bluuebunny/crossref_metadata_2025 huggingface dataset:
Drug-like analogues of the parasitic worm-derived immunomodulator ES-62 are therapeutic in the MRL/Lpr model of systemic lupus erythematosus
Authors: Rodgers D T , Pineda M A , Suckling C J , Harnett W , Harnett M M
Published: June 2015

Introduction

ES-62, a phosphorylcholine (PC)-containing immunomodulator secreted by the parasitic worm Acanthocheilonema viteae, protects against nephritis in the MRL/Lpr mouse model of systemic lupus erythematosus (SLE). However, ES-62 is not suitable for development as a therapy and thus we have designed drug-like small molecule analogues (SMAs) based around its active PC-moiety. To provide proof of concept that ES-62-based SMAs exhibit therapeutic potential in SLE, we have investigated the capacity of two SMAs to protect against nephritis when administered to MRL/Lpr mice after onset of kidney damage.

Methods

SMAs 11a and 12b were evaluated for their ability to suppress antinuclear antibody (ANA) generation and consequent kidney pathology in MRL/Lpr mice when administered after the onset of proteinuria.

Results

SMAs 11a and 12b suppressed development of ANA and proteinuria. Protection reflected downregulation of MyD88 expression by kidney cells and this was associated with reduced production of IL-6, a cytokine that exhibits promise as a therapeutic target for this condition.

Conclusions

SMAs 11a and 12b provide proof of principle that synthetic compounds based on the safe immunomodulatory mechanisms of parasitic worms can exhibit therapeutic potential as a novel class of drugs for SLE, a disease for which current therapies remain inadequate.
Socioeconomic status and organ damage in Mexican systemic lupus erythematosus women
Authors: Mendoza-Pinto C , Méndez-Martínez S , Soto-Santillán P , Galindo Herrera J , Pérez-Contreras I , Macías-Díaz S , Taboada-Cole A , García-Carrasco M
Published: June 2015

The objective of this cross-sectional study was to determine relationships between socioeconomic status and organ damage in Mexican systemic lupus erythematosus (SLE) patients. Demographic and clinical variables were assessed. Socioeconomic status was evaluated using the Graffar method and monthly household income. Lupus activity and organ damage were measured using the SLE disease activity scale, validated for the Mexican population (Mex-SLEDAI), and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) scale. The 143 Mexican female SLE patients included (mean age 40.1 ± 8.9 years, mean disease duration 8.9 ± 6.3 years) had a mean monthly household income of $ 407.2 ± 326.5. According to the Graffar index, 18.9%, 52.5%, and 28.7% had high/medium-high, medium, and medium-low/low socioeconomic status, respectively. Organ damage was observed in 61 patients (42.7%). Patients with organ damage had lower monthly household incomes ($241.4 ± 152.4 vs. $354.8 ± 288.3) and were more frequently unemployed (57.3% vs. 35.3%; p = 0.01) than those without. Low monthly income was not associated with lupus activity or self-reported health status. In the adjusted multivariate analysis, low monthly income ( < $300) was associated with organ damage. In conclusion, low income may be associated with organ damage in Mexican SLE patients.
I Have a Voice and Can Speak Up for Myself Through Writing!
Authors: Cuenca-Carlino Yojanna , Mustian April L. , Allen Ruth D. , Gilbert Jamillah
Published: June 2015

Writing can be a method of expression for those who cannot or do not feel comfortable expressing themselves verbally. For students with disabilities, however, writing can be a challenging task because they often fail to see writing as a process. This article examines how to use the self-regulated strategy development model of writing, an evidence-based practice, to teach middle and high school students with emotional/behavioral disabilities to use persuasive writing as a tool to advocate for their needs and wants. Writing can help students develop self-determination skills and self-expression with the time needed to reflect on what they want to say, making the process of writing an empowering one. Example lessons, guidelines, and sample materials are provided.
Effects of input training on second language syntactic representation entrenchment
Authors: Deng Taiping , Dunlap Susan , Chen Baoguo
Published: June 2015

Objectives:

The present study aimed to investigate the effects of linguistic input training on second language (L2) syntactic representation entrenchment using English subject–verb agreement structures as the stimuli.

Methodology:

A pre-test/training/first-post/delayed post-test experimental design was adopted. Sixty Chinese (L1)–English (L2) adult learners participated in the experiments and were randomly assigned to the experimental group (EG) and the control group (CG). In training sessions, EG learned the subject–verb structures, and CG learned other syntactic structures.

Data and analysis:

Reaction time and comprehension accuracy data were analyzed using a repeated-measures analysis of variance. P2 and P3 signified the key positions of the verb and the word immediately following the verb in the experimental sentence, respectively. For example, the reading time indicator was the time for reading the key positions of the example sentence “The book under the newspaper was interesting”. The words “newspaper”, “was”, and “interesting” were marked as P1, P2, and P3, respectively.

Findings/conclusions:

At pre-test, there was no difference between the EG and the CG in processing the subject–verb agreement structures. After two sessions of intensive training, the first post-test indicated that the EG had significantly longer reading times for the P2 and P3 positions of the ungrammatical sentences than those of the grammatical versions. The CG showed no differences in reading times. At delayed post-test, the EG had significantly longer reading times for the P3 position for all of the ungrammatical sentences than for the grammatical ones. The CG exhibited no differences in reading times. The results indicated both short-term and long-term efficacy of input training and transfer effects of input on representation entrenchment.

