bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Mixture of Functionally Oligoclonal Humanized Monoclonal Antibodies That Neutralize Clostridium difficile TcdA and TcdB with High Levels ofIn VitroPotency ShowsIn VivoProtection in a Hamster Infection Model
Authors: Davies Nicola L. , Compson Joanne E. , MacKenzie Brendon , O'Dowd Victoria L. , Oxbrow Amanda K. F. , Heads James T. , Turner Alison , Sarkar Kaushik , Dugdale Sarah L. , Jairaj Mark , Christodoulou Louis , Knight David E. O. , Cross Amanda S. , Hervé Karine J. M. , Tyson Kerry L. , Hailu Hanna , Doyle Carl B. , Ellis Mark , Kriek Marco , Cox Matthew , Page Matthew J. T. , Moore Adrian R. , Lightwood Daniel J. , Humphreys David P. 
Published: January 2013

ABSTRACTClostridium difficileinfections are a major cause of antibiotic-associated diarrhea in hospital and care facility patients. In spite of the availability of effective antibiotic treatments,C. difficileinfection (CDI) is still a major cause of patient suffering, death, and substantial health care costs.Clostridium difficileexerts its major pathological effects through the actions of two protein exotoxins, TcdA and TcdB, which bind to and disrupt gut tissue. Antibiotics target the infecting bacteria but not the exotoxins. Administering neutralizing antibodies against TcdA and TcdB to patients receiving antibiotic treatment might modulate the effects of the exotoxins directly. We have developed a mixture of three humanized IgG1 monoclonal antibodies (MAbs) which neutralize TcdA and TcdB to address three clinical needs: reduction of the severity and duration of diarrhea, reduction of death rates, and reduction of the rate of recurrence. The UCB MAb mixture showed higher potency in a variety ofin vitrobinding and neutralization assays (∼10-fold improvements), higher levels of protection in a hamster model of CDI (82% versus 18% at 28 days), and higher valencies of toxin binding (12 versus 2 for TcdA and 3 versus 2 for TcdB) than other agents in clinical development. Comparisons of the MAb properties also offered some insight into the potential relative importance of TcdA and TcdB in the disease process.
Performance of a Rapid Self-Test for Detection of Trichomonas vaginalis in South Africa and Brazil
Authors: Jones Heidi E. , Lippman Sheri A. , Caiaffa-Filho Helio H. , Young Taryn , van de Wijgert Janneke H. H. M. 
Published: January 2013

ABSTRACT

Women participating in studies in Brazil (
n
= 695) and South Africa (
n
= 230) performed rapid point-of-care tests for
Trichomonas vaginalis
on self-collected vaginal swabs. Using PCR as the gold standard, rapid self-testing achieved high specificity (99.1%; 95% confidence interval [CI], 98.2 to 99.6%) and moderate sensitivity (76.7%; 95% CI, 61.4 to 88.2%). These tests may be considered an alternative to syndromic management in resource-poor settings.
Towards a Molecular Definition of Enterohemorrhagic Escherichia coli (EHEC): Detection of Genes Located on O Island 57 as Markers To Distinguish EHEC from Closely Related Enteropathogenic E. coli Strains
Authors: Delannoy Sabine , Beutin Lothar , Fach Patrick 
Published: January 2013

