bluuebunny/crossref_metadata_2025_split huggingface dataset:
How safe is safe: new human immunodeficiency virus Type 1 variants missed by nucleic acid testing
Authors: Müller Benjamin , Nübling C. Micha , Kress Julia , Roth W. Kurt , De Zolt Silke , Pichl Lutz 
Published: June 2013

BackgroundNucleic acid amplification techniques (NAT) in routine blood donor screening considerably reduce the diagnostic window phase period. Nevertheless, several reports of false‐negative NAT results were published. Here, four cases of human immunodeficiency virus Type 1 (HIV‐1) RNA–positive blood donations that escaped detection by NAT screening are described.Study Design and MethodsA total of 2.7 million blood donations were screened for viral infections between January 2010 and October 2012 in our German Red Cross blood donation service. Four plasma specimens with false‐negative NAT results were comparatively investigated with 12 CE‐marked NAT assays. In two cases of putative HIV‐1 variants the target region of the NAT assay was sequenced allowing comparison with the respective primers and probes.ResultsMost of the NAT assays used in routine blood donor screening with the 5′‐long terminal repeat (LTR) as target region demonstrated deficiencies in detecting the viral variants and the low‐viral‐carrier donations. Sequence analysis revealed in one case a deletion of 56 nucleotides within the 5′‐LTR preventing the binding of the probe accompanied by a neighbored insertion of another 52 nucleotides and several primer mismatches in another case. No false‐negative results were obtained for these cases using dual‐target assays. The viral load of the remaining two false‐negative results was below the NAT's limit of detection.ConclusionHIV‐1 is characterized by a high mutation rate and rapid generation of new viral variants. By the use of one target region for HIV‐1 NAT assays there is a certain risk of false‐negative results. Employing HIV‐1 multi‐ and dual‐target assays in routine blood donor screening seems to be a reasonable possibility to minimize this problem.
Canine indolent and aggressive lymphoma: clinical spectrum with histologic correlation
Authors: Aresu L. , Martini V. , Rossi F. , Vignoli M. , Sampaolo M. , Aricò A. , Laganga P. , Pierini A. , Frayssinet P. , Mantovani R. , Marconato L. 
Published: June 2013

AbstractSixty‐three dogs with newly diagnosed lymphoma underwent complete staging and received the same chemotherapy. Diffuse large B‐cell lymphoma was the leading histotype (44.4%), followed by peripheral T‐cell lymphoma (20.6%). Indolent lymphomas accounted for 30.2% of cases. Most dogs with aggressive B‐cell lymphoma had stage IV disease. Dogs with indolent and aggressive T‐cell lymphoma had more often stage V disease and were symptomatic. Liver and bone marrow were predominantly involved in B‐cell and T‐cell lymphoma, respectively. The clinical stage was significantly related to substage, sex and total lactic dehydrogenase (LDH) levels. Aggressive B‐cell lymphomas were more likely to achieve remission. Median survival was 55 days for aggressive and indolent T‐cell lymphoma, 200 and 256 days for indolent and aggressive B‐cell lymphoma, respectively. The prognosis of advanced indolent lymphoma does not appear to be appreciably different from that of aggressive disease. Familiarity with the various histotypes is critical to make the correct diagnosis and drive therapy.
Influenza Virus Infection but Not H1N1 Influenza Virus Immunization Is Associated with Changes in Peripheral Blood NK Cell Subset Levels
Authors: Juárez-Reyes A. , Noyola D. E. , Monsiváis-Urenda A. , Alvarez-Quiroga C. , González-Amaro R. 
Published: June 2013