Originality:

In adult L2 syntactic literature, the current study empirically and directly explored the role of input training in entrenching L2 syntactic representation.

Significance:

The study suggested that input training can entrench representation. These results support the usage-based theory.
Dancing literacy: Expanding children’s and teachers’ literacy repertoires through embodied knowing
Authors: Leonard Alison E , Hall Anna H , Herro Danielle
Published: June 2015

This paper explores dance as literacy. Specifically, it examines qualitative case study research findings and student examples from a dance artist-in-residence that explored curricular content using dance as its primary mode of enquiry and expression. Throughout the residency, students constructed meaning through their dance experiences in dynamic and autonomous ways, exhibiting complex literacy practices of enquiry and communication. Focusing on the kindergarten student participants’ experiences, the authors highlight three themes in their dance literacy practices: (a) artistic autonomy, (b) embodied knowledge and (c) multimodality. As embodied knowledge, dance innately allowed for integrative literacy possibilities in the dance residency. The dance experiences observed and referenced in this research illustrate the complexities of dance as literacy, as both a unique literacy and in meaning making across literacies. Drawing on the findings of this study, the authors seek to inspire teachers to foster similar experiences to develop transformative literacy practices individually in their classrooms and collaboratively in their schools.
Rebuffing Refugee Journalists
Authors: Leff Laurel
Published: June 2015

When Nazi Germany forced Jewish scholars and professionals to flee Europe, many disciplines found homes for them in the United States. One did not. The journalism profession made little effort to help their European colleagues. The nation’s accredited journalism schools did not add a single displaced European scholar and rebuffed pleas to re-educate foreign journalists. If anything, practicing journalists were more hostile. This monograph seeks to fill a gap in the vast literature on the intellectual migration, explores the ways in which the American journalism community could have assisted their European colleagues, and offers possible explanations for their inaction.
Sealing zones have a greater influence than iliac anatomy on the occurrence of limb occlusion following endovascular aortic aneurysm repair
Authors: Daoudal Anne , Cardon Alain , Verhoye Jean-Philippe , Clochard Elodie , Lucas Antoine , Kaladji Adrien
Published: June 2015

Limb occlusion is a well-known complication following endovascular aortic aneurysm repair (EVAR), and it very often leads to reoperation. The aim of this study is to identify predictive factors for limb occlusion following EVAR. Two hundred and twenty-four patients undergoing EVAR between 2004 and 2012 were included in this retrospective study. Demographics, anatomic, and follow-up data were compared between two groups (with or without thrombosis). Preoperative anatomy was analyzed with a dedicated workstation, using the Society of Vascular Surgery reporting standards. Eleven (4.9%) patients presented with a limb occlusion during follow-up (46 ± 12 months). Univariate analyses were first performed to investigate the influence of preoperative variables on limb occlusion. Then, variables with a p value <0.1 were included in the multivariate analysis and showed that in the occlusion group there was a greater rate of chronic renal failure (18.2% vs. 3.8%, p = 0.012), a more frequent occurrence of distal landing zones in the external iliac artery (15.4% vs. 2.1%, p = 0.006), and a smaller aortic neck diameter (21.0 ± 2.9 mm vs. 23.6 ± 3.3 mm, p = 0.014). Although iliac anatomy does not appear to have a significant influence on limb occlusion rate in the multivariate analysis, proximal and distal sealing zones appear to be involved in this complication.
Multidisciplinary members’ perspectives on a pharmacist joining a rheumatology practice team
Authors: Wilbur Kerry , Kur Jason
Published: June 2015

Background:

Pharmacist participation in chronic disease management benefits patients in many ambulatory settings. We explored the attitudes and perceptions among multidisciplinary members of a rheumatology team towards the skills and responsibilities of a pharmacist joining their practice.

Methods:

The physicians, nurse, physiotherapist and staff of a rheumatology clinic were invited to participate in focus group and semistructured interviews. Practice members also completed an inventory of perceived health professional roles in the medication use process.

Results:

Discussions with 2 physicians, a nurse, physiotherapist and 1 office administrator were conducted. Concepts related to 3 key themes included positively viewed pharmacist roles broadly related to activities that encompass provision of medication-related services for the patients, the providers and the practice. Examples of such care included educational tasks related to therapies (rheumatological and otherwise) and maintenance of accurate drug histories. These findings were reflected in high scores for perceived pharmacist roles in education and medication review responsibilities using the Medication Use Processes Matrix instrument. Most members were not comfortable with pharmacists conducting physical assessments and emphasized the need for a team member who could adapt to variations in workflow preferences across rheumatologists in the practice.

Interpretation:

Perceived pharmacist roles expressed by existing rheumatology team members were largely consistent with the scope of pharmacist knowledge, skills and responsibilities in primary care.

Conclusion:

Overall, existing multidisciplinary staff exhibited favourable attitudes towards a pharmacist joining their practice setting. Data from this job analysis exercise were used to inform the development of a job description for a rheumatology clinical pharmacist.
Systematic review of interventional sickle cell trials registered in ClinicalTrials.gov
Authors: Lebensburger Jeffrey D , Hilliard Lee M , Pair Lauren E , Oster Robert , Howard Thomas H , Cutter Gary R
Published: June 2015

Background/Aims:

The registry ClinicalTrials.gov was created to provide investigators and patients an accessible database of relevant clinical trials.

