bluuebunny/crossref_metadata_2025 huggingface dataset:
The struggle of being Toba in contemporary Argentina: Processes of ethnic identification of indigenous children in contexts of language shift
Authors: Hecht Ana Carolina
Published: August 2012

The aim of this article is to study how children experience their ethnic identifications in relation to their knowledge of the Toba language through daily interactions with peers and adults (both indigenous and non-indigenous). The study is focused on an urban setting in Buenos Aires (Argentina) where monolingual (Spanish) practices are replacing bilingual ones (Spanish-Toba), and where the Toba language is a valuable feature of ethnicity. From an anthropological perspective, this article focuses on the identity constructions of the children. Finally, it re-examines the agency of the children and looks at how their life experiences impact on their contextual identities.
Knowledge flow in engineering design: An ontological framework
Authors: Zhang Zhi-Nan , Liu Ze-Lin , Chen Yong , Xie You-Bai
Published: August 2012

Engineering design is a structured and systematic process of finding solutions to meet certain requirements. Research in this field has focused heavily on developing more effective and efficient product realization process models. Today’s engineering design has become a knowledge intensive and collaborative process, requiring multidisciplinary design knowledge. Therefore, the modeling of knowledge flow plays a key role in determining a successful design alternative, which provides valuable insights into design problems for designers. This article proposes an ontological framework, purpose-function-working space-structure-behavior (PFWSB) for knowledge representation and knowledge flow based design process modeling. An illustrative case is also presented to demonstrate how to use the proposed framework to represent engineering design knowledge and describe the knowledge flow between decision makers during a design process. The results show that this framework can help designers capture the flow of knowledge in engineering design process more effectively.
Young Children Are Intrinsically Motivated to See Others Helped
Authors: Hepach Robert , Vaish Amrisha , Tomasello Michael
Published: August 2012

Young children help other people, but it is not clear why. In the current study, we found that 2-year-old children’s sympathetic arousal, as measured by relative changes in pupil dilation, is similar when they themselves help a person and when they see that person being helped by a third party (and sympathetic arousal in both cases is different from that when the person is not being helped at all). These results demonstrate that the intrinsic motivation for young children’s helping behavior does not require that they perform the behavior themselves and thus “get credit” for it, but rather requires only that the other person be helped. Thus, from an early age, humans seem to have genuine concern for the welfare of others.
Victim personal statements in England and Wales: Latest (and last) trends from the Witness and Victim Experience Survey
Authors: Roberts Julian V , Manikis Marie
Published: August 2012

Crime victims and victims’ advocates have for many years called for greater input into the criminal process, and in particular at the stage of sentencing. Today, victims in almost all common law countries have the opportunity to participate in the sentencing process, usually by providing information about the impact of the crime. This impact evidence is placed before a sentencing court in the form of a victim impact statement (VIS) or victim personal statement (VPS) as it is known in England and Wales. This article reviews findings from the last few years of data from the Witness and Victim Experience Survey (WAVES) which was conducted by the Ministry of Justice. We review findings from the last administrations of the survey. In the most recent administration of the survey (2009–2010), less than half (43%) of victims recalled being offered a statement. Over the most recent three-year period (2007–2010), a comparable percentage (42%) of the victims recalled being offered the opportunity to make a VPS; almost half (45%) explicitly responded that they had not been given an opportunity to make a VPS. In addition, significant variation emerged across local justice areas. The percentage of victims reporting having been offered a VPS varied from a low of 29 per cent in London to a high of 63 per cent in Northumbria – a range of 34 per cent. These and other findings suggest that the VPS scheme is being inconsistently implemented across the country.
A major determinant of the immunogenicity of factor VIII in a murine model is independent of its procoagulant function
Authors: Meeks Shannon L. , Cox Courtney L. , Healey John F. , Parker Ernest T. , Doshi Bhavya S. , Gangadharan Bagirath , Barrow Rachel T. , Lollar Pete
Published: August 2012

A main complication of treatment of patients with hemophilia A is the development of anti–factor VIII (fVIII) antibodies. The immunogenicity of fVIII potentially is a function of its procoagulant activity, which may result in danger signals that drive the immune response. Alternatively, intrinsic structural elements in fVIII may be particularly immunogenic. Finally, VWF, the carrier protein for fVIII in plasma, may play a role in immune recognition. We compared the immunogenicity of wild-type (wt) B domain–deleted fVIII and 2 inactive fVIII molecules, R372A/R1689A fVIII and V634M fVIII in fVIII−/− and fVIII−/−/VWF−/− mice. R372A/R1689A fVIII lacks proteolytic recognition sites and is not released from VWF. In contrast, V634M fVIII undergoes proteolytic cleavage and dissociation from VWF. No significant difference was observed in the immunogenicity of wt fVIII and V634M fVIII. R372A/R1689A fVIII was slightly less immunogenic in a subset of immunization regimens tested. High doses of wt fVIII were required to produce an immune response in fVIII−/−/VWF−/− mice. Our results indicate that a main component of the immune response to fVIII is independent of its procoagulant function, is both positively and negatively affected by its association with VWF, and may involve intrinsic elements of fVIII structure.
Outcome of high-risk acute myeloid leukemia after allogeneic hematopoietic cell transplantation: negative impact of abnl(17p) and −5/5q−
Authors: Middeke Jan M. , Beelen Dietrich , Stadler Michael , Göhring Gudrun , Schlegelberger Brigitte , Baurmann Herrad , Bug Gesine , Bellos Frauke , Mohr Brigitte , Buchholz Stefanie , Schwerdtfeger Rainer , Martin Hans , Hegenbart Ute , Ehninger Gerhard , Bornhäuser Martin , Schetelig Johannes
Published: August 2012

