bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimate of the global burden of cervical adenocarcinoma and potential impact of prophylactic human papillomavirus vaccination
Authors: Pimenta Jeanne M , Galindo Claudia , Jenkins David , Taylor Sylvia M 
Published: November 2013

Abstract

Background
Data on the current burden of adenocarcinoma (ADC) and histology-specific human papillomavirus (HPV) type distribution are relevant to predict the future impact of prophylactic HPV vaccines.

Methods
We estimate the proportion of ADC in invasive cervical cancer, the global number of cases of cervical ADC in 2015, the effect of cervical screening on ADC, the number of ADC cases attributable to high-risk HPV types -16, -18, -45, -31 and -33, and the potential impact of HPV vaccination using a variety of data sources including: GLOBOCAN 2008, Cancer Incidence in Five Continents (CI5) Volume IX, cervical screening data from the World Health Organization/Institut Català d'Oncologia Information Centre on HPV and cervical cancer, and published literature.

Results
ADC represents 9.4% of all ICC although its contribution varies greatly by country and region. The global crude incidence rate of cervical ADC in 2015 is estimated at 1.6 cases per 100,000 women, and the projected worldwide incidence of ADC in 2015 is 56,805 new cases. Current detection rates for HPV DNA in cervical ADC tend to range around 80–85%; the lower HPV detection rates in cervical ADC versus squamous cell carcinoma may be due to technical artefacts or to misdiagnosis of endometrial carcinoma as cervical ADC. Published data indicate that the five most common HPV types found in cervical ADC are HPV-16 (41.6%), -18 (38.7%), -45 (7.0%), -31 (2.2%) and -33 (2.1%), together comprising 92% of all HPV positive cases. Future projections using 2015 data, assuming 100% vaccine coverage and a true HPV causal relation of 100%, suggest that vaccines providing protection against HPV-16/18 may theoretically prevent 79% of new HPV-related ADC cases (44,702 cases annually) and vaccines additionally providing cross-protection against HPV-31/33/45 may prevent 89% of new HPV-related ADC cases (50,769 cases annually).

Conclusions
It is predicted that the currently available HPV vaccines will be highly effective in preventing HPV-related cervical ADC.
Glutamate acid decarboxylase 1 promotes metastasis of human oral cancer by β-catenin translocation and MMP7 activation
Authors: Kimura Ryota , Kasamatsu Atsushi , Koyama Tomoyoshi , Fukumoto Chonji , Kouzu Yukinao , Higo Morihiro , Endo-Sakamoto Yosuke , Ogawara Katsunori , Shiiba Masashi , Tanzawa Hideki , Uzawa Katsuhiro 
Published: November 2013

Abstract

Background
Glutamate decarboxylase 1 (GAD1), a rate-limiting enzyme in the production of γ-aminobutyric acid (GABA), is found in the GABAergic neurons of the central nervous system. Little is known about the relevance of GAD1 to oral squamous cell carcinoma (OSCC). We investigated the expression status of GAD1 and its functional mechanisms in OSCCs.

Methods
We evaluated GAD1 mRNA and protein expressions in OSCC-derived cells using real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and immunoblotting analyses. To assess the critical functions of GAD1, i.e., cellular proliferation, invasiveness, and migration, OSCC-derived cells were treated with the shRNA and specific GAD1 inhibitor, 3-mercaptopropionic acid (3-MPA). GAD1 expression in 80 patients with primary OSCCs was analyzed and compared to the clinicopathological behaviors of OSCC.

Results
qRT-PCR and immunoblotting analyses detected frequent up-regulation of GAD1 in OSCC-derived cells compared to human normal oral keratinocytes. Suppression of nuclear localization of β-catenin and MMP7 secretion was observed in GAD1 knockdown and 3-MPA-treated cells. We also found low cellular invasiveness and migratory abilities in GAD1 knockdown and 3-MPA-treated cells. In the clinical samples, GAD1 expression in the primary OSCCs was significantly (P < 0.05) higher than in normal counterparts and was correlated significantly (P < 0.05) with regional lymph node metastasis.

