bluuebunny/crossref_metadata_2025_split huggingface dataset:
Target enrichment using parallel nanoliter quantitative PCR amplification
Authors: De Wilde Bram , Lefever Steve , Dong Wes , Dunne Jude , Husain Syed , Derveaux Stefaan , Hellemans Jan , Vandesompele Jo 
Published: March 2014

Abstract

Background
Next generation targeted resequencing is replacing Sanger sequencing at high pace in routine genetic diagnosis. The need for well validated, high quality enrichment platforms to complement the bench-top next generation sequencing devices is high.

Results
We used the WaferGen Smartchip platform to perform highly parallelized PCR based target enrichment for a set of known cancer genes in a well characterized set of cancer cell lines from the NCI60 panel. Optimization of PCR assay design and cycling conditions resulted in a high enrichment efficiency. We provide proof of a high mutation rediscovery rate and have included technical replicates to enable SNP calling validation demonstrating the high reproducibility of our enrichment platform.

Conclusions
Here we present our custom developed quantitative PCR based target enrichment platform. Using highly parallel nanoliter singleplex PCR reactions makes this a flexible and efficient platform. The high mutation validation rate shows this platform’s promise as a targeted resequencing method for multi-gene routine sequencing diagnostics.
Patient and health system delays in the diagnosis and treatment of new and retreatment pulmonary tuberculosis cases in Malawi
Authors: Makwakwa Lumbani , Sheu Mei-ling , Chiang Chen-Yuan , Lin Shoei-Loong , Chang Peter W 
Published: March 2014

Abstract

Background
Tuberculosis (TB) control remains a challenge in Malawi despite the National TB Control Program since 1984. This study aimed at measuring patient and health system delays and identifying factors associated with these delays.

Methods
A cross-sectional survey of 588 pulmonary TB patients was conducted in three TB centres in Blantyre, Lilongwe, and Mzuzu, between July and December 2011 using a semi-structured questionnaire. Patient delay was defined as the time interval between the onset of TB symptom(s) (a common symptom being coughing) to the first visit to any health provider. Health system delay was the interval from the first care-seeking visit at any health provider to the initiation of anti-tuberculosis treatment. Participants were invited to participate in the study during intensive phase of treatment. The characteristics associated with patient and health system delays were analyzed.

Results
The median patient delay was 14 days for both new and retreatment TB cases (interquartile range [IQR] 14 – 28 and 7 – 21, respectively). The median health system delay was 59 days (IQR 26 – 108) for new and 40.5 days (IQR 21–90) for retreatment cases. Factors associated with longer patient delay in new cases included primary education (adjusted odds ratio [AOR] 2.2, 95% CI 1.3 – 3.9) and knowledge that more than three weeks of coughing is a sign of TB (AOR 1.9, 1.1 – 3.3). In retreatment cases, distance >10 Km (AOR 3.3, 1.1 – 9.6) and knowledge that more than three weeks of coughing is a sign of TB (AOR 3.7, 1.3 – 10.7; p < 0.05) were significant factors. Making the first visit to a health centre (OR 1.9, 0.9 – 3.8) or a drug store/ traditional healer (OR 5.1, 1.1 – 21.7) in new TB cases were associated with a longer health system delay (p < 0.05) while smear negative (OR 6.4, 1.5 – 28.3), and smear unknown or not done (OR 6.1, 1.3 – 26.9) among retreatment cases were associated with a longer health system delay (p < 0.05).

Conclusions
Effective management and new diagnostic techniques are needed especially among retreatment cases. It is also needed to address geographic barriers to accessing care and increasing TB awareness in the community.
Physical activity in subjects with multiple sclerosis with focus on gender differences: a survey
Authors: Anens Elisabeth , Emtner Margareta , Zetterberg Lena , Hellström Karin 
Published: March 2014

Abstract

Background
There is increasing research that examines gender-issues in multiple sclerosis (MS), but little focus has been placed on gender-issues regarding physical activity. The aim of the present study was to describe levels of physical activity, self-efficacy for physical activity, fall-related self-efficacy, social support for physical activity, fatigue levels and the impact of MS on daily life, in addition to investigating gender differences.