The European LeukemiaNet classification combines a heterogeneous group of aberrations as adverse-risk abnormalities. Our goal was to investigate the outcomes associated with distinct high-risk chromosomal abnormalities in acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (HSCT). We performed a retrospective cohort analysis in patients with high-risk AML who received first, HLA-compatible, allogeneic HSCT between January 2005 and December 2008. Data from 236 patients with a median age of 55 years were included. Because complex karyotype (CK), −5/5q−, and abnl(17p) are overlapping categories, a hierarchical classification system based on the presence or absence of abnl(17p) and −5/5q− was developed. Patients with abnl(17p) had a 2-year event-free survival (EFS) of 11% (95% confidence interval [CI], 0%-25%), patients with −5/5q− but no abnl(17p) a 2-year EFS of 29% (95% CI, 14%-44%), and patients with adverse-risk AML but neither of the 2 marker lesions a 2-year EFS of 49% (95% CI, 39%-59%). Notably, complex and monosomal karyotypes lost their prognostic value when these marker lesions were excluded. In conclusion, hierarchical classification of adverse-risk karyotypes by 2 marker lesions, abnl(17p) and −5/5q−, is effective in prognostication of the outcome of allogeneic HSCT in AML.
Pediatric-type nodal follicular lymphoma: an indolent clonal proliferation in children and adults with high proliferation index and no BCL2 rearrangement
Authors: Louissaint Abner , Ackerman Adam M. , Dias-Santagata Dora , Ferry Judith A. , Hochberg Ephraim P. , Huang Mary S. , Iafrate A. John , Lara Daniel O. , Pinkus Geraldine S. , Salaverria Itziar , Siddiquee Zakir , Siebert Reiner , Weinstein Howard J. , Zukerberg Lawrence R. , Harris Nancy Lee , Hasserjian Robert P.
Published: August 2012

Pediatric follicular lymphoma (PFL) is a variant of follicular lymphoma (FL) presenting as localized lymphadenopathy in children. Unlike conventional adult FL, PFL typically does not recur or progress. Clear diagnostic criteria for PFL are lacking, and it is uncertain whether this indolent lymphoma is defined by age or may occur in adults. We analyzed 27 FL in patients < 40 years of age and found that all 21 cases that lacked a BCL2 gene abnormality (BCL2-N; P < .0001) and had > 30% Ki67 fraction (high proliferation index, HPI; P = .0007) were stage I and did not progress or recur; in comparison, all 6 cases with BCL2 rearrangement and/or PI < 30% were stage III/IV, and 5 of 6 recurred or progressed. In a separate cohort of 58 adult FL (≥ 18 years of age), all 13 BCL2-N/HPI cases were stage I, and none progressed or relapsed, whereas 11 of 15 stage I cases with BCL2 gene abnormality and/or LPI relapsed or progressed (P = .0001). The adult and pediatric BCL2-N/HPI FL cases had similar morphologic features. Our results confirm the highly indolent behavior of PFL and suggest that these are characterized by HPI and absence of BCL2 gene abnormality. PFL-like cases also occur in adults and are associated with indolent behavior in this patient population.
Inhibition of apoptosis by BCL2 prevents leukemic transformation of a murine myelodysplastic syndrome
Authors: Slape Christopher I. , Saw Jesslyn , Jowett Jeremy B. M. , Aplan Peter D. , Strasser Andreas , Jane Stephen M. , Curtis David J.
Published: August 2012

Programmed cell death or apoptosis is a prominent feature of low-risk myelodysplastic syndromes (MDS), although the underlying mechanism remains controversial. High-risk MDS have less apoptosis associated with increased expression of the prosurvival BCL2-related proteins. To address the mechanism and pathogenic role of apoptosis and BCL2 expression in MDS, we used a mouse model resembling human MDS, in which the fusion protein NUP98-HOXD13 (NHD13) of the chromosomal translocation t(2;11)(q31;p15) is expressed in hematopoietic cells. Hematopoietic stem and progenitor cells from 3-month-old mice had increased rates of apoptosis associated with increased cell cycling and DNA damage. Gene expression profiling of these MDS progenitors revealed a specific reduction in Bcl2. Restoration of Bcl2 expression by a BCL2 transgene blocked apoptosis of the MDS progenitors, which corrected the macrocytic anemia. Blocking apoptosis also restored cell-cycle quiescence and reduced DNA damage in the MDS progenitors. We expected that preventing apoptosis would accelerate malignant transformation to acute myeloid leukemia (AML). However, contrary to expectations, preventing apoptosis of premalignant cells abrogated transformation to AML. In contrast to the current dogma that overcoming apoptosis is an important step toward cancer, this work demonstrates that gaining a survival advantage of premalignant cells may delay or prevent leukemic progression.
Characterization of microRNAs expression during maize seed development
Authors: Kang Mingming , Zhao Qian , Zhu Dengyun , Yu Jingjuan
Published: August 2012

Background

MicroRNAs (miRNAs) are approximately 20-22 nt non-coding RNAs that play key roles in many biological processes in both animals and plants. Although a number of miRNAs were identified in maize, the function of miRNA in seed development was merely discussed.

