bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assignment of Opsonic Values to Pneumococcal Reference Serum 007sp for Use in Opsonophagocytic Assays for 13 Serotypes
Authors: Burton R. L. , Antonello J. , Cooper D. , Goldblatt D. , Kim K. H. , Plikaytis B. D. , Roalfe L. , Wauters D. , Williams F. , Xie G. L. , Nahm M. H. , Akkoyunlu M. 
Published: January 2017

ABSTRACTOpsonophagocytic assays (OPAs) are routinely used for assessing the immunogenicity of pneumococcal vaccines, with OPA data often being utilized for licensure of new vaccine formulations. However, no reference serum for pneumococcal OPAs is available, making evaluation of data among different laboratories difficult. This international collaboration was initiated to (i) assign consensus opsonic indexes (OIs) to FDA pneumococcal reference serum lot 007sp (here referred to as 007sp) and a panel of serum samples used for calibration of the OPA and (ii) determine if the normalization of the OPA results obtained with test samples to those obtained with 007sp decreases the variability in OPA results among laboratories. To meet these goals, six participating laboratories tested a panel of serum samples in five runs for 13 serotypes. For each serum sample, consensus OIs were obtained using a mixed-effects analysis of variance model. For the calibration serum samples, normalized consensus values were also determined on the basis of the results obtained with 007sp. For each serotype, the overall reduction in interlaboratory variability was calculated by comparing the coefficients of variation of the unadjusted and the normalized values. Normalization of the results substantially reduced the interlaboratory variability, ranging from a 15% reduction in variability for serotype 9V to a 64% reduction for serotype 7F. Normalization also increased the proportion of data within 2-fold of the consensus value from approximately 70% (average for all serotypes) to >90%. On the basis of the data obtained in this study, pneumococcal reference standard lot 007sp will likely be a useful reagent for the normalization of pneumococcal OPA results from different laboratories. The data also support the use of the 16 FDA serum samples used for calibration of the OPA as part of the initial evaluation of new assays or periodic assessment of established assays.
Mechanism of Protein Kinase R Inhibition by Human Cytomegalovirus pTRS1
Authors: Vincent Heather A. , Ziehr Benjamin , Moorman Nathaniel J. 
Published: January 2017

ABSTRACT

Double-stranded RNAs (dsRNA) produced during human cytomegalovirus (HCMV) infection activate the antiviral kinase protein kinase R (PKR), which potently inhibits virus replication. The HCMV pTRS1 and pIRS1 proteins antagonize PKR to promote HCMV protein synthesis and replication; however, the mechanism by which pTRS1 inhibits PKR is unclear. PKR activation occurs in a three-step cascade. First, binding to dsRNA triggers PKR homodimerizaton. PKR dimers then autophosphorylate, leading to a conformational shift that exposes the binding site for the PKR substrate eIF2α. Consistent with previous
in vitro
studies, we found that pTRS1 bound and inhibited PKR. pTRS1 binding to PKR was not mediated by an RNA intermediate, and mutations in the pTRS1 RNA binding domain did not affect PKR binding or inhibition. Rather, mutations that disrupted the pTRS1 interaction with PKR ablated the ability of pTRS1 to antagonize PKR activation by dsRNA. pTRS1 did not block PKR dimerization and could bind and inhibit a constitutively dimerized PKR kinase domain. In addition, pTRS1 binding to PKR inhibited PKR kinase activity. Single amino acid point mutations in the conserved eIF2α binding domain of PKR disrupted pTRS1 binding and rendered PKR resistant to inhibition by pTRS1. Consistent with a critical role for the conserved eIF2α contact site in PKR binding, pTRS1 bound an additional eIF2α kinase, heme-regulated inhibitor (HRI), and inhibited eIF2α phosphorylation in response to an HRI agonist. Together our data suggest that pTRS1 inhibits PKR by binding to conserved amino acids in the PKR eIF2α binding site and blocking PKR kinase activity.