Conclusions
Our data showed that up-regulation of GAD1 was a characteristic event in OSCCs and that GAD1 was correlated with cellular invasiveness and migration by regulating β-catenin translocation and MMP7 activation. GAD1 might play an important role in controlling tumoral invasiveness and metastasis in oral cancer.
Ardipusilloside I induces apoptosis by regulating Bcl-2 family proteins in human mucoepidermoid carcinoma Mc3 cells
Authors: Xu Xiao-Fang , Zhang Tao-Li , Jin Song , Wang Rong , Xiao Xin , Zhang Wei-Dong , Wang Peng-Yuan , Wang Xiao-Juan 
Published: November 2013

Abstract

Background

Ardisia pusilla A. DC., family Myrsinaceae, is a traditional Chinese medicine named Jiu Jie Long with a variety of pharmacological functions including anti-cancer activities. In this study, we purified a natural triterpenoid saponin, ardipusilloside I, from Ardisia pusilla, and show that it exhibits inhibitory activities in human mucoepidermoid carcinoma Mc3 cells. We also investigated the underlying mechanisms of proliferation inhibition that ardipusilloside I exerts on Mc3 cells.

Methods
MTT test was used to detect cell proliferation. Cell apoptosis was detected by transmission electron microscopy, Hoechst-33342 staining, DNA fragmentation detection, and flow cytometry. We also used western blot analysis to detect the potential mechanisms of apoptosis.

Results
Ardipusilloside I affected the viability of Mc3 cells in a dose- and time-dependent manner. The IC50 of ardipusilloside I was approximately 9.98 μg/ml at 48 h of treatment. Characteristic morphological changes of apoptosis, including nuclear condensation, boundary aggregation and splitting, and DNA fragmentation, were seen after treatment with 10 μg/ml ardipusilloside I for 48 h. Western blots demonstrated that ardipusilloside I caused Mc3 cell death through the induction of apoptosis by downregulation of Bcl-2 protein levels and upregulation of Bax and caspase-3 protein levels.

Conclusions
Our results revealed that ardipusilloside I could be a new active substance for mucoepidermoid carcinoma treatment. We demonstrated that the potential mechanism of inhibition might be through the induction of apoptosis by regulation of Bcl-2 family protein levels. This suggests a further rationale for the development of ardipusilloside I as an anti-cancer agent.
Low frequency mechanical actuation accelerates reperfusion in-vitro
Authors: Marzencki Marcin , Kajbafzadeh Behrad , Khosrow-khavar Farzad , Tavakolian Kouhyar , Soleimani-Nouri Maxim , Hamburger Jaap , Kaminska Bozena , Menon Carlo 
Published: November 2013

Abstract

Background
Rapid restoration of vessel patency after acute myocardial infarction is key to reducing myocardial muscle death and increases survival rates. Standard therapies include thrombolysis and direct PTCA. Alternative or adjunctive emergency therapies that could be initiated by minimally trained personnel in the field are of potential clinical benefit. This paper evaluates a method of accelerating reperfusion through application of low frequency mechanical stimulus to the blood carrying vessels.

Materials and method
We consider a stenosed, heparinized flow system with aortic-like pressure variations subject to direct vessel vibration at the occlusion site or vessel deformation proximal and distal to the occlusion site, versus a reference system lacking any form of mechanical stimulus on the vessels.

Results
The experimental results show limited effectiveness of the direct mechanical vibration method and a drastic increase in the patency rate when vessel deformation is induced. For vessel deformation at occlusion site 95% of clots perfused within 11 minutes of application of mechanical stimulus, for vessel deformation 60 centimeters from the occlusion site 95% percent of clots perfused within 16 minutes of stimulus application, while only 2.3% of clots perfused within 20 minutes in the reference system.

Conclusion
The presented in-vitro results suggest that low frequency mechanical actuation applied during the pre-hospitalization phase in patients with acute myocardial infarction have potential of being a simple and efficient adjunct therapy.
Indium-doped ZnO nanowires with infrequent growth orientation, rough surfaces and low-density surface traps
Authors: Duan Hongfeng , He Haiping , Sun Luwei , Song Shiyan , Ye Zhizhen 
Published: November 2013

Abstract
Indium-doped ZnO nanowires have been prepared by vapor transport deposition. With increasing In content, the growth orientation of the nanowires switches from [10