Results

In this study, two small RNA libraries were sequenced, and a total reads of 9,705,761 and 9,005,563 were generated from developing seeds and growing leaves, respectively. Further analysis identified 125 known miRNAs in seeds and 127 known miRNAs in leaves. 54 novel miRNAs were identified and they were not reported in other plants. Additionally, some miRNA*s of these novel miRNAs were detected. Potential targets of all novel miRNAs were predicted based on our strict criteria. In addition to deep-sequencing, miRNA microarray study confirmed the higher expression of several miRNAs in seeds. In summary, our results indicated the distinct expression of miRNAs during seed development.

Conclusions

We had identified 125 and 127 known miRNAs from seeds and leaves in maize, and a total of 54 novel miRNAs were discovered. The different miRNA expression profile in developing seeds were revealed by both sequencing and microarray studies.
Expression of sialic acids and other nonulosonic acids in Leptospira
Authors: Ricaldi N Jessica , Matthias Michael A , Vinetz Joseph M , Lewis Amanda L
Published: August 2012

Background

Sialic acids are negatively charged nine carbon backbone sugars expressed on mammalian cell surfaces. Sialic acids are part of a larger family of nonulosonic acid (NulO) molecules that includes pseudaminic and legionaminic acids. Microbial expression of sialic acids and other nonulosonic acids has been shown to contribute to host-microbe interactions in a variety of contexts, including participation in colonization, immune subversion, and behaviors such as biofilm formation, autoagglutination and motility. Previous research has suggested that some spirochetes may also express these molecules.

Results

Here we use a combination of molecular tools to investigate the presence of NulO biosynthetic gene clusters among clinical and saprophytic isolates of the genus Leptospira. Polymerase chain reaction and Southern blotting suggested that a variety of leptospires encoded NulO biosynthetic pathways. High performance liquid chromatography and mass spectrometry analyses provided biochemical evidence that di-N-acetylated NulO molecules are expressed at relatively high levels by L. interrogans serovar Lai strain 55601, and at lower levels by L. alexanderi serovar Manhao and L. fainei serovar Hurstbridge. Endogenous expression of N-acetylneuraminic acid (Neu5Ac, the most common sialic acid) was documented in L. interrogans serovar Copenhageni strain L1-130. Neu5Ac biosynthesis is also supported by a unique gene fusion event resulting in an enzyme with an N-terminal N-acetylneuraminic acid synthase domain and a C-terminal phosphatase domain. This gene fusion suggests that L. interrogans uses a Neu5Ac biosynthetic pathway more similar to animals than to other bacteria. Analysis of the composition and phylogeny of putative NulO biosynthetic gene clusters in L. interrogans serovar Lai and serovar Copenhageni revealed that both strains have complete biosynthetic pathways for legionamimic acid synthesis, a molecule with the same stereochemistry as sialic acid. Lectin-based affinity purification of NulO-modified molecules, followed by mass spectrometric identification suggests post-translational modification of surface lipoproteins, including Loa22.

Conclusions

Leptospira species encode NulO biosynthetic pathways and synthesize multiple NulO molecules including sialic acid. Additional studies are needed to clarify the exact context and functional significance of NulO expression. These findings have implications for immune evasion during systemic leptospirosis.
Cell surface sialylation affects binding of enterovirus 71 to rhabdomyosarcoma and neuroblastoma cells
Authors: Su Pei-Yi , Liu Yueh-Tung , Chang Hsin-Yueh , Huang Sheng-Wen , Wang Ya-Fang , Yu Chun-Keung , Wang Jen-Ren , Chang Chuan-Fa
Published: August 2012

Background

Enterovirus 71 (EV71) is a major causative agent of hand-foot-and-mouth disease (HFMD), and infection of EV71 to central nerve system (CNS) may result in a high mortality in children less than 2 years old. Although there are two highly glycosylated membrane proteins, SCARB2 and PSGL-1, which have been identified as the cellular and functional receptors of EV71, the role of glycosylation in EV71 infection is still unclear.

Results

We demonstrated that the attachment of EV71 to RD and SK-N-SH cells was diminished after the removal of cell surface sialic acids by neuraminidase. Sialic acid specific lectins, Maackia amurensis (MAA) and Sambucus Nigra (SNA), could compete with EV71 and restrained the binding of EV71 significantly. Preincubation of RD cells with fetuin also reduced the binding of EV71. In addition, we found that SCARB2 was a sialylated glycoprotein and interaction between SCARB2 and EV71 was retarded after desialylation.

Conclusions

In this study, we demonstrated that cell surface sialic acids assist in the attachment of EV71 to host cells. Cell surface sialylation should be a key regulator that facilitates the binding and infection of EV71 to RD and SK-N-SH cells.
The adenylate cyclase gene MaAC is required for virulence and multi-stress tolerance of Metarhizium acridum
Authors: Liu Shuyang , Peng Guoxiong , Xia Yuxian
Published: August 2012

Background

The efficacy of entomopathogenic fungi in pest control is mainly affected by various adverse environmental factors, such as heat shock and UV-B radiation, and by responses of the host insect, such as oxidative stress, osmotic stress and fever. In this study, an adenylate cyclase gene (MaAC) was cloned from the locust-specific entomopathogenic fungus, Metarhizium acridum, which is homologous to various fungal adenylate cyclase genes. RNA silencing was adapted to analyze the role of MaAC in virulence and tolerance to adverse environmental and host insect factors.

