bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome and management in neonatal thrombocytopenia due to maternal idiopathic thrombocytopenic purpura
Authors: van der Lugt N. M. , van Kampen A. , Walther F. J. , Brand A. , Lopriore E. 
Published: June 2013

Background and ObjectivesPregnant women with Idiopathic thrombocytopenic purpura (ITP) can deliver neonates with severe thrombocytopenia. Clear evidence declaring the pathophysiological cause of this neonatal thrombocytopenia is lacking, as antiplatelet antibodies are not always detectable in maternal serum. Severe neonatal thrombocytopenia below 50 × 109/l is reported in 8–13% of the neonates from mothers with ITP and intracranial haemorrhage (ICH) in 0–2·9%. Evidence about the optimal postnatal treatment is scarce. Our objective was to evaluate the outcome and management in neonates with passive ITP.Materials and MethodsAll neonates from mothers with ITP born between 1980 and 2011 were included. Platelet counts during the first 10 days, presence of ICH and postnatal treatment were recorded. Maternal characteristics were analysed as possible risk factors for severe neonatal thrombocytopenia.ResultsSixty‐seven neonates were included. Severe thrombocytopenia (<50 × 109/l) occurred in 20/67 (29·9%) neonates. In three neonates, platelet count rose spontaneously, 18 neonates were treated (one with persistent moderate thrombocytopenia) with the following: platelet transfusions (3), prednisone (2), intravenous immunoglobulin (IVIG) (1), platelet transfusions and IVIG (11), platelet transfusion and prednisone (1). Recurrence of low platelet counts after transfusions was commonly seen. Risk factors for severe neonatal thrombocytopenia were a previous sibling with severe thrombocytopenia and low maternal platelet nadir during pregnancy.ConclusionIn this cohort, severe neonatal thrombocytopenia occurs more frequently than previously reported. To maintain a platelet count above 50 × 109/l, often multiple transfusions and IVIG are required. Multiple transfusions may be avoided by starting IVIG, when platelet count falls below 50 × 109/l after the first platelet transfusion.
Occurrence, Virulence Genes and Antibiotic Resistance of Enteropathogenic Escherichia coli (EPEC) from Twelve Bovine Farms in the North‐East of Ireland
Authors: Bolton D. J. , Ennis C. , McDowell D. 
Published: June 2013

SummaryCattle faecal samples (n = 480) were collected from a cluster of 12 farms, and PCR screened for the presence of the intimin gene (eae). Positive samples were cultured, and colonies were examined for the presence of eae and verocytotoxin (vtx) genes. Colonies which were positive for the intimin gene and negative for the verocytotoxin genes were further screened using PCR for a range of virulence factors including bfpA, espA, espB, tir ehxA, toxB, etpD, katP, saa, iha, lpfAO157/OI‐141 and lpfAO157/OI‐154. Of the 480 faecal samples, 5.8% (28/480) were PCR positive, and one isolate was obtained from each. All 28 isolates obtained were bfpA negative and therefore atypical EPEC (aEPEC). The serotypes detected included O2:H27, O8:H36, O15:H2, O49:H+, O84:H28, O105:H7 and O132:H34 but half of the isolates could not be serogrouped using currently available antisera. Twenty‐two (79%) of the isolates carried the tir gene but only 25% were espB positive, and all other virulence genes tested for were scarce or absent. Several isolates showed intermediate resistance to ciprofloxacin, kanamycin, nalidixic acid, minocycline and tetracycline; full resistance to nalidixic acid or tetracycline with one isolate (O−:H8) displaying resistance to aminoglycosides (kanamycin and streptomycin), quinolones (nalidixic acid) and sulphonamides. This study provides further evidence that cattle are a potential source of aEPEC and add to the very limited data currently available on virulence genes and antibiotic resistance in this pathogenic E. coli group in animals.
Fighting Rabies in Eastern Europe, the Middle East and Central Asia ‐ Experts Call for a Regional Initiative for Rabies Elimination
Authors: Aikimbayev A. , Briggs D. , Coltan G. , Dodet B. , Farahtaj F. , Imnadze P. , Korejwo J. , Moiseieva A. , Tordo N. , Usluer G. , Vodopija R. , Vranješ N. 
Published: June 2013