ABSTRACT

Among strains of Shiga-toxin (Stx) producing
Escherichia coli
(STEC), seven serogroups (O26, O45, O103, O111, O121, O145, and O157) are associated with severe clinical illness in humans. These strains are also called enterohemorrhagic
E. coli
(EHEC), and the development of methods for their reliable detection from food has been challenging thus far. PCR detection of major EHEC virulence genes
stx
1
,
stx
2
,
eae
, and O-serogroup-specific genes is useful but does not identify EHEC strains specifically. Searching for the presence of additional genes issued from
E. coli
O157:H7 genomic islands OI-122 and OI-71 increases the specificity but does not clearly discriminate EHEC from enteropathogenic
E. coli
(EPEC) strains. Here, we identified two putative genes, called Z2098 and Z2099, from the genomic island OI-57 that were closely associated with EHEC and their
stx
-negative derivative strains (87% for Z2098 and 91% for Z2099). Z2098 and Z2099 were rarely found in EPEC (10% for Z2098 and 12% for Z2099), STEC (2 and 15%), and apathogenic
E. coli
(1% each) strains. Our findings indicate that Z2098 and Z2099 are useful genetic markers for a more targeted diagnosis of typical EHEC and new emerging EHEC strains.
Cyclophilin A-Dependent Restriction to Capsid N121K Mutant Human Immunodeficiency Virus Type 1 in a Broad Range of Cell Lines
Authors: Takemura Taichiro , Kawamata Miyako , Urabe Miho , Murakami Tsutomu 
Published: January 2013

ABSTRACT
Human immunodeficiency virus type 1 (HIV-1) infection of most human cells is dependent on cyclophilin A (CypA); however, the opposite phenomenon, known as CypA-dependent inhibition, is also observed in the combination of some capsid (CA) mutations and cell lines. Here, we identified a CA N121K mutant whose infection of 293T, Jurkat, and HeLa cells was impaired by CypA. The N121K mutant could be a useful tool for analyzing the mechanisms underlying CypA-dependent restriction.
Similar Patterns of Infection with Bovine Foamy Virus in Experimentally Inoculated Calves and Sheep
Authors: Materniak Magdalena , Hechler Torsten , Löchelt Martin , Kuźmak Jacek 
Published: January 2013

ABSTRACT

Foamy viruses (FVs) are the least known retroviruses commonly found in primates, cats, horses, and cattle. Although FVs are considered apathogenic, simian and feline FVs have been shown to be associated with some transient health abnormalities in animal models. Currently, data regarding the course of infection with bovine FV (BFV) are not available. In this study, we conducted experimental infections of natural (cattle) and heterologous (sheep) hosts with the BFV
100
isolate and monitored infection patterns in both hosts during the early phase postinoculation as well as after long-term infection. Four calves and six sheep inoculated with BFV
100
showed no signs of pathology but developed persistent infection, as confirmed by virus rescue, consistent detection of BFV-specific antibodies, and presence of viral DNA. In both hosts, antibodies against BFV Gag and Bet appeared early after infection and persisted at high and stable levels while seroreactivity toward Env was consistently detectable only in BFV-infected sheep. Interestingly, the BFV proviral DNA load was highest in lung, spleen, and liver and moderate in leukocytes, while salivary glands contained either low or undetectable DNA loads in calves or sheep, respectively. Additionally, comparison of partial BFV sequences from inoculum and infected animals demonstrated very limited changes after long-term infection in the heterologous host, clearly less than those found in BFV field isolates. The persistence of BFV infection in both hosts suggests full replication competence of the BFV
100
isolate with no requirement of genetic adaptation for productive replication in the authentic and even in a heterologous host.
Is the TAM Receptor Axl a Receptor for Lymphocytic Choriomeningitis Virus?
Authors: Sullivan Brian M. , Welch Megan J. , Lemke Greg , Oldstone Michael B. A. 
Published: January 2013

ABSTRACT

A recent publication indicated that overexpression of Axl, a cellular receptor that negatively regulates Toll-like receptor signaling, enhanced the entry of viruses pseudotyped with the glycoprotein of lymphocytic choriomeningitis virus (LCMV)
in vitro
. In testing the biological relevance of these observations, we found differences in neither viral kinetics between LCMV infections of
Axl
−/−
and wild-type mice nor T-cell responses prior to spontaneous viral clearance. Thus, Axl is not required for productive LCMV infection of mice.
A Key Interaction between the Alphavirus Envelope Proteins Responsible for Initial Dimer Dissociation during Fusion
Authors: Fields Whitney , Kielian Margaret 
Published: January 2013