Methods
The sample for this cross-sectional cohort study consisted of 287 (84 men; 29.3%) adults with MS recruited from the Swedish Multiple Sclerosis Registry. A questionnaire was sent to the subjects consisting of the self-administrated measurements: Physical Activity Disability Survey – Revised, Exercise Self-Efficacy Scale, Falls- Efficacy Scale (Swedish version), Social Influences on Physical Activity, Fatigue Severity Scale and Multiple Sclerosis Impact Scale. Response rate was 58.2%.

Results
Men were less physically active, had lower self-efficacy for physical activity and lower fall-related self-efficacy than women. This was explained by men being more physically affected by the disease. Men also received less social support for physical activity from family members. The level of fatigue and psychological consequences of the disease were similar between the genders in the total sample, but subgroups of women with moderate MS and relapsing remitting MS experienced more fatigue than men.

Conclusions
Men were less physically active, probably a result of being more physically affected by the disease. Men being more physically affected explained most of the gender differences found in this study. However, the number of men in the subgroup analyses was small and more research is needed. A gender perspective should be considered in strategies for promoting physical activity in subjects with MS, e.g. men may need more support to be physically active.
Zoledronic acid inhibits pulmonary metastasis dissemination in a preclinical model of Ewing’s sarcoma via inhibition of cell migration
Authors: Odri Guillaume , Kim Pui-Pui , Lamoureux François , Charrier Céline , Battaglia Séverine , Amiaud Jérôme , Heymann Dominique , Gouin François , Redini Françoise 
Published: March 2014

Abstract

Background
Ewing’s sarcoma (ES) is the second most frequent primitive malignant bone tumor in adolescents with a very poor prognosis for high risk patients, mainly when lung metastases are detected (overall survival <15% at 5 years). Zoledronic acid (ZA) is a potent inhibitor of bone resorption which induces osteoclast apoptosis. Our previous studies showed a strong therapeutic potential of ZA as it inhibits ES cell growth in vitro and ES primary tumor growth in vivo in a mouse model developed in bone site. However, no data are available on lung metastasis. Therefore, the aim of this study was to determine the effect of ZA on ES cell invasion and metastatic properties.

Methods
Invasion assays were performed in vitro in Boyden’s chambers covered with Matrigel. Matrix Metalloproteinase (MMP) activity was analyzed by zymography in ES cell culture supernatant. In vivo, a relevant model of spontaneous lung metastases which disseminate from primary ES tumor was induced by the orthotopic injection of 106 human ES cells in the tibia medullar cavity of nude mice. The effect of ZA (50 μg/kg, 3x/week) was studied over a 4-week period. Lung metastases were observed macroscopically at autopsy and analysed by histology.

Results
ZA induced a strong inhibition of ES cell invasion, probably due to down regulation of MMP-2 and −9 activities as analyzed by zymography. In vivo, ZA inhibits the dissemination of spontaneous lung metastases from a primary ES tumor but had no effect on the growth of established lung metastases.

Conclusion
These results suggest that ZA could be used early in the treatment of ES to inhibit bone tumor growth but also to prevent the early metastatic events to the lungs.
Alleviation of Behavioral Hypersensitivity in Mouse Models of Inflammatory Pain with Two Structurally Different Casein Kinase 1 (CK1) Inhibitors
Authors: Kurihara Takashi , Sakurai Eri , Toyomoto Masayasu , Kii Isao , Kawamoto Daisuke , Asada Toshihide , Tanabe Tsutomu , Yoshimura Megumu , Hagiwara Masatoshi , Miyata Atsuro 
Published: March 2014

Background: The phylogenetically highly conserved CK1 protein kinases consisting of at least seven isoforms form a distinct family within the eukaryotic protein kinases. CK1 family members play crucial roles in a wide range of signaling activities. However, the functional role of CK1 in somatosensory pain signaling has not yet been fully understood. The aim of this study was to clarify the role of CK1 in the regulation of inflammatory pain in mouse carrageenan and complete Freund's adjuvant (CFA) models. Results: We have used two structurally different CK1 inhibitors, TG003 and IC261. TG003, which was originally identified as a cdc2-like kinase inhibitor, had potent inhibitory effects on CK1 isoforms in vitro and in cultured cells. Intrathecal injection of either TG003 (1–100 pmol) or IC261 (0.1–1 nmol) dose-dependently decreased mechanical allodynia and thermal hyperalgesia induced by carrageenan or CFA. Bath-application of either TG003 (1 μM) or IC261 (1 μM) had only marginal effects on spontaneous excitatory postsynaptic currents (sEPSCs) recorded in the substantia gelatinosa neurons of control mice. However, both compounds decreased the frequency of sEPSCs in both inflammatory pain models. Conclusions: These results suggest that CK1 plays an important pathophysiological role in spinal inflammatory pain transmission, and that inhibition of the CK1 activity may provide a novel strategy for the treatment of inflammatory pain.
Global health impacts of policies: lessons from the UK
Authors: Mwatsama Modi K , Wong Sidney , Ettehad Dena , Watt Nicola F 
Published: March 2014

