bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contribution of statistical tests to sparseness-based blind source separation
Authors: Aziz-Sbaï Si Mohamed , Aïssa-El-Bey Abdeldjalil , Pastor Dominique 
Published: August 2012

AbstractWe address the problem of blind source separation in the underdetermined mixture case. Two statistical tests are proposed to reduce the number of empirical parameters involved in standard sparseness-based underdetermined blind source separation (UBSS) methods. The first test performs multisource selection of the suitable time–frequency points for source recovery and is full automatic. The second one is dedicated to autosource selection for mixing matrix estimation and requires fixing two parameters only, regardless of the instrumented SNRs. We experimentally show that the use of these tests incurs no performance loss and even improves the performance of standard weak-sparseness UBSS approaches.
Adenosine A2B receptor-mediated leukemia inhibitory factor release from astrocytes protects cortical neurons against excitotoxicity
Authors: Moidunny Shamsudheen , Vinet Jonathan , Wesseling Evelyn , Bijzet Johan , Shieh Chu-Hsin , van Ijzendoorn Sven CD , Bezzi Paola , Boddeke Hendrikus WGM , Biber Knut 
Published: August 2012

AbstractBackgroundNeuroprotective and neurotrophic properties of leukemia inhibitory factor (LIF) have been widely reported. In the central nervous system (CNS), astrocytes are the major source for LIF, expression of which is enhanced following disturbances leading to neuronal damage. How astrocytic LIF expression is regulated, however, has remained an unanswered question. Since neuronal stress is associated with production of extracellular adenosine, we investigated whether LIF expression in astrocytes was mediated through adenosine receptor signaling.MethodsMouse cortical neuronal and astrocyte cultures from wild-type and adenosine A2Breceptor knock-out animals, as well as adenosine receptor agonists/antagonists and various enzymatic inhibitors, were used to study LIF expression and release in astrocytes. When needed, a one-way analysis of variance (ANOVA) followed by Bonferroni post-hoc test was used for statistical analysis.ResultsWe show here that glutamate-stressed cortical neurons induce LIF expression through activation of adenosine A2Breceptor subtype in cultured astrocytes and require signaling of protein kinase C (PKC), mitogen-activated protein kinases (MAPKs: p38 and ERK1/2), and the nuclear transcription factor (NF)-κB. Moreover, LIF concentration in the supernatant in response to 5′-N-ethylcarboxamide (NECA) stimulation was directly correlated tode novoprotein synthesis, suggesting that LIF release did not occur through a regulated release pathway. Immunocytochemistry experiments show that LIF-containing vesicles co-localize with clathrin and Rab11, but not with pHogrin, Chromogranin (Cg)A and CgB, suggesting that LIF might be secreted through recycling endosomes. We further show that pre-treatment with supernatants from NECA-treated astrocytes increased survival of cultured cortical neurons against glutamate, which was absent when the supernatants were pre-treated with an anti-LIF neutralizing antibody.ConclusionsAdenosine from glutamate-stressed neurons induces rapid LIF release in astrocytes. This rapid release of LIF promotes the survival of cortical neurons against excitotoxicity.
Pro-inflammatory interleukin-18 increases Alzheimer’s disease-associated amyloid-β production in human neuron-like cells
Authors: Sutinen Elina M , Pirttilä Tuula , Anderson George , Salminen Antero , Ojala Johanna O 
Published: August 2012

Abstract

Background
Alzheimer’s disease (AD) involves increased accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles as well as neuronal loss in various regions of the neocortex. Neuroinflammation is also present, but its role in AD is not fully understood. We previously showed increased levels of pro-inflammatory cytokine interleukin-18 (IL-18) in different regions of AD brains, where it co-localized with Aβ-plaques, as well as the ability of IL-18 to increase expression of glycogen synthase kinase-3β (GSK-3β) and cyclin dependent kinase 5, involved in hyperphosphorylation of tau-protein. Elevated IL-18 has been detected in several risk conditions for AD, including obesity, type-II diabetes, and cardiovascular diseases as well as in stress.

