bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of analgesia in mountain rescue casualties with moderate or severe pain
Authors: Ellerton John Alexander , Greene Mike , Paal Peter 
Published: February 2013

ObjectivesTo assess the effectiveness of analgesia used in mountain rescue (MR) in casualties with moderate or severe pain. To determine if a verbal numeric pain score is practical in this environment. To describe the analgesic strategies used by MR.DesignProspective, descriptive study.SettingFifty-one MR teams in England and Wales. The study period was 1 September 2008 to 31 August 2010.Participants92 MR casualties with a pain scoreof 4/10 or greater.Main outcome38% of casualties achieved a pain reduction of 50% or greater in their initial score at 15 min and 60.2% had achieved this at handover.ResultsThe initial pain score was 8 (median), reducing to 5 at 15 min and 3 at handover. The mean pain reduction was 2.5±2.4 at 15 min and 3.9±2.5 at handover. 80 casualties (87%) were treated with an opioid and seven had two different opioids administered. Seven main strategies were identified in which the principal agent was entonox, intramuscular opioid, oral analgesia, fentanyl lozenge, intranasal or intravenous opioid. The choice of strategy varied with the skills of the casualty carer.ConclusionsPain should be assessed using a pain score. When possible, intravenous opioid is the gold standard to achieve early and continuing pain control in patients with moderate or severe pain. Entonox and oral analgesics, as sole agents, have limited use in moderate or severe pain. Intranasal opioid and fentanyl lozenge are effective, and appropriate in MR. Research priorities include bioavailability in different environmental conditions and patient's satisfaction with their pain management.
Human Papillomavirus Load in Eyebrow Hair Follicles and Risk of Cutaneous Squamous Cell Carcinoma
Authors: Neale Rachel E. , Weissenborn Soenke , Abeni Damiano , Bavinck Jan Nico Bouwes , Euvrard Sylvie , Feltkamp Mariet C.W. , Green Adele C. , Harwood Catherine , de Koning Maurits , Naldi Luigi , Nindl Ingo , Pawlita Michael , Proby Charlotte , Quint Wim G. , Waterboer Tim , Wieland Ulrike , Pfister Herbert 
Published: February 2013

AbstractBackground: Beta-human papillomavirus (betaPV) may play a role in the development of cutaneous squamous cell carcinoma (SCC). However betaPV is highly prevalent, and it may only be people with a higher viral load who have increased risk of SCCs. We therefore examined the association between betaPV load and SCCs.Methods: We recruited 448 immunocompetent cases with SCCs and 464 controls from Italy and Australia and 497 immunosuppressed organ transplant recipients (OTR; 179 cases and 318 controls) from Europe. We used reverse hybridization to genotype 25 betaPV types in eyebrow hair follicles and determined the viral load for eight selected types using quantitative PCR. We used logistic regression to assess associations between type-specific and cumulative viral load and SCCs.Results: Australian and OTR participants in the highest cumulative load tertile were at significantly higher risk of SCCs than those in the lowest tertile. Those with more than four betaPV types in the high load tertile were at approximately three-fold increased risk of SCCs. In Australia, HPV23 and 36 loads were significantly associated with SCCs, with borderline associations for HPV5 and 38. In OTR, HPV8 and 38 loads were significantly associated and HPV20 and 36 were borderline. We found little evidence for an association between load and SCCs in Italy.Conclusions: High viral load may be associated with risk of cutaneous SCCs, with total load seemingly more important than the load of any specific type.Impact: Our findings lend weight to the hypothesis that HPV plays a role in skin carcinogenesis. Cancer Epidemiol Biomarkers Prev; 22(4); 719–27. ©2013 AACR.
First-in-Human Phase 0 Trial of Oral 5-Iodo-2-Pyrimidinone-2′-Deoxyribose in Patients with Advanced Malignancies
Authors: Kummar Shivaani , Anderson Larry , Hill Kimberly , Majerova Eva , Allen Deborah , Horneffer Yvonne , Ivy S. Percy , Rubinstein Larry , Harris Pamela , Doroshow James H. , Collins Jerry M. 
Published: February 2013