1
_

0] to infrequent [02

2
_

3] and the surface becomes rough. No surface-related exciton emission is observed in these nanowires. The results indicate that large surface-to-volume ratio, high free electron concentration, and low density of surface traps can be achieved simultaneously in ZnO nanowires via In doping. These unique properties make In-doped ZnO nanowire a potential material for photocatalysis application, which is demonstrated by the enhanced photocatalytic degradation of Rhodamine B.
Dual inhibition of HIV-1 replication by integrase-LEDGF allosteric inhibitors is predominant at the post-integration stage
Authors: Le Rouzic Erwann , Bonnard Damien , Chasset Sophie , Bruneau Jean-Michel , Chevreuil Francis , Le Strat Frédéric , Nguyen Juliette , Beauvoir Roxane , Amadori Céline , Brias Julie , Vomscheid Sophie , Eiler Sylvia , Lévy Nicolas , Delelis Olivier , Deprez Eric , Saïb Ali , Zamborlini Alessia , Emiliani Stéphane , Ruff Marc , Ledoussal Benoit , Moreau François , Benarous Richard 
Published: November 2013

Abstract

Background
LEDGF/p75 (LEDGF) is the main cellular cofactor of HIV-1 integrase (IN). It acts as a tethering factor for IN, and targets the integration of HIV in actively transcribed gene regions of chromatin. A recently developed class of IN allosteric inhibitors can inhibit the LEDGF-IN interaction.

Results
We describe a new series of IN-LEDGF allosteric inhibitors, the most active of which is Mut101. We determined the crystal structure of Mut101 in complex with IN and showed that the compound binds to the LEDGF-binding pocket, promoting conformational changes of IN which explain at the atomic level the allosteric effect of the IN/LEDGF interaction inhibitor on IN functions. In vitro, Mut101 inhibited both IN-LEDGF interaction and IN strand transfer activity while enhancing IN-IN interaction. Time of addition experiments indicated that Mut101 behaved as an integration inhibitor. Mut101 was fully active on HIV-1 mutants resistant to INSTIs and other classes of anti-HIV drugs, indicative that this compound has a new mode of action. However, we found that Mut101 also displayed a more potent antiretroviral activity at a post-integration step. Infectivity of viral particles produced in presence of Mut101 was severely decreased. This latter effect also required the binding of the compound to the LEDGF-binding pocket.

Conclusion
Mut101 has dual anti-HIV-1 activity, at integration and post-integration steps of the viral replication cycle, by binding to a unique target on IN (the LEDGF-binding pocket). The post-integration block of HIV-1 replication in virus-producer cells is the mechanism by which Mut101 is most active as an antiretroviral. To explain this difference between Mut101 antiretroviral activity at integration and post-integration stages, we propose the following model: LEDGF is a nuclear, chromatin-bound protein that is absent in the cytoplasm. Therefore, LEDGF can outcompete compound binding to IN in the nucleus of target cells lowering its antiretroviral activity at integration, but not in the cytoplasm where post-integration production of infectious viral particles takes place.
MC3: a steady-state model and constraint consistency checker for biochemical networks
Authors: Yousofshahi Mona , Ullah Ehsan , Stern Russell , Hassoun Soha 
Published: November 2013

Abstract

Background
Stoichiometric models provide a structural framework for analyzing steady-state cellular behavior. Models are developed either through augmentations of existing models or more recently through automatic reconstruction tools. There is currently no standardized practice or method for validating the properties of a model before placing it in the public domain. Considerable effort is often required to understand a model’s inconsistencies before its reuse within new research efforts.

Results
We present a review of common issues in stoichiometric models typically uncovered during pathway analysis and constraint-based optimization, and we detail succinct and efficient ways to find them. We present MC3, Model and Constraint Consistency Checker, a computational tool that can be used for two purposes: (a) identifying potential connectivity and topological issues for a given stoichiometric matrix, S, and (b) flagging issues that arise during constraint-based optimization. The MC3 tool includes three distinct checking components. The first examines the results of computing the basis for the null space for Sv = 0; the second uses connectivity analysis; and the third utilizes Flux Variability Analysis. MC3 takes as input a stoichiometric matrix and flux constraints, and generates a report summarizing issues.

Conclusions
We report the results of applying MC3 to published models for several systems including Escherichia coli, an adipocyte cell, a Chinese Hamster Ovary cell, and Leishmania major. Several issues with no prior documentation are identified. MC3 provides a standalone MATLAB-based comprehensive tool for model validation, a task currently performed either ad hoc or implemented in part within other computational tools.
Ltbp1Lis focally induced in embryonic mammary mesenchyme, demarcates the ductal luminal lineage and is upregulated during involution
Authors: Chandramouli Anupama , Simundza Julia , Pinderhughes Alicia , Hiremath Minoti , Droguett Gustavo , Frendewey David , Cowin Pamela 
Published: November 2013

Abstract
Introduction
Latent TGFβ binding proteins (LTBPs) govern TGFβ presentation and activation and are important for elastogenesis. Although TGFβ is well-known as a tumor suppressor and metastasis promoter, and LTBP1 is elevated in two distinct breast cancer metastasis signatures, LTBPs have not been studied in the normal mammary gland.

