bluuebunny/crossref_metadata_2025 huggingface dataset:
The pathobiology of the oncogenic tyrosine kinase NPM-ALK: a brief update
Authors: Lai Raymond , Ingham Robert J.
Published: January 2013

Extensive research has been carried out in the past two decades to study the pathobiology of nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), which is an oncogenic fusion protein found exclusively in a specific type of T-cell lymphoid malignancy, namely ALK-positive anaplastic large cell lymphoma. Results from these studies have provided highly useful insights into the mechanisms by which a constitutively tyrosine kinase, such as NPM-ALK, promotes tumorigenesis. Several previous publications have comprehensively summarized the advances in this field. In this review, we provide readers with a brief update on specific areas of NPM-ALK pathobiology. In the first part, the NPM-ALK/signal transducer and activator of transcription 3 (STAT3) signaling axis is discussed, with an emphasis on the existence of multiple biochemical defects that have been shown to amplify the oncogenic effects of this signaling axis. Specifically, findings regarding JAK3, SHP1 and the stimulatory effects of several cytokines including interleukin (IL)-9, IL-21 and IL-22 are summarized. New concepts stemming from recent observations regarding the functional interactions among the NPM-ALK/STAT3 axis, β catenin and glycogen synthase kinase 3β will be postulated. Lastly, new mechanisms by which the NPM-ALK/STAT3 axis promotes tumorigenesis, such as its modulations of Twist1, hypoxia-induced factor 1α, CD274, will be described. In the second part, we summarize recent data generated by mass spectrometry studies of NPM-ALK, and use MSH2 and heat shock proteins as examples to illustrate the use of mass spectrometry data in stimulating new research in this field. In the third part, the evolving field of microRNA in the context of NPM-ALK biology is discussed.
Safety and efficacy of deferasirox in the management of transfusion-dependent patients with myelodysplastic syndrome and aplastic anaemia: a perspective review
Authors: Adams Rebecca L.C. , Bird Robert J.
Published: January 2013

Deferasirox is an orally administered, once-daily iron chelator with a generally good safety and efficacy profile. Reported adverse events in the older myelodysplastic population are somewhat different to the more intensively investigated and younger thalassaemic population. Renal impairment is the most concerning adverse event, but this is reversible if identified and the drug is withdrawn early. Gastrointestinal effects, particularly diarrhoea, can be troublesome for older patients, but can be minimized with tailored therapy. Negative iron balance can be achieved in most patients with a median dose of 20 mg/kg/day, and doses up to 40 mg/kg are possible in patients with severe iron overload, who are at risk of cardiac decompensation.
An ounce of time, a pound of responsibilities and a ton of weight to lose: An autoethnographic journey of barriers, message adherence and the weight-loss process
Authors: Johnson Christal R.S. , Eaves Katherine L.
Published: January 2013

This article uses an autoethnographic approach to determine how the intersectionality of identities affects message perceptions about weight loss from the lens of two doctoral students. This autoethnography links our personal experiences with the societal and cultural phenomena of obesity and weight loss, and the rhetoric of messages. We know there is a gap in public relations literature about autoethnography, health communication and intersectionality, and we hope to fill it. We also know health communicators seek more effective ways to reach an increasingly diverse audience; we hope to shed light on the issue. We know that many women want to lose weight and hope our narratives will resonate with them. Finally, we recognize autoethnographic skeptics exist in academia, and we hope our article provides insight into and understanding of the usefulness of autoethnographies in the field of public relations.
Public relations and ‘its’ media: Exploring the role of trade media in the enactment of public relations’ professional project
Authors: Edwards Lee , Pieczka Magda
Published: January 2013

This article explores the relationship between trade media and the construction of occupational legitimacy in the context of professional projects, using the example of public relations. We suggest that the practices of trade journalism result in such media playing the role of an institutional sub-system within occupational fields such as public relations, helping to construct occupational archetypes that have disciplinary effects on practitioners and provide the basis for public claims to legitimacy. We illustrate our argument by presenting the results of a critical discourse analysis of PRWeek, the main trade publication for public relations in the UK, to demonstrate how jurisdiction, practice and practitioners are constructed through media discourses in ways that serve the professional project articulated by the powerful actors in the field.
Frame, Set, Match! Towards a model of successful crisis rhetoric
Authors: Nord Lars W. , Olsson Eva-Karin
Published: January 2013

This article explores the mechanisms behind the ability of political leaders to win praise and support in times of crisis by Studying one such case of crisis exploitation: the Swedish government’s communication during the 2008 financial crisis. Looking back at the first term in office for the centre-right Alliance government, the government was initially struggling with historically low results in the regular opinion polls and a new electoral victory seemed to be beyond reach. However, this trend changed completely in the midst of the financial crisis when the government and its most prominent ministers from the dominant Moderate Party regained public support and confidence, and were able to win the next national election in 2010. The article argues that in order to explain successful political communication in times of crisis both the frames advocated by the political actors themselves and the media need to be taken into account. Based on this assumption the article proposes that successful political communication in crisis depends on a three-step process with interrelated aspects: the actor’s ability for frame promotion, setting and matching. Frame selection here refers to actors’ ability to use active frames (herein managerial, moral and responsibility frames), their ability to set the frame contexts so that they create a coherent logic resulting in frame reinforcement and, finally, their ability to match the political frames with the media’s framing.
Reframing trust, power and public relations in global financial discourses: Experts and the production of mistrust in life insurance
Authors: Bourne Clea
Published: January 2013

