bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Types of Methicillin-Resistant Staphylococcus aureus and Methicillin-Sensitive S. aureus Strains Causing Skin and Soft Tissue Infections and Nasal Colonization, Identified in Community Health Centers in New York City
Authors: Pardos de la Gandara Maria , Raygoza Garay Juan Antonio , Mwangi Michael , Tobin Jonathan N. , Tsang Amanda , Khalida Chamanara , D'Orazio Brianna , Kost Rhonda G. , Leinberger-Jabari Andrea , Coffran Cameron , Evering Teresa H. , Coller Barry S. , Balachandra Shirish , Urban Tracie , Parola Claude , Salvato Scott , Jenks Nancy , Wu Daren , Burgess Rhonda , Chung Marilyn , de Lencastre Herminia , Tomasz Alexander 
Published: June 2015

ABSTRACT

In November 2011, The Rockefeller University Center for Clinical and Translational Science (CCTS), the Laboratory of Microbiology and Infectious Diseases, and Clinical Directors Network (CDN) launched a research and learning collaborative project with six community health centers in the New York City metropolitan area to determine the nature (clonal type) of community-acquired
Staphylococcus aureus
strains causing skin and soft tissue infections (SSTIs). Between November 2011 and March 2013, wound and nasal samples from 129 patients with active SSTIs suspicious for
S. aureus
were collected and characterized by molecular typing techniques. In 63 of 129 patients, the skin wounds were infected by
S. aureus
: methicillin-resistant
S. aureus
(MRSA) was recovered from 39 wounds and methicillin-sensitive
S. aureus
(MSSA) was recovered from 24. Most—46 of the 63–wound isolates belonged to the CC8/Panton-Valentine leukocidin-positive (PVL
+
) group of
S. aureus
clone USA300: 34 of these strains were MRSA and 12 were MSSA. Of the 63 patients with
S. aureus
infections, 30 were also colonized by
S. aureus
in the nares: 16 of the colonizing isolates were MRSA, and 14 were MSSA, and the majority of the colonizing isolates belonged to the USA300 clonal group. In most cases (70%), the colonizing isolate belonged to the same clonal type as the strain involved with the infection. In three of the patients, the identity of invasive and colonizing MRSA isolates was further documented by whole-genome sequencing.
Antibody and Viral Nucleic Acid Testing of Serum and Cerebrospinal Fluid for Diagnosis of Eastern Equine Encephalitis
Authors: Sherwood James A. , Brittain David C. , Howard John J. , Oliver JoAnne 
Published: June 2015

ABSTRACT
Eastern equine encephalitis diagnostic serum antibody can appear 6 days after the onset of symptoms, and its numbers can increase 4-fold in 4 days, arguing for early and frequent serum testing. In populations where cerebrospinal fluid viral nucleic acid testing sensitivity and specificity remain undetermined, cerebrospinal antibody testing should also be performed.
Comparison of Three Different FDA-Approved Plasma HIV-1 RNA Assay Platforms Confirms the Virologic Failure Endpoint of 200 Copies per Milliliter Despite Improved Assay Sensitivity
Authors: Lalama Christina M. , Jennings Cheryl , Johnson Victoria A. , Coombs Robert W. , McKinnon John E. , Bremer James W. , Cobb Bryan R. , Cloherty Gavin A. , Mellors John W. , Ribaudo Heather J. 
Published: June 2015