Methods
To address this we have examined Ltbp1 promoter activity throughout mammary development using an Ltbp1L-LacZ reporter as well as expression of both Ltbp1L and 1S mRNA and protein by qRT-PCR, immunofluorescence and flow cytometry.

Results
Our data show that Ltbp1L is transcribed coincident with lumen formation, providing a rare marker distinguishing ductal from alveolar luminal lineages. Ltbp1L and Ltbp1S are silent during lactation but robustly induced during involution, peaking at the stage when the remodeling process becomes irreversible. Ltbp1L is also induced within the embryonic mammary mesenchyme and maintained within nipple smooth muscle cells and myofibroblasts. Ltbp1 protein exclusively ensheaths ducts and side branches.

Conclusions
These data show Ltbp1 is transcriptionally regulated in a dynamic manner that is likely to impose significant spatial restriction on TGFβ bioavailability during mammary development. We hypothesize that Ltbp1 functions in a mechanosensory capacity to establish and maintain ductal luminal cell fate, support and detect ductal distension, trigger irreversible involution, and facilitate nipple sphincter function.
Mental health and psychological support in UK armed forces
personnel deployed to Afghanistan in 2010 and 2011
Authors: Jones Norman , Mitchell Paul , Clack John , Fertout Mohammed , Fear Nicola T. , Wessely Simon , Greenberg Neil 
Published: November 2013

BackgroundMost accounts of deployment mental health in UK armed forces personnel
rely on retrospective assessments.AimsWe present data relating to the burden of mental ill health and the
effect of support measures including operational, family, welfare and
medical support obtained on two occasions some 18 months apart.MethodA total of 2794 personnel completed a survey while deployed to
Afghanistan; 1363 in 2011 and 1431 in 2010. Their responses were compared
and contrasted.ResultsThe prevalence of self-report mental health disorder was low and not
significantly different between the surveys; the rates of probable
post-traumatic stress disorder (PTSD) were 2.8% in 2010 and 1.8% in 2011;
for common mental health disorders the rates were 17.0% and 16.0%
respectively. Remembering receiving predeployment psychoeducation,
perceptions of good leadership and good family support were all
significantly associated with better mental health. Seeking support from
non-medical sources and reporting sick for medical reasons were both
significantly associated with poorer mental health.ConclusionsOver a period of 18 months, deployment mental health symptoms in UK armed
forces personnel were fewer than those obtained from a military
population sample despite continuing deployment in a high-threat context
and were associated with perceptions of support.
Variable immune molecules in invertebrates
Authors: Cerenius Lage , Söderhäll Kenneth 
Published: November 2013

Summary
Recently it has become evident that invertebrates may mount a highly variable immune response that is dependent on which pathogen is involved. The molecular mechanisms behind this diversity are beginning to be unravelled and in several invertebrate taxa immune proteins exhibiting a broad range of diversity have been found. In some cases, evidence has been gathered suggesting that this molecular diversity translates into the ability of an affected invertebrate to mount a defence that is specifically aimed at a particular pathogen.
The role of reduced oxygen in the developmental physiology of growth and metamorphosis initiation inDrosophila melanogaster
Authors: Callier Viviane , Shingleton Alexander W. , Brent Colin S. , Ghosh Shampa M. , Kim Jinkyu , Harrison Jon F. 
Published: November 2013

SUMMARYRearing oxygen level is known to affect final body size in a variety of insects, but the physiological mechanisms by which oxygen affects size are incompletely understood. In Manduca sexta and Drosophila melanogaster, the larval size at which metamorphosis is initiated largely determines adult size, and metamorphosis is initiated when larvae attain a critical mass. We hypothesized that oxygen effects on final size might be mediated by oxygen effects on the critical weight and the ecdysone titers, which regulate growth rate and the timing of developmental transitions. Our results showed that oxygen affected critical weight, the basal ecdysone titers and the timing of the ecdysone peak, providing clear evidence that oxygen affected growth rate and developmental rate. Hypoxic third instar larvae (10% oxygen) exhibited a reduced critical weight, slower growth rate, delayed pupariation, elevated baseline ecdysone levels and a delayed ecdysone peak that occurred at a lower larval mass. Hyperoxic larvae exhibited increased basal ecdysone levels, but no change in critical weight compared with normoxic larvae and no significant change in timing of pupariation. Previous studies have shown that nutrition is crucial for regulating growth rate and the timing of developmental transitions. Here we show that oxygen level is one of multiple cues that together regulate adult size and the timing and dynamics of growth, developmental rate and ecdysone signaling.
Synthesis and Magnetic Properties of Nitronyl Nitroxides with an Adjacent Chiral Group
Authors: Tanimoto Ryu , Suzuki Shuichi , Kozaki Masatoshi , Shiomi Daisuke , Sato Kazunobu , Takui Takeji , Okada Keiji 
Published: November 2013