This study challenges the validity of a role for public relations (PR) as ‘trust strategist’ in global financial markets, by reframing trust, power and PR. The reframing takes place in three stages: First, by shifting the trajectory of PR research to focus on Giddens’s system trust theory, which, until now, has received little prominence in PR scholarship. Second, by drawing on Foucauldian perspectives to link system trust relations and power relations through discourse; revealing the strategies and practices used to produce trust in global discourses. Third, by locating PR activity within discursive moments of trust/ mistrust production, repositioning PR as a ‘trust intermediary’ in global discourses.
Is CTKUB the gold standard in assessing flank pain with diagnostic uncertainty? A one-year review of 228 cases
Authors: Dyer J , Syratt T , Singh G
Published: January 2013

The use of computed tomography of the kidneys, ureters and bladder (CTKUB) in a "renal colic pathway" has been reported to yield high diagnosis rates and also identifies other non-urological pathology accounting for patients’ symptoms. Our study explores the diagnostic yield of CTKUB as the first-line investigation for suspected renal colic with regard to urolithiasis and additional findings. All CTKUB performed in cases of suspected renal colic were extracted from our radiology database from 1 April 2010 to 1 April 2011. Extracted information included: demographics, the department ordering the investigation, presence of ureteric calculi, presence of renal calculi and any additional findings that could account for patients’ symptoms, or otherwise. During the study 228 CTKUB were performed. The diagnosis rate of ureteric calculi was 33.7%. In the absence of a ureteric stone, additional findings as well as alternative diagnoses were higher (additional finding 49.7% ( n=75) vs. 35% ( n=27); alternative diagnosis 33.1% ( n=50) vs. 15.6% ( n=12) p < 0.05). In patients with ureteric calculi, the alternative diagnosis yield of 15.6% falls within the range of that previously documented. This study illustrates that when diagnostic clarity is not reached, CTKUB is being overused. This leads to unnecessary radiation exposure and resource wastage.
Direct evidence of the importance of vitronectin and its interaction with the urokinase receptor in tumor growth
Authors: Pirazzoli Valentina , Ferraris Gian Maria Sarra , Sidenius Nicolai
Published: January 2013

Key Points

We demonstrate that vitronectin plays an important role in tumor growth. We show that the urokinase receptor can promote tumor growth through its interaction with vitronectin.
The Rac GTPase effector p21-activated kinase is essential for hematopoietic stem/progenitor cell migration and engraftment
Authors: Dorrance Adrienne M. , De Vita Serena , Radu Maria , Reddy Pavankumar N. G. , McGuinness Meaghan K. , Harris Chad E. , Mathieu Ronald , Lane Steven W. , Kosoff Rachelle , Milsom Michael D. , Chernoff Jonathan , Williams David A.
Published: January 2013

Key Points

The Rac effector p21-activated kinase (Pak) regulates hematopoietic engraftment. Pak integrates cytoskeletal changes and proliferation pathways.
Identification of Dirofilaria immitis miRNA using illumina deep sequencing
Authors: Fu Yan , Lan Jingchao , Wu Xuhang , Yang Deying , Zhang Zhihe , Nie Huaming , Hou Rong , Zhang Runhui , Zheng Wanpeng , Xie Yue , Yan Ning , Yang Zhi , Wang Chengdong , Luo Li , Liu Li , Gu Xiaobin , Wang Shuxian , Peng Xuerong , Yang Guangyou
Published: January 2013

The heartwormDirofilaria immitisis the causative agent of cardiopulmonary dirofilariosis in dogs and cats, which also infects a wide range of wild mammals and humans. The complex life cycle ofD. immitiswith several developmental stages in its invertebrate mosquito vectors and its vertebrate hosts indicates the importance of miRNA in growth and development, and their ability to regulate infection of mammalian hosts. This study identified the miRNA profiles ofD. immitisof zoonotic significance by deep sequencing. A total of 1063 conserved miRNA candidates, including 68 anti-sense miRNA (miRNA*) sequences, were predicted by computational methods and could be grouped into 808 miRNA families. A significant bias towards family members, family abundance and sequence nucleotides was observed. Thirteen novel miRNA candidates were predicted by alignment with theBrugia malayigenome. Eleven out of 13 predicted miRNA candidates were verified by using a PCR-based method. Target genes of the novel miRNA candidates were predicted by using the heartworm transcriptome dataset. To our knowledge, this is the first report of miRNA profiles inD. immitis, which will contribute to a better understanding of the complex biology of this zoonotic filarial nematode and the molecular regulation roles of miRNA involved. Our findings may also become a useful resource for small RNA studies in other filarial parasitic nematodes.
Development and validation of microsatellite markers for Brachiaria ruziziensisobtained by partial genome assembly of Illumina single-end reads
Authors: Silva Pedro IT , Martins Alexandre M , Gouvea Ediene G , Pessoa-Filho Marco , Ferreira Márcio E
Published: January 2013

Background

Brachiaria ruziziensis is one of the most important forage species planted in the tropics. The application of genomic tools to aid the selection of superior genotypes can provide support to B. ruziziensis breeding programs. However, there is a complete lack of information about the B. ruziziensis genome. Also, the availability of genomic tools, such as molecular markers, to support B. ruziziensis breeding programs is rather limited. Recently, next-generation sequencing technologies have been applied to generate sequence data for the identification of microsatellite regions and primer design. In this study, we present a first validated set of SSR markers for Brachiaria ruziziensis, selected from a de novo partial genome assembly of single-end Illumina reads.