ABSTRACT

Discrepancies between HIV-1 RNA results assayed by different FDA-approved platforms have been reported. Plasma samples collected from 332 randomly selected clinical trial participants during the second year of antiretroviral treatment were assayed with three FDA-approved platforms: UltraSensitive Roche Amplicor Monitor, v1.5 (Monitor), the Abbott RealTime HIV-1 test on the m2000 system (Abbott), and the Roche TaqMan HIV-1 test, v2.0 (TaqMan). Samples from 61 additional participants with confirmed HIV-1 RNA levels of >50 copies/ml during trial follow-up were also included. Endpoints were HIV-1 RNA quantification of ≤50 copies/ml versus >50 copies/ml at an individual-sample level (primary) and determination of confirmed virologic failure (VF) from longitudinal samples. A total of 389 participants had results obtained from all assays on at least one sample (median = 6). Proportions of results of >50 copies/ml were 19% (Monitor), 22% (TaqMan), and 25% (Abbott). Despite indication of strong agreement (Cohen's kappa, 0.76 to 0.82), Abbott was more likely to detect HIV-1 RNA levels of >50 copies/ml than Monitor (matched-pair odds ratio [mOR] = 4.2; modified Obuchowski
P
< 0.001) and TaqMan (mOR = 2.1;
P
< 0.001); TaqMan was more likely than Monitor (mOR = 2.6;
P
< 0.001). Despite strong agreement in classifying VF across assay comparisons (kappa, 0.75 to 0.92), at a 50-copies/ml threshold, differences in the probability of VF classification (in the same direction as primary) were apparent (all McNemar's
P
< 0.007). At a 200-copies/ml VF threshold, no differences between assays were apparent (all
P
> 0.13). Despite strong agreement among assays, significant differences were observed with respect to detecting HIV-1 RNA levels of >50 copies/ml and identifying VF at the 50-copies/ml threshold. This has important implications for the definition of VF in clinical trials and clinical practice.
Cytomegalovirus Infection Management in Allogeneic Stem Cell Transplant Recipients: a National Survey in Spain
Authors: Solano Carlos , de la Cámara Rafael , Vázquez Lourdes , López Javier , Giménez Estela , Navarro David 
Published: June 2015

ABSTRACT
This study gathered information about current practices of cytomegalovirus (CMV) infection management in allogeneic stem cell transplant recipients at Spanish centers. A wide variety of preemptive antiviral therapy strategies for CMV infection guided by real-time PCR assays was found, yet the incidence of CMV disease was low (<3%).
Candida quercitrusa Candidemia in a 6-Year-Old Child
Authors: Westblade Lars F. , Rostad Christina A. , Hilinski Joseph A. , Stanley Theresa , Jerris Robert C. , Wilkey Kathy , Pincus David H. 
Published: June 2015

ABSTRACT

We present the first case of candidemia due to
Candida quercitrusa
in a pediatric patient. The identification of the isolate was protracted and ultimately dependent upon sequence analysis of the internal transcribed spacer region. To further define the antifungal susceptibility characteristics of this species, we performed antifungal susceptibility testing of clinical and type strains. In light of the antifungal susceptibility testing results, we caution against the use of fluconazole for treating
C. quercitrusa
infections.
Human Papillomavirus Infectious Entry and Trafficking Is a Rapid Process
Authors: Broniarczyk Justyna , Massimi Paola , Bergant Martina , Banks Lawrence 
Published: June 2015

ABSTRACT

Previous studies have indicated that human papillomavirus (HPV) infectious entry is slow, requiring many hours after initial infection for the virus to gain entry into the nucleus. However, intracellular transport pathways typically are very rapid, and in the context of a natural HPV infection in a wounded epithelium, such slow intracellular transport would seem to be at odds with a normal viral infection. Using synchronized cell populations, we show that HPV trafficking can be a rapid process. In cells that are infected in the late S-early G
2
/M phase of the cell cycle, HPV16 pseudovirion (PsV) reporter DNA gene expression is detectable by 8 h postinfection. Likewise, reporter DNA can be visualized within the nucleus in conjunction with PML nuclear bodies 1 h to 2 h postinfection in cells that are infected with PsVs just prior to mitotic entry. This demonstrates that endosomal trafficking of HPV is rapid, with mitosis being the main restriction on nuclear entry.

IMPORTANCE
HPV infectious entry appears to be slow and requires mitosis to occur before the incoming viral DNA can access the nucleus. In this study, we show that HPV trafficking in the cell actually is very rapid. This demonstrates that in the context of a normal virus infection, the cell cycle state will have a major influence on the time it takes for an incoming virus to enter the nucleus and initiate viral gene expression.
Differential Impact of
In Vivo
CD8
+
T Lymphocyte Depletion in Controller versus Progressor Simian Immunodeficiency Virus-Infected Macaques
Authors: Chowdhury Ankita , Hayes Timothy L. , Bosinger Steven E. , Lawson Benton O. , Vanderford Thomas , Schmitz Joern E. , Paiardini Mirko , Betts Michael , Chahroudi Ann , Estes Jacob D. , Silvestri Guido 
Published: June 2015

