bluuebunny/crossref_metadata_2025 huggingface dataset:
Maintaining Scholarly Standards in Feminist Literature
Authors: Esterson Allen
Published: March 2013

In the editorial Introduction to Women, Science, and Technology: A Reader in Feminist Science Studies, published in 2001, can be found the exemplary statement that among the norms for acquiring scientific knowledge is “skepticism (all claims should be scrutinized for errors)”. In this article, I address a section relating to historical contentions in the same volume that, I argue, fails to live up to this basic standard of scholarly research. It is now quite widely believed that Mileva Marić, Einstein’s first wife, played an active role in Einstein’s early scientific work until well after they married in 1903. Some commentators go so far as to argue that she coauthored his three major 1905 papers, while others contend that she solved the mathematical problems for him. I examine the claims made in relation to Marić in the section in question in the above-cited volume, and investigate the sources of the evidential claims that have been adduced to support them. I conclude that the several claims are without reliable evidential bases.
Explosives, Genomics, and the Environment
Authors: O’Doherty Kieran C. , MacKenzie Michael K. , Badulescu Dan , Burgess Michael M.
Published: March 2013

RDX is an explosive that is also a neurotoxin and implicated in adverse health outcomes. Because of its widespread use in military and civilian operations, there is growing concern about potential environmental and health implications. One promising method of bioremediation involves genomic studies of soil microbes. These health concerns and technological issues intersect with social and political dimensions raising questions about public responses to genomic technologies and the degree of environmental accounting expected from the military. In cases of novel technologies entering into contested social spaces, public engagement can be useful to inform broader policy debates. Building on previous work, in this article, we outline the rationale, methods, and results of a public deliberation on these issues. To our knowledge, this is the first study of its kind on the issues of RDX pollution and microbial genomics, and thus provides an important baseline on public sentiment on these issues.
A Case of Possible Darunavir/Ritonavir-Induced Peripheral Neuropathy
Authors: Lorber Margalit
Published: March 2013

A 65-year-old man, M.S.M., known as being HIV infected for 20 years, presented with muscle ache and progressive weakness 3 months after initiation of darunavir as a part of his antiretroviral therapy (ART). The patient's treatment included darunavir/ritonavir 600/100 mg twice daily, plus a backbone of didanosine and abacavir which were the backbone in his previous regimen for several years according to his drug resistance profile. Three months after initiation of darunavir/ritonavir the patient exhibited clinical symptoms of severe pain and progressive weakness of his lower limbs; he was unable to walk and was totally wheelchair-bound. Severe sensory peripheral polyneuropathy was revealed on electromyogram (EMG). All medications, including ART, were stopped. Within two months, concomitantly with initiation of raltegravir, etravirine and emcitricabine/tenofovir, the patient recovered, gained weight, resumed walking and his CD4 counts rose from 270 to 450 cells/mm3. A second EMG study 3 months after initiation of his new ART regimen showed compete recovery of the previously diagnosed peripheral neuropathy. In this report, we present a case of severe HIV-1-related acute demyelinating polyneuropathy which initiated after new generation PI darunavir/ritonavir was given and resolved after cessation of the drug without the use of immune-based therapies. The variety of HIV-related polyneuropathies will be discussed.
IL-12 receptor β1 deficiency alters in vivo T follicular helper cell response in humans
Authors: Schmitt Nathalie , Bustamante Jacinta , Bourdery Laure , Bentebibel Salah Eddine , Boisson-Dupuis Stephanie , Hamlin Fran , Tran Mau V. , Blankenship Derek , Pascual Virginia , Savino Daniel A. , Banchereau Jacques , Casanova Jean-Laurent , Ueno Hideki
Published: March 2013

Key Points

IL-12Rβ1–deficient subjects displayed substantially less circulating memory Tfh and memory B cells than control subjects. The IL-12–STAT4 axis is associated with the development and functions of Tfh cells in vivo in humans.
Soluble vascular endothelial growth factor receptor 3 is essential for corneal alymphaticity
Authors: Singh Nirbhai , Tiem Michelle , Watkins Ryan , Cho Yang Kyung , Wang Ying , Olsen Thomas , Uehara Hironori , Mamalis Christina , Luo Ling , Oakey Zackery , Ambati Balamurali K.
Published: March 2013

Key Points

Endogenous sVEGFR-3 that is expressed by the cornea binds and sequesters VEGF-C and is critical for corneal alymphaticity. sVEGFR-3 overexpression enhances murine corneal graft transplant survival 5-fold by blocking lymphangiogenesis and hemangiogenesis.
BCL6 breaks occur at different AID sequence motifs in Ig–BCL6 and non-Ig–BCL6 rearrangements
Authors: Lu Zhengfei , Tsai Albert G. , Akasaka Takashi , Ohno Hitoshi , Jiang Yanwen , Melnick Ari M. , Greisman Harvey A. , Lieber Michael R.
Published: March 2013

Key Points

Chromosomal breaks in BCL6 translocations occur at two distinct DNA sequence motifs associated with AID activity. Motif usage correlates with the type of BCL6 partner gene, suggesting mechanistic differences between Ig–BCL6 and non-Ig–BCL6 rearrangements.
A specific antidote for dabigatran: functional and structural characterization
Authors: Schiele Felix , van Ryn Joanne , Canada Keith , Newsome Corey , Sepulveda Eliud , Park John , Nar Herbert , Litzenburger Tobias
Published: March 2013

Key Points

We present an antidote for dabigatran that effectively reverses its anticoagulative effect in human plasma in vitro and in rats in vivo. The antidote shares structural features with thrombin in the mode of binding but has no activity in coagulation tests.
Smoking decreases the response of human lung macrophages to double-stranded RNA by reducing TLR3 expression
Authors: Todt Jill C , Freeman Christine M , Brown Jeanette P , Sonstein Joanne , Ames Theresa M , McCubbrey Alexandra L , Martinez Fernando J , Chensue Stephen W , Beck James M , Curtis Jeffrey L
Published: March 2013

Background

Cigarette smoking is associated with increased frequency and duration of viral respiratory infections, but the underlying mechanisms are incompletely defined. We investigated whether smoking reduces expression by human lung macrophages (Mø) of receptors for viral nucleic acids and, if so, the effect on CXCL10 production.