Methods
We differentiated SH-SY5Y neuroblastoma cells as neuron-like and exposed them to IL-18 for various times. We examined the protein levels of amyloid-β precursor protein (APP) and its processing products, its cleaving enzymes, involved in amyloidogenic processing of APP, and markers of apoptosis.

Results
IL-18 increased protein levels of the β-site APP-cleaving enzyme BACE-1, the N-terminal fragment of presenilin-1 and slightly presenilin enhancer 2, both of which are members of the γ-secretase complex, as well as Fe65, which is a binding protein of the C-terminus of APP and one regulator for GSK-3β. IL-18 also increased APP expression and phosphorylation, which preceded increased BACE-1 levels. Further, IL-18 altered APP processing, increasing Aβ40 production in particular, which was inhibited by IL-18 binding protein. Increased levels of soluble APPβ were detected in culture medium after the IL-18 exposure. IL-18 also increased anti-apoptotic bcl-xL levels, which likely counteracted the minor increase of the pro-apoptotic caspase-3. Lactate dehydrogenase activity in culture medium was unaffected.

Conclusions
The IL-18 induction of BACE-1, APP processing, and Aβ is likely to be linked to stress-associated adaptations in neurons during the course of normal functioning and development. However, in the course of wider changes in the aging brain, and particularly in AD, the effects of heightened or prolonged levels of IL-18 may contribute to the process of AD, including via increased Aβ.
Next-generation sequencing of cervical DNA detects human papillomavirus types not detected by commercial kits
Authors: Meiring Tracy L , Salimo Anna T , Coetzee Beatrix , Maree Hans J , Moodley Jennifer , Hitzeroth Inga I , Freeborough Michael-John , Rybicki Ed P , Williamson Anna-Lise 
Published: August 2012

Abstract

Background
Human papillomavirus (HPV) is the aetiological agent for cervical cancer and genital warts. Concurrent HPV and HIV infection in the South African population is high. HIV positive (+) women are often infected with multiple, rare and undetermined HPV types. Data on HPV incidence and genotype distribution are based on commercial HPV detection kits, but these kits may not detect all HPV types in HIV + women. The objectives of this study were to (i) identify the HPV types not detected by commercial genotyping kits present in a cervical specimen from an HIV positive South African woman using next generation sequencing, and (ii) determine if these types were prevalent in a cohort of HIV-infected South African women.

Methods
Total DNA was isolated from 109 cervical specimens from South African HIV + women. A specimen within this cohort representing a complex multiple HPV infection, with 12 HPV genotypes detected by the Roche Linear Array HPV genotyping (LA) kit, was selected for next generation sequencing analysis. All HPV types present in this cervical specimen were identified by Illumina sequencing of the extracted DNA following rolling circle amplification. The prevalence of the HPV types identified by sequencing, but not included in the Roche LA, was then determined in the 109 HIV positive South African women by type-specific PCR.

Results
Illumina sequencing identified a total of 16 HPV genotypes in the selected specimen, with four genotypes (HPV-30, 74, 86 and 90) not included in the commercial kit. The prevalence’s of HPV-30, 74, 86 and 90 in 109 HIV positive South African women were found to be 14.6%, 12.8%, 4.6% and 8.3% respectively.

Conclusions
Our results indicate that there are HPV types, with substantial prevalence, in HIV positive women not being detected in molecular epidemiology studies using commercial kits. The significance of these types in relation to cervical disease remains to be investigated.
Establishing and sustaining research partnerships in Africa: a case study of the UK-Africa Academic Partnership on Chronic Disease
Authors: de-Graft Aikins Ama , Arhinful Daniel K , Pitchforth Emma , Ogedegbe Gbenga , Allotey Pascale , Agyemang Charles 
Published: August 2012