Methods:

To understand the state of sickle cell disease clinical trials, a comprehensive review of all 174 “closed,” “interventional” sickle cell trials registered at ClinicalTrials.gov was completed in January 2015.

Results:

The majority of registered sickle cell disease clinical trials listed an academic center as the primary sponsor and were an early phase trial. The primary outcome for sickle cell disease trials focused on pain (23%), bone marrow transplant (BMT) (13%), hydroxyurea (8%), iron overload (8%), and pulmonary hypertension (8%). A total of 52 trials were listed as terminated or withdrawn, including 25 (14% of all trials) terminated for failure to enroll participants. At the time of this review, only 19 trials uploaded results and 29 trials uploaded a manuscript in the ClinicalTrials.gov database. A systematic review of pubmed.gov revealed that only 35% of sickle cell studies completed prior to 2014 resulted in an identified manuscript. In comparison, of 80 thalassemia trials registered in ClinicalTrials.gov, four acknowledged failure to enroll participants as a reason for trial termination or withdrawal, and 48 trials (60%) completed prior to 2014 resulted in a currently identified manuscript.

Conclusion:

ClinicalTrials.gov can be an important database for investigators and patients with sickle cell disease to understand the current available research trials. To enhance the validity of the website, investigators must update their trial results and upload trial manuscripts into the database. This study, for the first time, quantifies outcomes of sickle cell disease trials and provides support to the belief that barriers exist to successful completion, publication, and dissemination of sickle cell trial results.
Narrow-band imaging bronchoscopy in the detection of premalignant airway lesions: a meta-analysis of diagnostic test accuracy
Authors: Iftikhar Imran H. , Musani Ali I.
Published: June 2015

Objectives:

Both autofluorescence imaging bronchoscopy and narrow-band imaging have shown promise in the detection of premalignant airway lesions, each by utilizing different bandwidths of lights for better characterization of the mucosal and submucosal vascular grid. Since previously published meta-analyses have shown poor specificity of autofluorescence imaging bronchoscopy, we specifically studied the diagnostic accuracy of narrow-band imaging alone and in combination with autofluorescence imaging bronchoscopy in the detection of premalignant airway lesions.

Methods:

After an extensive search of eligible studies from PubMed and Medline, extracted data were pooled with weighted averages. Symmetrical summary–receiver operating characteristic curves were constructed to summarize the results quantitatively. Study heterogeneity was assessed by the I2 index.

Results:

Analysis of data from eight studies on narrow-band imaging showed a pooled sensitivity of 0.80 [95% confidence interval (CI): 0.77–0.83] and a pooled specificity of 0.84 (95% CI: 0.81–0.86). Summary–receiver operating characteristic curves from the data on narrow-band imaging calculated an area-under-the-curve of 0.908 (standard error 0.01). The diagnostic odds ratio of narrow-band imaging was 31.49 (95% CI: 12.17–81.45). Data from studies where narrow-band imaging and autofluorescence imaging bronchoscopy were used together showed a pooled sensitivity, specificity, area-under-the-curve and diagnostic odds ratios of 0.86 (95% CI: 0.82–0.89), 0.75 (95% CI: 0.71–0.79), 0.964 (standard error 0.05) and 27.96 (95% CI: 3.04–257.21), respectively.

Conclusions:

Our findings indicate that in the evaluation of premalignant airway lesions, narrow-band imaging has a higher sensitivity, specificity and diagnostic odds ratios compared with autofluorescence imaging bronchoscopy. However, combining autofluorescence imaging bronchoscopy and narrow-band imaging does not significantly improve test performance characteristics.
Communicating With Distant Others
Authors: Joshi Priyanka D. , Wakslak Cheryl J. , Raj Medha , Trope Yaacov
Published: June 2015

We introduce the construct of relational scope to refer to the degree to which an individual engages in communication with a more or less distant audience, with a contractive relational scope indicating a near audience and an expansive relational scope indicating a distant audience. Drawing on construal level theory, we argue that speakers use abstract messages strategically when faced with an expansive relational scope in order to be widely relevant and relatable. We show that speakers communicate more abstractly with distant others than near others (Studies 1–3) and experience greater fit when message framing matches audience distance (Study 4). We also demonstrate that framing messages abstractly prompts broader relational scope, with speakers more likely to direct concrete (abstract) messages to near (distal) audiences (Study 5). Finally, we show that when procedural information is critical to communication, communication with distant (vs. proximal) others will increasingly emphasize procedures over end states (Study 6).
Structure and stability of as cast AlCrFeMnNiTi high entropy alloy
Authors: Nong Z.-S. , Zhu J.-C. , Lai Z.-H. , Liu Y.
Published: June 2015

An as cast high entropy alloy AlCrFeMnNiTi was synthesised to investigate the microstructures and crystal structure. The atomic structure models of this AlCrFeMnNiTi alloy were also built to further investigate the stability and bonding behaviour. It was found that the as cast AlCrFeMnNiTi alloy formed two body centred cubic structures, and typical dendrite and interdendrite microstructures were observed. Two reasonably models based on AlNi and Fe matrix were built to simulate the structures of two phases formed in as cast AlCrFeMnNiTi high entropy alloy. The electron density difference and atomic Mulliken population were also calculated, which revealed the chemical bonding in as cast AlCrFeMnNiTi high entropy alloy. In this study, the probable process of spinodal decomposition in this alloy was also discussed and presented.
Thermal behaviour of gas atomised Al–20Mg–2Zr alloy powder
Authors: Li L. , Zou H. , Cai S.
Published: June 2015