Methods

We collected alveolar macrophages (AMø) by bronchoalveolar lavage of radiographically-normal lungs of subjects undergoing bronchoscopies for solitary nodules (n = 16) and of volunteers who were current or former smokers (n = 7) or never-smokers (n = 13). We measured expression of mRNA transcripts for viral nucleic acid receptors by real-time PCR in those AMø and in the human Mø cell line THP-1 following phorbol myristate acetate/vitamin D3 differentiation and exposure to cigarette smoke extract, and determined TLR3 protein expression using flow cytometry and immunohistochemistry. We also used flow cytometry to examine TLR3 expression in total lung Mø from subjects undergoing clinically-indicated lung resections (n = 25). Of these, seven had normal FEV1 and FEV1/FVC ratio (three former smokers, four current smokers); the remaining 18 subjects (14 former smokers; four current smokers) had COPD of GOLD stages I-IV. We measured AMø production of CXCL10 in response to stimulation with the dsRNA analogue poly(I:C) using Luminex assay.

Results

Relative to AMø of never-smokers, AMø of smokers demonstrated reduced protein expression of TLR3 and decreased mRNA for TLR3 but not TLR7, TLR8, TLR9, RIG-I, MDA-5 or PKR. Identical changes in TLR3 gene expression were induced in differentiated THP-1 cells exposed to cigarette smoke-extract in vitro for 4 hours. Among total lung Mø, the percentage of TLR3-positive cells correlated inversely with active smoking but not with COPD diagnosis, FEV1% predicted, sex, age or pack-years. Compared to AMø of never-smokers, poly(I:C)-stimulated production of CXCL10 was significantly reduced in AMø of smokers.

Conclusions

Active smoking, independent of COPD stage or smoking duration, reduces both the percent of human lung Mø expressing TLR3, and dsRNA-induced CXCL10 production, without altering other endosomal or cytoplasmic receptors for microbial nucleic acids. This effect provides one possible mechanism for increased frequency and duration of viral lower respiratory tract infections in smokers.

Trial registration

ClinicalTrials.gov NCT00281190, NCT00281203 and NCT00281229.
An improved sequence based prediction protocol for DNA-binding proteins using SVM and comprehensive feature analysis
Authors: Zou Chuanxin , Gong Jiayu , Li Honglin
Published: March 2013

Background

DNA-binding proteins (DNA-BPs) play a pivotal role in both eukaryotic and prokaryotic proteomes. There have been several computational methods proposed in the literature to deal with the DNA-BPs, many informative features and properties were used and proved to have significant impact on this problem. However the ultimate goal of Bioinformatics is to be able to predict the DNA-BPs directly from primary sequence.

Results

In this work, the focus is how to transform these informative features into uniform numeric representation appropriately and improve the prediction accuracy of our SVM-based classifier for DNA-BPs. A systematic representation of some selected features known to perform well is investigated here. Firstly, four kinds of protein properties are obtained and used to describe the protein sequence. Secondly, three different feature transformation methods (OCTD, AC and SAA) are adopted to obtain numeric feature vectors from three main levels: Global, Nonlocal and Local of protein sequence and their performances are exhaustively investigated. At last, the mRMR-IFS feature selection method and ensemble learning approach are utilized to determine the best prediction model. Besides, the optimal features selected by mRMR-IFS are illustrated based on the observed results which may provide useful insights for revealing the mechanisms of protein-DNA interactions. For five-fold cross-validation over the DNAdset and DNAaset, we obtained an overall accuracy of 0.940 and 0.811, MCC of 0.881 and 0.614 respectively.

Conclusions

The good results suggest that it can efficiently develop an entirely sequence-based protocol that transforms and integrates informative features from different scales used by SVM to predict DNA-BPs accurately. Moreover, a novel systematic framework for sequence descriptor-based protein function prediction is proposed here.
EGFR inhibition prevents in vitro tumor growth of salivary adenoid cystic carcinoma
Authors: Huang Yi , Yu Tao , Fu Xiaoyue , Chen Jiao , Liu Ying , Li Chunjie , Xia Yichao , Zhang Zhuoyuan , Li Longjiang
Published: March 2013

Background

Epidermal growth factor receptor (EGFR) is involved in the development of many human malignant tumors and plays an important role in tumor growth and metastasis. Antagonists of EGFR can suppress the growth of several malignancies; however, their therapeutic effect in adenoid cystic carcinoma (ACC) is controversial.

Results

The increased proliferation of two ACC cell lines induced by EGF-treatment was reversed by nimotuzumab. Regardless of EGF stimulation, nimotuzumab-treated ACC cells were arrested in G1 phase and showed decreased expression of Ki67. In addition, EGF activated the MAPK-dependent pathway and up-regulated the expression of matrix metalloproteinase-9 and Snail, enhancing the invasive potential of an ACC cell line (ACC-M). The effects of EGF were down-regulated by nimotuzumab treatment.