Abstract
Purpose: Iododeoxyuridine (IdUrd), a halogenated nucleoside analog, produced clinical responses when administered as a radiosensitizer via continuous intravenous (c.i.v.) infusion over the course of radiotherapy. We conducted a phase 0 trial of 5-iodo-2-pyrimidinone-2′-deoxyribose (IPdR), an oral prodrug of IdUrd, in patients with advanced malignancies to assess whether the oral route was a feasible alternative to c.i.v. infusion before embarking on large-scale clinical trials. Plasma concentrations of IPdR, IdUrd, and other metabolites were measured after a single oral dose of IPdR.
Experimental Design: Eligible patients had advanced refractory malignancies. A single oral dose of IPdR was administered per patient and patients were followed for 14 days for safety assessments; dose escalations were planned (150, 300, 600, 1,200, and 2,400 mg) with one patient per dose level and 6 patients at the highest dose level. Blood sampling was conducted over a 24-hour period for pharmacokinetic analysis.
Results: There were no drug-related adverse events. Plasma concentrations of IdUrd generally increased as the dose of IPdR escalated from 150 to 2,400 mg. All patients at the 2,400 mg dose achieved peak IdUrd levels of (mean ± SD) 4.0 μmol/L ± 1.02 μmol/L at 1.67 ± 1.21 hours after IPdR administration.
Conclusions: Adequate plasma levels of IdUrd were obtained to justify proceeding with a phase I trial of IPdR in combination with radiation. This trial shows the ability of a small, phase 0 study to provide critical information for decision-making regarding future development of a drug. Clin Cancer Res; 19(7); 1852–7. ©2013 AACR.
The Natural History of Depression up to 15 Years After Stroke
Authors: Ayerbe Luis , Ayis Salma , Crichton Siobhan , Wolfe Charles D.A. , Rudd Anthony G. 
Published: February 2013

Background and Purpose—
Evidence on the natural history of depression after stroke is still insufficient to inform prognosis and treatment strategies. This study estimates the incidence, cumulative incidence, prevalence, time of onset, duration, and recurrence rate of depression up to 15 years after stroke.

Methods—
Data from patients registered in the South London Stroke Register between 1995 and 2009 were used (N=4022 at registration. Maximum number of participants for these analyses n=1233). Depression was assessed in all patients with the Hospital Anxiety and Depression Scale (scores >7=depression) 3 months after stroke, 1 year after stroke, and annually thereafter up to 15 years after stroke. Inverse probability weighting was used to calculate the estimates accounting for missing data.

Results—
The poststroke incidence of depression ranged from 7% to 21% in the 15 years after a stroke, with cumulative incidence of 55% and prevalence ranging from 29% to 39%. Most episodes of depression started within a year of stroke, with 33% of the cases starting in the 3 months after a stroke, and none from year 10 onward. Fifty percent of the patients with depression at 3 months had recovered 1 year after stroke. The proportion of recurrent episodes of depression after stroke increased gradually from 38% in year 2 to 100% in years 14 and 15.

Conclusions—
The natural history of depression after stroke is dynamic. Depression affects most of the stroke patients with episodes that have a short duration but a high risk of recurrence in the long term.
Factors Associated With Advance Care Planning Discussions by Area Agency on Aging Care Managers
Authors: Hazelett Susan , Baughman Kristin R. , Palmisano Barbara R. , Sanders Margaret , Ludwick Ruth E. 
Published: February 2013

Background: Initiating advance care planning (ACP) discussions in the home may prevent avoidable hospitalizations by elucidating goals of care. Area agencies on aging care managers (AAACMs) work in the home with high-risk consumers. Purpose: To determine which AAACM characteristics contribute to an increased frequency of ACP discussions. Method: Cross-sectional investigator-generated surveys administered to AAACMs at 3 AAAs in Ohio. Results: Of 289 AAACMs, 182 (63%) responded. The more experience and comfort AAACMs felt with ACP discussions, the more likely they were to initiate ACP discussions. Discussion: It may be necessary to build interactive educational experiences where, for example, AAACMs are asked to fill out their own advance directives and/or facilitate others in ACP discussions to improve experience and comfort with ACP discussions.
Effects of antihypertensive therapy on glucose, insulin metabolism, left ventricular diastolic dysfunction and renin system in overweight and obese hypertensives
Authors: De Rosa Maria Leonarda , Musella Francesca , Ilardi Federica , D’Amore Carmen , Luciano Rossella , Maresca Fabio 
Published: February 2013