ABSTRACT
Alphaviruses such as Semliki Forest virus (SFV) are enveloped viruses whose surface is covered by an organized lattice composed of trimers of E2-E1 heterodimers. The E1 envelope protein, a class II fusion protein, contains the hydrophobic fusion loop and refolds to drive virus fusion with the endosome membrane. The E2 protein is synthesized as a precursor p62, whose processing by furin primes the heterodimer for dissociation during virus entry. Dissociation of the E2-E1 heterodimer is an essential step during low-pH-triggered fusion, while the dissociation of the immature p62-E1 dimer is relatively pH resistant. Previous structural studies described an “acid-sensitive region” in E2 that becomes disordered at low pH. Within this region, the conserved E2 H170 is in position to form a hydrogen bond with the underlying E1 S57. Here we experimentally tested the role of this interaction in regulating dimer dissociation in mature and immature virus. Alanine substitutions of E1 S57 and E2 H170 destabilized the heterodimer and produced a higher pH threshold for exposure of the E1 fusion loop and for fusion of the immature virus. E1 S57K or S57D mutations were lethal and caused transport and assembly defects that were partially abrogated by neutralization of the exocytic pathway. The lethal phenotype of E1 S57K was rescued by second-site mutations at E2 H170/M171. Together, our results define a key role for the E1 S57-E2 H170 interaction in dimer stability and the pH dependence of fusion and provide evidence for stepwise dissociation of the E2-E1 dimer at low pH.
Water is a safe and effective alternative to sterile normal saline for wound irrigation prior to suturing: a prospective, double-blind, randomised, controlled clinical trial
Authors: Weiss Eric Alan , Oldham George , Lin Michelle , Foster Tammy , Quinn James Victor 
Published: January 2013

ObjectiveTo determine if there is a significant difference in the infection rates of wounds irrigated with sterile normal saline (SS) versus tap water (TW), before primary wound closure.DesignSingle centre, prospective, randomised, double-blind controlled trial. Wound irrigation solution type was computer randomised and allocation was done on a sequential basis.SettingStanford University Medical Center Department of Emergency Medicine.ParticipantsPatients older than 1 year of age, who presented to the emergency department with a soft tissue laceration requiring repair, were entered into the study under informed consent. Exclusion criteria included any underlying immunocompromising illness, current use of antibiotics, puncture or bite wounds, underlying tendon or bone involvement, or wounds more than 9 h old.InterventionsNon-caregivers used a computer generated randomisation code to prepare irrigation basins prior to treatment. Patients had their wounds irrigated either with TW or SS prior to closure, controlling for the volume and irrigation method used. The patient, the treating physician and the physician checking the wound for infection were all blind regarding solution type. Structured follow-up was completed at 48 h and 30 days to determine the presence of infection.Main outcome measuresThe primary outcome measured was the difference in wound infection rates between the two randomised groups.ResultsDuring the 18-month study period, 663 consecutive patients were enrolled. After enrolment, 32 patients were later excluded; 29 patients because they were concurrently on antibiotics; two patients secondary to steroid use and one because of tendon involvement. Of the 631 remaining patients, 318 were randomised into the TW group and 313 into the SS group. Six patients were lost to follow-up (5 SS, 1 TW). A total of 625 patients were included in the statistical analysis. There were no differences in the demographic and clinical characteristics of the two groups. There were 20 infections 6.4% (95% CI 9.1% to 3.7%) in the SS group compared with 11 infections 3.5% (95% CI 5.5% to 1.5%) in the TW group, a difference of 2.9% (95% CI −0.4% to 5.7%).ConclusionsThere is no difference in the infection rate of wounds irrigated with either TW or SS solution, with a clinical trend towards fewer wound infections in the TW group, making it a safe and cost-effective alternative to SS for wound irrigation.
Massively Parallel Tumor Multigene Sequencing to Evaluate Response to Panitumumab in a Randomized Phase III Study of Metastatic Colorectal Cancer
Authors: Peeters Marc , Oliner Kelly S. , Parker Alex , Siena Salvatore , Van Cutsem Eric , Huang Jing , Humblet Yves , Van Laethem Jean-Luc , André Thierry , Wiezorek Jeffrey , Reese David , Patterson Scott D. 
Published: January 2013