Conclusions

These results suggest that nimotuzumab can inhibit the growth and invasion of ACC cells induced by EGF, probably through inactivation of ERK phosphorylation. Thus, nimotuzumab should be considered as a promising novel agent for the treatment of ACC.
Pearl millet [Pennisetum glaucum(L.) R. Br.] consensus linkage map constructed using four RIL mapping populations and newly developed EST-SSRs
Authors: Rajaram Vengaldas , Nepolean Thirunavukkarasu , Senthilvel Senapathy , Varshney Rajeev K , Vadez Vincent , Srivastava Rakesh K , Shah Trushar M , Supriya Ambawat , Kumar Sushil , Ramana Kumari Basava , Bhanuprakash Amindala , Lakshmi Narasu Mangamoori , Riera-Lizarazu Oscar , Hash Charles Thomas
Published: March 2013

Background

Pearl millet [Pennisetum glaucum (L.) R. Br.] is a widely cultivated drought- and high-temperature tolerant C4 cereal grown under dryland, rainfed and irrigated conditions in drought-prone regions of the tropics and sub-tropics of Africa, South Asia and the Americas. It is considered an orphan crop with relatively few genomic and genetic resources. This study was undertaken to increase the EST-based microsatellite marker and genetic resources for this crop to facilitate marker-assisted breeding.

Results

Newly developed EST-SSR markers (99), along with previously mapped EST-SSR (17), genomic SSR (53) and STS (2) markers, were used to construct linkage maps of four F7 recombinant inbred populations (RIP) based on crosses ICMB 841-P3 × 863B-P2 (RIP A), H 77/833-2 × PRLT 2/89-33 (RIP B), 81B-P6 × ICMP 451-P8 (RIP C) and PT 732B-P2 × P1449-2-P1 (RIP D). Mapped loci numbers were greatest for RIP A (104), followed by RIP B (78), RIP C (64) and RIP D (59). Total map lengths (Haldane) were 615 cM, 690 cM, 428 cM and 276 cM, respectively. A total of 176 loci detected by 171 primer pairs were mapped among the four crosses. A consensus map of 174 loci (899 cM) detected by 169 primer pairs was constructed using MergeMap to integrate the individual linkage maps. Locus order in the consensus map was well conserved for nearly all linkage groups. Eighty-nine EST-SSR marker loci from this consensus map had significant BLAST hits (top hits with e-value ≤ 1E-10) on the genome sequences of rice, foxtail millet, sorghum, maize and Brachypodium with 35, 88, 58, 48 and 38 loci, respectively.

Conclusion

The consensus map developed in the present study contains the largest set of mapped SSRs reported to date for pearl millet, and represents a major consolidation of existing pearl millet genetic mapping information. This study increased numbers of mapped pearl millet SSR markers by >50%, filling important gaps in previously published SSR-based linkage maps for this species and will greatly facilitate SSR-based QTL mapping and applied marker-assisted selection programs.
The genome- and transcriptome-wide analysis of innate immunity in the brown planthopper, Nilaparvata lugens
Authors: Bao Yan-Yuan , Qu Lv-Yu , Zhao Dong , Chen Li-Bo , Jin Hong-Yuan , Xu Liang-Min , Cheng Jia-An , Zhang Chuan-Xi
Published: March 2013

Background

The brown planthopper (Nilaparvata lugens) is one of the most serious rice plant pests in Asia. N. lugens causes extensive rice damage by sucking rice phloem sap, which results in stunted plant growth and the transmission of plant viruses. Despite the importance of this insect pest, little is known about the immunological mechanisms occurring in this hemimetabolous insect species.

Results

In this study, we performed a genome- and transcriptome-wide analysis aiming at the immune-related genes. The transcriptome datasets include the N. lugens intestine, the developmental stage, wing formation, and sex-specific expression information that provided useful gene expression sequence data for the genome-wide analysis. As a result, we identified a large number of genes encoding N. lugens pattern recognition proteins, modulation proteins in the prophenoloxidase (proPO) activating cascade, immune effectors, and the signal transduction molecules involved in the immune pathways, including the Toll, Immune deficiency (Imd) and Janus kinase signal transducers and activators of transcription (JAK-STAT) pathways. The genome scale analysis revealed detailed information of the gene structure, distribution and transcription orientations in scaffolds. A comparison of the genome-available hemimetabolous and metabolous insect species indicate the differences in the immune-related gene constitution. We investigated the gene expression profiles with regards to how they responded to bacterial infections and tissue, as well as development and sex expression specificity.

Conclusions

The genome- and transcriptome-wide analysis of immune-related genes including pattern recognition and modulation molecules, immune effectors, and the signal transduction molecules involved in the immune pathways is an important step in determining the overall architecture and functional network of the immune components in N. lugens. Our findings provide the comprehensive gene sequence resource and expression profiles of the immune-related genes of N. lugens, which could facilitate the understanding of the innate immune mechanisms in the hemimetabolous insect species. These data give insight into clarifying the potential functional roles of the immune-related genes involved in the biological processes of development, reproduction, and virus transmission in N. lugens.
Auditory-motor adaptation to frequency-altered auditory feedback occurs when participants ignore feedback
Authors: Keough Dwayne , Hawco Colin , Jones Jeffery A
Published: March 2013

Background

Auditory feedback is important for accurate control of voice fundamental frequency (F
0). The purpose of this study was to address whether task instructions could influence the compensatory responding and sensorimotor adaptation that has been previously found when participants are presented with a series of frequency-altered feedback (FAF) trials. Trained singers and musically untrained participants (nonsingers) were informed that their auditory feedback would be manipulated in pitch while they sang the target vowel [/ɑ /]. Participants were instructed to either ‘compensate’ for, or ‘ignore’ the changes in auditory feedback. Whole utterance auditory feedback manipulations were either gradually presented (‘ramp’) in -2 cent increments down to -100 cents (1 semitone) or were suddenly (’constant‘) shifted down by 1 semitone.