ABSTRACT

The innate immune system constitutes the first line of defense against viral agents, and NK cells seem to have an important protective role during the early phases of influenza virus infections. We decided to assess the levels of NK and NKT lymphocytes and the expression levels of different membrane receptors (NKp44, NKp46, NKG2A, killer cell immune-like receptor [KIR] 3DL1/DS1, KIR2DL1/DS1, and CD161) in peripheral blood samples of patients with influenza (
n
= 17) and healthy individuals immunized against this virus (seasonal and [H1N1]pdm2009 influenza vaccines;
n
= 15 and 12, respectively). Blood samples were obtained from all individuals, and NK and NKT cell subsets were analyzed by multiparametric flow cytometry. We found that the patients with severe influenza (
n
= 9) showed significant increases in the percentages of NKp46
+
NKp44
+
NK cells and the proportions of NK and NKT lymphocytes expressing KIR2DL1 and KIR3DL1 and reductions in the percentages of NKp46
+
NKp44
−
NK cells compared to those in the healthy controls (
n
= 27). In contrast, influenza immunization, against either the seasonal or the pandemic H1N1 virus, was not associated with important changes in the levels of NK and NKT lymphocytes or the expression levels of the different receptors by these cells. Our data suggest that severe influenza is associated with important and complex alterations on NK cells, which might contribute to the pathogenesis of this condition.
Evaluation of the LightCycler Methicillin-Resistant Staphylococcus aureus (MRSA) Advanced Test for Detection of MRSA Nasal Colonization
Authors: Yam W. C. , Siu Gilman K. H. , Ho P. L. , Ng T. K. , Que T. L. , Yip K. T. , Fok Cathie P. K. , Chen Jonathan H. K. , Cheng Vincent C. C. , Yuen K. Y. 
Published: June 2013

ABSTRACT

Rapid detection of methicillin-resistant
Staphylococcus aureus
(MRSA) nasal colonization is crucial for the prevention and control of MRSA infections in health care settings. The LightCycler MRSA Advanced Test (Roche Diagnostics) is a commercially available real-time PCR assay for direct detection of MRSA nasal colonization by targeting of the staphylococcal cassette chromosome
mec
(SCC
mec
)-
orfX
junction. The diagnostic performance of the assay was compared with that of ChromID MRSA agar (bioMérieux) culture and an in-house duplex real-time PCR assay. Among 1,246 nasal swab specimens collected from 2 general hospitals in Hong Kong, 174 (14%) were considered true positive for MRSA. Chromogenic culture and the in-house real-time PCR assay identified 147 (84.5%) and 133 (76.4%) true-positive cases with specificities of 100% and 98.6%, respectively. Based on the target melting temperature (

T
m

) values (57.0 to 62.0°C) defined by the manufacturer, the LightCycler MRSA Advanced Test identified only 85 (48.9%) true-positive specimens. Interestingly, an additional 60 (34.5%) true-positive specimens were detected despite atypical

T
m

values of 55°C, providing overall sensitivity and specificity values of 83.3% and 99%, respectively. Among isolates with

T
m

values of 55°C, most were typed as clonal complex 45 (CC45). By sequence analysis of the SCC
mec-orfX
junction, characteristic single-nucleotide polymorphisms (SNPs) were identified only in isolates with

T
m

values of 55°C and not in those with typical

T
m

values. It is conceivable that those SNPs were located inside the target region of the proprietary hybridization probes, which resulted in a

T
m

shift in the melting curve analysis. Our study highlights the importance of a global evaluation of commercial kits so that the interpretation algorithm covers different lineages of MRSA clones prevalent in various geographical regions.
Effects of Aggregate and Individual Antibiotic Exposure on Vancomycin MICs for Staphylococcus aureus Isolates Recovered from Pediatric Patients
Authors: Rose Lucia , Chan Shannon , Hossain Jobayer , Di Pentima M. Cecilia 
Published: June 2013