Results

Compared with the wild type, the vegetative growth of the RNAi mutant was decreased in PD (potato dextrose medium), Czapek-dox and PDA plates, respectively, demonstrating that MaAC affected vegetative growth. The cAMP levels were also reduced in PD liquid culture, and exogenous cAMP restored the growth of RNAi mutants. These findings suggested that MaAC is involved in cAMP synthesis. The knockdown of MaAC by RNAi led to a reduction in virulence after injection or topical inoculation. Furthermore, the RNAi mutant grew much slower than the wild type in the haemolymph of locust in vitro and in vivo, thus demonstrating that MaAC affects the virulence of M. acridum via fungal growth inside the host locust. A plate assay indicated that the tolerances of the MaAC RNAi mutant under oxidative stress, osmotic stress, heat shock and UV-B radiation was decreased compared with the wild type.

Conclusion

MaAC is required for virulence and tolerance to oxidative stress, osmotic stress, heat shock and UV-B radiation. MaAC affects fungal virulence via vegetative growth inside the insect and tolerance against oxidative stress, osmotic stress and locust fever.
Bioinformatic cis-element analyses performed in Arabidopsis and rice disclose bZIP- and MYB-related binding sites as potential AuxRE-coupling elements in auxin-mediated transcription
Authors: Berendzen Kenneth W , Weiste Christoph , Wanke Dierk , Kilian Joachim , Harter Klaus , Dröge-Laser Wolfgang
Published: August 2012

Background

In higher plants, a diverse array of developmental and growth-related processes is regulated by the plant hormone auxin. Recent publications have proposed that besides the well-characterized Auxin Response Factors (ARFs) that bind Auxin Response Elements (AuxREs), also members of the bZIP- and MYB-transcription factor (TF) families participate in transcriptional control of auxin-regulated genes via bZIP Response Elements (ZREs) or Myb Response Elements (MREs), respectively.

Results

Applying a novel bioinformatic algorithm, we demonstrate on a genome-wide scale that singular motifs or composite modules of AuxREs, ZREs, MREs but also of MYC2 related elements are significantly enriched in promoters of auxin-inducible genes. Despite considerable, species-specific differences in the genome structure in terms of the GC content, this enrichment is generally conserved in dicot (Arabidopsis thaliana) and monocot (Oryza sativa) model plants. Moreover, an enrichment of defined composite modules has been observed in selected auxin-related gene families. Consistently, a bipartite module, which encompasses a bZIP-associated G-box Related Element (GRE) and an AuxRE motif, has been found to be highly enriched. Making use of transient reporter studies in protoplasts, these findings were experimentally confirmed, demonstrating that GREs functionally interact with AuxREs in regulating auxin-mediated transcription.

Conclusions

Using genome-wide bioinformatic analyses, evolutionary conserved motifs have been defined which potentially function as AuxRE-dependent coupling elements to establish auxin-specific expression patterns. Based on these findings, experimental approaches can be designed to broaden our understanding of combinatorial, auxin-controlled gene regulation.
Is there a role of whole-body bone scan in patients with esophageal squamous cell carcinoma
Authors: Li Shau-Hsuan , Huang Yung-Cheng , Huang Wan-Ting , Lin Wei-Che , Liu Chien-Ting , Tien Wan-Yu , Lu Hung-I
Published: August 2012

Background

Correct detection of bone metastases in patients with esophageal squamous cell carcinoma is pivotal for prognosis and selection of an appropriate treatment regimen. Whole-body bone scan for staging is not routinely recommended in patients with esophageal squamous cell carcinoma. The aim of this study was to investigate the role of bone scan in detecting bone metastases in patients with esophageal squamous cell carcinoma.

Methods

We retrospectively evaluated the radiographic and scintigraphic images of 360 esophageal squamous cell carcinoma patients between 1999 and 2008. Of these 360 patients, 288 patients received bone scan during pretreatment staging, and sensitivity, specificity, positive predictive value, and negative predictive value of bone scan were determined. Of these 360 patients, surgery was performed in 161 patients including 119 patients with preoperative bone scan and 42 patients without preoperative bone scan. Among these 161 patients receiving surgery, 133 patients had stages II + III disease, including 99 patients with preoperative bone scan and 34 patients without preoperative bone scan. Bone recurrence-free survival and overall survival were compared in all 161 patients and 133 stages II + III patients, respectively.

Results

The diagnostic performance for bone metastasis was as follows: sensitivity, 80%; specificity, 90.1%; positive predictive value, 43.5%; and negative predictive value, 97.9%. In all 161 patients receiving surgery, absence of preoperative bone scan was significantly associated with inferior bone recurrence-free survival (P = 0.009, univariately). In multivariate comparison, absence of preoperative bone scan (P = 0.012, odds ratio: 5.053) represented the independent adverse prognosticator for bone recurrence-free survival. In 133 stages II + III patients receiving surgery, absence of preoperative bone scan was significantly associated with inferior bone recurrence-free survival (P = 0.003, univariately) and overall survival (P = 0.037, univariately). In multivariate comparison, absence of preoperative bone scan was independently associated with inferior bone recurrence-free survival (P = 0.009, odds ratio: 5.832) and overall survival (P = 0.029, odds ratio: 1.603).

Conclusions

Absence of preoperative bone scan was significantly associated with inferior bone recurrence-free survival, suggesting that whole-body bone scan should be performed before esophagectomy in patients with esophageal squamous cell carcinoma, especially in patients with advanced stages.
Characterization of aldehyde dehydrogenase isozymes in ovarian cancer tissues and sphere cultures
Authors: Saw Yu-Ting , Yang Junzheng , Ng Shu-Kay , Liu Shubai , Singh Surendra , Singh Margit , Welch William R , Tsuda Hiroshi , Fong Wing-Ping , Thompson David , Vasiliou Vasilis , Berkowitz Ross S , Ng Shu-Wing
Published: August 2012

Background

Aldehyde dehydrogenases belong to a superfamily of detoxifying enzymes that protect cells from carcinogenic aldehydes. Of the superfamily, ALDH1A1 has gained most attention because current studies have shown that its expression is associated with human cancer stem cells. However, ALDH1A1 is only one of the 19 human ALDH subfamilies currently known. The purpose of the present study was to determine if the expression and activities of other major ALDH isozymes are associated with human ovarian cancer and ovarian cancer sphere cultures.