A novel ternary alloy with the composition of Al–20Mg–2Zr (wt-%) was prepared by close coupled gas atomisation. The thermal oxidation behaviour of the powder was examined by thermogravimetry–differential thermal analysis. The results showed that the oxidation proceeded in single step, and the violent exothermic reaction occurred after 900°C was almost complete. The activation energy of the oxidation was ∼250 kJ mol− 1, and the frequency factor was ∼1.47 × 1011 s− 1 and 3.36 × 1011 s− 1 using the Kissinger and Ozawa method respectively. The special feature of the pulsed oxidation was explained by the melt dispersion oxidation mechanism. The excellent thermal reactivity exhibited by the Al–20Mg–2Zr powder suggested that this novel alloy could become one of the most promising materials in energetic applications.
Utility of baseline 18FDG-PET/CT functional parameters in defining prognosis of primary mediastinal (thymic) large B-cell lymphoma
Authors: Ceriani Luca , Martelli Maurizio , Zinzani Pier Luigi , Ferreri Andrés J. M. , Botto Barbara , Stelitano Caterina , Gotti Manuel , Cabras Maria Giuseppina , Rigacci Luigi , Gargantini Livio , Merli Francesco , Pinotti Graziella , Mannina Donato , Luminari Stefano , Stathis Anastasios , Russo Eleonora , Cavalli Franco , Giovanella Luca , Johnson Peter W. M. , Zucca Emanuele
Published: June 2015

Key Points

18FDG PET/CT is a very important staging tool for patients with PMBCL. Metabolic activity defined by TLG on the baseline PET scan is a powerful predictor of PMBCL outcome.
Perturbation of the normal immune system in patients with CLL
Authors: Forconi Francesco , Moss Paul
Published: June 2015

Immune dysregulation is a cardinal feature of chronic lymphocytic leukemia (CLL) from its early stage and worsens during clinical observation, even in absence of disease progression. Although the mechanisms remain unclear, new insights are emerging into the complex relationship between the CLL clone and its immune environment. T cells are increased in early-stage disease and show progressive accumulation and exhaustion. The mechanisms that drive this expansion may include auto-antigens involved in the original clonal expansion. In addition, chronic viral infections such as cytomegalovirus generate huge virus-specific immune responses, which are further expanded in CLL. Attention is now focused largely on the direct immunosuppressive properties of the tumor. Remarkably, CLL clones often have features of the recently described regulatory B cells producing immunosuppressive IL-10. Better knowledge of the regulatory properties intrinsic to CLL cells may soon become more important with the switch from chemotherapy-based treatments, which trade control of CLL with further impairment of immune function, to the new agents targeting CLL B-cell receptor–associated signaling. Treatment with these new agents is associated with evidence of immune recovery and reduced infectious complications. As such, they offer the prospect of immunologic rehabilitation and a platform from which to ultimately replace chemotherapy.
The prevalence of primary headache disorders and their associated factors among nursing staff in North China
Authors: Wang Yan , Xie Jingdan , Yang Fei , Wu Shiwen , Wang Hebo , Zhang Xiaolan , Liu Hua , Deng Xin , Yu Shengyuan
Published: June 2015

Background

Epidemiological data on the prevalence of headache in nursing staff in Mainland China are lacking. We therefore performed a study to assess the prevalence of headache, and factors associated with headaches, in nursing staff in three hospitals in North China.

Methods

Stratified random cluster sampling was used to select 1102 nurses from various departments in three hospitals. A structured questionnaire was used to collect epidemiological data, headache characteristics and associated factors.

Results

The response rate was 93.0%. Among nursing staff, the 1-year prevalence of primary headache disorders was 45.3%, of migraine 14.8% (migraine with aura 3.4%, migraine without aura 11.4%), of tension-type headache (TTH) 26.2%, of chronic daily headache (CDH) 2.7%. Multivariate analysis showed that seniority (≥5 years) was a risk factor for migraine (OR 2.280), obesity (BMI ≥ 25) was a risk factor for TTH and CDH (OR 1.684 and 3.184), and age (≥40 years) was a risk factor for CDH (OR 8.455). Nurses working in internal medicine were more likely to suffer CDH than those in other departments. Working a greater number of night shifts was also associated with increased prevalence of headache.

Conclusion

The prevalence of primary headache disorders in nurses is higher than that in the general population in China, and occupational factors may play an important role. Therefore, the prevalence of headache in nurses should be a focus of attention, and coping strategies should be provided. Such measures could contribute to improving patient care.
Association between HIF-1α C1772T/G1790A polymorphisms and cancer susceptibility: an updated systematic review and meta-analysis based on 40 case-control studies
Authors: Yan Qing , Chen Pin , Wang Songtao , Liu Ning , Zhao Peng , Gu Aihua
Published: June 2015

Background

HIF-1 (hypoxia-inducible factor 1) is a transcriptional activator that functions as a critical regulator of oxygen homeostasis. Recently, a large number of epidemiological studies have investigated the relationship between HIF-1α C1772T/G1790A polymorphisms and cancer susceptibility. However, the results remain inconclusive. Therefore, we performed a meta-analysis on all of the available case-control studies to systematically summarize the possible association.