Abstract

Background
The UK government committed to undertaking impact assessments of its policies on the health of populations in low and middle-income countries in its cross-government strategy “Health is Global”. To facilitate this process, the Department of Health, in collaboration with the National Heart Forum, initiated a project to pilot the use of a global health impact assessment guidance framework and toolkit for policy-makers. This paper aims to stimulate debate about the desirability and feasibility of global health impact assessments by describing and drawing lessons from the first stage of the project.

Discussion
Despite the attraction of being able to assess and address potential global health impacts of policies, there is a dearth of existing information and experience. A literature review was followed by discussions with policy-makers and an online survey about potential barriers, preferred support mechanisms and potential policies on which to pilot the toolkit. Although policy-makers were willing to engage in hypothetical discussions about the methodology, difficulties in identifying potential pilots suggest a wider problem in encouraging take up without legislative imperatives. This is reinforced by the findings of the survey that barriers to uptake included lack of time, resources and expertise. We identified three lessons for future efforts to mainstream global health impact assessments: 1) Identify a lead government department and champion – to some extent, this role was fulfilled by the Department of Health, however, it lacked a high-level cross-government mechanism to support implementation. 2) Ensure adequate resources and consider embedding the goals and principles of global health impact assessments into existing processes to maximise those resources. 3) Develop an effective delivery mechanism involving both state actors, and non-state actors who can ensure a “voice” for constituencies who are affected by government policies and also provide the “demand” for the assessments.

Summary
This paper uses the initial stages of a study on global health impact assessments to pose the wider question of incentives for policy-makers to improve global health. It highlights three lessons for successful development and implementation of global health impact assessments in relation to stewardship, resources, and delivery mechanisms.
Procalcitonin for diagnosis of bacterial pneumonia in critically ill patients during 2009 H1N1 influenza pandemic: a prospective cohort study, systematic review and individual patient data meta-analysis
Authors: Pfister Roman , Kochanek Matthias , Leygeber Timo , Brun-Buisson Christian , Cuquemelle Elise , Machado MarianaBenevides Paiva , Piacentini Enrique , Hammond Naomi E , Ingram Paul R , Michels Guido 
Published: March 2014

Abstract
Introduction
Procalcitonin (PCT) is helpful for diagnosing bacterial infections. The diagnostic utility of PCT has not been examined thoroughly in critically ill patients with suspected H1N1 influenza.

Methods
Clinical characteristics and PCT were prospectively assessed in 46 patients with pneumonia admitted to medical ICUs during the 2009 and 2010 influenza seasons. An individual patient data meta-analysis was performed by combining our data with data from five other studies on the diagnostic utility of PCT in ICU patients with suspected 2009 pandemic influenza A(H1N1) virus infection identified by performing a systematic literature search.

Results
PCT levels, measured within 24 hours of ICU admission, were significantly elevated in patients with bacterial pneumonia (isolated or coinfection with H1N1; n = 77) (median = 6.2 μg/L, interquartile range (IQR) = 0.9 to 20) than in patients with isolated H1N1 influenza pneumonia (n = 84; median = 0.56 μg/L, IQR = 0.18 to 3.33). The area under the curve of the receiver operating characteristic curve of PCT was 0.72 (95% confidence interval (CI) = 0.64 to 0.80; P < 0.0001) for diagnosis of bacterial pneumonia, but increased to 0.76 (95% CI = 0.68 to 0.85; P < 0.0001) when patients with hospital-acquired pneumonia and immune-compromising disorders were excluded. PCT at a cut-off of 0.5 μg/L had a sensitivity (95% CI) and a negative predictive value of 80.5% (69.9 to 88.7) and 73.2% (59.7 to 84.2) for diagnosis of bacterial pneumonia, respectively, which increased to 85.5% (73.3 to 93.5) and 82.2% (68.0 to 92.0) in patients without hospital acquired pneumonia or immune-compromising disorder.

