.
The duration of sleep promoting efficacy by dual orexin receptor antagonists is dependent upon receptor occupancy threshold
Authors: Gotter Anthony L , Winrow Christopher J , Brunner Joseph , Garson Susan L , Fox Steven V , Binns Jacquelyn , Harrell Charles M , Cui Donghui , Yee Ka Lai , Stiteler Mark , Stevens Joanne , Savitz Alan , Tannenbaum Pamela L , Tye Spencer J , McDonald Terrence , Yao Leon , Kuduk Scott D , Uslaner Jason , Coleman Paul J , Renger John J 
Published: August 2013

Abstract

Background
Drugs targeting insomnia ideally promote sleep throughout the night, maintain normal sleep architecture, and are devoid of residual effects associated with morning sedation. These features of an ideal compound are not only dependent upon pharmacokinetics, receptor binding kinetics, potency and pharmacodynamic activity, but also upon a compound’s mechanism of action.

Results
Dual orexin receptor antagonists (DORAs) block the arousal-promoting activity of orexin peptides and, as demonstrated in the current work, exhibit an efficacy signal window dependent upon oscillating levels of endogenous orexin neuropeptide. Sleep efficacy of structurally diverse DORAs in rat and dog was achieved at plasma exposures corresponding to orexin 2 receptor (OX2R) occupancies in the range of 65 to 80%. In rats, the time course of OX2R occupancy was dependent upon receptor binding kinetics and was tightly correlated with the timing of active wake reduction. In rhesus monkeys, direct comparison of DORA-22 with GABA-A modulators at similar sleep-inducing doses revealed that diazepam produced next-day residual sleep and both diazepam and eszopiclone induced next-day cognitive deficits. In stark contrast, DORA-22 did not produce residual effects. Furthermore, DORA-22 evoked only minimal changes in quantitative electroencephalogram (qEEG) activity during the normal resting phase in contrast to GABA-A modulators which induced substantial qEEG changes.

Conclusion
The higher levels of receptor occupancy necessary for DORA efficacy require a plasma concentration profile sufficient to maintain sleep for the duration of the resting period. DORAs, with a half-life exceeding 8 h in humans, are expected to fulfill this requirement as exposures drop to sub-threshold receptor occupancy levels prior to the wake period, potentially avoiding next-day residual effects at therapeutic doses.
Human immunodeficiency virus, hepatitis C, and inflammatory biomarkers in individuals with alcohol problems: a cross-sectional study
Authors: Armah Kaku A , Quinn Emily K , Cheng Debbie M , Tracy Russell P , Baker Jason V , Samet Jeffrey H , Freiberg Matthew S 
Published: August 2013

AbstractBackgroundAssessing whether hepatitis C (HCV) co-infection with human immunodeficiency virus (HIV) is associated with increased inflammation is complex. The liver, integral to inflammatory biomarker synthesis, is compromised by HCV and alcohol abuse. Using single liver-synthesized biomarkers (e.g. C-reactive protein) to represent inflammation may not be appropriate in HIV/HCV co-infection. We hypothesized that 1) detectable HIV/HCV RNA was independently associated with increased inflammation; 2) a composite inflammation measure describes inflammation differently from single inflammatory biomarkers.MethodsWe compared inflammation by HIV/HCV group in a cohort of 361 HIV infected participants from the HIV-Longitudinal Interrelationships of Viruses and Ethanol study. Inflammatory biomarkers >75th percentile were considered elevated. Associations between HIV/HCV group and elevated biomarkers were analyzed as a composite measure (inflammatory burden) or individually. We defined inflammatory burden as number of concurrently elevated biomarkers. Biomarkers included interleukin-6 (IL-6), C-reactive protein (CRP), cystatin C, serum amyloid-A (SAA), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10). Covariates: alcohol, liver fibrosis, comorbidities, CD4 count, antiretroviral therapy, substance use.ResultsDetectable HIV and HCV RNA (OR = 2.49; 95% CI = 1.05–5.89) and detectable HCV RNA alone (2.95; 1.08–8.01) were independently associated with increased odds of having a greater inflammatory burden compared to undetectable viremia. Elevated IL-10 (7.79; 1.90–31.97) and TNF-α (7.70; 1.42–41.83) were independently associated with detectable HIV and HCV RNA. Elevated IL-10 was also associated with detectable HCV RNA alone (5.51; 1.17, 25.84).ConclusionsDetectable HIV and HCV replication versus undetectable replication was associated with inflammatory burden and certain inflammatory biomarkers independently of alcohol consumption, liver fibrosis and other comorbidities.