Results

Results indicated that singers and nonsingers could not suppress their compensatory responses to FAF, nor could they reduce the sensorimotor adaptation observed during both the ramp and constant FAF trials.

Conclusions

Compared to previous research, these data suggest that musical training is effective in suppressing compensatory responses only when FAF occurs after vocal onset (500-2500 ms). Moreover, our data suggest that compensation and adaptation are automatic and are influenced little by conscious control.
Expression profiling of tomato pre-abscission pedicels provides insights into abscission zone properties including competence to respond to abscission signals
Authors: Nakano Toshitsugu , Fujisawa Masaki , Shima Yoko , Ito Yasuhiro
Published: March 2013

Background

Detachment of plant organs occurs in abscission zones (AZs). During plant growth, the AZ forms, but does not develop further until the cells perceive abscission-promoting signals and initiate detachment. Upon signal perception, abscission initiates immediately; if there is no signal, abscission is not induced and the organ remains attached to the plant. However, little attention has been paid to the genes that maintain competence to respond to the abscission signal in the pre-abscission AZ. Recently, we found that the tomato (Solanum lycopersicum) transcription factors BLIND (Bl), GOBLET (GOB), Lateral suppressor (Ls) and a tomato WUSCHEL homologue (LeWUS) are expressed specifically in pre-abscission tissue, the anthesis pedicel AZs. To advance our understanding of abscission, here we profiled genome-wide gene expression in tomato flower pedicels at the pre-abscission stage.

Results

We examined the transcriptomes of three tomato flower pedicel regions, the AZ and flanking proximal- (Prox) and distal- (Dis) regions, and identified 89 genes that were preferentially expressed in the AZ compared to both Prox and Dis. These genes included several transcription factors that regulate apical or axillary shoot meristem activity. Also, genes associated with auxin activity were regulated in a Prox-Dis region-specific manner, suggesting that a gradient of auxin exists in the pedicel. A MADS-box gene affecting floral transition was preferentially expressed in the Prox region and other MADS-box genes for floral organ identification were preferentially expressed in Dis, implying that the morphologically similar Prox and Dis regions have distinct identities. We also analyzed the expression of known regulators; in anthesis pedicels, Bl, GOB, Ls and LeWUS were expressed in the vascular cells of the AZ region. However, after an abscission signal, Bl was up-regulated, but GOB, Ls and LeWUS were down-regulated, suggesting that Bl may be a positive regulator of abscission, but the others may be negative regulators.

Conclusions

This study reveals region-specific gene expression in tomato flower pedicels at anthesis and identifies factors that may determine the physiological properties of the pre-abscission pedicel. The region-specific transcriptional regulators and genes for auxin activity identified here may prevent flower abscission in the absence of signal or establish competence to respond to the abscission signal.
Trial Protocol: A randomised controlled trial of extended anticoagulation treatment versus routine anticoagulation treatment for the prevention of recurrent VTE and post thrombotic syndrome in patients being treated for a first episode of unprovoked VTE (The ExACT Study)
Authors: Tullett Jayne , Murray Ellen , Nichols Linda , Holder Roger , Lester Will , Rose Peter , Hobbs FD Richard , Fitzmaurice David
Published: March 2013

Background

Venous thromboembolism comprising pulmonary embolism and deep vein thrombosis is a common condition with an incidence of approximately 1 per 1,000 per annum causing both mortality and serious morbidity. The principal aim of treatment of a venous thromboembolism with heparin and warfarin is to prevent extension or recurrence of clot. However, the recurrence rate following a deep vein thrombosis remains approximately 10% per annum following treatment cessation irrespective of the duration of anticoagulation therapy. Patients with raised D-dimer levels after discontinuing oral anticoagulation treatment have also been shown to be at high risk of recurrence.

Post thrombotic syndrome is a complication of a deep vein thrombosis which can lead to chronic venous insufficiency and ulceration. It has a cumulative incidence after 2 years of around 25% and it has been suggested that extended oral anticoagulation should be investigated as a possible preventative measure.

Methods/design

Patients with a first idiopathic venous thromboembolism will be recruited through anticoagulation clinics and randomly allocated to either continuing or discontinuing warfarin treatment for a further 2 years and followed up on a six monthly basis. At each visit D-dimer levels will be measured using a Roche Cobas h 232 POC device. In addition a venous sample will be taken for laboratory D-dimer analysis at the end of the study. Patients will be examined for signs and symptoms of PTS using the Villalta scale and complete VEINES and EQ5D quality of life questionnaires.

Discussion

The primary aim of the study is to investigate whether extending oral anticoagulation treatment (prior to discontinuing treatment) beyond 3–6 months for patients with a first unprovoked proximal deep vein thrombosis or pulmonary embolism prevents recurrence. The study will also determine the role of extending anticoagulation for patients with elevated D-dimer levels prior to discontinuing treatment and identify the potential of D-dimer point of care testing for identification of high risk patients within a primary care setting.