Abstract
This paper examines the challenges and opportunities in establishing and sustaining north–south research partnerships in Africa through a case study of the UK-Africa Academic Partnership on Chronic Disease. Established in 2006 with seed funding from the British Academy, the partnership aimed to bring together multidisciplinary chronic disease researchers based in the UK and Africa to collaborate on research, inform policymaking, train and support postgraduates and create a platform for research dissemination. We review the partnership’s achievements and challenges, applying established criteria for developing successful partnerships. During the funded period we achieved major success in creating a platform for research dissemination through international meetings and publications. Other goals, such as engaging in collaborative research and training postgraduates, were not as successfully realised. Enabling factors included trust and respect between core working group members, a shared commitment to achieving partnership goals, and the collective ability to develop creative strategies to overcome funding challenges. Barriers included limited funding, administrative support, and framework for monitoring and evaluating some goals. Chronic disease research partnerships in low-income regions operate within health research, practice, funding and policy environments that prioritise infectious diseases and other pressing public health and developmental challenges. Their long-term sustainability will therefore depend on integrated funding systems that provide a crucial capacity building bridge. Beyond the specific challenges of chronic disease research, we identify social capital, measurable goals, administrative support, creativity and innovation and funding as five key ingredients that are essential for sustaining research partnerships.
Isolated right coronary lesion and anterolateral papillary muscle rupture - case report and review of the literature
Authors: Stefanovski Dime , Walfisch Asnat , Kedev Saško , Tager Salis 
Published: August 2012

Abstract
Ischemic rupture of the anterolateral papillary muscle is uncommon due to its dual blood supply. It usually follows an ischemic event involving branches of the left circumflex or left anterior descending arteries. We present a case of a patient admitted with an acute inferior wall myocardial infarction and an isolated distal right coronary artery occlusion. Acute mitral regurgitation with rupture of the anterolateral papillary muscle was diagnosed on the fifth post-infarction day. The patient underwent mitral valve replacement and coronary artery bypass grafting to the posterior descending artery. We conclude that anterolateral papillary muscle rupture may also result from an isolated right coronary lesion.
Inferring transcriptional gene regulation network of starch metabolism in Arabidopsis thaliana leaves using graphical Gaussian model
Authors: Ingkasuwan Papapit , Netrphan Supatcharee , Prasitwattanaseree Sukon , Tanticharoen Morakot , Bhumiratana Sakarindr , Meechai Asawin , Chaijaruwanich Jeerayut , Takahashi Hideki , Cheevadhanarak Supapon 
Published: August 2012

AbstractBackgroundStarch serves as a temporal storage of carbohydrates in plant leaves during day/night cycles. To study transcriptional regulatory modules of this dynamic metabolic process, we conducted gene regulation network analysis based on small-sample inference of graphical Gaussian model (GGM).ResultsTime-series significant analysis was applied forArabidopsisleaf transcriptome data to obtain a set of genes that are highly regulated under a diurnal cycle. A total of 1,480 diurnally regulated genes included 21 starch metabolic enzymes, 6 clock-associated genes, and 106 transcription factors (TF). A starch-clock-TF gene regulation network comprising 117 nodes and 266 edges was constructed by GGM from these 133 significant genes that are potentially related to the diurnal control of starch metabolism. From this network, we found that β-amylase 3 (b-amy3: At4g17090), which participates in starch degradation in chloroplast, is the most frequently connected gene (a hub gene). The robustness of gene-to-gene regulatory network was further analyzed by TF binding site prediction and by evaluating global co-expression of TFs and target starch metabolic enzymes. As a result, two TFs, indeterminate domain 5 (AtIDD5: At2g02070) and constans-like (COL: At2g21320), were identified as positive regulators of starch synthase 4 (SS4: At4g18240). The inference model of AtIDD5-dependent positive regulation ofSS4gene expression was experimentally supported by decreasedSS4mRNA accumulation inAtidd5mutant plants during the light period of both short and long day conditions. COL was also shown to positively controlSS4mRNA accumulation. Furthermore, the knockout of AtIDD5 and COL led to deformation of chloroplast and its contained starch granules. This deformity also affected the number of starch granules per chloroplast, which increased significantly in both knockout mutant lines.ConclusionsIn this study, we utilized a systematic approach of microarray analysis to discover the transcriptional regulatory network of starch metabolism inArabidopsisleaves. With this inference method, the starch regulatory network ofArabidopsiswas found to be strongly associated with clock genes and TFs, of which AtIDD5 and COL were evidenced to controlSS4gene expression and starch granule formation in chloroplasts.
Attitudes toward depression among Japanese non-psychiatric medical doctors: a cross-sectional study
Authors: Ohtsuki Tsuyuka , Kodaka Manami , Sakai Rumi , Ishikura Fuminobu , Watanabe Yoichiro , Mann Anthony , Haddad Mark , Yamada Mitsuhiko , Inagaki Masatoshi 
Published: August 2012