SummaryMEEREB is an informal network of rabies experts from the Middle East, Eastern Europe and Central Asia, seeking to eliminate rabies from the region. They met for the second time to review the current rabies situation, both globally and in their respective countries, highlighting current rabies control problems and potential solutions. Success stories in Latin America, in Western Europe, in some Asian countries, as well as in Croatia and Serbia prove that elimination of human rabies is achievable in the MEEREB region. It requires political willingness and cooperation of all stakeholders, including Ministries of Health and of Agriculture; adequate management of animal bites through post‐exposure prophylaxis; pre‐exposure prophylaxis for populations at high risk of rabies exposure, animal vaccination and humane control of stray dog populations. MEEREB members called for a regional initiative for rabies elimination in Eastern Europe and the Middle East. They are confident that the elimination of human rabies of canine origin can be achieved in the region through adopting a One Health approach, and that campaigns for rabies elimination will have significant benefit for public health, including strengthening the structure for control of other zoonoses.
The arc space of horospherical varieties and motivic integration
Authors: Batyrev Victor , Moreau Anne 
Published: June 2013

AbstractFor an arbitrary connected reductive group $G$, we consider the motivic integral over the arc space of an arbitrary $ \mathbb{Q} $-Gorenstein horospherical $G$-variety ${X}_{\Sigma } $ associated with a colored fan $\Sigma $ and prove a formula for the stringy $E$-function of ${X}_{\Sigma } $ which generalizes the one for toric varieties. We remark that, in contrast to toric varieties, the stringy $E$-function of a Gorenstein horospherical variety ${X}_{\Sigma } $ may be not a polynomial if some cones in $\Sigma $ have nonempty sets of colors. Using the stringy $E$-function, we can formulate and prove a new smoothness criterion for locally factorial horospherical varieties. We expect that this smoothness criterion holds for arbitrary spherical varieties.
Metaproteomics Reveals Abundant Transposase Expression in Mutualistic Endosymbionts
Authors: Kleiner Manuel , Young Jacque C. , Shah Manesh , VerBerkmoes Nathan C. , Dubilier Nicole 
Published: June 2013

ABSTRACT

Transposases, enzymes that catalyze the movement of mobile genetic elements, are the most abundant genes in nature. While many bacteria encode an abundance of transposases in their genomes, the current paradigm is that the expression of transposase genes is tightly regulated and generally low due to its severe mutagenic effects. In the current study, we detected the highest number of transposase proteins ever reported in bacteria, in symbionts of the gutless marine worm
Olavius algarvensis
with metaproteomics. At least 26 different transposases from 12 different families were detected, and genomic and proteomic analyses suggest that many of these are active. This high expression of transposases indicates that the mechanisms for their tight regulation have been disabled or no longer exist.

IMPORTANCE
The expansion of transposable elements (TE) within the genomes of host-restricted symbionts and pathogens plays an important role in their emergence and evolution and might be a key mechanism for adaptation to the host environment. However, little is known so far about the underlying causes and evolutionary mechanisms of this TE expansion. The current model of genome evolution in host-restricted bacteria explains TE expansion within the confines of the paradigm that transposase expression is always low. However, recent work failed to verify this model. Based on our data, we hypothesize that increased transposase expression, which has not previously been described, may play a role in TE expansion, and could be one explanation for the sometimes very rapid emergence and evolution of new obligate symbionts and pathogens from facultative ones.
Mutations in the IMD Pathway and Mustard Counter Vibrio cholerae Suppression of Intestinal Stem Cell Division in
Drosophila
Authors: Wang Zhipeng , Hang Saiyu , Purdy Alexandra E. , Watnick Paula I. 
Published: June 2013

ABSTRACT

Vibrio cholerae
is an estuarine bacterium and an intestinal pathogen of humans that causes severe epidemic diarrhea. In the absence of adequate mammalian models in which to study the interaction of
V. cholerae
with the host intestinal innate immune system, we have implemented
Drosophila melanogaster
as a surrogate host. We previously showed that immune deficiency pathway loss-of-function and
mustard
gain-of-function mutants are less susceptible to
V. cholerae
infection. We find that although the overall burden of intestinal bacteria is not significantly different from that of control flies, intestinal stem cell (ISC) division is increased in these mutants. This led us to examine the effect of
V. cholerae
on ISC division. We report that
V. cholerae
infection and cholera toxin decrease ISC division. Because IMD pathway and Mustard mutants, which are resistant to
V. cholerae
, maintain higher levels of ISC division during
V. cholerae
infection, we hypothesize that suppression of ISC division is a virulence strategy of
V. cholerae
and that accelerated epithelial regeneration protects the host against
V. cholerae
. Extension of these findings to mammals awaits the development of an adequate experimental model.