Trial registration

ISRCTN73819751
Schizophrenia susceptibility and NMDA-receptor mediated signalling: an association study involving 32 tagSNPs of DAO, DAOA, PPP3CC, and DTNBP1genes
Authors: Sacchetti Emilio , Scassellati Catia , Minelli Alessandra , Valsecchi Paolo , Bonvicini Cristian , Pasqualetti Patrizio , Galluzzo Alessandro , Pioli Rosaria , Gennarelli Massimo
Published: March 2013

Background

Recent studies supported associations between four NMDA-receptor-mediated signalling genes (D-amino acid oxidase, DAO; D-amino acid oxidase activator, DAOA; protein phosphatase 3 catalytic subunit gamma isoform, PPP3CC; dystrobrevin-binding protein 1, DTNBP1) and schizophrenia susceptibility, even though with contrasting results.

Methods

In an attempt to replicate these findings for the first time in an Italian population, a panel of 32 tagSNPs was analysed in a representative case-control sample involving 879 subjects.

Results

An association in the allele frequency was observed for the estimated PPP3CC CAG triplotype in the SNP window rs4872499 T/C-rs11780915 A/G-rs13271367 G/A (pcorrect = 0.001). Similarly, the clustered genotype frequencies of the estimated/phased CAG triplotype differed between cases and controls (p = 0.004), with the carriers having a higher frequency in the control population (p = 0.002, odd ratio OR = 0.59, 95% confident interval CI: 0.43-0.82).

Following the phenotypic dissection strategy, the analysis of single SNPs evidenced a protective effect in males of rs11780915 and rs13271367 in PPP3CC gene (pcorrect = 0.02, pcorrect = 0.04 respectively). Moreover the estimated/phased GT diplotype (rs2070586A/G-rs3741775G/T) carriers of the DAO gene were more highly represented in female controls (p = 0.017, OR = 0.58, 95% CI: 0.37-0.90), as were the estimated/phased CAG triplotype carriers of the PPP3CC gene in females (p = 0.01, OR = 0.53, 95% CI: 0.32-0.87). In addition, we performed an interaction analysis, and a 66% (p = 0.003, OR = 0.34, 95% CI: 0.17-0.70) lower risk of developing schizophrenia for female (CAG + GT) carriers versus non-CAG or -GT carriers was observed. For DTNBP1, we found a protective effect in males for the rs6459409 (pcorrect = 0.02) and the estimated/phased CT diplotype (rs6459409-rs9476886) carriers (p = 3x10-4
, OR = 0.46, 95% CI: 0.30-0.70).

In relation to diagnostic subtypes, the estimated/phased DAO GT diplotype and PPP3CC CAG triplotype female carriers were found to show relative risk ratio (RRR) values of 0.52 and 0.54 lower risk for a paranoid phenotype respectively.

Conclusions

Although the results are preliminary and needed replication in a larger sample, this study suggests that NMDA receptor-mediated signalling genes (DAO, PPP3CC, DTNBP1) might be involved in schizophrenia pathogenic mechanisms related to gender.
Preeclampsia and long-term risk of cardiovascular disease: what do obstetrician-gynecologists know?
Authors: Heidrich May-Britt , Wenzel Daniela , von Kaisenberg Constantin S , Schippert Cordula , von Versen-Höynck Frauke M
Published: March 2013

Background

Preeclampsia (PE), a hypertensive disorder of pregnancy affects 2-8% of women and is associated with increased cardiovascular disease (CVD) risk later in life. There is little information about the knowledge of obstetrician-gynecologists in German outpatient care setting regarding the future health risk of PE and knowledge of the current guidelines on treatment and counseling patients post PE. This study aimed to assess whether obstetrician-gynecologists are aware of PE’s association with maternal long-term adverse outcomes and providing appropriate counseling.

Methods

A random sample of 500 obstetrician-gynecologists in the federal state of Lower Saxony was mailed a survey and a reminder with a second copy of the survey. The questionnaire elicited both personal information, and knowledge on future disease risks, e.g. cardiovascular disease (CVD) and current guidelines as well as on counseling practice. Descriptive analysis was used to analyze the responses.

Results

A total of 212 obstetrician-gynecologists (42.4%) responded to the questionnaire. A large proportion of physicians stated that PE was associated with a higher risk for the development for hypertension (86.6%), stroke (78.5%) and kidney disease (78.0%). Of the participants 75.8% reported that women after PE have a shorter life expectancy. Respondents with knowledge of the current guidelines of the German Association of Obstetrics and Gynecology concerning follow up and risk management of PE (45.2%) were more often aware of the development of CVD and stroke and counseled patients on self -blood-pressure measurement, meaning and long-term-risks of PE and attached importance to family history of PE compared to physicians with no knowledge of the guidelines.

Conclusion

Although the majority of obstetrician-gynecologists were aware of higher CVD risk after PE, weaknesses exist in the follow up care and counseling of these patients. These deficiencies would be amendable to directed educational activities to improve the implementation of current guidelines.
Hypoxia induces epithelial-mesenchymal transition via activation of SNAI1 by hypoxia-inducible factor -1α in hepatocellular carcinoma
Authors: Zhang Lin , Huang Gang , Li Xiaowu , Zhang Yujun , Jiang Yan , Shen Junjie , Liu Jia , Wang Qingliang , Zhu Jin , Feng Xiaobin , Dong Jiahong , Qian Cheng
Published: March 2013

Background

High invasion and metastasis are the primary factors causing poor prognosis of patients with hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying these biological behaviors have not been completely elucidated. In this study, we investigate the molecular mechanism by which hypoxia promotes HCC invasion and metastasis through inducing epithelial-mesenchymal transition (EMT).