Abstract

Background
Under-recognition of depression is common in many countries. Education of medical staff, focusing on their attitudes towards depression, may be necessary to change their behavior and enhance recognition of depression. Several studies have previously reported on attitudes toward depression among general physicians. However, little is known about attitudes of non-psychiatric doctors in Japan. In the present study, we surveyed non-psychiatric doctors’ attitude toward depression.

Methods
The inclusion criteria of participants in the present study were as follows: 1) Japanese non-psychiatric doctors and 2) attendees in educational opportunities regarding depression care. We conveniently approached two populations: 1) a workshop to depression care for non-psychiatric doctors and 2) a general physician-psychiatrist (G-P) network group. We contacted 367 subjects. Attitudes toward depression were measured using the Depression Attitude Questionnaire (DAQ), a 20-item self-report questionnaire developed for general physicians. We report scores of each DAQ item and factors derived from exploratory factor analysis.

Results
We received responses from 230 subjects, and we used DAQ data from 187 non-psychiatric doctors who met the inclusion criteria. All non-psychiatric doctors (n = 187) disagreed with "I feel comfortable in dealing with depressed patients' needs," while 60 % (n = 112) agreed with "Working with depressed patients is heavy going." Factor analysis indicated these items comprised a factor termed "Depression should be treated by psychiatrists" - to which 54 % of doctors (n = 101) agreed. Meanwhile, 67 % of doctors (n = 126) thought that nurses could be useful in depressed patient support. The three factors derived from the Japanese DAQ differed from models previously derived from British GP samples. The attitude of Japanese non-psychiatric doctors concerning whether depression should be treated by psychiatrists was markedly different to that of British GPs.

Conclusions
Japanese non-psychiatric doctors believe that depression care is beyond the scope of their duties. It is suggested that educational programs or guidelines for depression care developed in other countries such as the UK are not directly adaptable for Japanese non-psychiatric doctors. Developing a focused educational program that motivates non-psychiatric doctors to play a role in depression care is necessary to enhance recognition and treatment of depression in Japan.
Scenario drafting to anticipate future developments in technology assessment
Authors: Retèl Valesca P , Joore Manuela A , Linn Sabine C , Rutgers Emiel JT , van Harten Wim H 
Published: August 2012

Abstract

Background
Health Technology Assessment (HTA) information, and in particular cost-effectiveness data is needed to guide decisions, preferably already in early stages of technological development. However, at that moment there is usually a high degree of uncertainty, because evidence is limited and different development paths are still possible. We developed a multi-parameter framework to assess dynamic aspects of a technology -still in development-, by means of scenario drafting to determine the effects, costs and cost-effectiveness of possible future diffusion patterns. Secondly, we explored the value of this method on the case of the clinical implementation of the 70-gene signature for breast cancer, a gene expression profile for selecting patients who will benefit most from chemotherapy.

Methods
To incorporate process-uncertainty, ten possible scenarios regarding the introduction of the 70-gene signature were drafted with European experts. Out of 5 most likely scenarios, 3 drivers of diffusion (non-compliance, technical failure, and uptake) were quantitatively integrated in a decision-analytical model. For these scenarios, the cost-effectiveness of the 70-gene signature expressed in Incremental Cost-Effectiveness Ratios (ICERs) was compared to clinical guidelines, calculated from the past (2005) until the future (2020).