IMPORTANCE
The antiviral kinase PKR plays a critical role in controlling HCMV replication. This study furthered our understanding of how HCMV evades inhibition by PKR and identified new strategies for how PKR activity might be restored during infection to limit HCMV disease.
Thymidine Kinase-Negative Herpes Simplex Virus 1 Can Efficiently Establish Persistent Infection in Neural Tissues of Nude Mice
Authors: Huang Chih-Yu , Yao Hui-Wen , Wang Li-Chiu , Shen Fang-Hsiu , Hsu Sheng-Min , Chen Shun-Hua 
Published: January 2017

ABSTRACTHerpes simplex virus 1 (HSV-1) establishes latency in neural tissues of immunocompetent mice but persists in both peripheral and neural tissues of lymphocyte-deficient mice. Thymidine kinase (TK) is believed to be essential for HSV-1 to persist in neural tissues of immunocompromised mice, because infectious virus of a mutant with defects in both TK and UL24 is detected only in peripheral tissues, but not in neural tissues, of severe combined immunodeficiency mice (T. Valyi-Nagy, R. M. Gesser, B. Raengsakulrach, S. L. Deshmane, B. P. Randazzo, A. J. Dillner, and N. W. Fraser, Virology 199:484–490, 1994,https://doi.org/10.1006/viro.1994.1150). Here we find infiltration of CD4 and CD8 T cells in peripheral and neural tissues of mice infected with a TK-negative mutant. We therefore investigated the significance of viral TK and host T cells for HSV-1 to persist in neural tissues using three genetically engineered mutants with defects in only TK or in both TK and UL24 and two strains of nude mice. Surprisingly, all three mutants establish persistent infection in up to 100% of brain stems and 93% of trigeminal ganglia of adult nude mice at 28 days postinfection, as measured by the recovery of infectious virus. Thus, in mouse neural tissues, host T cells block persistent HSV-1 infection, and viral TK is dispensable for the virus to establish persistent infection. Furthermore, we found 30- to 200-fold more virus in neural tissues than in the eye and detected glycoprotein C, a true late viral antigen, in brainstem neurons of nude mice persistently infected with the TK-negative mutant, suggesting that adult mouse neurons can support the replication of TK-negative HSV-1.IMPORTANCEAcyclovir is used to treat herpes simplex virus 1 (HSV-1)-infected immunocompromised patients, but treatment is hindered by the emergence of drug-resistant viruses, mostly those with mutations in viral thymidine kinase (TK), which activates acyclovir. TK mutants are detected in brains of immunocompromised patients with persistent infection. However, answers to the questions as to whether TK-negative (TK−) HSV-1 can establish persistent infection in brains of immunocompromised hosts and whether neuronsin vivoare permissive for TK−HSV-1 remain elusive. Using three genetically engineered HSV-1 TK−mutants and two strains of nude mice deficient in T cells, we found that all three HSV-1 TK−mutants can efficiently establish persistent infection in the brain stem and trigeminal ganglion and detected glycoprotein C, a true late viral antigen, in brainstem neurons. Our study provides evidence that TK−HSV-1 can persist in neural tissues and replicate in brain neurons of immunocompromised hosts.
Within-Host Evolution of Simian Arteriviruses in Crab-Eating Macaques
Authors: Moncla Louise H. , Weiler Andrea M. , Barry Gabrielle , Weinfurter Jason T. , Dinis Jorge M. , Charlier Olivia , Lauck Michael , Bailey Adam L. , Wahl-Jensen Victoria , Nelson Chase W. , Johnson Joshua C. , Caì Yíngyún , Goldberg Tony L. , O'Connor David H. , Jahrling Peter B. , Kuhn Jens H. , Friedrich Thomas C. 
Published: January 2017

ABSTRACT
Simian arteriviruses are a diverse clade of viruses infecting captive and wild nonhuman primates. We recently reported that Kibale red colobus virus 1 (KRCV-1) causes a mild and self-limiting disease in experimentally infected crab-eating macaques, while simian hemorrhagic fever virus (SHFV) causes lethal viral hemorrhagic fever. Here we characterize how these viruses evolved during replication in cell culture and in experimentally infected macaques. During passage in cell culture, 68 substitutions that were localized in open reading frames (ORFs) likely associated with host cell entry and exit became fixed in the KRCV-1 genome. However, we did not detect any strong signatures of selection during replication in macaques. We uncovered patterns of evolution that were distinct from those observed in surveys of wild red colobus monkeys, suggesting that these species may exert different adaptive challenges for KRCV-1. During SHFV infection, we detected signatures of selection on ORF 5a and on a small subset of sites in the genome. Overall, our data suggest that patterns of evolution differ markedly among simian arteriviruses and among host species.