ABSTRACT

We evaluated the evolution of vancomycin MICs for
Staphylococcus aureus
and their relationship with vancomycin use among hospitalized children.
S. aureus
isolates recovered from sterile sites were prospectively tested for vancomycin susceptibility using the Etest between 1 April 2000 and 31 March 2008. Vancomycin MICs were grouped into three categories: ≤1, 1.5, and 2 μg/ml. The association between vancomycin MICs and aggregate vancomycin use and individual patient vancomycin exposure 6 months prior to the documented infection was assessed. The geometric mean values for vancomycin MICs for
S. aureus
fluctuated over time without a significant trend (
P
= 0.146). Of the 436 patients included in the study, 363 (83%) had methicillin-susceptible
S. aureus
(MSSA) and 73 (17%) had methicillin-resistant
S. aureus
(MRSA) infections. The rate of isolates with a vancomycin MIC of 2 μg/ml increased from 4% (2 of 46) in 2000 to 2001 to 24% (11 of 46) in 2007 to 2008, despite a decrease in vancomycin use (
r
= −0.11;
P
= 0.825). The percentage of isolates with a vancomycin MIC of 2 μg/ml was higher for MRSA (15%; 11 of 73) than for MSSA strains (5.2%; 19 of 363) (χ
2
= 9.2;
P
= 0.01). Individual patient vancomycin exposure was not associated with a higher vancomycin MIC. In the unadjusted model, in which we compared patients with
S. aureus
infections with MICs of ≤1 μg/ml, the odds ratios of exposure rates for patients with isolates with MICs of 1.5 μg/ml and 2 μg/ml were 1.02 (
P
= 0.929) and 1.13 (
P
= 0.767), respectively. In our experience, the geometric means of vancomycin MICs from
S. aureus
isolates recovered from hospitalized children oscillated over time and were not associated with previous individual patient vancomycin exposure or aggregate vancomycin use.
Acute-Phase CD8 T Cell Responses That Select for Escape Variants Are Needed to Control Live Attenuated Simian Immunodeficiency Virus
Authors: Harris Max , Burns Charles M. , Becker Ericka A. , Braasch Andrew T. , Gostick Emma , Johnson Randall C. , Broman Karl W. , Price David A. , Friedrich Thomas C. , O'Connor Shelby L. 
Published: June 2013

ABSTRACT

The overall CD8 T cell response to human/simian immunodeficiency virus (HIV/SIV) targets a collection of discrete epitope specificities. Some of these epitope-specific CD8 T cells emerge in the weeks and months following infection and rapidly select for sequence variants, whereas other CD8 T cell responses develop during the chronic infection phase and rarely select for sequence variants. In this study, we tested the hypothesis that acute-phase CD8 T cell responses that do not rapidly select for escape variants are unable to control viral replication
in vivo
as well as those that do rapidly select for escape variants. We created a derivative of live attenuated SIV (SIVmac239Δnef) in which we ablated five epitopes that elicit early CD8 T cell responses and rapidly accumulate sequence variants in SIVmac239-infected Mauritian cynomolgus macaques (MCMs) that are homozygous for the M3 major histocompatibility complex (MHC) haplotype. This live attenuated SIV variant was called m3KOΔnef. Viremia was significantly higher in M3 homozygous MCMs infected with m3KOΔnef than in either MHC-mismatched MCMs infected with m3KOΔnef or MCMs infected with SIVmac239Δnef. Three CD8 T cell responses, including two that do not rapidly select for escape variants, predominated during early m3KOΔnef infection in the M3 homozygous MCMs, but these animals were unable to control viral replication. These results provide evidence that acute-phase CD8 T cell responses that have the potential to rapidly select for escape variants in the early phase of infection are needed to establish viral control
in vivo
.
Provenance of late Palaeozoic terrestrial sediments on the northern flank of the Mid North Sea High: detrital zircon geochronology and rutile geochemical constraints
Authors: Lundmark Anders Mattias , Bue Edina Pózer , Gabrielsen Roy H. , Flaat Kjersti , Strand Tor , Ohm Sverre E. 
Published: June 2013

Abstract
Zircon U–Pb and rutile trace element data are used to investigate the provenance of late Devonian to early Permian terrestrial sandstones in the Embla and Flora oil fields on the north flank of the Mid North Sea High, central North Sea. Two Old Red Sandstone samples (ORS 1) are dominated by 1.2–0.9 Ga Grenvillian zircons and low- to medium-grade rutile, with sparse Cambro-Ordovician Caledonian zircons (2–4%) and high-grade rutiles (0–5%). The samples are interpreted as recycled metasediments from the Scottish Caledonides. Two other Old Red Sandstone samples (ORS 2) contain a high proportion of Caledonian, mainly Silurian zircons (15–19%) and high-grade rutiles (15–18%); we propose that these components are traceable to the Krummedal sequence on East Greenland (and related sediments). We interpret the data to reflect a temporal evolution of the regional drainage system from northwestern to northeastern sources, with high-grade detritus reaching the Mid North Sea High in the Famennian–early Carboniferous. A late Carboniferous and an early Permian sandstone yielded zircon and rutile signatures compatible with recycling of Palaeozoic sediments north of southernmost Scotland, probably reflecting inversion tectonics. Recycling of Mesoproterozoic to Palaeozoic sediments is thus a prominent feature of the studied late Palaeozoic sandstones.