Abstract
We have designed and synthesized chiral molecules with nitronyl nitroxide (NN) radicals directly bound to the chiral centers, (S)-1,3-dioxolane-4-NN (1) and (R)-oxazolidine-4-NN (2). These radicals were synthesized from d-mannitol in four steps for 1 and from l-serine in six steps for 2 in moderate yields. They were characterized by means of mass spectrometry, electron spin resonance, elemental analyses, and X-ray crystal structure analyses. Their magnetic properties were also investigated using a SQUID magnetometer. The temperature dependence of paramagnetic susceptibility (χp) indicates the presence of a weak antiferromagnetic intermolecular interaction with J/kB = −3.1 K and θ = −5.5 K for 1, and a weak ferromagnetic intermolecular interaction with J/kB = +0.5 K for 2. We also succeeded in preparing the metal complex [Mn(hfac)2(2)]2–[Cu(hfac)2], which was characterized by a strong antiferromagnetic interaction (J/kB = −140 K) between [Mn(hfac)2] and 2 along with a much weaker antiferromagnetic interaction (J/kB = −0.11 K) between the [Mn(hfac)2(2)] unit and [Cu(hfac)2].
Large Pseudocapacitance in Quinone-Functionalized Zeolite-Templated Carbon
Authors: Itoi Hiroyuki , Nishihara Hirotomo , Ishii Takafumi , Nueangnoraj Khanin , Berenguer-Betrián Raúl , Kyotani Takashi 
Published: November 2013

Abstract
Zeolite-templated carbon (ZTC), which can be obtained as a negative replica of a zeolite, consists of buckybowl-like nanographenes assembled into a three-dimensional regular network. ZTC is characterized not only by this unique framework structure but also by a very large number of carbon edge sites. In this paper, we report that the edge sites of ZTC are easily functionalized by a large amount of quinone groups through electrochemical oxidation unlike general carbonaceous materials, and the quinone-functionalized ZTC shows a high electrochemical capacitance (ca. 300–500 F g−1) in an aqueous electrolyte solution (1 M H2SO4) as a result of the large pseudocapacitance derived from a quinone/hydroquinone redox couple. Moreover, ZTC keeps its high capacitance even after thousands of charge–discharge cycles.
Thousands of exon skipping events differentiate among splicing patterns in sixteen human tissues
Authors: Florea Liliana , Song Li , Salzberg Steven L 
Published: November 2013

Alternative splicing is widely recognized for its roles in regulating genes and creating gene diversity. However, despite many efforts, the repertoire of gene splicing variation is still incompletely characterized, even in humans. Here we describe a new computational system, ASprofile, and its application to RNA-seq data from Illumina’s Human Body Map project (>2.5 billion reads). Using the system, we identified putative alternative splicing events in 16 different human tissues, which provide a dynamic picture of splicing variation across the tissues. We detected 26,989 potential exon skipping events representing differences in splicing patterns among the tissues. A large proportion of the events (>60%) were novel, involving new exons (~3000), new introns (~16000), or both. When tracing these events across the sixteen tissues, only a small number (4-7%) appeared to be differentially expressed (‘switched’) between two tissues, while 30-45% showed little variation, and the remaining 50-65% were not present in one or both tissues compared. Novel exon skipping events appeared to be slightly less variable than known events, but were more tissue-specific. Our study represents the first effort to build a comprehensive catalog of alternative splicing in normal human tissues from RNA-seq data, while providing insights into the role of alternative splicing in shaping tissue transcriptome differences. The catalog of events and the ASprofile software are freely available from the Zenodo repository(http://zenodo.org/record/7068; doi:10.5281/zenodo.7068) and from our web site http://ccb.jhu.edu/software/ASprofile.