Conclusions
In critically ill patients with pneumonia during the influenza season, PCT is a reasonably accurate marker for detection of bacterial pneumonia, particularly in patients with community-acquired disease and without immune-compromising disorders, but it might not be sufficient as a stand-alone marker for withholding antibiotic treatment.
Vitamin D Increases Serum Levels of the Soluble Receptor for Advanced Glycation End Products in Women With PCOS
Authors: Irani Mohamad , Minkoff Howard , Seifer David B. , Merhi Zaher 
Published: March 2014

Context:
Elevation of serum proinflammatory advanced glycation end products (AGEs) is involved in the pathogenesis of polycystic ovary syndrome (PCOS). The soluble receptor for AGEs (sRAGE) acts as a decoy by binding circulating AGEs. Vitamin D supplementation attenuates the deposition of AGEs in the vascular system of diabetic animals and improves some metabolic aspects of vitamin D-deficient women with PCOS. Additionally, serum anti-Mullerian hormone (AMH) is elevated in women with PCOS, reflecting abnormal ovarian folliculogenesis.

Objective:
The objective of the study was to evaluate the effect of 1,25 dihydroxyvitamin D3 (vit D3) supplementation on serum sRAGE and AMH in vitamin D-deficient women with PCOS.

Design, Settings, Participants, and Intervention:
Sixty-seven women with (n = 22) or without (control; n = 45) PCOS who were diagnosed with vitamin D deficiency were enrolled. Fifty-one women were replaced with oral vit D3 for 8 weeks (16 with PCOS and 35 controls) and 16 women were not treated (six with PCOS and 10 controls). Serum 25-hydroxyvitamin D (25 OH-D), sRAGE, and AMH concentrations were measured at baseline and after vit D3 supplementation in the treated group and 8 weeks apart in the nontreated group.

Main Outcome Measure(s):
Changes in serum sRAGE and AMH concentrations after vit D3 replacement were measured.

Results:
In all participants, there was a negative correlation between body mass index and serum sRAGE levels (r = −0.3, P = .01). In women with PCOS, but not in controls, vit D3 increased serum sRAGE (P = .03) and decreased serum AMH levels (P &lt; .001). The increase in serum sRAGE positively correlated with the increase in serum 25 OH-D after supplementation in women with PCOS (r = 0.6, P = .01).

Conclusion:
In women with PCOS, vit D3 might exert a protective effect against the inflammatory action of AGEs by increasing circulating sRAGE. The normalization in serum AMH induced by vit D3 replacement suggests an improvement in folliculogenesis.
Constitutive Somatostatin Receptor Subtype-3 Signaling Suppresses Growth Hormone Synthesis
Authors: Eigler Tamar , Ben-Shlomo Anat , Zhou Cuiqi , Khalafi Ramtin , Ren Song-Guang , Melmed Shlomo 
Published: March 2014

AbstractSomatostatin signals through somatostatin receptor subtypes (SSTR) 2 and 5 to attenuate GH secretion. Although expressed in normal pituitary glands and in GH-secreting pituitary tumors, SSTR3 function was unclear, and we have now determined the role of SSTR3 in somatotroph function. Stable rat pituitary tumor cell (GC) transfectants of human SSTR3 (GpSSTR3WT) showed suppression of rat (r) GH promoter activity, GH mRNA expression, and secreted GH concordant with suppressed cAMP/protein kinase A (PKA) signaling. In contrast, cAMP levels and GH expression were unchanged in cells expressing a mutant SSTR3 DRY motif (GpSSTR3R141A). GH expression was rescued by treatment of GpSSTR3WT with forskolin and 8-bromo-cAMP. GpSSTR3WT exhibited activation of glycogen synthase kinase3-β (GSK3-β), a PKA substrate, which was also reversed by 8-Bromo-cAMP treatment. Moreover, SSTR3-dependent GH transcriptional inhibition was rescued by inhibition of GSK3-β. GpSSTR3WT exhibited elevated Pit-1 serine phosphorylation and decreased Pit-1 occupancy of the rGH promoter with sustained Pit-1 expression. GSK3-β and Pit-1 physically interacted with each other, indicating that Pit-1 may be a GSK3-β phosphorylation substrate. In conclusion, constitutive SSTR3 activity mediates transcriptional repression of GH through cAMP/PKA, leading to subsequent activation of GSK3-β and increased Pit-1 phosphorylation and ultimately attenuating Pit-1 binding to the rGH promoter.
Influence of Trimethylamine N-Oxide (TMAO) on the Three-dimensional Distribution and Alignment of Solvent Molecules in Aqueous Solution
Authors: Doi Hideo , Watanabe Yudai , Aida Misako 
Published: March 2014