IMPORTANCE
Here we show that
Vibrio cholerae
and cholera toxin suppress intestinal stem cell (ISC) division. This is the first evidence of manipulation of ISC division by
V. cholerae
and demonstrates the utility of the
Drosophila
model in generating novel hypotheses regarding the interaction of
V. cholerae
with the intestinal epithelium. Furthermore, we add to the body of data suggesting that the IMD pathway and the Mustard protein modulate ISC division independently of the overall load of commensal intestinal bacteria.
A Short Hairpin RNA Screen of Interferon-Stimulated Genes Identifies a Novel Negative Regulator of the Cellular Antiviral Response
Authors: Li Jianqing , Ding Steve C. , Cho Hyelim , Chung Brian C. , Gale Michael , Chanda Sumit K. , Diamond Michael S. 
Published: June 2013

ABSTRACT

The type I interferon (IFN) signaling pathway restricts infection of many divergent families of RNA and DNA viruses by inducing hundreds of IFN-stimulated genes (ISGs), some of which have direct antiviral activity. We screened 813 short hairpin RNA (shRNA) constructs targeting 245 human ISGs using a flow cytometry approach to identify genes that modulated infection of West Nile virus (WNV) in IFN-β-treated human cells. Thirty ISGs with inhibitory effects against WNV were identified, including several novel genes that had antiviral activity against related and unrelated positive-strand RNA viruses. We also defined one ISG, activating signal cointegrator complex 3 (
ASCC3
), which functioned as a negative regulator of the host defense response. Silencing of
ASCC3
resulted in upregulation of multiple antiviral ISGs, which correlated with inhibition of infection of several positive-strand RNA viruses. Reciprocally, ectopic expression of human
ASCC3
or mouse
Ascc3
resulted in downregulation of ISGs and increased viral infection. Mechanism-of-action and RNA sequencing studies revealed that
ASCC3
functions to modulate ISG expression in an IRF-3- and IRF-7-dependent manner. Compared to prior ectopic ISG expression studies, our shRNA screen identified novel ISGs that restrict infection of WNV and other viruses and defined a new counterregulatory ISG,
ASCC3
, which tempers cell-intrinsic immunity.

IMPORTANCE
West Nile virus (WNV) is a mosquito-transmitted virus that continues to pose a threat to public health. Innate immune responses, especially those downstream of type I interferon (IFN) signaling, are critical for controlling virus infection and spread. We performed a genetic screen using a gene silencing approach and identified 30 interferon-stimulated genes (ISGs) that contributed to the host antiviral response against WNV. As part of this screen, we also identified a novel negative regulatory protein, ASCC3, which dampens expression of ISGs, including those with antiviral or proinflammatory activity. In summary, our studies define a series of heretofore-uncharacterized ISGs with antiviral effects against multiple viruses or counterregulatory effects that temper IFN signaling and likely minimize immune-mediated pathology.
Determining the wounding effects of ballistic projectiles to inform future injury models: a systematic review
Authors: Breeze John , Sedman A J , James G R , Newbery T W , Hepper A E 
Published: June 2013