Abstract
Purpose: To investigate whether EGF receptor (EGFR) pathway mutations predicted response to monotherapy with panitumumab, an anti-EGFR monoclonal antibody, in a randomized phase III study of metastatic colorectal cancer.
Experimental Design: Using massively parallel multigene sequencing, we analyzed 320 samples for 9 genes, with multigene sequence data from 288 (90%) samples.
Results: Mutation rates were: KRAS (45%), NRAS (5%), BRAF (7%), PIK3CA (9%), PTEN (6%), TP53 (60%), EGFR (1%), AKT1 (&lt;1%), and CTNNB1 (2%). In the randomized study and open-label extension, 22 of 138 (16%) wild-type KRAS (codons 12/13/61) patients versus 0 of 103 mutant KRAS (codons 12/13) patients had objective responses. Of 6 mutant KRAS (codon 61) patients, 1 with a Q61H mutation achieved partial response during the extension. Among wild-type KRAS (codons 12/13/61) patients, 0 of 9 patients with NRAS mutations, 0 of 13 with BRAF mutations, 2 of 10 with PIK3CA mutations, 1 of 9 with PTEN mutations, and 1 of 2 with CTNNB1 mutations responded to panitumumab. No patients responded to best supportive care alone. Panitumumab treatment was associated with longer progression-free survival (PFS) among wild-type KRAS (codons 12/13/61) patients [HR, 0.39; 95% confidence interval (CI), 0.28–0.56]. Among wild-type KRAS patients, a treatment effect for PFS favoring panitumumab occurred in patients with wild-type NRAS (HR, 0.39; 95% CI, 0.27–0.56) and wild-type BRAF (HR, 0.37; 95% CI, 0.24–0.55) but not mutant NRAS (HR, 1.94; 95% CI, 0.44–8.44).
Conclusions: These results show the feasibility and potential clinical use of next-generation sequencing for evaluating predictive biomarkers. Clin Cancer Res; 19(7); 1902–12. ©2012 AACR.
Desiccation and storage of Panagrolaimus sp. (strain NFS-24-5)
Authors: Honnens Hilke , Assheuer Thomas , Ehlers Ralf-Udo 
Published: January 2013

Panagrolaimus sp. strain NFS-24-5 has potential to be used as live food for early stages of fish and crustacean species in marine aquaculture. One constraint to its commercialisation is the lack of a method that enables storage of nematodes over a longer time span. The objective of this study was to develop a procedure to transfer nematodes into a dormant state by desiccation. The nematodes were concentrated at densities of 25, 50, 100 and 200 × 103 individials cm−2 on nylon net or cellulose paper, preconditioned for 72 h at 97.3% relative humidity (RH) and then stored at 52.9 or 32.8% RH for 1 week. Cellulose was a better carrier for the nematodes. Survival of the nematodes was reduced only at the highest nematode density on both materials. The water activity of desiccated nematodes was 0.44 and 0.33 at 52.9% and 32.8% RH, respectively, well beyond a point to prevent microbial growth. After storage over a period of 10 weeks at 25 × 103 nematodes cm−2 at 52.9 and 32.8% RH, 92% of the nematodes were still alive. Monitoring the size distribution revealed no changes at 52.9% RH, but there were more of the larger nematodes dying at 32.8% RH in two out of three experiments. The method can be used to store quiescent Panagrolaimus sp. (strain NFS-24-5) for transportation and use in small scale feeding experiments for marine fish and crustacean larvae.
The Praefatio (Prologus) Sancti Cyrilli de Paschate and the 437-year (not 418!) Paschal list attributed to Theophilus
Authors: Mosshammer Alden A. 
Published: January 2013