Methods

Immunohistochemistry was used to delineate ALDH isozyme localization in clinical ovarian tissues. Western Blot analyses were performed on lysates prepared from cancer cell lines and ovarian cancer spheres to confirm the immunohistochemistry findings. Quantitative reverse transcription-polymerase chain reactions were used to measure the mRNA expression levels. The Aldefluor® assay was used to measure ALDH activity in cancer cells from the four tumor subtypes.

Results

Immunohistochemical staining showed significant overexpression of ALDH1A3, ALDH3A2, and ALDH7A1 isozymes in ovarian tumors relative to normal ovarian tissues. The expression and activity of ALDH1A1 is tumor type-dependent, as seen from immunohistochemisty, Western blot analysis, and the Aldefluor® assay. The expression was elevated in the mucinous and endometrioid ovarian epithelial tumors than in serous and clear cell tumors. In some serous and most clear cell tumors, ALDH1A1 expression was found in the stromal fibroblasts. RNA expression of all studied ALDH isozymes also showed higher expression in endometrioid and mucinous tumors than in the serous and clear cell subtypes. The expression of ALDH enzymes showed tumor type-dependent induction in ovarian cancer cells growing as sphere suspensions in serum-free medium.

Conclusions

The results of our study indicate that ALDH enzyme expression and activity may be associated with specific cell types in ovarian tumor tissues and vary according to cell states. Elucidating the function of the ALDH isozymes in lineage differentiation and pathogenesis may have significant implications for ovarian cancer pathophysiology.
Multi-center randomized double-blind controlled clinical study of chemotherapy combined with or without traditional Chinese medicine on quality of life of postoperative non-small cell lung cancer patients
Authors: Xu Ling , Li HeGen , Xu ZhenYe , Wang ZhongQi , Liu LingShuang , Tian JianHui , Sun JianLi , Zhou Lei , Yao YiLin , Jiao LiJing , Su Wan , Guo HuiRu , Chen PeiQi , Liu JiaXiang
Published: August 2012

Background

Traditional Chinese medicine (TCM) is a widely applied complementary therapy for cancer patients. It can reduce the chemical drugs induced toxic effects to improve the quality of life (QOL). This study applies the highest quality of clinical trial methodology to examine the role of TCM in improving QOL of postoperative non-small-cell lung cancer patients.

Methods and design

This study is a multi-center, randomized, placebo-controlled, double-blind trial. Four hundred eighty patients will be recruited into seven different research centers in China. These patients that meet the inclusion criteria will be randomized into either a treatment group or a placebo group. Each group will receive treatments of 3-weekly chemotherapy with TCM or placebo for four cycles. The primary outcome will involve the evaluation of QOL and the secondary outcome assessments will include two-year disease-free survival rate and disease-free survival. Other efficacy assessments are changes of TCM symptoms and toxicity. Side effects and safety profile of the therapy would be evaluated at the same time. The investigators expect that TCM therapy combined with chemotherapy is superior to chemotherapy solely in terms of QOL improvement and disease-free survival extension. "Intention-to-treat" analysis will include all randomized participants.

Discussion

The results from the clinical trial will provide evidence for the effectiveness of chemotherapy combined with or without TCM in QOL of postoperative NSCLC patients.

Trial registration

Clinical Trials.gov (Identifier: NCT01441752).
Combinational risk factors of metabolic syndrome identified by fuzzy neural network analysis of health-check data
Authors: Ushida Yasunori , Kato Ryuji , Niwa Kosuke , Tanimura Daisuke , Izawa Hideo , Yasui Kenji , Takase Tomokazu , Yoshida Yasuko , Kawase Mitsuo , Yoshida Tsutomu , Murohara Toyoaki , Honda Hiroyuki
Published: August 2012

Background

Lifestyle-related diseases represented by metabolic syndrome develop as results of complex interaction. By using health check-up data from two large studies collected during a long-term follow-up, we searched for risk factors associated with the development of metabolic syndrome.

Methods

In our original study, we selected 77 case subjects who developed metabolic syndrome during the follow-up and 152 healthy control subjects who were free of lifestyle-related risk components from among 1803 Japanese male employees. In a replication study, we selected 2196 case subjects and 2196 healthy control subjects from among 31343 other Japanese male employees. By means of a bioinformatics approach using a fuzzy neural network (FNN), we searched any significant combinations that are associated with MetS. To ensure that the risk combination selected by FNN analysis was statistically reliable, we performed logistic regression analysis including adjustment.

Results

We selected a combination of an elevated level of γ-glutamyltranspeptidase (γ-GTP) and an elevated white blood cell (WBC) count as the most significant combination of risk factors for the development of metabolic syndrome. The FNN also identified the same tendency in a replication study. The clinical characteristics of γ-GTP level and WBC count were statistically significant even after adjustment, confirming that the results obtained from the fuzzy neural network are reasonable. Correlation ratio showed that an elevated level of γ-GTP is associated with habitual drinking of alcohol and a high WBC count is associated with habitual smoking.