IntroductionPenetrating wounds from explosively propelled fragments and bullets are the most common causes of combat injury experienced by UK service personnel on current operations. There is a requirement for injury models capable of simulating such a threat in order to optimise body armour design.MethodA systematic review of the open literature was undertaken using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. Original papers describing the injurious effects of projectiles on skin, bone, muscle, large vessels and nerves were identified.ResultsProjectiles injure these tissues by producing a permanent wound tract (PWT), comprised of a central permanent wound cavity, in conjunction with a zone of irreversible macroscopic tissue damage laterally. The primary mechanism of injury was the crushing and cutting effect of the presented surface of the projectile, with an additional smaller component due to macroscopic damage produced by the radial tissue displacement from the temporary tissue cavity (TTC). No conclusive evidence could be found for permanent pathological effects produced by the pressure wave or that any microscopic tissue changes due to the TTC (in the absence of visible macroscopic damage) led to permanent injury.DiscussionInjury models should use the PWT to delineate the area of damage to tissues from penetrating ballistic projectiles. The PWT, or its individual components, will require quantification in terms of the amount of damage produced by different projectiles penetrating these tissues. There is a lack of information qualifying the injurious effect of the temporary cavity, particularly in relation to that caused by explosive fragments, and future models should introduce modularity to potentially enable incorporation of these mechanisms at a later date were they found to be significant.
Nyamulagira’s magma plumbing system inferred from 15 years of InSAR
Authors: Wauthier C. , Cayol V. , Poland M. , Kervyn F. , d’Oreye N. , Hooper A. , Samsonov S. , Tiampo K. , Smets B. 
Published: June 2013

Abstract

Nyamulagira, located in the east of the Democratic Republic of Congo on the western branch of the East African rift, is Africa’s most active volcano, with an average of one eruption every 3 years since 1938. Owing to the socio-economical context of that region, the volcano lacks ground-based geodetic measurements but has been monitored by interferometric synthetic aperture radar (InSAR) since 1996. A combination of 3D Mixed Boundary Element Method and inverse modelling, taking into account topography and source interactions, is used to interpret InSAR ground displacements associated with eruptive activity in 1996, 2002, 2004, 2006 and 2010. These eruptions can be fitted by models incorporating dyke intrusions, and some (namely the 2006 and 2010 eruptions) require a magma reservoir beneath the summit caldera. We investigate inter-eruptive deformation with a multi-temporal InSAR approach. We propose the following magma plumbing system at Nyamulagira by integrating numerical deformation models with other available data: a deep reservoir (
c
. 25 km depth) feeds a shallower reservoir (
c
. 4 km depth); proximal eruptions are fed from the shallow reservoir through dykes while distal eruptions can be fed directly from the deep reservoir. A dyke-like conduit is also present beneath the upper southeastern flank of Nyamulagira.
Combined Alloreactive CTL Cellular Therapy with Prodrug Activator Gene Therapy in a Model of Breast Cancer Metastatic to the Brain
Authors: Hickey Michelle J. , Malone Colin C. , Erickson Kate L. , Lin Amy , Soto Horacio , Ha Edward T. , Kamijima Shuichi , Inagaki Akihito , Takahashi Masamichi , Kato Yuki , Kasahara Noriyuki , Mueller Barbara M. , Kruse Carol A. 
Published: June 2013

AbstractPurpose: Individual or combined strategies of cellular therapy with alloreactive CTLs (alloCTL) and gene therapy using retroviral replicating vectors (RRV) encoding a suicide prodrug activating gene were explored for the treatment of breast tumors metastatic to the brain.Experimental Design: AlloCTL, sensitized to the HLA of MDA-MB-231 breast cancer cells, were examined in vitro for antitumor functionality toward breast cancer targets. RRV encoding the yeast cytosine deaminase (CD) gene was tested in vivo for virus spread, ability to infect, and kill breast cancer targets when exposed to 5-fluorocytosine (5-FC). Individual and combination treatments were tested in subcutaneous and intracranial xenograft models with 231BR, a brain tropic variant.Results: AlloCTL preparations were cytotoxic, proliferated, and produced IFN-γ when coincubated with target cells displaying relevant HLA. In vivo, intratumorally placed alloCTL trafficked through one established intracranial 231BR focus to another in contralateral brain and induced tumor cell apoptosis. RRV-CD efficiently spread in vivo, infected 231BR and induced their apoptosis upon 5-FC exposure. Subcutaneous tumor volumes were significantly reduced in alloCTL and/or gene therapy–treated groups compared to control groups. Mice with established intracranial 231BR tumors treated with combined alloCTL and RRV-CD had a median survival of 97.5 days compared with single modalities (50–83 days); all experimental treatment groups survived significantly longer than sham-treated groups (median survivals 31.5 or 40 days) and exhibited good safety/toxicity profiles.Conclusion: The results indicate combining cellular and suicide gene therapies is a viable strategy for the treatment of established breast tumors in the brain. Clin Cancer Res; 19(15); 4137–48. ©2013 AACR.
Predicting Drug Responsiveness in Human Cancers Using Genetically Engineered Mice
Authors: Usary Jerry , Zhao Wei , Darr David , Roberts Patrick J. , Liu Mei , Balletta Lorraine , Karginova Olga , Jordan Jamie , Combest Austin , Bridges Arlene , Prat Aleix , Cheang Maggie C. U. , Herschkowitz Jason I. , Rosen Jeffrey M. , Zamboni William , Sharpless Norman E. , Perou Charles M. 
Published: June 2013