Methods

A literature search was performed using PubMed and the Web of Science database to obtain relevant published studies. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the relationship between HIF-1α C1772T/G1790A polymorphisms and cancer susceptibility were calculated using fixed- and random-effects models when appropriate. Heterogeneity tests, sensitivity analyses and publication bias assessments were also performed in our meta-analysis.

Results

A total of 40 studies met the inclusion criteria were included in the meta-analysis: 40 studies comprised of 10869 cases and 14289 controls for the HIF-1α C1772T polymorphism and 30 studies comprised of 7117 cases and 10442 controls for the HIF-1α G1790A polymorphism. The results demonstrated that there were significant association between the HIF-1α C1772T polymorphism and cancer susceptibility under four genetic models (TTvs.CC: OR = 1.63, 95% CI = 1.02-2.60; CT + TTvs.CC: OR = 1.15, 95% CI = 1.01-1.34; TTvs.CT + CC: OR = 2.11, 95% CI = 1.32-3.77; Tvs.C: OR = 1.21, 95% CI = 1.04-1.41). Similarly, the statistically significant association between the HIF-1α G1790A polymorphism and cancer susceptibility was found to be consistently strong in all of the genetic models. Moreover, increased cancer risk was observed when the data were stratified by cancer type, ethnicity and the source of controls.

Conclusions

This meta-analysis demonstrates that both the C1772T and G1790A polymorphisms in the HIF-1α gene likely contribute to increased cancer susceptibility, especially in the Asian population and in breast cancer, lung cancer, pancreatic cancer and oral cancer. However, further research is necessary to evaluate the relationship between these polymorphisms and cancer risk.
Bu-Zhong-Yi-Qi pill alleviate the chemotherapy-related fatigue in 4 T1 murine breast cancer model
Authors: Ouyang Mingzi , Liu Yanyan , Tan Wei , Xiao Ya , Yu Keqiang , Sun Xiaomin , Huang Ying , Cheng JingRu , Luo Ren , Zhao Xiaoshan
Published: June 2015

Background

Paclitaxel induced fatigue still remains underrecognized and undertreated, partly because of limited understanding of its pathophysiology and lack of effective treatments. This study is aim to evaluate the anti-fatigue effects and mechanism of Bu-Zhong-Yi-Qi pill in murine 4 T1 breast cancer mice were treated with paclitaxel.

Methods

Breast cancer mice established with murine 4 T1 cells were randomly and repectively divided into five groups: negative control group (NC), tumor control group (TC), paclitaxel group (PTX), Bu-Zhong-Yi-Qi pill group (BZYQ) and Bu-Zhong-Yi-Qi pill plus paclitaxel group (BZYQ + PTX). The mice were administered for 21 days. During this period, the tumor volume, body weight and the weight-loaded swimming time were measured. After the last administration, all mice were sacrificed, weighted the tumor, measured immune cell cytokines and oxidative stress indicator. The remaining 10 mice in each group were observed for survival analysis.

Results

Treatments with BZYQ + PTX and PTX significantly reduced the rates of tumor volume in comparison with TC starting on the 9th day and the 18th day respectively (P < 0.05-0.01), and presented decreased tumor weight compared to TC (P < 0.05-0.01). Compared with mice in TC group, the median survival time and the average survival time in BZYQ + PTX group, BZYQ group and PTX group were significantly prolonged (P < 0.05-0.01). The swimming time of the BZYQ + PTX group gradually increased, which is longer than the PTX group on Day 14 and Day 21 (P < 0.01). The level of TNF-α was lower in BZYQ + PTX group than PTX group (P < 0.01). The level of SOD activity in BZYQ + PTX group was lower than the NC group (P <0.01), but much higher than the PTX group (P < 0.01). The level of MDA of BZYQ + PTX group was higher than the NC group (P < 0.01), but significant lower than the PTX group (P < 0.01).

Conclusions

BZYQ has the potential of alleviating paclitaxel chemotherapy-related fatigue in 4 T1 breast cancer mice by reducing the serum levels of TNF-α and modulating the level of MDA and the SOD activity.
Existence of solutions for fractional q-difference equation with mixed nonlinear boundary conditions
Authors: Li Xinhui , Han Zhenlai , Sun Shurong , Zhao Ping
Published: June 2015

In this paper, we study the boundary value problem for a class of nonlinear fractional q-difference equation with mixed nonlinear conditions involving the fractional q-derivative of Riemann-Liouuville type. By means of the Guo-Krasnosel’skii fixed point theorem on cones, some results concerning the existence of solutions are obtained. Finally, examples are presented to illustrate our main results.

MSC:39A13, 34B18, 34A08.
tmChem: a high performance approach for chemical named entity recognition and normalization
Authors: Leaman Robert , Wei Chih-Hsuan , Lu Zhiyong
Published: June 2015

Chemical compounds and drugs are an important class of entities in biomedical research with great potential in a wide range of applications, including clinical medicine. Locating chemical named entities in the literature is a useful step in chemical text mining pipelines for identifying the chemical mentions, their properties, and their relationships as discussed in the literature.