Conclusions

This result obtained by fuzzy neural network analysis of health check-up data from large long-term studies can be useful in providing a personalized novel diagnostic and therapeutic method involving the γ-GTP level and the WBC count.
The detection of pfcrt and pfmdr1 point mutations as molecular markers of chloroquine drug resistance, Pahang, Malaysia
Authors: Atroosh Wahib M , Al-Mekhlafi Hesham M , Mahdy Mohammed AK , Surin Johari
Published: August 2012

Background

Malaria is still a public health problem in Malaysia with chloroquine (CQ) being the first-line drug in the treatment policy of uncomplicated malaria. There is a scarcity in information about the magnitude of Plasmodium falciparum CQ resistance. This study aims to investigate the presence of single point mutations in the P. falciparum chloroquine-resistance transporter gene (pfcrt) at codons 76, 271, 326, 356 and 371 and in P. falciparum multi-drug resistance-1 gene (pfmdr1) at codons 86 and 1246, as molecular markers of CQ resistance.

Methods

A total of 75 P. falciparum blood samples were collected from different districts of Pahang state, Malaysia. Single nucleotide polymorphisms in pfcrt gene (codons 76, 271, 326, 356 and 371) and pfmdr1 gene (codons 86 and 1246) were analysed by using mutation-specific nested PCR and restriction fragment length polymorphism (PCR-RFLP) methods.

Results

Mutations of pfcrt K76T and pfcrt R371I were the most prevalent among pfcrt gene mutations reported by this study; 52% and 77%, respectively. Other codons of the pfcrt gene and the positions 86 and 1246 of the pfmdr1 gene were found mostly of wild type. Significant associations of pfcrt K76T, pfcrt N326S and pfcrt I356T mutations with parasitaemia were also reported.

Conclusion

The high existence of mutant pfcrt T76 may indicate the low susceptibility of P. falciparum isolates to CQ in Peninsular Malaysia. The findings of this study establish baseline data on the molecular markers of P. falciparum CQ resistance, which may help in the surveillance of drug resistance in Peninsular Malaysia.
A cross-sectional study of sub-clinical Plasmodium falciparum infection in HIV-1 infected and uninfected populations in Mozambique, South-Eastern Africa
Authors: Noormahomed Emilia V , Orlov Marika , do Rosario Virgilio , Petersen Brett W , Guthrie Carly , Badaro Roberto , Schooley Robert T
Published: August 2012

Background

Plasmodium falciparum and HIV-1 infection cause substantial morbidity and mortality in sub-Saharan Africa. Increasing evidence suggests these two pathogens interact negatively when infecting the same individual.

Methods

A cross-sectional study among HIV-1 infected and uninfected populations was recruited in Mocuba and Maputo, Mozambique to determine the prevalence of sub-clinical malarial parasitaemia using light microscopy and a nested PCR assay.

Results

The prevalence of sub-clinical P. falciparum parasitaemia was low in Maputo, whether determined by microscopy (0.4%) or PCR (1.9%), but substantially higher in Mocuba (7.6 and 14.7%, respectively). Nested PCR detected nearly 70% more cases of sub-clinical parasitaemia than microscopy, but differences occur by locality. HIV-1 infected persons were more likely to be sub-clinically parasitaemic than HIV-1 uninfected individuals recruited from the same geographic areas. Trimethoprim-sulphamethoxazole use did not substantially reduce sub-clinical parasitaemia.

Conclusions

Dried blood spots are a convenient and sensitive technique for detecting sub-clinical infection with P. falciparum by nested PCR. Prevalence of P. falciparum is substantially lower in Maputo where malaria control programmes have been more active than in the rural town of Mocuba. In Mocuba, among those presenting for HIV-1 counseling and testing, the prevalence of P. falciparum is substantially higher in those who test positive for HIV-1 than those without HIV-1 infection. The clinical implications of sub-clinical P. falciparum infection among HIV-1 infected persons warrant additional study.
Insights into deregulated TNF and IL-10 production in malaria: implications for understanding severe malarial anaemia
Authors: Boeuf Philippe S , Loizon Séverine , Awandare Gordon A , Tetteh John KA , Addae Michael M , Adjei George O , Goka Bamenla , AL Kurtzhals Jørgen , Puijalon Odile , Hviid Lars , Akanmori Bartholomew D , Behr Charlotte
Published: August 2012

Background

Severe malarial anaemia (SMA) is a major life-threatening complication of paediatric malaria. Protracted production of pro-inflammatory cytokines promoting erythrophagocytosis and depressing erythropoiesis is thought to play an important role in SMA, which is characterized by a high TNF/IL-10 ratio. Whether this TNF/IL-10 imbalance results from an intrinsic incapacity of SMA patients to produce IL-10 or from an IL-10 unresponsiveness to infection is unknown. Monocytes and T cells are recognized as the main sources of TNF and IL-10 in vivo, but little is known about the activation status of those cells in SMA patients.

Methods

The IL-10 and TNF production capacity and the activation phenotype of monocytes and T cells were compared in samples collected from 332 Ghanaian children with non-overlapping SMA (n = 108), cerebral malaria (CM) (n = 144) or uncomplicated malaria (UM) (n = 80) syndromes. Activation status of monocytes and T cells was ascertained by measuring HLA-DR+ and/or CD69+ surface expression by flow cytometry. The TNF and IL-10 production was assessed in a whole-blood assay after or not stimulation with lipopolysaccharide (LPS) or phytohaemaglutinin (PHA) used as surrogate of unspecific monocyte and T cell stimulant. The number of circulating pigmented monocytes was also determined.