Supplementary material:

Electron microprobe data from rutile trace element analyses, additional rutile temperature plots and zircon LA-ICPMS U–Pb data are available at
http://www.geolsoc.org.uk/SUP18617
.
Global Strong Solutions to Some Nonlinear Dirac Equations in Super-Critical Space
Authors: Huh Hyungjin 
Published: June 2013

We study the initial value problem of some nonlinear Dirac equations which areLmℝcritical. Corresponding to the structure of nonlinear terms, global strong solutions can be obtained in different Lebesgue spaces by using solution representation formula. The uniqueness of weak solutions is proved for the solutionU∈L∞0,T; Ym+2ℝ.
Contact- and agonist-regulated microvesiculation of human platelets
Authors: Liu Xiao , Liu Li , Zaske Ana-Maria , Zhou Zhou , Fu Yuanyuan , Yang Xi , Conyers Jodie , Li Min , Zhang Yanjun , Dong Jing-fei , Zhang Jianning 
Published: June 2013

SummaryAfter exposure to an agonist, platelets are activated and become aggregated. They also shed membrane microparticles that participate in the pathogenesis of thrombosis, hyper-coagulation and inflammation. However, microvesiculation can potentially disrupt the integrity of platelet aggregation by shedding the membrane receptors and phosphatidylserine critical for forming and stabilising a platelet clot. We tested the hypothesis that adhesion and microvesiculation are functions of different subsets of platelets at the time of haemostasis by real-time monitoring of agonist-induced morphological changes and microvesiculation of human platelets. We identified two types of platelets that are adherent to fibrinogen: a high density bubble shape (HDBS) and low-density spread shape (LDSS). Adenosine diphosphate (ADP) predominantly induced HDBS platelets to vesiculate, whereas LDSS platelets were highly resistant to such vesiculation. Thrombin-receptor activating peptide (TRAP) stabilised platelets against microvesiculation by promoting a rapid HDBS-to-LDSS morphological transition. These activities of ADP and TRAP were reversed for platelets in suspension, independent of an engagement integrin αIIbβ 3. As the result of membrane contact, LDSS platelets inhibited the microvesiculation of HDBS platelets in response to ADP. Aspirin and clopidogrel inhibited ADP-induced microvesiculation through different mechanisms. These results suggest that platelet aggregation and microvesiculation occur in different subsets of platelets and are differently regulated by agonists, platelet-platelets and platelet-fibrinogen interactions.
Ideal Cardiovascular Health in Young Adult Populations From the United States, Finland, and Australia and Its Association With cIMT: The International Childhood Cardiovascular Cohort Consortium
Authors: Oikonen Mervi , Laitinen Tomi T. , Magnussen Costan G. , Steinberger Julia , Sinaiko Alan R. , Dwyer Terence , Venn Alison , Smith Kylie J. , Hutri‐Kähönen Nina , Pahkala Katja , Mikkilä Vera , Prineas Ronald , Viikari Jorma S. A. , Morrison John A. , Woo Jessica G. , Chen Wei , Nicklas Theresa , Srinivasan Sathanur R. , Berenson Gerald , Juonala Markus , Raitakari Olli T. 
Published: June 2013

Background

Goals for cardiovascular (
CV
) disease prevention were set by the
A
merican
H
eart
A
ssociation in 2010 for the concept of
CV
health. Ideal
CV
health is defined by 7
CV
health metrics: blood pressure, glucose, cholesterol, body mass index, and physical activity on recommended levels; nonsmoking; and a healthy diet. We studied the prevalence of ideal
CV
health and its associations with ultrasonographically measured carotid intima‐media thickness (
cIMT
) cross‐sectionally in 5 international populations.

Methods and Results

Prevalence of ideal
CV
health was assessed among 5785 young adults (age, 36.6±3.2 years) comprising 335 participants from the
M
inneapolis
C
hildhood
C
ohort
S
tudies (
M
innesota), 723 from the
P
rinceton
F
ollow‐up
S
tudy, 981 from the
B
ogalusa
H
eart
S
tudy (
BHS
), 1898 from the
C
ardiovascular
R
isk in
Y
oung
F
inns
S
tudy (
YFS
), and 1848 from the
C
hildhood
D
eterminants of
A
dult
H
ealth
S
tudy (
CDAH
). Only 1% of the participants had all 7 ideal
CV
health metrics. The number of ideal
CV
health metrics associated inversely with
cIMT
in the 4 cohorts in which
cIMT
was available: for each additional ideal
CV
health metric,
cIMT
was 12.7 μm thinner in
M
innesota (
P
=0.0002), 9.1 μm thinner in
BHS
(
P
=0.05), 10.4 μm thinner in
YFS
(
P
<0.0001), and 3.4 μm thinner in
CDAH
(
P
=0.03).