Abstract
The Editio Princeps of the Prologus Sancti Cyrilli de Paschate was published by Denis Petau in 1627 from a manuscript in which the author attributed a 418-year list of dates for Passover and Easter to Theophilus of Alexandria, which the author claimed to have abbreviated to 95 years. Bruno Krusch used two additional manuscripts for his 1880 edition, in which the number attributed to Theophilus is 428. Scholars have argued that 418 must be the correct original number, because 428 is not a multiple of 19. Three previously neglected manuscripts show that the number was originally 437. The author of this text deduced that the 95-year list began approximately 438 years after the birth of Christ and therefore surmised that it was a continuation of a 437-year list that began with Passover in the first year after the Nativity. The 418 years may have been substituted by a redactor who was misled by a postscript that appears in two of the manuscripts.
Five new species of Notosacantha Chevrolat (Coleoptera: Chrysomelidae: Cassidinae) from Borneo, with a key to the Bornean species and new faunistic data
Authors: BOROWIEC LECH , TAKIZAWA HARUO , ŚWIĘTOJAŃSKA JOLANTA 
Published: January 2013

Five new species of Notosacantha are described from Borneo (Sabah): N. flaviventris Borowiec and Takizawa sp. nov. (also described from Sumatra), N. flavosuturata Świętojańska and Takizawa sp. nov., N. minuta Świętojańska and Takizawa sp. nov., N. obscuricornis Borowiec and Takizawa sp. nov. and N. ovoidea Borowiec and Świętojańska sp. nov. New records for nine other species, a check list and key to Bornean Notosacantha are given. Myrsinaceae and Myristicaceae are new host plant families for tortoise beetles and Ardisia elliptica Thunb., Ardisia sp., Embelia sp., Gironiema sp. (all Myrsinaceae) and Knema sp. (Myristicaceae) are new host plants for Notosacantha.
Effects of Topography on Baroclinic Instability
Authors: Chen Changheng , Kamenkovich Igor 
Published: January 2013

Abstract
The importance of bottom topography in the linear baroclinic instability of zonal flows on the β plane is examined by using analytical calculations and a quasigeostrophic eddy-resolving numerical model. The particular focus is on the effects of a zonal topographic slope, compared with the effects of a meridional slope. A zonal slope always destabilizes background zonal flows that are otherwise stable in the absence of topography regardless of the slope magnitude, whereas the meridional slopes stabilize/destabilize zonal flows only through changing the lower-level background potential vorticity gradient beyond a known critical value. Growth rates, phase speeds, and vertical structure of the growing solutions strongly depend on the slope magnitude. In the numerical simulations configured with an isolated meridional ridge, unstable modes develop on both sides of the ridge and propagate eastward of the ridge, in agreement with analytical results.
Offshore Transport of Shelf Waters through Interaction of Vortices with a Shelfbreak Current
Authors: Cenedese Claudia , Todd Robert E. , Gawarkiewicz Glen G. , Owens W. Brechner , Shcherbina Andrey Y. 
Published: January 2013

Abstract
Interactions between vortices and a shelfbreak current are investigated, with particular attention to the exchange of waters between the continental shelf and slope. The nonlinear, three-dimensional interaction between an anticyclonic vortex and the shelfbreak current is studied in the laboratory while varying the ratio ε of the maximum azimuthal velocity in the vortex to the maximum alongshelf velocity in the shelfbreak current. Strong interactions between the shelfbreak current and the vortex are observed when ε &gt; 1; weak interactions are found when ε &lt; 1. When the anticyclonic vortex comes in contact with the shelfbreak front during a strong interaction, a streamer of shelf water is drawn offshore and wraps anticyclonically around the vortex. Measurements of the offshore transport and identification of the particle trajectories in the shelfbreak current drawn offshore from the vortex allow quantification of the fraction of the shelfbreak current that is deflected onto the slope; this fraction increases for increasing values of ε. Experimental results in the laboratory are strikingly similar to results obtained from observations in the Middle Atlantic Bight (MAB); after proper scaling, measurements of offshore transport and offshore displacement of shelf water for vortices in the MAB that span a range of values of ε agree well with laboratory predictions.
Delivery of viral-vectored vaccines by B cells represents a novel strategy to accelerate CD8+ T-cell recall responses
Authors: Zhang Liang , Bridle Byram W. , Chen Lan , Pol Jonathan , Spaner David , Boudreau Jeanette E. , Rosen Allison , Bassett Jennifer D. , Lichty Brian D. , Bramson Jonathan L. , Wan Yonghong 
Published: January 2013