Results

Monocytes and T cells from SMA and CM patients showed similar activation profiles with a comparable decreased HLA-DR expression on monocytes and increased frequency of CD69+ and HLA-DR+ T cells. In contrast, the acute-phase IL-10 production was markedly decreased in SMA compared to CM (P = .003) and UM (P = .004). Although in SMA the IL-10 response to LPS-stimulation was larger in amplitude than in CM (P = .0082), the absolute levels of IL-10 reached were lower (P = .013). Both the amplitude and levels of TNF produced in response to LPS-stimulation were larger in SMA than CM (P = .019). In response to PHA-stimulation, absolute levels of IL-10 produced in SMA were lower than in CM (P = .005) contrasting with TNF levels, which were higher (P = .001).

Conclusions

These data reveal that SMA patients have the potential to mount efficient IL-10 responses and that the TNF/IL-10 imbalance may reflect a specific monocyte and T cell programming/polarization pattern in response to infection.
Anti-plasmodial action of de novo-designed, cationic, lysine-branched, amphipathic, helical peptides
Authors: Kaushik Naveen K , Sharma Jyotsna , Sahal Dinkar
Published: August 2012

Background

A lack of vaccine and rampant drug resistance demands new anti-malarials.

Methods

In vitro blood stage anti-plasmodial properties of several de novo-designed, chemically synthesized, cationic, amphipathic, helical, antibiotic peptides were examined against Plasmodium falciparum using SYBR Green assay. Mechanistic details of anti-plasmodial action were examined by optical/fluorescence microscopy and FACS analysis.

Results

Unlike the monomeric decapeptides {(Ac-GXRKXHKXWA-NH2) (X = F,ΔF) (Fm, ΔFm IC50 >100 μM)}, the lysine-branched,dimeric versions showed far greater potency {IC50 (μM) Fd 1.5 , ΔFd 1.39}. The more helical and proteolytically stable ΔFd was studied for mechanistic details. ΔFq, a K-K2 dendrimer of ΔFm and (ΔFm)2 a linear dimer of ΔFm showed IC50 (μM) of 0.25 and 2.4 respectively. The healthy/infected red cell selectivity indices were >35 (ΔFd), >20 (ΔFm)2 and 10 (ΔFq). FITC-ΔFd showed rapid and selective accumulation in parasitized red cells. Overlaying DAPI and FITC florescence suggested that ΔFd binds DNA. Trophozoites and schizonts incubated with ΔFd (2.5 μM) egressed anomalously and Band-3 immunostaining revealed them not to be associated with RBC membrane. Prematurely egressed merozoites from peptide-treated cultures were found to be invasion incompetent.

Conclusion

Good selectivity (>35), good resistance index (1.1) and low cytotoxicity indicate the promise of ΔFd against malaria.
Stereotactic body radiation therapy for abdominal oligometastases: a biological and clinical review
Authors: Almaghrabi Mohammed Yahia , Supiot Stéphane , Paris Francois , Mahé Marc-André , Rio Emmanuel
Published: August 2012

Advances in imaging and biological targeting have led to the development of stereotactic body radiation therapy (SBRT) as an alternative treatment of extracranial oligometastases. New radiobiological concepts, such as ceramide-induced endothelial apoptosis after hypofractionated high-dose SBRT, and the identification of patients with oligometastatic disease by microRNA expression may yet lead to further developments. Key factors in SBRT are delivery of a high dose per fraction, proper patient positioning, target localisation, and management of breathing–related motion. Our review addresses the radiation doses and schedules used to treat liver, abdominal lymph node (LN) and adrenal gland oligometastases and treatment outcomes. Reported local control (LC) rates for liver and abdominal LN oligometastases are high (median 2-year actuarial LC: 61 -100% for liver oligometastases; 4-year actuarial LC: 68% in a study of abdominal LN oligometastases). Early toxicity is low-to-moderate; late adverse effects are rare. SBRT of adrenal gland oligometastases shows promising results in the case of isolated lesions. In conclusion, properly conducted SBRT procedures are a safe and effective treatment option for abdominal oligometastases.
The release of IL‐31 and IL‐13 after nasal allergen challenge and their relation to nasal symptoms
Authors: Baumann Ralf , Rabaszowski Matthaeus , Stenin Igor , Gaertner‐Akerboom Maria , Scheckenbach Kathrin , Wiltfang Jens , Schipper Joerg , Wagenmann Martin
Published: August 2012

Background

IL‐31, a recently discovered member of the gp130/IL‐6 cytokine family, is mainly expressed by human mast cells and T helper type 2 cells. IL‐31 is a key trigger of atopic dermatitis. Recent studies also suggest a role of IL‐31 in the pathogenesis of other allergic diseases including allergic rhinitis. In the present study we studied the release of IL‐31 and IL‐13 in allergen‐challenged allergic rhinitis patients.

Methods

Seven seasonal allergic volunteers underwent unilateral nasal provocation with allergen (and a control challenge) with the disc method out of the allergy season. Nasal symptom scores (rhinorrhea, itching, sneezing, obstruction) and bilateral nasal secretions were quantified before and after allergen provocation. IL‐13 and IL‐31 in nasal secretions and serum were measured by electrochemiluminescent immunoassay or ELISA, respectively.