We introduce the tmChem system, a chemical named entity recognizer created by combining two independent machine learning models in an ensemble. We use the corpus released as part of the recent CHEMDNER task to develop and evaluate tmChem, achieving a micro-averaged f-measure of 0.8739 on the CEM subtask (mention-level evaluation) and 0.8745 f-measure on the CDI subtask (abstract-level evaluation). We also report a high-recall combination (0.9212 for CEM and 0.9224 for CDI). tmChem achieved the highest f-measure reported in the CHEMDNER task for the CEM subtask, and the high recall variant achieved the highest recall on both the CEM and CDI tasks.

We report that tmChem is a state-of-the-art tool for chemical named entity recognition and that performance for chemical named entity recognition has now tied (or exceeded) the performance previously reported for genes and diseases. Future research should focus on tighter integration between the named entity recognition and normalization steps for improved performance.

The source code and a trained model for both models of tmChem is available at: http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/Demo/tmChem. The results of running tmChem (Model 2) on PubMed are available in PubTator: http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/Demo/PubTator
Dynamics of natural populations of the dertitivorous mudsnail Potamopyrgus antipodarum (Gray) (Hydrobiidae) in two interconnected Lakes differing in trophic state
Authors: Dorgelo Jaap , van der Geest Harm G , Hunting Ellard R
Published: June 2015

Here we investigate the allocation of resources between growth and reproduction by surveying the dynamics of natural populations of the aquatic detritivorous mudsnail Potamopyrgus antipodarum from two interconnected lakes that differ in trophic state. The size distributions and reproductive output of the snail populations was analyzed monthly by field surveys spanning 3 years, and in a controlled microcosm experiment to evaluate the reproductive potential under laboratory conditions. Snails in the meso-oligotrophic lake showed reduced growth and a smaller size compared to snails in the eutrophic lake. However, the numbers of eggs and nearly-neonates per adult snail did not differ significantly between the two populations. It is speculated that P. antipodarum populations living under meso-oligotrophic conditions may consistently invest more internal energy in reproduction at the expense of growth and that food quantity may be an important driver for macro-invertebrate resource allocation in detrital food webs.
Microbiological profiling and the demonstration of in vitro anti-bacterial traits of the major oral herbal medicines used in Dhaka Metropolis
Authors: Sharmin Marufa , Nur Ifra Tun , Acharjee Mrityunjoy , Munshi Saurab Kishore , Noor Rashed
Published: June 2015

Present study attempted to assess the level of microbiological contamination in oral herbal medicines, frequently used for medications, through conventional cultural and biochemical tests along with the antibiogram of the isolates. Moreover, the anti-bacterial potential of the herbal medicines was also aimed to be checked by the agar well diffusion method and minimum inhibitory concentration (MIC) assay. Out of 10 categories of liquid oral herbal medicine samples (n = 50) studied, all were found to be contaminated with bacteria (103-105 cfu/mL), specifically with Staphylococcus spp. in 8 samples; while 2 samples harbored Klebsiella spp. Fungal presence was observed only in one sample. Study of antibiogram revealed Klebsiella spp. to be strongly resistant against penicillin G and erythromycin, whereas S. aureus possessed 80% sensitivity. The in vitro anti-bacterial activity was observed in 7 samples. Of them, one sample was found to exhibit the activity against almost all the test bacteria and another was found effective against 5 out of 8 test bacteria. Five samples showed the activity within a minor range while 3 samples were devoid of such trait. Samples 2 and 4 were found to stall the bacterial growth below 10 mg/mL of concentration in MIC test. Overall, the prevalence of specific pathogens was not so significant in the samples studied as well as only one drug-resistant isolate was identified. Besides, the anti-bacterial trait of 5 samples indicated that most of herbal medicines might be considered effective for medication.
The potential utility of urinary biomarkers for risk prediction in combat casualties: a prospective observational cohort study
Authors: Stewart Ian J. , Glass Kristen R. , Howard Jeffrey T. , Morrow Benjamin D. , Sosnov Jonathan A. , Siew Edward D. , Wickersham Nancy , Latack Wayne , Kwan Hana K. , Heegard Kelly D. , Diaz Christina , Henderson Aaron T. , Saenz Kristin K. , Ikizler T. Alp , Chung Kevin K.
Published: June 2015

Introduction

Traditional risk scoring prediction models for trauma use either anatomically based estimations of injury or presenting vital signs. Markers of organ dysfunction may provide additional prognostic capability to these models. The objective of this study was to evaluate if urinary biomarkers are associated with poor outcomes, including death and the need for renal replacement therapy.

Methods

We conducted a prospective, observational study in United States Military personnel with traumatic injury admitted to the intensive care unit at a combat support hospital in Afghanistan.

Results

Eighty nine patients with urine samples drawn at admission to the intensive care unit were studied. Twelve patients subsequently died or needed renal replacement therapy. Median admission levels of urinary cystatin C (CyC), interleukin 18 (IL-18), L-type fatty acid binding protein (LFABP) and neutrophil gelatinase-associated lipocalin (NGAL) were significantly higher in patients that developed the combined outcome of death or need for renal replacement therapy. Median admission levels of kidney injury molecule-1 were not associated with the combined outcome. The area under the receiver operating characteristic curves for the combined outcome were 0.815, 0.682, 0.842 and 0.820 for CyC, IL-18, LFABP and NGAL, respectively. Multivariable regression adjusted for injury severity score, revealed CyC (OR 1.97, 95 % confidence interval 1.26-3.10, p = 0.003), LFABP (OR 1.92, 95 % confidence interval 1.24-2.99, p = 0.004) and NGAL (OR 1.80, 95 % confidence interval 1.21-2.66, p = 0.004) to be significantly associated with the composite outcome.