Results

A total of 85,567 perfect microsatellite loci were detected in contigs with a minimum 10X coverage. We selected a set of 500 microsatellite loci identified in contigs with minimum 100X coverage for primer design and synthesis, and tested a subset of 269 primer pairs, 198 of which were polymorphic on 11 representative B. ruziziensis accessions. Descriptive statistics for these primer pairs are presented, as well as estimates of marker transferability to other relevant brachiaria species. Finally, a set of 11 multiplex panels containing the 30 most informative markers was validated and proposed for B. ruziziensis genetic analysis.

Conclusions

We show that the detection and development of microsatellite markers from genome assembled Illumina single-end DNA sequences is highly efficient. The developed markers are readily suitable for genetic analysis and marker assisted selection of Brachiaria ruziziensis. The use of this approach for microsatellite marker development is promising for species with limited genomic information, whose breeding programs would benefit from the use of genomic tools. To our knowledge, this is the first set of microsatellite markers developed for this important species.
Identification and profiling of conserved and novel microRNAs from Chinese Qinchuan bovine longissimus thoracis
Authors: Sun Jiajie , Li Mijie , Li Zhuanjian , Xue Jing , Lan Xianyong , Zhang Chunlei , Lei Chuzhao , Chen Hong
Published: January 2013

Background

MicroRNAs (miRNAs) are a family of ~22 nucleotide small RNA molecules that regulate gene expression by fully or partially binding to their complementary sequences. Recently, a large number of miRNAs and their expression patterns have been identified in various species. However, to date no miRNAs have been reported to modulate muscle development in beef cattle.

Results

Total RNAs from the Chinese Qinchuan bovine longissimus thoracis at fetal and adult stages were used to construct small RNA libraries for Solexa SBS technology sequencing. A total of 15,454,182 clean reads were obtained from the fetal bovine library and 13,558,164 clean reads from the adult bovine library. In total, 521 miRNAs including 104 novel miRNA candidates were identified. Furthermore, the nucleotide bias, base edit and family of the known miRNAs were also analyzed. Based on stem-loop qPCR, 25 high-read miRNAs were detected, and the results showed that bta-miRNA-206, miRNA-1, miRNA-133, miRNAn12, and miRNAn17 were highly expressed in muscle-related tissue or organs, suggesting that these miRNAs may play a role in the development of bovine muscle tissues.

Conclusions

This study confirmed the authenticity of 417 known miRNAs, discovered 104 novel miRNAs in bos taurus, and identified five muscle-specific miRNAs. The identification of novel miRNAs significantly expanded the repertoire of bovine miRNAs and could contribute to further studies on the muscle development of cattle.
A qualitative exploration of Malaysian cancer patients’ perceptions of cancer screening
Authors: Farooqui Maryam , Hassali Mohamed Azmi , Knight Aishah , Shafie Asrul Akmal , Farooqui Muhammad Aslam , Saleem Fahad , Haq Noman-ul , Aljadhey Hisham
Published: January 2013

Background

Despite the existence of different screening methods, the response to cancer screening is poor among Malaysians. The current study aims to examine cancer patients’ perceptions of cancer screening and early diagnosis.

Methods

A qualitative methodology was used to collect in-depth information from cancer patients. After obtaining institutional ethical approval, patients with different types and stages of cancer from the three major ethnic groups (Malay, Chinese and Indian) were approached. Twenty semi-structured interviews were conducted. All interviews were audiotaped, transcribed verbatim, and translated into English for thematic content analysis.

Results

Thematic content analysis yielded four major themes: awareness of cancer screening, perceived benefits of cancer screening, perceived barriers to cancer screening, and cues to action. The majority of respondents had never heard of cancer screening before their diagnosis. Some participants reported hearing about mammogram and Pap smear tests but did not undergo screening due to a lack of belief in personal susceptibility. Those who had negative results from screening prior to diagnosis perceived such tests as untrustworthy. Lack of knowledge and financial constraints were reported as barriers to cancer screening. Finally, numerous suggestions were given to improve screening behaviour among healthy individuals, including the role of mass media in disseminating the message ‘prevention is better than cure’.

Conclusions

Patients’ narratives revealed some significant issues that were in line with the Health Belief Model which could explain negative health behaviour. The description of the personal experiences of people with cancer could provide many cues to action for those who have never encountered this potentially deadly disease, if incorporated into health promotion activities.
Prevalence and risk factors of hepatitis B and C virus infections among the general population and blood donors in Morocco
Authors: Baha Warda , Foullous Abderrahim , Dersi Noureddine , They-they Thierry Paluku , alaoui Khadija El , Nourichafi Nadia , Oukkache Bouchra , Lazar Fatiha , Benjelloun Soumaya , Ennaji My Mustapha , Elmalki Abdelouhad , Mifdal Hassan , Bennani Abdelouaheb
Published: January 2013

Background

Viral hepatitis is a serious public health problem affecting billions of people globally. Limited information is available on this issue in Morocco. This cross-sectional study was undertaken with the aim of determining the seroprevalence and risk factors of hepatitis B virus (HBV) and hepatitis C virus (HCV) among the general population and among blood donors.