IMPORTANCE
Certain RNA viruses can cross species barriers and cause disease in new hosts. Simian arteriviruses are a diverse group of related viruses that infect captive and wild nonhuman primates, with associated disease severity ranging from apparently asymptomatic infections to severe, viral hemorrhagic fevers. We infected nonhuman primate cell cultures and then crab-eating macaques with either simian hemorrhagic fever virus (SHFV) or Kibale red colobus virus 1 (KRCV-1) and assessed within-host viral evolution. We found that KRCV-1 quickly acquired a large number of substitutions in its genome during replication in cell culture but that evolution in macaques was limited. In contrast, we detected selection focused on SHFV ORFs 5a and 5, which encode putative membrane proteins. These patterns suggest that in addition to diverse pathogenic phenotypes, these viruses may also exhibit distinct patterns of within-host evolution both
in vitro
and
in vivo
.
The Obesity Paradox in Survival after Cancer Diagnosis: Tools for Evaluation of Potential Bias
Authors: Mayeda Elizabeth Rose , Glymour M. Maria 
Published: January 2017

Abstract
The effects of overweight or obesity on survival after cancer diagnosis are difficult to discern based on observational data because these associations reflect the net impact of both causal and spurious phenomena. We describe two sources of bias that might lead to underestimation of the effect of increased body weight on survival after cancer diagnosis: collider stratification bias and heterogeneity in disease bias. Given the mixed evidence on weight status, weight change, and postdiagnosis survival for cancer patients, systematic evaluation of alternative explanations is critical. The plausible magnitudes of these sources of bias can be quantified on the basis of expert knowledge about particular cancer types using simulation tools. We illustrate each type of bias, describe the assumptions researchers need make to evaluate the plausible magnitude of the bias, and provide a simple example of each bias using the setting of renal cancer. Findings from simulations, tailored to specific types of cancer, could help distinguish real from spurious effects of body weight on patient survival. Using these results can improve guidance for patients and providers about the relative importance of weight management after a diagnosis. Cancer Epidemiol Biomarkers Prev; 26(1); 17–20. ©2017 AACR.
Protective personality traits: High openness and low neuroticism linked to better memory in multiple sclerosis
Authors: Leavitt Victoria M , Buyukturkoglu Korhan , Inglese Matilde , Sumowski James F 
Published: January 2017

Background: Memory impairment in multiple sclerosis (MS) is common, although few risk/protective factors are known. Objective: To examine relationships of personality to memory/non-memory cognition in MS. Method: 80 patients completed a cognitive battery and a personality scale measuring the “Big 5” traits: openness, neuroticism, agreeableness, extraversion, and conscientiousness. Results: Memory was most related to openness, with higher openness linked to better memory and lower risk for memory impairment, controlling for age, atrophy, education, and intelligence quotient (IQ). Lower neuroticism was also related to better memory, and lower conscientiousness to memory impairment. Non-memory cognition was unrelated to personality. Conclusion: Personality may inform predictive models of memory impairment in MS.
Parallel implementation of color-based particle filter for object tracking in embedded systems
Authors: Truong Mai Thanh Nhat , Kim Sanghoon 
Published: January 2017

AbstractRecently, embedded systems have become popular because of the rising demand for portable, low-power devices. A common task for these devices is object tracking, which is an essential part of various applications. Until now, object tracking in video sequences remains a challenging problem because of the visual properties of objects and their surrounding environments. Among the common approaches, particle filter has been proven effective in dealing with difficulties in object tracking. In this research, we develop a particle filter based object tracking method using color distributions of video frames as features, and deploy it in an embedded system. Because particle filter is a high-complexity algorithm, we utilize computing power of embedded systems by implementing a parallel version of the algorithm. The experimental results show that parallelization can enhance the performance of particle filter when deployed in embedded systems.
Complete genome sequence of Pseudomonas brassicacearum strain L13-6-12, a biological control agent from the rhizosphere of potato
Authors: Zachow Christin , Müller Henry , Monk Jana , Berg Gabriele 
Published: January 2017

AbstractPseudomonas brassicacearum strain L13-6-12 is a rhizosphere colonizer of potato, lettuce and sugar beet. Previous studies have shown that this motile, Gram-negative, non-sporulating bacterium is an effective biocontrol agent against different phytopathogens. Here, we announce and describe the complete genome sequence of P. brassicacearum L13-6-12 consisting of a single 6.7 Mb circular chromosome that consists of 5773 protein coding genes and 85 RNA-only encoding genes. Genome analysis revealed genes encoding specialized functions for pathogen suppression, thriving in the rhizosphere and interacting with eukaryotic organisms.
Age-specific acceleration in malignant melanoma
Authors: Diffey Brian L , Frank Steven A 
Published: January 2017