Conclusions

Urinary biomarker levels at the time of admission are associated with death or need for renal replacement therapy. Larger multicenter studies will be required to determine how urinary biomarkers can best be used in future prediction models.
Anti-high mobility group box-1 monoclonal antibody treatment provides protection against influenza A virus (H1N1)-induced pneumonia in mice
Authors: Nosaka Nobuyuki , Yashiro Masato , Yamada Mutsuko , Fujii Yosuke , Tsukahara Hirokazu , Liu Keyue , Nishibori Masahiro , Matsukawa Akihiro , Morishima Tsuneo
Published: June 2015

Introduction

Provision for the emergence of an influenza pandemic is an urgent issue. The discovery of a novel anti-influenza therapeutic approach would increase the effectiveness of traditional virus-based strategies. This study was undertaken to evaluate the therapeutic effects of anti-high mobility group box-1 (HMGB1) monoclonal antibody (mAb) treatment on influenza A virus (H1N1)-induced pneumonia in mice.

Methods

Nine-week-old male C57BL/6 mice were inoculated with H1N1, then anti-HMGB1 mAb or control mAb were administered intravenously at 1, 24 and 48 hours after H1N1 inoculation and the survival rate was analyzed. Lung lavage and histopathological analysis were performed on days 3, 5, 7 and 10 after inoculation.

Results

Anti-HMGB1 mAb significantly improved the survival rate of H1N1-inoculated mice (1 out of 15 versus 8 out of 15 deaths in the anti-HMGB1 mAb-treated group versus the control mAb-treated group,p < 0.01), although the treatment did not affect virus propagation in the lungs. The treatment also significantly attenuated histological changes and neutrophil infiltration in the lungs of H1N1-inoculated mice. This was associated with inhibition of HMGB1 and suppression of inflammatory cytokine/chemokine expression and oxidative stress enhancement, which were observed in H1N1-inoculated mice. The expression of receptor for advanced glycation end products and nuclear factor κB was attenuated by the treatment.

Conclusions

Anti-HMGB1 mAb may provide a novel and effective pharmacological strategy for severe influenza virus infection in humans by reducing the inflammatory responses induced by HMGB1.
Deep sequencing reveals cell-type-specific patterns of single-cell transcriptome variation
Authors: Dueck Hannah , Khaladkar Mugdha , Kim Tae Kyung , Spaethling Jennifer M. , Francis Chantal , Suresh Sangita , Fisher Stephen A. , Seale Patrick , Beck Sheryl G. , Bartfai Tamas , Kuhn Bernhard , Eberwine James , Kim Junhyong
Published: June 2015

Background

Differentiation of metazoan cells requires execution of different gene expression programs but recent single-cell transcriptome profiling has revealed considerable variation within cells of seeming identical phenotype. This brings into question the relationship between transcriptome states and cell phenotypes. Additionally, single-cell transcriptomics presents unique analysis challenges that need to be addressed to answer this question.

Results

We present high quality deep read-depth single-cell RNA sequencing for 91 cells from five mouse tissues and 18 cells from two rat tissues, along with 30 control samples of bulk RNA diluted to single-cell levels. We find that transcriptomes differ globally across tissues with regard to the number of genes expressed, the average expression patterns, and within-cell-type variation patterns. We develop methods to filter genes for reliable quantification and to calibrate biological variation. All cell types include genes with high variability in expression, in a tissue-specific manner. We also find evidence that single-cell variability of neuronal genes in mice is correlated with that in rats consistent with the hypothesis that levels of variation may be conserved.

Conclusions

Single-cell RNA-sequencing data provide a unique view of transcriptome function; however, careful analysis is required in order to use single-cell RNA-sequencing measurements for this purpose. Technical variation must be considered in single-cell RNA-sequencing studies of expression variation. For a subset of genes, biological variability within each cell type appears to be regulated in order to perform dynamic functions, rather than solely molecular noise.
Single-cell mRNA sequencing identifies subclonal heterogeneity in anti-cancer drug responses of lung adenocarcinoma cells
Authors: Kim Kyu-Tae , Lee Hye Won , Lee Hae-Ock , Kim Sang Cheol , Seo Yun Jee , Chung Woosung , Eum Hye Hyeon , Nam Do-Hyun , Kim Junhyong , Joo Kyeung Min , Park Woong-Yang
Published: June 2015

Background

Intra-tumoral genetic and functional heterogeneity correlates with cancer clinical prognoses. However, the mechanisms by which intra-tumoral heterogeneity impacts therapeutic outcome remain poorly understood. RNA sequencing (RNA-seq) of single tumor cells can provide comprehensive information about gene expression and single-nucleotide variations in individual tumor cells, which may allow for the translation of heterogeneous tumor cell functional responses into customized anti-cancer treatments.

Results

We isolated 34 patient-derived xenograft (PDX) tumor cells from a lung adenocarcinoma patient tumor xenograft. Individual tumor cells were subjected to single cell RNA-seq for gene expression profiling and expressed mutation profiling. Fifty tumor-specific single-nucleotide variations, including KRAS
G12D
, were observed to be heterogeneous in individual PDX cells. Semi-supervised clustering, based on KRAS
G12D
mutant expression and a risk score representing expression of 69 lung adenocarcinoma-prognostic genes, classified PDX cells into four groups. PDX cells that survived in vitro anti-cancer drug treatment displayed transcriptome signatures consistent with the group characterized by KRAS
G12D
and low risk score.