Methods

Blood samples from volunteers, have been screened with ELISA tests for detecting the hepatitis-B surface antigen (HBsAg) and anti-HCV. Within the seroreactive patients for HCV in the general population, RT-PCR was performed by the Cobas Ampliprep/Cobas Amplicor.

Results

HCV and HBV-seropositivity was documented in 1.58% and 1.81% out of 41269 and 23578 participants respectively from the general population. Two patients were found to be co-infected. HCV-RNA was detected by PCR in 70.9% of the 195 anti-HCV positive subjects. The anti-HCV prevalence was not different among males and females (P = 0.3). It increased with age; the highest prevalence was observed among subjects with >50 years old (3.12%). Various risk factors for acquiring HCV infection were identified; age, dental treatment, use of glass syringes and surgical history. In addition to these factors, gender and sexual risk behaviors were found to be associated with higher prevalence of hepatitis B. The HBV positivity was significantly higher among males than females participants in all age groups (P < 0.01). The peak was noticed among males aged 30–49 years (2.4%). None of the 152 persons younger than 20 years had HBsAg or anti-HCV. The prevalence of anti-HCV and HBsAg among 169605 blood donors was 0.62% and 0.96% respectively.

Conclusions

Our study provided much important information concerning hepatitis B and C prevalence and risk factors; it confirmed the intermediate endemicity for HCV infection and pointed to a decreasing trend of HBV incidence, which might reclassify Morocco in low HBV endemicity area. This could be attributed primarily to the universal HBV vaccination among infants and healthcare workers over the past 13 years. HCV and HBV infections in the present survey were mainly associated with nosocomial exposures. Prevention and control of HBV infection are needed to reduce HBV transmission between adults.
Illness perceptions in patients receiving rheumatology rehabilitation: association with health and outcomes at 12 months
Authors: Løchting Ida , Fjerstad Elin , Garratt Andrew M
Published: January 2013

Background

Illness perceptions have been found to change over time and following health care. Hence, addressing illness perceptions alongside existing health care interventions may be important for the sustainment of health gains following rehabilitation. The aim of this study was to measure the illness perceptions of patients receiving inpatient rheumatology rehabilitation and assess the association with aspects of health and outcomes at baseline, discharge and 12 months.

Methods

Patients with a rehabilitation stay of one week or more at three institutions in Norway in 2009 were invited to participate in the study. At baseline, discharge and 12 months, patients completed The Rheumatic Disease Illness Perception Questionnaire (RD-IPQ) which includes aspects of illness perceptions important to patients with rheumatic diseases. Stepwise regression analysis was used to assess associations between RD-IPQ scores and different aspects of health at baseline and follow-up after controlling for other aspects of health and sociodemographic variables.

Results

For the 134 patients included in the study, baseline RD-IPQ scores had a mean of 58.2 (SD 14.9) on a 0–100 scale, where 100 is the worst possible. Scores showed improvement after the rehabilitation stay which were maintained at 12 months. RD-IPQ scores were positively associated with health and outcomes. At baseline RD-IPQ scores were statistically significant in explaining variation in pain, physical function and SF-36 mental health scores. Baseline RD-IPQ scores were significant in explaining fatigue, pain, SF-36 role limitations and social function scores following rehabilitation and at 12 months.

Conclusion

Illness perceptions as measured by the RD-IPQ were associated with health and outcomes as measured by rheumatology-specific and generic instruments. The consideration of illness perceptions as a component of rehabilitation may be important in achieving desired outcomes.
POU1F1 is a novel fusion partner of NUP98 in acute myeloid leukemia with t(3;11)(p11;p15)
Authors: Lisboa Susana , Cerveira Nuno , Bizarro Susana , Correia Cecília , Vieira Joana , Torres Lurdes , Mariz José M , Teixeira Manuel R
Published: January 2013

Background

NUP98 gene rearrangements have been reported in acute myeloid leukemia, giving rise to fusion proteins that seem to function as aberrant transcription factors, and are thought to be associated with poor prognosis.

Findings

A patient with treatment-related acute myeloid leukemia presented a t(3;11)(p11;p15) as the only cytogenetic abnormality. FISH and molecular genetic analyses identified a class 1 homeobox gene, POU1F1, located on chromosome 3p11, as the fusion partner of NUP98. In addition, we have found that the patient harbored an FLT3-ITD mutation, which most likely collaborated with the NUP98-POU1F1 fusion gene in malignant transformation.

Conclusions

We have identified POU1F1 as the NUP98 fusion partner in therapy-related AML with a t(3;11)(p11;p15). This is the first POU family member identified as a fusion partner in human cancer.
Deep transcriptome-sequencing and proteome analysis of the hydrothermal vent annelid Alvinella pompejana identifies the CvP-bias as a robust measure of eukaryotic thermostability
Authors: Holder Thomas , Basquin Claire , Ebert Judith , Randel Nadine , Jollivet Didier , Conti Elena , Jékely Gáspár , Bono Fulvia
Published: January 2013

Background

Alvinella pompejana is an annelid worm that inhabits deep-sea hydrothermal vent sites in the Pacific Ocean. Living at a depth of approximately 2500 meters, these worms experience extreme environmental conditions, including high temperature and pressure as well as high levels of sulfide and heavy metals. A. pompejana is one of the most thermotolerant metazoans, making this animal a subject of great interest for studies of eukaryotic thermoadaptation.