Results

Nasal allergen challenge induced the typical clinical symptoms and physiological changes. IL‐31 and IL‐13 in nasal secretions increased in four and five, respectively, volunteers at 5 h after allergen but not after control challenge. We observed correlation trends between nasal IL‐31 concentrations and IL‐13 concentrations (r = 0.9, p = 0.002), and IL‐31 contents and symptom scores (r = 0.9, p = 0.013) 5 h after allergen provocation. No IL‐31 could be detected contralaterally or systemically in the sera.

Conclusions

The observed local upregulation of IL‐31 mainly during the late phase reaction after nasal allergen challenge suggests a role of IL‐31 in allergic rhinitis. In which way IL‐31 modulates the inflammatory reaction and type 2 responses in allergic rhinitis remains to be investigated.
Ciliary and non-ciliary expression and function of PACRGduring vertebrate development
Authors: Thumberger Thomas , Hagenlocher Cathrin , Tisler Matthias , Beyer Tina , Tietze Nina , Schweickert Axel , Feistel Kerstin , Blum Martin
Published: August 2012

Background

Park2-co-regulated gene (PACRG) is evolutionarily highly conserved from green algae to mammals. In Chlamydomonas and trypanosomes, the PACRG protein associates with flagella. Loss of PACRG results in shortened or absent flagella. In mouse the PACRG protein is required for spermatogenesis. The purpose of the present study was to analyze (1) the expression patterns of PACRG during vertebrate embryogenesis, and (2) whether the PACRG protein was required for left-right (LR) axis specification through cilia-driven leftward flow in Xenopus laevis.

Methods

PACRG cDNAs were cloned and expression was analyzed during early embryonic development of Xenopus, mouse, rabbit and zebrafish. Antisense morpholino oligonucleotide (MO) mediated gene knockdown was applied in Xenopus to investigate LR development at the level of tissue morphology, leftward flow and asymmetric marker gene expression, using timelapse videography, scanning electron microscopy (SEM) and whole-mount in situ hybridization. Results were statistically evaluated using Wilcoxon paired and χ2 tests.

Results

PACRG mRNA expression was found in cells and tissues harboring cilia throughout the vertebrates. Highly localized expression was also detected in the brain. During early development, PACRG was specifically localized to epithelia where leftward flow arises, that is, the gastrocoel roof plate (GRP) in Xenopus, the posterior notochord (PNC) in mammals and Kupffer’s vesicle (KV) in zebrafish. Besides its association with ciliary axonemes, subcellular localization of PACRG protein was found around the nucleus and in a spotty pattern in the cytoplasm. A green fluorescent protein (GFP) fusion construct preferentially labeled cilia, rendering PACRG a versatile marker for live imaging. Loss-of-function in the frog resulted dose dependently in LR, neural tube closure and gastrulation defects, representing ciliary and non-ciliary functions of PACRG.

Conclusions

The PACRG protein is a novel essential factor of cilia in Xenopus.
Perspectives on the Incredible Years programme: psychological
management of conduct disorder
Authors: Bywater Tracey J.
Published: August 2012

Two out of three children diagnosed with conduct disorder will not outgrow
it without treatment. It is costly to the individual in terms of negative
life outcomes and to society in terms of increased health, social and
education service use. Psychosocial interventions are effective in
psychologically managing and preventing the onset of conduct disorder.
Adjustment disorder: implications for ICD-11 and
DSM-5
Authors: Casey Patricia , Doherty Anne
Published: August 2012

Adjustment disorder has been a recognised disorder for decades but has been
the subject of little epidemiological research. Now researchers have
identified the prevalence of adjustment disorder in primary care, and found
general practitioner recognition very low but with high rates of
antidepressant prescribing. Possible reasons for the seemingly low
prevalence, recognition rate and inappropriate management include its
recognition as a residual category in diagnostic instruments and poor
delineation from other disorders or from normal stress responses. These
problems could be rectified in ICD-11 and DSM-5 if changes according it full
syndromal status, among others, were made. This would have an impact on
future research.
Clinical usefulness of the triaxial system in super-selective transcatheter arterial chemoembolization for hepatocellular carcinoma
Authors: Shimohira Masashi , Ogino Hiroyuki , Kawai Tatsuya , Sakurai Keita , Nakagawa Motoo , Shibamoto Yuta
Published: August 2012

Background

Transcatheter arterial chemoembolization (TACE) has been widely performed for inoperable hepatocellular carcinoma (HCC). Super-selective TACE is preferable to non-selective therapy and it is important to advance the catheter tip as close to the tumor as possible in the feeding artery. A new microcatheter with a 1.9-Fr non-tapered tip has recently become available and this new microcatheter can be inserted into a 2.7-Fr. microcatheter. It is called the triple co-axial (triaxial) system.

Purpose

To evaluate the clinical usefulness of super-selective TACE for HCC using the triaxial system.

Material and Methods

We evaluated 63 HCCs that underwent super-selective TACE. Requirements for inclusion in this study were: (a) HCCs 3 cm or less in diameter; (b) TACE performed by a single operator; and (c) no additional treatment in the absence of local progression. All patients were followed for more than 1 year after TACE. The median follow-up period for surviving patients was 20 months (range, 17–31 months). The conventional system was used in 35 HCCs (control group), and the triaxial system was used in 28 (triaxial group). We reviewed angiographies at TACE and follow-up CT, and then evaluated local tumor status in the two groups.

Results

Local tumor control rates at 3, 6, and 18 months were 64%, 36%, and 29%, respectively, in the triaxial group, and 40%, 14%, and 8.6%, respectively, in the control group ( P = 0.0086). There were no major complications in either group.

Conclusion

The triaxial system appears to be useful for super-selective TACE and may contribute to achieving higher local control rates for HCC.