Background: We attempted to test the hypothesis that the direct renin inhibitor aliskiren can improve diastolic dysfunction, glucose, and insulin metabolism (GIM) in overweight and obese hypertensive patients. Methods and results: Seventy-eight hypertensive patients were divided into two groups: 38 treated with aliskiren for six months, and 40 treated without aliskiren but with only traditional anti-hypertensive therapy, as controls. Doppler mitral flow velocity patterns were assessed before and after aliskiren during a six-month period. GIM (three-hour intravenous glucose tolerance test) was measured after four to six weeks of washout and six months of treatment. The mitral E/A ratio increased from 0.65 ± 0.11 to 0.75 ± 0.19. None of the indexes changed in the control group. In the control group, GIM parameters, fasting glucose levels (5.3 ± 0.9 to 6.0 ± 1.5 mmol/l; p = 0.003), fasting insulin levels (121 ± 121 to 189 ± 228 pmol/l; p = 0.03), and most other relevant metabolic measures ( p < 0.05 for all) significantly worsened. Aliskiren did not affect GIM. In the control group LVM/height was not affected (119 ± 12 to 120 ± 17 g/m; p = 0.8), whereas aliskiren significantly reduced LVM/height (120 ± 13 to 111 ± 19 g/m; p = 0.04). Conclusions: Optimal target BP was achieved in the group as a whole and in both obese patient groups, while benefits to cardiac structure were of a smaller magnitude. In high-risk, overweight/obese patients with hypertension, traditional therapy provides significantly greater BP- versus aliskiren-lowering throughout the 24-hour dosing interval. Therefore in obese, hypertensive individuals, adequate and similar blood pressure control was achieved with aliskiren; however, the aliskiren group and not the control group was associated with a more favorable GIM profile and led to a significant regression of LVM; overall aliskiren-based treatment offers sustained control of PRA.
Continuing clozapine with granulocyte colony-stimulating factor in patients with neutropenia
Authors: Khan Al Aditya , Harvey Jake , Sengupta Samrat 
Published: February 2013

Background: The current guidelines dictate that clozapine should be stopped following the emergence of neutropenia. Various alternative approaches have been tried in the past, among them one rarely used alternative being to continue treatment with clozapine with coprescription of granulocyte colony-stimulating factor (G-CSF). Aim and method: In this case series we aim to describe the treatment and progress of a number of patients in a secure psychiatric hospital in the UK. These patients were restarted on clozapine in combination with G-CSF, in spite of previous neutropenia associated with clozapine treatment. Discussion and conclusion: We hope that this case series will raise the profile of a potentially effective alternative to discontinuing clozapine after neutropenia.
Discovery of novel biomarkers and phenotypes by semantic technologies
Authors: Trugenberger Carlo A , Wälti Christoph , Peregrim David , Sharp Mark E , Bureeva Svetlana 
Published: February 2013

Abstract

Background
Biomarkers and target-specific phenotypes are important to targeted drug design and individualized medicine, thus constituting an important aspect of modern pharmaceutical research and development. More and more, the discovery of relevant biomarkers is aided by in silico techniques based on applying data mining and computational chemistry on large molecular databases. However, there is an even larger source of valuable information available that can potentially be tapped for such discoveries: repositories constituted by research documents.

Results
This paper reports on a pilot experiment to discover potential novel biomarkers and phenotypes for diabetes and obesity by self-organized text mining of about 120,000 PubMed abstracts, public clinical trial summaries, and internal Merck research documents. These documents were directly analyzed by the InfoCodex semantic engine, without prior human manipulations such as parsing. Recall and precision against established, but different benchmarks lie in ranges up to 30% and 50% respectively. Retrieval of known entities missed by other traditional approaches could be demonstrated. Finally, the InfoCodex semantic engine was shown to discover new diabetes and obesity biomarkers and phenotypes. Amongst these were many interesting candidates with a high potential, although noticeable noise (uninteresting or obvious terms) was generated.