Results

In order to complement existing EST resources we performed deep sequencing of the A. pompejana transcriptome. We identified several thousand novel protein-coding transcripts, nearly doubling the sequence data for this annelid. We then performed an extensive survey of previously established prokaryotic thermoadaptation measures to search for global signals of thermoadaptation in A. pompejana in comparison with mesophilic eukaryotes. In an orthologous set of 457 proteins, we found that the best indicator of thermoadaptation was the difference in frequency of charged versus polar residues (CvP-bias), which was highest in A. pompejana. CvP-bias robustly distinguished prokaryotic thermophiles from prokaryotic mesophiles, as well as the thermophilic fungus Chaetomium thermophilum from mesophilic eukaryotes. Experimental values for thermophilic proteins supported higher CvP-bias as a measure of thermal stability when compared to their mesophilic orthologs. Proteome-wide mean CvP-bias also correlated with the body temperatures of homeothermic birds and mammals.

Conclusions

Our work extends the transcriptome resources for A. pompejana and identifies the CvP-bias as a robust and widely applicable measure of eukaryotic thermoadaptation.

Reviewer

This article was reviewed by Sándor Pongor, L. Aravind and Anthony M. Poole.
C-reactive protein, haptoglobin, serum amyloid A and pig major acute phase protein response in pigs simultaneously infected with H1N1 swine influenza virus and Pasteurella multocida
Authors: Pomorska-Mól Małgorzata , Markowska-Daniel Iwona , Kwit Krzysztof , Stępniewska Katarzyna , Pejsak Zygmunt
Published: January 2013

Background

Swine influenza (SI) is an acute respiratory disease caused by swine influenza virus (SIV). Swine influenza is generally characterized by acute onset of fever and respiratory symptoms. The most frequent complications of influenza are secondary bacterial pneumonia. The objective of this work was to study the acute phase proteins (APP) responses after coinfection of piglets with H1N1 swine influenza virus (SwH1N1) and Pasteurella multocida (Pm) in order to identify whether the individual APP response correlate with disease severity and whether APP could be used as markers of the health status of coinfected pigs.

Results

In all coinfected pigs clinical sings, including fever, coughing and dyspnea, were seen. Viral shedding was observed from 2 to 7 dpi. The mean level of antibodies against Pm dermonecrotoxin in infected piglets increase significantly from 7 dpi. Anti-SwH1N1 antibodies in the serum were detected from 7 dpi. The concentration of C-reactive protein (CRP) increased significantly at 1 dpi as compared to control pigs, and remained significantly higher to 3 dpi. Level of serum amyloid A (SAA) was significantly higher from 2 to 3 dpi. Haptoglobin (Hp) was significantly elevated from 3 dpi to the end of study, while pig major acute phase protein (Pig-MAP) from 3 to 7 dpi. The concentrations of CRP, Hp and SAA significantly increased before specific antibodies were detected. Positive correlations were found between serum concentration of Hp and SAA and lung scores, and between clinical score and concentrations of Pig-MAP and SAA.

Conclusions

The results of current study confirmed that monitoring of APP may revealed ongoing infection, and in this way may be useful in selecting clinically healthy pigs (i.e. before integration into an uninfected herd). Present results corroborated our previous findings that SAA could be a potentially useful indicator in experimental infection studies (e.g. vaccine efficiency investigations) or as a marker for disease severity, because of correlation observed between its concentration in serum and disease severity (lung scores, clinical scores).
SignaLink 2 – a signaling pathway resource with multi-layered regulatory networks
Authors: Fazekas Dávid , Koltai Mihály , Türei Dénes , Módos Dezső , Pálfy Máté , Dúl Zoltán , Zsákai Lilian , Szalay-Bekő Máté , Lenti Katalin , Farkas Illés J , Vellai Tibor , Csermely Péter , Korcsmáros Tamás
Published: January 2013

Background

Signaling networks in eukaryotes are made up of upstream and downstream subnetworks. The upstream subnetwork contains the intertwined network of signaling pathways, while the downstream regulatory part contains transcription factors and their binding sites on the DNA as well as microRNAs and their mRNA targets. Currently, most signaling and regulatory databases contain only a subsection of this network, making comprehensive analyses highly time-consuming and dependent on specific data handling expertise. The need for detailed mapping of signaling systems is also supported by the fact that several drug development failures were caused by undiscovered cross-talk or regulatory effects of drug targets. We previously created a uniformly curated signaling pathway resource, SignaLink, to facilitate the analysis of pathway cross-talks. Here, we present SignaLink 2, which significantly extends the coverage and applications of its predecessor.