ABSTRACT

Numerous studies have demonstrated that CD8
+
T lymphocytes suppress virus replication during human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection. However, the mechanisms underlying this activity of T cells remain incompletely understood. Here, we conducted CD8
+
T lymphocyte depletion in 15 rhesus macaques (RMs) infected intravenously (i.v.) with SIV
mac239
. At day 70 postinfection, the animals (10 progressors with high viremia and 5 controllers with low viremia) were CD8 depleted by i.v. administration of the antibody M-T807R1. As expected, CD8 depletion resulted in increased virus replication, more prominently in controllers than progressors, which correlated inversely with predepletion viremia. Of note, the feature of CD8
+
T lymphocyte predepletion that correlated best with the increase in viremia postdepletion was the level of CD8
+
T-bet
+
lymphocytes. We next found that CD8 depletion resulted in a homogenous increase of SIV RNA in superficial and mesenteric lymph nodes, spleen, and the gastrointestinal tract of both controllers and progressors. Interestingly, the level of SIV DNA increased postdepletion in both CD4
+
central memory T lymphocytes (T
CM
) and CD4
+
effector memory T lymphocytes (T
EM
) in progressor RMs but decreased in the CD4
+
T
CM
of 4 out of 5 controllers. Finally, we found that CD8 depletion is associated with a greater increase in CD4
+
T lymphocyte activation (measured by Ki-67 expression) in controllers than in progressors. Overall, these data reveal a differential impact of CD8
+
T lymphocyte depletion between controller and progressor SIV-infected RMs, emphasizing the complexity of the
in vivo
antiviral role of CD8
+
T lymphocytes.

IMPORTANCE
In this study, we further dissect the impact of CD8
+
T lymphocytes on HIV/SIV replication during SIV infection. CD8
+
T lymphocyte depletion leads to a relatively homogenous increase in viral replication in peripheral blood and tissues. CD8
+
T lymphocyte depletion resulted in a more prominent increase in viral loads and CD4
+
T lymphocyte activation in controllers than in progressors. Interestingly, we found T-bet expression on CD8
+
T lymphocytes to be the best predictor of viral load increase following depletion. The levels of SIV DNA increase postdepletion in both CD4
+
T
CM
and T
EM
in progressor RMs but decrease in the CD4
+
T
CM
of controllers. The findings described in this study provide key insights into the differential functions of CD8
+
T lymphocytes in controller and progressor RMs.
Characterization of Two Human Monoclonal Antibodies Neutralizing Influenza A H7N9 Viruses
Authors: Wang Jianmin , Chen Zhe , Bao Linlin , Zhang Weijia , Xue Ying , Pang XingHuo , Zhang Xi , Qin Chuan , Jin Qi 
Published: June 2015

ABSTRACT
H7N9 was a cause of significant global health concern due to its severe infection and approximately 35% mortality in humans. By screening a Fab antibody phage library derived from patients who recovered from H7N9 infections, we characterized two human monoclonal antibodies (HuMAbs), HNIgGD5 and HNIgGH8. The epitope of these two antibodies was dependent on two residues in the receptor binding site at positions V186 and L226 of the hemagglutinin glycoprotein. Both antibodies possessed high neutralizing activity.
After revision anterior cruciate ligament reconstruction, who returns to sport? A systematic review and meta-analysis
Authors: Grassi Alberto , Zaffagnini Stefano , Marcheggiani Muccioli Giulio Maria , Neri Maria Pia , Della Villa Stefano , Marcacci Maurilio 
Published: June 2015

BackgroundReturn to sport and to pre-injury level represents an important outcome after both primary and revision anterior cruciate ligament (ACL) reconstructions.PurposeThe aim of the present meta-analysis was to determine the return to sport rate after revision ACL reconstruction.Material and methodsA systematic search was performed of the MEDLINE, Embase and the Cochrane Central Register of Controlled Trials Databases. All the studies that reported return to sport, return to pre-injury sport level and return to high level/competitive sport was considered for the meta-analysis. The overall pooled mean of post-operative knee laxity and pooled rate of positive pivot-shift and objective International Knee Documentation Committee (IKDC) categories was calculated as well.ResultsOverall, 472 abstracts were identified and screened for inclusion and only 16 studies reported the rate of return to any level of sport activity at the final follow-up of 4.7 years (range 1.0–13.2 years), showing a pooled rate of 85.3% (CI 79.7 to 90.2). The return to pre-injury sport level was achieved in 53.4% (CI 37.8 to 68.7) of cases. Normal or quasi-normal objective IKDC, less than 5 mm of side-to-side difference at arthrometric evaluations and grade I-II pivot-shift test were reported in 84%, 88% and 93% patients, respectively.ConclusionsIn spite of almost 8 patients out of 10 returning to sport after revision ACL reconstruction and showing good stability, only half of the patients returned to the same pre-injury sport level.
How do GPs in Switzerland perceive their patients’ satisfaction and expectations? An observational study
Authors: Sebo Paul , Herrmann François R , Haller Dagmar M 
Published: June 2015