Abstract
Purpose: To use genetically engineered mouse models (GEMM) and orthotopic syngeneic murine transplants (OST) to develop gene expression-based predictors of response to anticancer drugs in human tumors. These mouse models offer advantages including precise genetics and an intact microenvironment/immune system.
Experimental Design: We examined the efficacy of 4 chemotherapeutic or targeted anticancer drugs, alone and in combination, using mouse models representing 3 distinct breast cancer subtypes: Basal-like (C3(1)-T-antigen GEMM), Luminal B (MMTV-Neu GEMM), and Claudin-low (T11/TP53−/− OST). We expression-profiled tumors to develop signatures that corresponded to treatment and response, and then tested their predictive potential using human patient data.
Results: Although a single agent exhibited exceptional efficacy (i.e., lapatinib in the Neu-driven model), generally single-agent activity was modest, whereas some combination therapies were more active and life prolonging. Through analysis of RNA expression in this large set of chemotherapy-treated murine tumors, we identified a pair of gene expression signatures that predicted pathologic complete response to neoadjuvant anthracycline/taxane therapy in human patients with breast cancer.
Conclusions: These results show that murine-derived gene signatures can predict response even after accounting for common clinical variables and other predictive genomic signatures, suggesting that mice can be used to identify new biomarkers for human patients with cancer. Clin Cancer Res; 19(17); 4889–99. ©2013 AACR.
Apoptotic Circulating Tumor Cells in Early and Metastatic Breast Cancer Patients
Authors: Kallergi Galatea , Konstantinidis Georgios , Markomanolaki Harris , Papadaki Maria A. , Mavroudis Dimitris , Stournaras Christos , Georgoulias Vassilis , Agelaki Sofia 
Published: June 2013

Abstract
The detection of circulating tumor cells (CTC) in breast cancer is strongly associated with disease relapse. Since it is unclear whether all CTCs are capable of generating metastasis, we investigated their apoptotic and proliferative status in 56 CTC-positive (29 early and 27 metastatic) patients with breast cancer. Double-staining immunofluorescence experiments were carried out in peripheral blood mononuclear cells (PBMC) cytospins, using the pancytokeratin A45-B/B3 antibody and either M30 (apoptotic marker) or Ki67 (proliferation marker) antibodies. Apoptosis was also evaluated using a polycaspase detection kit. Patients with metastatic disease had significantly lower numbers of apoptotic CTCs compared with patients with early breast cancer (polycaspase kit: 8.1% vs. 47.4% of the total CTC number; P = 0.0001; M30-antibody: 32.1% vs. 76.63%; P = 0.002). The median percentage of apoptotic CTCs per patient was also lower in patients with advanced compared with those with early disease (polycaspase kit: 0% vs. 53.6%; M30-antibody: 15% vs. 80%). Ki67-positive CTCs were identified in 51.7% and 44% of patients with early and metastatic disease, respectively. Adjuvant chemotherapy reduced both the number of CTCs per patient and the number of proliferating CTCs (63.9% vs. 30%). In conclusion, apoptotic CTCs could be detected in patients with breast cancer irrespective of their clinical status, though the incidence of detection is higher in early compared with metastatic patients. The detection of CTCs that survive despite adjuvant therapy implies that CTC elimination should be attempted using agents targeting their distinctive molecular characteristics. Mol Cancer Ther; 12(9); 1886–95. ©2013 AACR.