Conclusions
The reported approach of employing autonomous self-organising semantic engines to aid biomarker discovery, supplemented by appropriate manual curation processes, shows promise and has potential to impact, conservatively, a faster alternative to vocabulary processes dependent on humans having to read and analyze all the texts. More optimistically, it could impact pharmaceutical research, for example to shorten time-to-market of novel drugs, or speed up early recognition of dead ends and adverse reactions.
Common bean (Phaseolus vulgarisL.) PvTIFY orchestrates global changes in transcript profile response to jasmonate and phosphorus deficiency
Authors: Aparicio-Fabre Rosaura , Guillén Gabriel , Loredo Montserrat , Arellano Jesús , Valdés-López Oswaldo , Ramírez Mario , Íñiguez Luis P , Panzeri Dario , Castiglioni Bianca , Cremonesi Paola , Strozzi Francesco , Stella Alessandra , Girard Lourdes , Sparvoli Francesca , Hernández Georgina 
Published: February 2013

Abstract

Background

TIFY is a large plant-specific transcription factor gene family. A subgroup of TIFY genes named JAZ (Jasmonate-ZIM domain) has been identified as repressors of jasmonate (JA)-regulated transcription in Arabidopsis and other plants. JA signaling is involved in many aspects of plant growth/development and in defense responses to biotic and abiotic stresses. Here, we identified the TIFY genes (designated PvTIFY) from the legume common bean (Phaseolus vulgaris) and functionally characterized PvTIFY10C as a transcriptional regulator.

Results
Nineteen genes from the PvTIFY gene family were identified through whole-genome sequence analysis. Most of these were induced upon methyl-JA elicitation. We selected PvTIFY10C as a representative JA-responsive PvTIFY gene for further functional analysis. Transcriptome analysis via microarray hybridization using the newly designed Bean Custom Array 90 K was performed on transgenic roots of composite plants with modulated (RNAi-silencing or over-expression) PvTIFY10C gene expression. Data were interpreted using Gene Ontology and MapMan adapted to common bean. Microarray differential gene expression data were validated by real-time qRT-PCR expression analysis. Comparative global gene expression analysis revealed opposite regulatory changes in processes such as RNA and protein regulation, stress responses and metabolism in PvTIFY10C silenced vs. over-expressing roots. These data point to transcript reprogramming (mainly repression) orchestrated by PvTIFY10C. In addition, we found that several PvTIFY genes, as well as genes from the JA biosynthetic pathway, responded to P-deficiency. Relevant P-responsive genes that participate in carbon metabolic pathways, cell wall synthesis, lipid metabolism, transport, DNA, RNA and protein regulation, and signaling were oppositely-regulated in control vs. PvTIFY10C-silenced roots of composite plants under P-stress. These data indicate that PvTIFY10C regulates, directly or indirectly, the expression of some P-responsive genes; this process could be mediated by JA-signaling.

Conclusion
Our work contributes to the functional characterization of PvTIFY transcriptional regulators in common bean, an agronomically important legume. Members from the large PvTIFY gene family are important global transcriptional regulators that could participate as repressors in the JA signaling pathway. In addition, we propose that the JA-signaling pathway involving PvTIFY genes might play a role in regulating the plant response/adaptation to P-starvation.
Application of neural oscillators to study the effects of walking speed on rhythmic activations at the ankle
Authors: Chong Sook-Yee , Wagner Heiko , Wulf Arne 
Published: February 2013

Abstract

Background
Spinal pattern generators (SPG) are neural networks in the spinal cord that do not require a central input from the brain to generate a motor output. We wanted to determine whether SPG can adapt to the changing motor demands from walking at different speeds, and performing silly walks.

Methods
An SPG model consisting of an oscillator made up of two neurons was utilised in this study; one neuron activates the soleus and the other activates the tibialis anterior. The outputs of the SPG model therefore represent the electromyographic measurements from each muscle. Seven healthy subjects were requested to perform silly walks, normal walking at self-selected speed (4.8 ± 0.5 km/h), 3.5 km/h, 4.0 km/h and 4.5 km/h on a treadmill. Loading and hip angles were used as inputs into the model.

Results
No significant differences in the model parameters were found between normal walking at self-selected speed and other walking speeds. Only the adaptation time constant for the ankle flexor during silly walks was significantly different from the other normal walking trials.