ObjectivesTo assess doctors’ perceptions of their patients’ satisfaction and expectations in primary care.Study designCross-sectional study using questionnaires completed by general practitioners (GPs) and their patients.SettingPrimary care practices in Geneva, Switzerland.Participants23 GPs from a random list of 75 GPs practising in the canton of Geneva (participation rate 31%), who each recruited between 50 and 100 consecutive patients coming to the practice for a scheduled medical consultation, leading to a total of 1637 patients (participation rate: 97%, women: 63%, mean age: 54 years). Patient exclusion criteria were: new patients, those consulting in an emergency situation or suffering from disorders affecting their ability to consent, and those who did not speak French.Main outcome measuresPatients satisfaction with and expectations from the care they received in this practice; GPs perceptions of their patient's satisfaction and expectations.ResultsGPs underestimated all patient satisfaction items (p<0.001 for all items) whereas they overestimated their expectations, except for equipment (laboratory and X-ray) and some accessibility items. In a multivariate analysis to assess which GP factors were associated with correct assessment of their patients’ views, only GPs’ certification status was a significant factor.ConclusionsGPs tend to underestimate patients’ satisfaction but overestimate their expectations in primary care. These findings may help GPs to understand patients’ views in order to adequately meet their expectations and concerns.
Magnetoencephalography to investigate central perception of exercise-induced breathlessness in people with chronic lung disease: a feasibility pilot
Authors: Johnson Miriam J , Simpson Michael IG , Currow David C , Millman Rebecca E , Hart Simon P , Green Gary 
Published: June 2015

ObjectivesNeuroimaging in chronic breathlessness is challenging. The study objective was to test the feasibility of magnetoencephalography (MEG) for functional neuroimaging of people with chronic breathlessness.DesignFeasibility pilot study.SettingRespiratory clinic out-patients.Participants8 patients (mean age=62; (range 47–83); 4 men) with chronic non-malignant lung disease; modified MRC breathlessness score ≥3 (median mMRC=4), intensity of exercise-induced breathlessness >3/10; no contraindication to MRI scanning.Methods and measures4 MEG scans were conducted for each participant: (1) at rest (5 mins), (2) postseated leg exercise-induced breathlessness during recovery (10 mins). Recovery scans (2) were conducted with/without facial airflow in random order; both scans were repeated 1 h later. Participants rated breathlessness intensity (0–10 Numerical Rating Scale (NRS)) at baseline, maximal exertion and every minute during recovery, and rated acceptability of study procedures at the end of the study (0–10 NRS). A structural MRI scan was conducted for MEG coregistration and source-space analyses. Rest data were compared with data from healthy volunteers (N=6; 5 men; mean age=30.7 years±3.9 years).ResultsExercises and MEG scanning were acceptable to all participants; 7/8 completed the MRI scans. Maximum breathlessness intensity was induced by 5 min’ exercise. The same level was induced for repeat scans (median=8; IQR=7–8). All recovered to baseline by 10 min. Time-frequency profiles of data from the first and last 3 min were analysed in MEG source space based on breathlessness location estimates. Source localisation was performed, but anatomical source inference was limited to the level of the lobe. Differences in areas of activity were seen: during recovery scans; with and without airflow; and between participants/normal volunteers at rest.ConclusionsMEG is a feasible method to investigate exercise-induced breathlessness in people breathless with chronic lung disease, and able to identify neural activity related to changes in breathlessness.
The effect of environmental changes on the evolution and extinction of Late Devonian trilobites from the northern Canning Basin, Western Australia
Authors: McNamara Kenneth J. , Feist Raimund 
Published: June 2015