Description

We developed a novel concept to integrate and utilize different subsections (i.e., layers) of the signaling network. The multi-layered (onion-like) database structure is made up of signaling pathways, their pathway regulators (e.g., scaffold and endocytotic proteins) and modifier enzymes (e.g., phosphatases, ubiquitin ligases), as well as transcriptional and post-transcriptional regulators of all of these components. The user-friendly website allows the interactive exploration of how each signaling protein is regulated. The customizable download page enables the analysis of any user-specified part of the signaling network. Compared to other signaling resources, distinctive features of SignaLink 2 are the following: 1) it involves experimental data not only from humans but from two invertebrate model organisms, C. elegans and D. melanogaster; 2) combines manual curation with large-scale datasets; 3) provides confidence scores for each interaction; 4) operates a customizable download page with multiple file formats (e.g., BioPAX, Cytoscape, SBML). Non-profit users can access SignaLink 2 free of charge at http://SignaLink.org.

Conclusions

With SignaLink 2 as a single resource, users can effectively analyze signaling pathways, scaffold proteins, modifier enzymes, transcription factors and miRNAs that are important in the regulation of signaling processes. This integrated resource allows the systems-level examination of how cross-talks and signaling flow are regulated, as well as provide data for cross-species comparisons and drug discovery analyses.
Topical tacrolimus 0.1% ointment for treatment of cutaneous Crohn’s Disease
Authors: Rice Shantini A , Woo Pick N , El-Omar Emad , Keenan Ronald A , Ormerod Anthony D
Published: January 2013

Background

Cutaneous Crohn’s Disease is a notoriously difficult condition to treat and causes significant morbidity, impacting heavily on quality of life. This is the first study in adults examining the effect of topical tacrolimus on the different cutaneous manifestations of Crohn’s Disease.

Methods

This open label observational study of 20 patients with heterogeneous forms of cutaneous Crohn’s disease used topical tacrolimus 0.1% ointment once daily to affected areas for 12 weeks with a maximal total dose of 90g. Therapy was stopped at 12 weeks to assess whether the condition relapsed. Thereafter relapsing patients optionally continued an open label extension of topical tacrolimus therapy and were observed for a total of 12 months.

Results

Of seventeen patients completing the twelve-week study, fifteen improved using a specifically designed physicians’ global severity scale. One patient cleared, four showed a pronounced improvement (51-75%) and ten demonstrated a mild (1-25%) or moderate improvement (25-50%) in twelve weeks. Over twelve months eleven patients remained in the study, nine of which improved, one cleared and one showed no change. Perineal disease responded better with two out of twelve clearing, four showing pronounced benefit and four mild to moderate improvement. Long-term application of 0.1% tacrolimus applied to broken skin and mucosa was safe and serum levels of tacrolimus were undetectable in all subjects throughout the study.

Conclusion

0.1% tacrolimus ointment was safe and effective in treating cutaneous manifestations of Crohn’s disease, particularly perineal disease and pyoderma gangrenosum, yet it seldom cleared the condition.

Clinical trial registration

ClinicalTrials.gov Protocol Registration System ID: 33000332
Compartmentalization of lipid peroxidation in sepsis by multidrug-resistant gram-negative bacteria: experimental and clinical evidence
Authors: Toufekoula Chryssoula , Papadakis Vassileios , Tsaganos Thomas , Routsi Christina , Orfanos Stylianos E , Kotanidou Anastasia , Carrer Dionyssia-Pinelopi , Raftogiannis Maria , Baziaka Fotini , Giamarellos-Bourboulis Evangelos J
Published: January 2013

Introduction

Recent evidence suggests a link between excess lipid peroxidation and specific organ failures in sepsis. No study has been performed in sepsis by multidrug-resistant (MDR) Gram-negative bacteria.

Methods

Lethal sepsis was induced in rats by the intraperitoneal injection of one MDR isolate of Pseudomonas aeruginosa. Produced malondialdehyde (MDA) was measured in tissues 5 hours after bacterial challenge with the thiobarbiturate assay followed by high-performance liquid chromatography (HPLC) analysis. Results were compared with those from a cohort of patients with ventilator-associated pneumonia (VAP) and sepsis by MDR Gram-negative bacteria. More precisely, serum MDA was measured on 7 consecutive days, and it was correlated with clinical characteristics.

Results

MDA of septic rats was greater in the liver, spleen, and aortic wall, and it was lower in the right kidney compared with sham operated-on animals. Findings were confirmed by the studied cohort. Circulating MDA was greater in patients with hepatic dysfunction and acute respiratory distress syndrome (ARDS) compared with patients without any organ failures. The opposite was found for patients with acute renal dysfunction. No differences were found between patients with ARDS without or with cardiovascular (CV) failure and patients without any organ failure. Serial measurements of MDA in serum of patients indicated that levels of MDA were greater in survivors of hepatic dysfunction and ARDS and lower in survivors of acute renal dysfunction.

Conclusions

Animal findings and results of human sepsis are complementary, and they suggest a compartmentalization of lipid peroxidation in systemic infections by MDR gram-negative bacteria.
Lower tidal volume at initiation of mechanical ventilation may reduce progression to acute respiratory distress syndrome: a systematic review
Authors: Fuller Brian M , Mohr Nicholas M , Drewry Anne M , Carpenter Christopher R
Published: January 2013

Introduction

The most appropriate tidal volume in patients without acute respiratory distress syndrome (ARDS) is controversial and has not been rigorously examined. Our objective was to determine whether a mechanical ventilation strategy using lower tidal volume is associated with a decreased incidence of progression to ARDS when compared with a higher tidal volume strategy.