Methods

The expression of EMT markers was analyzed by immunohistochemistry. Effect of hypoxia on induction of EMT and ability of cell migration and invasion were performed. Luciferase reporter system was used for evaluation of Snail regulation by hypoxia-inducible factor -1α (HIF-1α).

Results

We found that overexpression of HIF-1α was observed in HCC liver tissues and was related to poor prognosis of HCC patients. HIF-1α expression profile was correlated with the expression levels of SNAI1, E-cadherin, N-cadherin and Vimentin. Hypoxia was able to induce EMT and enhance ability of invasion and migration in HCC cells. The same phenomena were also observed in CoCl2-treated cells. The shRNA-mediated HIF-1α suppression abrogated CoCl2-induced EMT and reduced ability of migration and invasion in HCC cells. Luciferase assay showed that HIF-1α transcriptional regulated the expression of SNAI1 based on two hypoxia response elements (HREs) in SNAI1 promoter.

Conclusions

We demonstrated that hypoxia-stabilized HIF1α promoted EMT through increasing SNAI1 transcription in HCC cells. This data provided a potential therapeutic target for HCC treatment.
A new chronobiological approach to discriminate between acute and chronic depression using peripheral temperature, rest-activity, and light exposure parameters
Authors: Moraes Cláudia Ávila , Cambras Trinitat , Diez-Noguera Antoni , Schimitt Regina , Dantas Giovana , Levandovski Rosa , Hidalgo Maria Paz
Published: March 2013

Background

Circadian theories for major depressive disorder have suggested that the rhythm of the circadian pacemaker is misaligned. Stable phase relationships between internal rhythms, such as temperature and rest/activity, and the external day-night cycle, are considered to be crucial for adapting to life in the external environmental. Therefore, the relationship and possible alterations among (i) light exposure, (ii) activity rhythm, and (iii) temperature rhythm could be important factors in clinical depression. This study aimed to investigate the rhythmic alterations in depression and evaluate the ability of chronobiological parameters to discriminate between healthy subjects and depressed patients.

Methods

Thirty female subjects, including healthy subjects, depressed patients in the first episode, and major recurrent depression patients. Symptoms were assessed using Hamilton Depression Scale, Beck Depression Inventory and Montgomery-Äsberg Scale. Motor activity, temperature, and light values were determined for 7 days by actigraph, and circadian rhythms were calculated.

Results

Depressed groups showed a lower amplitude in the circadian rhythm of activity and light exposure, but a higher amplitude in the rhythm of peripheral temperature. The correlation between temperature and activity values was different in the day and night among the control and depressed groups. For the same level of activity, depressed patients had lowest temperature values during the day. The amplitudes of temperature and activity were the highest discriminant parameters.

Conclusions

These results indicate that the study of rhythms is useful for diagnosis and therapy for depressive mood disorders.
Two series of new semisynthetic triterpene derivatives: differences in anti-malarial activity, cytotoxicity and mechanism of action
Authors: da Silva Gloria NS , Maria Nicole RG , Schuck Desirée C , Cruz Laura N , de Moraes Miriam S , Nakabashi Myna , Graebin Cedric , Gosmann Grace , Garcia Célia RS , Gnoatto Simone CB
Published: March 2013

Background

The discovery and development of anti-malarial compounds of plant origin and semisynthetic derivatives thereof, such as quinine (QN) and chloroquine (CQ), has highlighted the importance of these compounds in the treatment of malaria. Ursolic acid analogues bearing an acetyl group at C-3 have demonstrated significant anti-malarial activity. With this in mind, two new series of betulinic acid (BA) and ursolic acid (UA) derivatives with ester groups at C-3 were synthesized in an attempt to improve anti-malarial activity, reduce cytotoxicity, and search for new targets. In vitro activity against CQ-sensitive Plasmodium falciparum 3D7 and an evaluation of cytotoxicity in a mammalian cell line (HEK293T) are reported. Furthermore, two possible mechanisms of action of anti-malarial compounds have been evaluated: effects on mitochondrial membrane potential (ΔΨm) and inhibition of β-haematin formation.

Results

Among the 18 derivatives synthesized, those having shorter side chains were most effective against CQ-sensitive P. falciparum 3D7, and were non-cytotoxic. These derivatives were three to five times more active than BA and UA. A DiOC6(3) ΔΨm assay showed that mitochondria are not involved in their mechanism of action. Inhibition of β-haematin formation by the active derivatives was weaker than with CQ. Compounds of the BA series were generally more active against P. falciparum 3D7 than those of the UA series.

Conclusions

Three new anti-malarial prototypes were obtained from natural sources through an easy and relatively inexpensive synthesis. They represent an alternative for new lead compounds for anti-malarial chemotherapy.
Efficacy of vitamin C as an adjunct to fluoxetine therapy in pediatric major depressive disorder: a randomized, double-blind, placebo-controlled pilot study
Authors: Amr Mostafa , El-Mogy Ahmed , Shams Tarek , Vieira Karen , Lakhan Shaheen E
Published: March 2013

Background

Current antidepressants used to treat pediatric patients have the disadvantage of limited efficacy and potentially serious side effects. The purpose of this study was to assess the efficacy of vitamin C as an adjuvant agent in the treatment of pediatric major depressive disorder in a six-month, double-blind, placebo-controlled pilot trial.