Abstract

The Frasnian–Famennian Virgin Hills Formation represents fore-reef facies deposited as part of the extensive Late Devonian reef system that fringed the SW Kimberley Block in Western Australia. It contains a rich trilobite fauna dominated primarily by proetids and, to a lesser extent, harpetids, phacopids, scutelluids and odontopleurids. To date, 49 taxa have been described, 40 of these being restricted to the Frasnian. Herein five Frasnian taxa are described, three in open nomenclature, and two the new species
Telopeltis intermedia
and
Otarion fugitivum
. Evolutionary trends in the Virgin Hills trilobites are dominated by a reduction in body size and eye size and, to a lesser extent, a reduction in exoskeletal vaulting. Although recording no sedimentological signature, the fauna was strongly affected by the two globally recognized Kellwasser extinction events. The first, at the end of conodont Zone 12, affected taxa at the species and genus level. The second, within Zone 13b, had a much greater impact on the fauna, causing extinctions at the familial and ordinal levels. Evidence is presented to suggest that evolutionary trends in the trilobites during the late Frasnian reflect selection for forms adapted to low nutrient conditions. The two intensive Kellwasser extinction episodes may reflect periodic massive inputs of nutrients from the terrestrial into the shallow-marine environment.
Efficacy and Tolerability of a GD2-Directed Trifunctional Bispecific Antibody in a Preclinical Model: Subcutaneous Administration Is Superior to Intravenous Delivery
Authors: Deppisch Nina , Ruf Peter , Eissler Nina , Neff Frauke , Buhmann Raymund , Lindhofer Horst , Mocikat Ralph 
Published: June 2015

AbstractTrifunctional bispecific antibodies (trAb) are novel anticancer drugs that recruit and activate different types of immune effector cells at the targeted tumor. Thus, tumor cells are effectively eliminated and a long-lasting tumor-specific T-cell memory is induced. The trAb Ektomab is directed against human CD3 on T cells and the tumor-associated ganglioside GD2, which is an attractive target for immunotherapy of melanoma in humans. To optimize clinical applicability, we studied different application routes with respect to therapeutic efficacy and tolerability by using the surrogate trAb Surek (anti-GD2 × anti-murine CD3) and a murine melanoma engineered to express GD2. We show that subcutaneous injection of the trAb is superior to the intravenous delivery pathway, which is the standard application route for therapeutic antibodies. Despite lower plasma levels after subcutaneous administration, the same tumor-protective potential was observed in vivo compared with intravenous administration of Surek. However, subcutaneously delivered Surek showed better tolerability. This could be explained by a continuous release of the antibody leading to constant plasma levels and a delayed induction of proinflammatory cytokines. Importantly, the induction of counter-regulatory mechanisms was reduced after subcutaneous application. These findings are relevant for the clinical application of trifunctional bispecific antibodies and, possibly, also other immunoglobulin constructs. Mol Cancer Ther; 14(8); 1877–83. ©2015 AACR.
Sensitization of Glioblastoma Cells to Irradiation by Modulating the Glucose Metabolism
Authors: Shen Han , Hau Eric , Joshi Swapna , Dilda Pierre J. , McDonald Kerrie L. 
Published: June 2015

Abstract
Because radiotherapy significantly increases median survival in patients with glioblastoma, the modulation of radiation resistance is of significant interest. High glycolytic states of tumor cells are known to correlate strongly with radioresistance; thus, the concept of metabolic targeting needs to be investigated in combination with radiotherapy. Metabolically, the elevated glycolysis in glioblastoma cells was observed postradiotherapy together with upregulated hypoxia-inducible factor (HIF)-1α and its target pyruvate dehydrogenase kinase 1 (PDK1). Dichloroacetate, a PDK inhibitor currently being used to treat lactic acidosis, can modify tumor metabolism by activating mitochondrial activity to force glycolytic tumor cells into oxidative phosphorylation. Dichloroacetate alone demonstrated modest antitumor effects in both in vitro and in vivo models of glioblastoma and has the ability to reverse the radiotherapy-induced glycolytic shift when given in combination. In vitro, an enhanced inhibition of clonogenicity of a panel of glioblastoma cells was observed when dichloroacetate was combined with radiotherapy. Further mechanistic investigation revealed that dichloroacetate sensitized glioblastoma cells to radiotherapy by inducing the cell-cycle arrest at the G2–M phase, reducing mitochondrial reserve capacity, and increasing the oxidative stress as well as DNA damage in glioblastoma cells together with radiotherapy. In vivo, the combinatorial treatment of dichloroacetate and radiotherapy improved the survival of orthotopic glioblastoma-bearing mice. In conclusion, this study provides the proof of concept that dichloroacetate can effectively sensitize glioblastoma cells to radiotherapy by modulating the metabolic state of tumor cells. These findings warrant further evaluation of the combination of dichloroacetate and radiotherapy in clinical trials. Mol Cancer Ther; 14(8); 1794–804. ©2015 AACR.