Methods

A systematic search of MEDLINE, EMBASE, CINAHL, the Cochrane Library, conference proceedings, and clinical trial registration was performed with a comprehensive strategy. Studies providing information on mechanically ventilated patients without ARDS at the time of initiation of mechanical ventilation, and in which tidal volume was independently studied as a predictor variable for outcome, were included. The primary outcome was progression to ARDS.

Results

The search yielded 1,704 studies, of which 13 were included in the final analysis. One randomized controlled trial was found; the remaining 12 studies were observational. The patient cohorts were significantly heterogeneous in composition and baseline risk for developing ARDS; therefore, a meta-analysis of the data was not performed. The majority of the studies (n = 8) showed a decrease in progression to ARDS with a lower tidal volume strategy. ARDS developed early in the course of illness (5 hours to 3.7 days). The development of ARDS was associated with increased mortality, lengths of stay, mechanical ventilation duration, and nonpulmonary organ failure.

Conclusions

In mechanically ventilated patients without ARDS at the time of endotracheal intubation, the majority of data favors lower tidal volume to reduce progression to ARDS. However, due to significant heterogeneity in the data, no definitive recommendations can be made. Further randomized controlled trials examining the role of lower tidal volumes in patients without ARDS, controlling for ARDS risk, are needed.

2013 Fuller et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Microseismicity-constrained discrete fracture network models for stimulated reservoir simulation
Authors: Williams-Stroud Sherilyn , Ozgen Chet , Billingsley Randall L.
Published: January 2013

The effectiveness of hydraulic fracture stimulation in low-permeability reservoirs was evaluated by mapping microseismic events related to rock fracturing. The geometry of stage by stage event point sets were used to infer fracture orientation, particularly in the case where events line up along an azimuth, or have a planar distribution in three dimensions. Locations of microseismic events may have a higher degree of uncertainty when there is a low signal-to-noise ratio (either due to low magnitude or to propagation effects). Low signal-to-noise events are not as accurately located in the reservoir, or may fall below the detectability limit, so that the extent of fracture stimulated reservoir may be underestimated. In the Bakken Formation of the Williston Basin, we combined geologic analysis with process-based and stochastic fracture modeling to build multiple possible discrete fracture network (DFN) model realizations. We then integrated the geologic model with production data and numerical simulation to evaluate the impact on estimated ultimate recovery (EUR). We tested assumptions used to create the DFN model to determine their impact on dynamic calibration of the simulation model, and their impact on predictions of EUR. Comparison of simulation results, using fracture flow properties generated from two different calibrated DFN scenarios, showed a 16% difference in amount of oil ultimately produced from the well. The amount of produced water was strongly impacted by the geometry of the DFN model. The character of the DFN significantly impacts the relative amounts of fluids produced. Monitoring water cut with production can validate the appropriate DFN scenario, and provide critical information for the optimal method for well production. The results indicated that simulation of enhanced permeability using induced microseismicity to constrain a fracture flow property model is an effective way to evaluate the performance of reservoirs stimulated by hydraulic fracture treatments.
Upper Extremity Venous Thrombosis in Patients With Cancer With Peripherally Inserted Central Venous Catheters: A Retrospective Analysis of Risk Factors
Authors: Ahn Daniel H. , Illum Henrik Bo , Wang David H. , Sharma Anant , Dowell Jonathan E.
Published: January 2013

Specific factors significantly increase the risk of upper extremity venous thrombosis in patients with cancer with PICCs, whereas use of anti-platelet agents seems to have a protective effect against it.
Inpatient Hospitalization of Oncology Patients: Are We Missing an Opportunity for End-of-Life Care?
Authors: Rocque Gabrielle B. , Barnett Anne E. , Illig Lisa C. , Eickhoff Jens C. , Bailey Howard H. , Campbell Toby C. , Stewart James A. , Cleary James F.
Published: January 2013

The authors conclude that the inpatient oncology service predominantly cares for a population nearing the end of life; therefore, goals should include symptom control and end-of-life planning.
Tracking the Workforce: The American Society of Clinical Oncology Workforce Information System
Authors: Kirkwood M. Kelsey , Kosty Michael P. , Bajorin Dean F. , Bruinooge Suanna S. , Goldstein Michael A.
Published: January 2013

Reports generated by the workforce information system can be used by ASCO and others in the oncology community to advocate for needed health care system and policy changes to help offset future workforce shortages.
Human Rights, the Laws of War, and Reciprocity
Authors: Posner Eric A.
Published: January 2013

Human rights law does not appear to enjoy as high a level of compliance as the laws of war, yet is institutionalized to a greater degree. This Article argues that the reason for this difference is related to the strategic structure of international law. The laws of war are governed by a regime of reciprocity, which can produce selfenforcing patterns of behavior, whereas the human rights regime attempts to produce public goods and is thus subject to collective action problems. The more elaborate human rights institutions are designed to overcome these problems but fall prey to second-order collective action problems. The simple laws of war institutions have been successful because they can exploit the logic of reciprocity. The Article also suggests that limits on military reprisals are in tension with self-enforcement of the laws of war. The U.S. conflict with Al Qaeda is discussed.
Justice in Asymmetric Wars: A Contractarian Analysis
Authors: Benbaji Yitzhak
Published: January 2013