Methods

The study group (n=12) was given fluoxetine (10–20 mg/day) plus vitamin C (1000 mg/day) and control group (n=12) administered fluoxetine (10–20 mg/day) plus placebo. The data were analyzed by ANOVA andt-test for independent samples.

Results

Both groups demonstrated significantly improved scores on the Children’s Depression Rating Scale (CDRS), the Children’s Depression Inventory (CDI), and the Clinical Global Impression (CGI). ANOVA was significantly different on all clinical measurements (group effect, time effect, and interaction), with the exception of group effect and interaction for CGI. Patients treated for six months with fluoxetine and vitamin C showed a significant decrease in depressive symptoms in comparison to the fluoxetine plus placebo group as measured by the CDRS (t=11.36,P<0.0001) and CDI (t=12.27,P<0.0001), but not CGI (t=0.13,P=0.90). No serious adverse effects were observed.

Conclusions

These preliminary results suggest that vitamin C may be an effective adjuvant agent in the treatment of MDD in pediatric patients.
Primary tracheobronchial mucoepidermoid carcinoma - a retrospective study of 32 patients
Authors: Song Zhengbo , Liu Zhuo , Wang Jiwen , Zhu Huineng , Zhang Yiping
Published: March 2013

Background

This retrospective study was designed to investigate the clinical characteristics, diagnosis, treatment and prognosis of primary tracheobronchial mucoepidermoid carcinoma (MEC).

Methods

Clinical data were retrospectively analyzed from 32 patients with pathologically confirmed primary tracheobronchial MEC between January 1990 and December 2010 at Zhejiang Cancer Hospital. The Kaplan-Meier methods were used to estimate and compare survival rates.

Results

There were 19 males and 13 females ranging in age from 7 to 73 years, with a median age of 28 years. Twenty-six of the 32 patients were treated with surgery alone. The other six patients were treated with surgery plus postoperative radiotherapy or chemotherapy. Six patients died during the follow-up time. The overall five-year survival rates were 81.25%, whereas the five-year survival rate of seven patients with high-grade tumors was only 28.6%. Stage I and II patients experienced better survival than Stage III and IV patients (the five-year survival rate was 100% and 43.6% respectively, P<0.001).

Conclusions

Primary tracheobronchial MEC is a rare disease. Histologic grading and TNM (tumor-node-metastasis)staging are independent prognostic factors. Surgical resection is the primary treatment.
Extranodal Rosai–Dorfman disease: a rare soft tissue neoplasm masquerading as a sarcoma
Authors: Komaragiri Mahathi , Sparber Lauren S , Santos-Zabala Maria Laureana , Dardik Michael , Chamberlain Ronald S
Published: March 2013

Introduction

Rosai–Dorfman disease (RDD) is a rare proliferative histiocytic disorder of unknown etiology. RDD typically presents with generalized lymphadenopathy and polymorphic histiocytic infiltration of the lymph node sinuses; however, occurrences of extranodal soft tissue RDD may rarely occur when masquerading as a soft tissue sarcoma.

Materials and methods

A comprehensive search of all published cases of soft tissue RDD without associated lymphadenopathy was conducted using PubMed and Google Scholar for the years 1988 to 2011. Ophthalmic RDD was excluded.

Results

Thirty-six cases of extranodal soft tissue RDD, including the current one, have been reported since 1988. Anatomical distribution varied among patients. Four (11.1%) patients presented with bilateral lesions in the same anatomic region. Pain was the most common symptom in six (16.8%) patients. Sixteen (41.6%) patients were managed surgically, of which one (2.8%) case experienced recurrence of disease.

Conclusion

RDD is a rare inflammatory non-neoplastic process that should be considered in the differential diagnosis of a soft tissue tumor. Thus, differentiation of extranodal RDD from more common soft tissue tumors such as soft tissue sarcoma or inflammatory myofibroblastic tumor is often difficult and typically requires definitive surgical excision with histopathological examination. While the optimal treatment for extranodal RDD remains ill-defined and controversial, surgical excision is typically curative.
Depth of colorectal-wall invasion and lymph-node involvement as major outcome factors influencing surgical strategy in patients with advanced and recurrent ovarian cancer with diffuse peritoneal metastases
Authors: Di Giorgio Angelo , Cardi Maurizio , Biacchi Daniele , Sibio Simone , Accarpio Fabio , Ciardi Antonio , Cornali Tommaso , Framarino Marialuisa , Sammartino Paolo
Published: March 2013

Background

More information is needed on the anatomopathological outcome variables indicating the appropriate surgical strategy for the colorectal resections often needed during cytoreduction for ovarian cancer.

Methods

From a phase-II study cohort including 70 patients with primary advanced or recurrent ovarian cancer with diffuse peritoneal metastases treated from November 2000 to April 2009, we selected for this study the 52 consecutive patients who needed colorectal resection. Data collected included type of colorectal resection, peritoneal cancer index (PCI), histopathology (depth of bowel-wall invasion and lymph-node spread), cytoreduction rate and outcome. Correlations were tested between possible prognostic factors and Kaplan-Meier five-year overall and disease-free survival. A Cox multivariate regression model was used to identify independent variables associated with outcome.

Results

In the 52 patients, the optimal cytoreduction rate was 86.5% (CC0/1). In all patients, implants infiltrated deeply into the bowel wall, in 75% of the cases up to the muscular and mucosal layer. Lymph-node metastases were detected in 50% of the cases; mesenteric nodes were involved in 42.3%. Most patients (52%) had an uneventful postoperative course. Operative mortality was 3.8%. The five-year survival rate was 49.9% and five-year disease-free survival was 36.7%. Cox regression analysis identified as the main prognostic factors completeness of cytoreduction and depth of bowel wall invasion.