Conclusions

Single-cell RNA-seq on viable PDX cells identified a candidate tumor cell subgroup associated with anti-cancer drug resistance. Thus, single-cell RNA-seq is a powerful approach for identifying unique tumor cell-specific gene expression profiles which could facilitate the development of optimized clinical anti-cancer strategies.
Brave new epigenomes: the dawn of epigenetic engineering
Authors: Köferle Anna , Stricker Stefan H. , Beck Stephan
Published: June 2015

Editorial summary

New methods for epigenome editing now make it possible to manipulate the epigenome in living cells with unprecedented specificity and efficiency. These ground-breaking approaches are beginning to yield novel insights into the function of individual chromatin marks in the context of cellular phenotype.
Stress Doppler echocardiography for early detection of systemic sclerosis-associated pulmonary arterial hypertension
Authors: Nagel Christian , Henn Philipp , Ehlken Nicola , D’Andrea Antonello , Blank Norbert , Bossone Eduardo , Böttger Anke , Fiehn Christoph , Fischer Christine , Lorenz Hanns-Martin , Stöckl Frank , Grünig Ekkehard , Egenlauf Benjamin
Published: June 2015

Introduction

In patients with systemic sclerosis (SSc), associated pulmonary arterial hypertension (SSc-APAH) is the leading cause of death. The objective of this prospective screening study was to analyse sensitivity and specificity of stress Doppler echocardiography (SDE) in detecting pulmonary hypertension (PH).

Methods

Pulmonary artery pressures and further parameters of PH were assessed by echocardiography and right heart catheterisation (RHC) at rest and during exercise in patients with SSc. Investigators of RHC were blinded to the results of non-invasive measurements.

Results

Of 76 patients with SSc (64 were female and mean age was 58±14 years), 22 (29 %) had manifest PH confirmed by RHC: four had concomitant left heart diseases, three had lung diseases, and 15 had SSc-APAH. Echocardiography at rest missed PH diagnosis in five of 22 patients with PH when a cutoff value for systolic pulmonary arterial pressure (PASP) was more than 40 mm Hg at rest. The sensitivity of echocardiography at rest was 72.7 % (95 % confidence interval (CI) 0.52–0.88), and specificity was 88.2 % (95 % CI 0.78–0.95). When a cutoff value for PASP was more than 45 mm Hg during low-dose exercise, SDE missed PH diagnosis in one of the 22 patients with PH and improved sensitivity to 95.2 % (95 % CI 0.81–1.0) but reduced specificity to 84.9 % (95 % CI 0.74–0.93). Reduction of specificity was partly due to concomitant left heart disease.

Conclusions

The results of this prospective cross-sectional study using RHC as gold standard in all patients showed that SDE markedly improved sensitivity in detecting manifest PH to 95.2 % compared with 72.7 % using echocardiography at rest only. Thus, for PH screening in patients with SSc, echocardiography should be performed at rest and during exercise.

Trial registration

ClinicalTrials.gov NCT01387035. Registered 29 June 2011.
Generation of human iPSCs from cells of fibroblastic and epithelial origin by means of the oriP/EBNA-1 episomal reprogramming system
Authors: Drozd Anna M. , Walczak Maciej P. , Piaskowski Sylwester , Stoczynska-Fidelus Ewelina , Rieske Piotr , Grzela Dawid P.
Published: June 2015

Introduction

The prospect of therapeutic applications of the induced pluripotent stem cells (iPSCs) is based on their ability to generate virtually any cell type present in human body. Generation of iPSCs from somatic cells has opened up new possibilities to investigate stem cell biology, to better understand pathophysiology of human diseases, and to design new therapy approaches in the field of regenerative medicine. In this study, we focus on the ability of the episomal system, a non-viral and integration-free reprogramming method to derive iPSCs from somatic cells of various origin.

Methods

Cells originating from neonatal and adult tissue, renal epithelium, and amniotic fluid were reprogrammed by using origin of replication/Epstein-Barr virus nuclear antigen-1 (oriP/EBNA-1)-based episomal vectors carrying defined factors. The iPSC colony formation was evaluated by using immunocytochemistry and alkaline phosphatase assay and by investigating gene expression profiles. The trilineage formation potential of generated pluripotent cells was assessed by embryoid body-mediated differentiation. The impact of additionally introduced factors on episome-based reprogramming was also investigated.

Results

Reprogramming efficiencies were significantly higher for the epithelial cells compared with fibroblasts. The presence of additional factor miR 302/367 in episomal system enhanced reprogramming efficiencies in fibroblasts and epithelial cells, whereas the downregulation of Mbd3 expression increased iPSC colony-forming efficiency in fibroblasts solely.

Conclusions

In this study, we performed a side-by-side comparison of iPSC colony-forming efficiencies in fibroblasts and epithelial cells transiently transfected with episomal plasmids and demonstrated that iPSC generation efficiency was highest when donor samples were derived from epithelial cells. We determined that reprogramming efficiency of episomal system could be further improved. Considering results obtained in the course of this study, we believe that episomal reprogramming provides a simple, reproducible, and efficient tool for generating clinically relevant pluripotent cells.