This Article aims to extend contractarianism in just war theory to the case of asymmetric war of independence. Its main thesis is that within asymmetric wars, the traditional rule of noncombatant immunity has no contractarian justification: It systematically discriminates against the weak part to the conflict, and thus it is unfair. On the other hand, a rule that allows those who take themselves to be freedom fighters to threaten civic life, yet prohibits deliberately targeting individuals, is fair and mutually beneficial. The branch of the war convention I called “justice in asymmetric war” instructs militants to treat civilians as if they bear no personal responsibility for the evil that their society causes.
Reciprocal Antidiscrimination Arguments
Authors: Tirosh Yofi
Published: January 2013

This Article addresses a common characteristic of antidiscrimination law: To what extent should one antidiscrimination campaign be held accountable for other, related, discriminatory structures that it does not and cannot purport to correct? Plaintiffs in antidiscrimination cases are sometimes expected to account for the larger social context in which their claim is made. Defendants invoke this larger context as a way of rebutting the discrimination claim, by arguing that the plaintiff’s claim has “discriminatory residue” that would exacerbate related discriminatory structures. For example, in a case in which same-sex couples seek the right to contract with surrogate mothers, the defendant can argue that accepting the plaintiffs’ claim that they are discriminated against on the basis of sexuality might exacerbate the exploitation of surrogate mothers. This Article dubs such rebuttal claims RADARs: reciprocal antidiscrimination arguments. It offers a framework for weighing RADARs’ feasibility, by mapping both their potential and their limitations. It concludes that RADARs can be useful analytical tools for legislators and policymakers when assessing the overall impact of specific antidiscrimination measures. RADARs are also helpful for cause lawyers in considering the long term impacts of antidiscrimination litigation. In contrast, courts should be cautious in accepting RADARs made by defendants in antidiscrimination cases due to the inherent institutional and procedural limitations of adjudication.
Note: Reciprocity of Rights and Duties, Benefits and Burdens: National Service for Israeli Arabs
Authors: Statman Daniel
Published: January 2013

Jews and Arabs in Israel often agree that there is a reciprocal relation between rights and duties, though they derive opposing conclusions from it. Jews infer that Arabs are not entitled to the same rights and privileges as Jews are, since they do not shoulder an equal share of the duties. Arabs, by contrast, argue that they are under no duty to share the burdens, particularly military or national service, since their rights are not fully respected. The Paper assesses these opposing claims and ends up rejecting both. It argues that the rights to which citizens are entitled do not depend on citizens carrying out all their social or legal duties, while the citizens’ duty to contribute to the welfare of their countries by national service or other means is generally not contingent on the countries’ fulfillment of its duties towards them. The Paper focuses on national service by Israeli Arabs and suggests that (a) that there is nothing wrong in making such service mandatory though there are practical considerations against doing so and (b) that making such service optional is an excellent alternative, one that should be encouraged as much as possible.
A simple and efficient synthesis of novel naphthyridine-1-H-pyrazole-4-carboxylic acid esters/carbaldehydes using Vilsmeier-Haack reagent
Authors: Chaitanya Muggu V.S.R.K. , Dubey Pramod K.
Published: January 2013

The reaction of hydrazide 4 with β-keto esters 5 gave hydrazones 6. Cyclization of 6 with Vilsmeier-Haack reagent (DMF-POCl3) for 20 min at room temperature gave 1-(4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carbonyl)-1H-pyrazole-4-carboxylic acid ethyl esters 7. The treatment of 4 with substituted acetophenones 8 yielded the corresponding hydrazones 9 of substituted acetophenones. The treatment of 9 with Vilsmeier-Haack reagent (DMF-POCl3) for 30 min at room temperature gave product 10, the reaction of which with (diacetoxyiodo)benzene in ethanol at room temperature for 12 h in the presence of molecular iodine furnished 7.
Patterns of contraception choice among Hispanic and non-Hispanic female adolescents
Authors: Desrosiers Florence , Arden Martha , Fisher Martin
Published: January 2013

Background: This study examines contraception choices among Hispanic and non-Hispanic girls, to determine if there are differences when the barrier of cost is removed by facilitating enrollment in a Title X Family Planning Program.

Methods: Charts of adolescent females aged 13–19 years, seen for the first time at a university hospital clinic from January 1, 2005 to December 31, 2007, were reviewed. Access to contraception was facilitated by enrollment in the Title X Family Planning Program. Patients were categorized as public insurance if they had Medicaid or Child/Family Health Plus or chose to enroll in the Title X program.

Results: Among the 666 eligible patients, 27% were Hispanic, with a mean age of 14.9 years. At least 20% had used one form of contraception before their first clinic visit. About one-third of the youth were enrolled in the Title X Family Planning Program, with no statistical difference between Hispanic and non-Hispanic youth. Three hundred and ninety subjects (58%) chose contraception during their visit. Hispanic subjects, who represented 32% of the group, were more likely to choose condoms and oral contraceptive pills compared to non-Hispanic subjects. The privately insured adolescents chose condoms less often than the publicly insured adolescents, and this was true regardless of ethnicity.

Conclusion: There are significant differences in contraception choices between Hispanic and non-Hispanic youth. The Title X Family Planning Program allowed young women to make independent choices. Adolescents may benefit from further improvements in culturally sensitive family planning programs.