Key PointsUsing B cells to target antigens into the follicular regions represents a novel approach to accelerate CD8+ T-cell recall responses.
Heparin rescues factor V Leiden–associated placental failure independent of anticoagulation in a murine high-risk pregnancy model
Authors: An Jianzhong , Waitara Magarya S. , Bordas Michelle , Arumugam Vidhyalakshmi , Hoffmann Raymond G. , Petrich Brian G. , Sinha Uma , North Paula E. , Sood Rashmi 
Published: January 2013

Key Points
Heparin may have beneficial effects on placental health beyond anticoagulation. Thrombin receptor activation on maternal platelets is implicated in placental developmental failure independent of thrombosis.
International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) & European Competence Network on Mastocytosis (ECNM) consensus response criteria in advanced systemic mastocytosis
Authors: Gotlib Jason , Pardanani Animesh , Akin Cem , Reiter Andreas , George Tracy , Hermine Olivier , Kluin-Nelemans Hanneke , Hartmann Karin , Sperr Wolfgang R. , Brockow Knut , Schwartz Lawrence B. , Orfao Alberto , DeAngelo Daniel J. , Arock Michel , Sotlar Karl , Horny Hans-Peter , Metcalfe Dean D. , Escribano Luis , Verstovsek Srdan , Tefferi Ayalew , Valent Peter 
Published: January 2013

Abstract
Systemic mastocytosis (SM) is characterized by accumulation of neoplastic mast cells and is classified into indolent and aggressive forms. The latter include aggressive SM (ASM), mast cell leukemia (MCL), and SM associated with a myeloid neoplasm wherein 1 or both disease compartments exhibit advanced features. These variants, henceforth collectively referred to as advanced SM for the purposes of this report, are typically characterized by organ damage and shortened survival duration. In contrast to indolent SM, in which symptoms are usually managed by noncytotoxic antimediator therapy, cytoreduction is usually necessary for disease control in advanced SM. Unfortunately, current drug treatment of these patients rarely results in complete clinical and histopathologic remissions or improved survival time. Previously defined response criteria were adapted to the heterogeneous presentations of advanced SM and the limited effects of available drugs. However, recent advances in understanding the molecular pathogenesis of SM and the corresponding prospect in targeted therapy make it a priority to modify these criteria. Our current study is the product of an international group of experts and summarizes the challenges in accomplishing this task and forwards a new proposal for response criteria, which builds on prior proposals and should facilitate response evaluation in clinical trials.
Engineered AAV vector minimizes in vivo targeting of transduced hepatocytes by capsid-specific CD8+ T cells
Authors: Martino Ashley T. , Basner-Tschakarjan Etiena , Markusic David M. , Finn Jonathan D. , Hinderer Christian , Zhou Shangzhen , Ostrov David A. , Srivastava Arun , Ertl Hildegund C. J. , Terhorst Cox , High Katherine A. , Mingozzi Federico , Herzog Roland W. 
Published: January 2013

Key Points
A murine model was developed for capsid-specific CD8 cell responses in AAV gene therapy for hemophilia. Y-F mutant capsid minimizes the effect of anticapsid CD8+ T cells on hepatocyte-derived factor IX expression in mice and in human cells.