Conclusion
We showed that SPG in the spinal cord can interpret and respond accordingly to velocity-dependent afferent information. Changes in walking speed do not require a different motor control mechanism provided there is no disruption to the alternating muscular activations generated at the ankle.
Basic surface-active properties in the homologous series of β-alkyl (C12H25/C18H37) polyethyleneoxy (n = 0-20) propionamides
Authors: Riviş Adrian , Bujanca Gabriel , Traşcă Teodor 
Published: February 2013

Abstract

Background
Heterogeneous β-Alkyl (C12H25/C18H37) polyethyleneoxy (n = 0-20) propionamides [R(EO)nPD] represent new “hybrid” nonionic-ionic colloidal structures in the field of surface-active products (technical products). These “niche” compounds have three structural and compositional characteristics that also define their basic colloidal properties: mixture of R and PEO chain homologues; specific conformations due to the PEO chains; and the presence of side products from the addition of higher alcohols, polyethyleneglycols and traces of water to acrylamide. The proposed major objective of this paper is the basic informative colloidal characterization (functional classification, HLB balance, surface tension, critical micelle concentration) in direct correlation with the structural changes in the homologous series of LM(EO)nPD and CS(EO)nPD. The structures were obtained either indirectly by cyanoethylation followed by partial acid hydrolysis of the corresponding β-propionitriles, or directly by the nucleophilic addition under alkaline catalysis of linear higher alcohols C12H25/C14H29 (7/3) (LM) and C16H33/C18H37 (CS) as such and heterogeneous polyethoxylated (n = 3-20) to acrylamide monomer, through an adapted classic reaction scheme.

Results
In the series of basic colloidal characteristics investigated the structure-surface activity dependence is confirmed. Their indicative character for R(EO)nPD is based on the assumption that the structures studied are not unitary (heterogeneous) because: a) the hydrophobic chains C12H25/C18H37 have been grouped in two variants, C12H25/C14H29 (LM); C16H33/C18H37 (CS), each with an internal mass ratio of 7/3; b) the hydrophilic polyoxyethylene chains (n = 3-20) have polydisperse character; the meaning and value the oligomerization degree, n, is that of weighted average. In these conditions the surface tension increases proportionally with the oligomerization degree of the polyoxyethylene chain, while the critical micelle concentration decreases in the same homologous series as well as with the increase of the hydrophobic chain in the C12H25 to C18H37 series. A mechanism of micellization is proposed, consistent with the experimental data recorded and the hypotheses known from the consulted literature.

Conclusions
The idea of the obtaining and basic colloidal characterization of heterogeneous R(EO)nPD is justified. The knowledge and constructive approach of the heterogeneous character confirm the basic surface-active potential of R(EO)nPD, the structure-colloidal characteristics dependence and justifies further, more extensive research.
Transporter engineering for improved tolerance against alkane biofuels in Saccharomyces cerevisiae
Authors: Chen Binbin , Ling Hua , Chang Matthew Wook 
Published: February 2013

Abstract

Background
Hydrocarbon alkanes, components of major fossil fuels, are considered as next-generation biofuels because their biological production has recently been shown to be possible. However, high-yield alkane production requires robust host cells that are tolerant against alkanes, which exhibit cytotoxicity. In this study, we aimed to improve alkane tolerance in Saccharomyces cerevisiae, a key industrial microbial host, by harnessing heterologous transporters that potentially pump out alkanes.

Results
To this end, we attempted to exploit ABC transporters in Yarrowia lipolytica based on the observation that it utilizes alkanes as a carbon source. We confirmed the increased transcription of ABC2 and ABC3 transporters upon exposure to a range of alkanes in Y. lipolytica. We then showed that the heterologous expression of ABC2 and ABC3 transporters significantly increased tolerance against decane and undecane in S. cerevisiae through maintaining lower intracellular alkane level. In particular, ABC2 transporter increased the tolerance limit of S. cerevisiae about 80-fold against decane. Furthermore, through site-directed mutagenesis for glutamate (E988 for ABC2, and E989 for ABC3) and histidine (H1020 for ABC2, and H1021 for ABC3), we provided the evidence that glutamate was essential for the activity of ABC2 and ABC3 transporters, with ATP most likely to be hydrolyzed by a catalytic carboxylate mechanism.

Conclusions
Here, we demonstrated that transporter engineering through expression of heterologous efflux pumps led to significantly improved tolerance against alkane biofuels in S. cerevisiae. We believe that our results laid the groundwork for developing robust alkane-producing yeast cells through transporter engineering, which will greatly aid in next-generation alkane biofuel production and recovery.