Abstract
By means of Monte Carlo simulations together with an ab initio molecular orbital method, we present the influence of trimethylamine N-oxide (TMAO), which is a highly polarized spherical-polyhedron, on the distribution and the alignment of surrounding water molecules. The specific alignment of the average dipole moments of solvent water around TMAO is observed in the MC simulation. The number of water molecules in the first hydration shell from MC simulation was in good agreement with the experimental value. A cluster model of TMAO with 12 water molecules was presented as a representative hydration structure of TMAO.
Coordination Oligomers and Polymers of an Oxazole-appended Zinc Chlorophyll Derivative
Authors: Shinozaki Yoshinao , Yoshikawa Isao , Araki Koji , Ohara Kazuaki , Yamaguchi Kentaro , Kawano Shin-ichiro , Tanaka Kentaro , Araki Yasuyuki , Wada Takehiko , Otsuki Joe 
Published: March 2014

Abstract
The self-assembled structures of an oxazole-appended zinc chlorophyll derivative in solution and in a crystal are reported. Cyclic oligomers formed in chloroform, while staircase-like coordination polymers formed in the crystal, both mediated by intermolecular axial coordination of the nitrogen atom in the oxazole moiety to the zinc center in another chlorophyll molecule.
Fliposomes: stimuli-triggered conformational flip of novel amphiphiles causes an instant cargo release from liposomes
Authors: Samoshin Vyacheslav V. 
Published: March 2014

AbstractThis review presents a new strategy for the design of stimuli-responsive liposomes for targeted delivery – the construction of a liposome membrane (lipid bilayer) using amphiphiles able to perform a stimuli-triggered conformational flip (‘flipids’). When done simultaneously by a major or significant part of the bilayer molecules, this massive flip disrupts the liposome membrane and induces a rapid release of the liposome load specifically in response to the initial stimulus. The conformational switches incorporated into the amphiphilic molecules could potentially be controlled by various internal or external factors (pH, metal complexation, light, electric field, etc.). Using this concept, we designed a series of pH-triggerable flipids, and prepared and tested ‘fliposomes’ with extraordinary characteristics: high stability in storage and in serum combined with an instant release of their cargo in response to a weakly acidic medium.
The Future of US Health Care: Is Medicare Really Better at “Saving” Money?
Authors: Edlin Aaron , Goldman Dana P. , Leive Adam A. 
Published: March 2014

Abstract
Paul Krugman, Robert Reich, and others see Medicare as a panacea. Krugman, for example, points out that average Medicare costs have grown only 400 percent while private insurance costs have grown 700 percent. Should the US move to Medicare for all? The case is not as clear as such statistics suggest.
Co-supervision of Doctoral Students: Enhancing the Learning Experience
Authors: Paul Pauline , Olson Joanne K. , Gul Raisa B. 
Published: March 2014

AbstractThe purpose of this paper is to examine the advantages and challenges of co-supervision of doctoral students, as found in the literature and from our experiences. We define co-supervision and then discuss the process in detail. Examples are based on experiences of co-supervision from faculty perspectives as well as from the point of view of a former doctoral student. We propose that the advantages of co-supervision far outweigh the challenges and should be regularly considered by seasoned academics to enhance student learning. In addition, we suggest that co-supervision is intellectually stimulating for academics.
Minimal faithful permutation degrees for irreducible Coxeter groups and binary polyhedral groups
Authors: Saunders Neil 
Published: March 2014

Abstract
The minimal faithful permutation degree of a finite group G, denoted by μ(G), is the least non-negative integer n such that G embeds inside Sym(n). In this article we calculate the
minimal faithful permutation degree for all of the irreducible Coxeter groups. We also exhibit new examples of finite groups that possess a quotient whose minimal degree is strictly greater than that of the group.