Results
In 2005 the ICER was €1,9 million/quality-adjusted-life-year (QALY), meaning that the 70-gene signature was not yet cost-effective compared to the current clinical guideline. The ICER for the 70-gene signature improved over time with a range of €1,9 million to €26,145 in 2010 and €1,9 million to €11,123/QALY in 2020 depending on the separate scenario used. From 2010, the 70-gene signature should be cost-effective, based on the combined scenario. The uptake-scenario had strongest influence on the cost-effectiveness.

Conclusions
When optimal diffusion of a technology is sought, incorporating process-uncertainty by means of scenario drafting into a decision model may reveal unanticipated developments and can demonstrate a range of possible cost-effectiveness outcomes. The effect of scenarios give additional information on the speed with cost effectiveness might be reached and thus provide a more realistic picture for policy makers, opinion leaders and manufacturers.
Homozygous A polymorphism of the complement C1qA
276
correlates with prolonged overall survival in patients with diffuse large B cell lymphoma treated with R-CHOP
Authors: Jin Xuan , Ding Huirong , Ding Ning , Fu Zhiying , Song Yuqin , Zhu Jun 
Published: August 2012

Abstract

Background
The precise mechanism of action for rituximab (R) is not fully elucidated. Besides antibody-dependent cellular cytotoxicity (ADCC), complements may also play an important role in the clinical response to rituximab-based therapy in diffuse large B cell lymphoma (DLBCL). The purpose of this study was to explore the relationship between C1qA

[276]
polymorphism and the clinical response to standard frontline treatment with R-CHOP in DLBCL patients.

Methods
Genotyping for C1qA

[276A/G]
was done in 164 patients with DLBCL. 129 patients treated with R-CHOP as frontline therapy (R ≥ 4 cycles) were assessable for the efficacy.

Results
Patients with homozygous A were found to have a higher overall response rate than those with heterozygous or homozygous G alleles (97.3% vs. 83.7%,P = 0.068). The complete response rate in patients with homozygous A was statistically higher than that in AG and GG allele carriers (89.2% vs. 51.1%,P = 0.0001). The overall survival of patients with homozygous A was longer than that of the G allele carriers (676 days vs. 497 days, P = 0.023). Multivariate Cox regression analysis showed that C1qA A/A allele was an independent favorable prognostic factor for DLBCL patients treated with R-CHOP as first-line therapy.

Conclusion
These results suggest that C1qA polymorphism may be a biomarker to predict response to R-CHOP as frontline therapy for DLBCL patients.
Conversion of epidermal growth factor receptor 2 and hormone receptor expression in breast cancer metastases to the brain
Authors: Duchnowska Renata , Dziadziuszko Rafał , Trojanowski Tomasz , Mandat Tomasz , Och Waldemar , Czartoryska-Arłukowicz Bogumiła , Radecka Barbara , Olszewski Wojciech , Szubstarski Franciszek , Kozłowski Wojciech , Jarosz Bożena , Rogowski Wojciech , Kowalczyk Anna , Limon Janusz , Biernat Wojciech , Jassem Jacek ,   the Polish Brain Metastasis Consortium
Published: August 2012

Abstract
Introduction
We investigated the status of estrogen receptor alpha (ERα), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) in primary tumor and in the corresponding brain metastases in a consecutive series of breast cancer patients. Additionally, we studied factors potentially influencing conversion and evaluated its association with survival.

Methods
The study group included 120 breast cancer patients. ERα, PR, and HER2 status in primary tumors and in matched brain metastases was determined centrally by immunohistochemistry and/or fluorescence in situ hybridization.

Results
Using the Allred score of ≥ 3 as a threshold, conversion of ERα and PR in brain metastases occurred in 29% of cases for both receptors, mostly from positive to negative. Conversion of HER2 occurred in 14% of patients and was more balanced either way. Time to brain relapse and the use of chemotherapy or trastuzumab did not influence conversion, whereas endocrine therapy induced conversion of ERα (P = 0.021) and PR (P = 0.001), mainly towards their loss. Receptor conversion had no significant impact on survival.

Conclusions
Receptor conversion, particularly loss of hormone receptors, is a common event in brain metastases from breast cancer, and endocrine therapy may increase its incidence. Receptor conversion does not significantly affect survival.