Conclusions

Our findings suggest that the major independent prognostic factors in patients with advanced ovarian cancer needing colorectal resections are completeness of cytoreduction and depth of bowel wall invasion. Surgical management and pathological assessment should be aware of and deal with dual locoregional and mesenteric lymphatic spread.
Radar detection with the Neyman–Pearson criterion using supervised-learning-machines trained with the cross-entropy error
Authors: Jarabo-Amores María-Pilar , la Mata-Moya David de , Gil-Pita Roberto , Rosa-Zurera Manuel
Published: March 2013

The application of supervised learning machines trained to minimize the Cross-Entropy error to radar detection is explored in this article. The detector is implemented with a learning machine that implements a discriminant function, which output is compared to a threshold selected to fix a desired probability of false alarm. The study is based on the calculation of the function the learning machine approximates to during training, and the application of a sufficient condition for a discriminant function to be used to approximate the optimum Neyman–Pearson (NP) detector. In this article, the function a supervised learning machine approximates to after being trained to minimize the Cross-Entropy error is obtained. This discriminant function can be used to implement the NP detector, which maximizes the probability of detection, maintaining the probability of false alarm below or equal to a predefined value. Some experiments about signal detection using neural networks are also presented to test the validity of the study.
Amelioration of autoimmune neuroinflammation by the fusion molecule Fn14·TRAIL
Authors: Prinz-Hadad Hodaya , Mizrachi Tehila , Irony-Tur-Sinai Michal , Prigozhina Tatyana B , Aronin Alexandra , Brenner Talma , Dranitzki-Elhalel Michal
Published: March 2013

Background

Multiple sclerosis (MS) is a, T cell-mediated autoimmune disease, the management of which remains challenging. The recently described fusion protein, Fn14·TRAIL, combining the extracellular domain of Fn14 (capable of blocking the pro-inflammatory TWEAK ligand) fused to the extracellular domain of the TRAIL ligand (capable of sending apoptotic signals through its receptors on activated inflammatory cells) was designed to modulate the immune system as an anti-inflammatory agent. The present study explores the efficacy of this purified protein as an anti-inflammatory agent, using the animal model of MS - experimental autoimmune encephalomyelitis (EAE).

Methods

EAE was induced by myelin oligodendrocyte glycoprotein (MOG). Fn14·TRAIL or vehicle were injected daily for 4 to 16 days, at different time points after disease induction. Animals were examined daily and evaluated for EAE clinical signs. Lymphocytes were analyzed for ex vivo re-stimulation, cytokine secretion, transcription factor expression and subtype cell analysis. Spinal cords were checked for inflammatory foci. The Mann- Whitney rank sum test, Student’s t-test or ANOVA were used for statistical analysis.

Results

Significant improvement of EAE in the group treated with Fn14·TRAIL was noted from day 6 of disease onset and lasted until the end of follow-up (day 40 from disease induction), even in animals treated for 4 days only. Clinical improvement was linked to decreased lymphocyte infiltrates in the central nervous system (CNS) and to decreased Th1 and Th17 responses and to increased number of T- regulatory in the treated mice. No liver or kidney toxicity was evident. In vitro assays established the ability of Fn14·TRAIL to induce apoptosis of T cell lines expressing TRAIL receptors and TWEAK.

Conclusions

In this study we established the potency of Fn14·TRAIL, a unique fusion protein combining two potentially functional domains, in inhibiting the clinical course of EAE, even when given for a short time, without apparent toxicity. These findings make Fn14·TRAIL a highly promising agent to be used for targeted amelioration of neuro-inflammatory processes, as well as other autoimmune pathologies.
Modeling the obesity epidemic: social contagion and its implications for control
Authors: Ejima Keisuke , Aihara Kazuyuki , Nishiura Hiroshi
Published: March 2013

Background

As an obesity epidemic has grown worldwide, a variety of intervention programs have been considered, but a scientific approach to comparatively assessing the control programs has still to be considered. The present study aims to describe an obesity epidemic by employing a simple mathematical model that accounts for both social contagion and non-contagious hazards of obesity, thereby comparing the effectiveness of different types of interventions.

Methods

An epidemiological model is devised to describe the time- and age-dependent risk of obesity, the hazard of which is dealt with as both dependent on and independent of obesity prevalence, and parameterizing the model using empirically observed data. The equilibrium prevalence is investigated as our epidemiological outcome, assessing its sensitivity to different parameters that regulate the impact of intervention programs and qualitatively comparing the effectiveness. We compare the effectiveness of different types of interventions, including those directed to never-obese individuals (i.e. primary prevention) and toward obese and ex-obese individuals (i.e. secondary prevention).

Results

The optimal choice of intervention programs considerably varies with the transmission coefficient of obesity, and a limited transmissibility led us to favour preventing weight gain among never-obese individuals. An abrupt decline in the prevalence is expected when the hazards of obesity through contagious and non-contagious routes fall into a particular parameter space, with a high sensitivity to the transmission potential of obesity from person to person. When a combination of two control strategies can be selected, primary and secondary preventions yielded similar population impacts and the superiority of the effectiveness depends on the strength of the interventions at an individual level.

Conclusions

The optimality of intervention programs depends on the contagiousness of obesity. Filling associated data gaps of obesity transmission would help systematically understand the epidemiological dynamics and consider required control programs.