Conclusions

The number of ideal
CV
health metrics was inversely associated with
cIMT
in the cohorts in which
cIMT
was available, indicating that ideal
CV
health metrics are associated with vascular health at the population level. Ideal
CV
health was rare in this large international sample of young adults, emphasizing the need for effective strategies for health promotion.
Testing times: testing patient acceptance and ability to self-screen for a No-Talk Testing service
Authors: Fernando I , Thompson C 
Published: June 2013

Summary Genitourinary medicine (GUM) departments need to be resource efficient to manage the increasing numbers of patients seeking to access services. At the Edinburgh GUM department, we wished to develop a new No-Talk Testing (NTT) clinic for asymptomatic, low-risk patients attending for routine sexually transmitted infection (STI) screening. We undertook a questionnaire feasibility study to determine patient acceptability and ability to self-screen for this service. A total of 267 respondents completed questionnaires regarding acceptability of a future NTT service; 227 agreed to comparison of their self-screen with clinician risk-assessment. Overall, patient acceptability for a future NTT service was high, with an average of 7.8/10 awarded for opinion. Seventy-three percent of patients agreed they would consider utilizing such a service in the future. Sixty-one percent of respondents suggested at least one benefit to a future NTT service; principally, prospects for increased speed, efficiency, capacity and reduced waiting times. Comparing STI risk self-assessment with clinician assessment, discrepancies were identified for 37% of individuals. However, a majority (70%) of the discrepancies identified were due to a risk being noted in the self-screen alone, and missed from clinician notes. In summary, the study demonstrated NTT as acceptable and feasible. Based on these results, we have now successfully introduced such a service within our department.
Managing clinical research permissions electronically: A novel approach to enhancing recruitment and managing consents
Authors: Sanderson Iain C , Obeid Jihad S , Madathil Kapil Chalil , Gerken Katherine , Fryar Katrina , Rugg Daniel , Alstad Colin E , Alexander Randall , Brady Kathleen T , Gramopadhye Anand K , Moskowitz Jay 
Published: June 2013

Background One mechanism to increase participation in research is to solicit potential research participants’ general willingness to be recruited into clinical trials. Such research permissions and consents typically are collected on paper upon patient registration. We describe a novel method of capturing this information electronically. Purpose The objective is to enable the collection of research permissions and informed consent data electronically to permit tracking of potential research participants’ interest in current and future research involvement and to provide a foundation for facilitating the research workflow. Methods The project involved systematic analysis focused on key areas, including existing business practices, registration processes, and permission collection workflows, and ascertaining best practices for presenting consent information to users via tablet technology and capturing permissions data. Analysis was followed by an iterative software development cycle with feedback from subject matter experts and users. Results An initial version of the software was piloted at one institution in South Carolina for a period of 1 year, during which consents and permission were collected during 2524 registrations of patients. The captured research permission data were transmitted to a clinical data warehouse. The software was later released as an open-source package that can be adopted for use by other institutions. Limitations There are significant ethical, legal, and informatics challenges that must be addressed at an institution to deploy such a system. We have not yet assessed the long-term impact of the system on recruitment of patients to clinical trials. Conclusions We propose that by improving the ability to track willing potential research participants, we can improve recruitment into clinical trials and, in the process, improve patient education by introducing multimedia to informed consent documents.
Inositol hexakisphosphate kinase 1 maintains hemostasis in mice by regulating platelet polyphosphate levels
Authors: Ghosh Somadri , Shukla Dhananjay , Suman Komjeti , Lakshmi B. Jyothi , Manorama R. , Kumar Satish , Bhandari Rashna 
Published: June 2013

Key Points
Inositol hexakisphosphate kinase 1 (IP6K1) knockout mice display lower inorganic polyphosphate levels in platelets. Low platelet polyphosphate leads to lengthened clotting time, altered clot architecture, and protection against pulmonary thromboembolism.