Background:The overall incidence of melanoma has increased steadily for several years. The relative change in incidence at different ages has not been fully described. Objective:To describe how incidence at different ages has changed over time and to consider what aspects of tumour biology may explain the observed pattern of change in incidence. Methods:The slope of incidencevsage measures the acceleration of cancer incidence with age. We described the pattern of change over time in the overall incidence of melanoma, as well as in acceleration. We used data for males and females from 3 different countries in the 17 sequential 5-year birth-cohort categories from 1895-99 to 1975-79, from which we derived the incidence patterns. Results:Over time, there has been a tendency for the overall incidence of melanoma to increase and for the acceleration (slope) of the age-incidence curves to decline. The changing patterns of melanoma incidence and acceleration differ between males and females and between the countries analysed. Conclusions:The observed pattern in melanoma of rising incidence and declining acceleration occurs in other cancers in response to genetic knockouts of mechanisms that protect against cancer. Perhaps some protective mechanism with respect to melanoma may be less effective now than in the past, possibly because of more intense environmental challenges.
Healthcare benefits linked with Below Poverty Line registration in India: Observations from Maharashtra Anaemia Study (MAS)
Authors: Ahankari Anand , Fogarty Andrew , Tata Laila , Myles Puja 
Published: January 2017

A 2015 Lancet paper by Patel et al. on healthcare access in India comprehensively discussed national health programmes where some benefits are linked with the country’s Below Poverty Line (BPL) registration scheme. BPL registration aims to support poor families by providing free/subsidised healthcare. Technical issues in obtaining BPL registration by poor families have been previously reported in the Indian literature; however there are no data on family assets of BPL registrants. Here, we provide evidence of family-level assets among BPL registration holders (and non-BPL households) using original research data from the Maharashtra Anaemia Study (MAS). Social and health data from 287 pregnant women and 891 adolescent girls (representing 1178 family households) across 34 villages in Maharashtra state, India, were analysed. Several assets were shown to be similarly distributed between BPL and non-BPL households; a large proportion of families who would probably be eligible were not registered, whereas BPL-registered families often had significant assets that should not make them eligible. This is likely to be the first published evidence where asset distribution such as agricultural land, housing structures and livestock are compared between BPL and non-BPL households in a rural population. These findings may help planning BPL administration to allocate health benefits equitably, which is an integral part of national health programmes.
biojs-io-biom, a BioJS component for handling data in Biological Observation Matrix (BIOM) format
Authors: Ankenbrand Markus J. , Terhoeven Niklas , Hohlfeld Sonja , Förster Frank , Keller Alexander 
Published: January 2017

The Biological Observation Matrix (BIOM) format is widely used to store data from high-throughput studies. It aims at increasing interoperability of bioinformatic tools that process this data. However, due to multiple versions and implementation details, working with this format can be tricky. Currently, libraries in Python, R and Perl are available, whilst such for JavaScript are lacking. Here, we present a BioJS component for parsing BIOM data in all format versions. It supports import, modification, and export via a unified interface. This module aims to facilitate the development of web applications that use BIOM data. Finally, we demonstrate its usefulness by two applications that already use this component. Availability: https://github.com/molbiodiv/biojs-io-biom, https://dx.doi.org/10.5281/zenodo.218277
Factors affecting mortality in patients with COPD exacerbations requiring ICU admission
Authors: Limsuwat Chok , Nantsupawat Nopakoon , Umyarova Elvira , Ussavarungsi Kamonpun , Nugent Kenneth 
Published: January 2017

Background: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) often require hospital admission and have a significant mortality rate. Patients with AECOPD who need intensive care (ICU) have higher mortality rates. Identifying factors associated with increased mortality might change approaches to treatment and improve communication with patients’ families about prognosis. Methods: Patients with AECOPD (ICD 9 code 491.21) directly admitted to the ICU between 1/1/2006 and 12/31/2010 were retrospectively reviewed. The inclusion criteria were age 45 years or older, diagnosis of AECOPD, and admission to an ICU. The exclusion criteria included any history of another respiratory disease or decompensated cardiac disease. The primary goal was to determine factors which affect survival. Result: Two hundred and seventeen patients were included this study. The mean ages were 70.4±10.4 years in the in-hospital death group and 66.4±10.9 years in the survivors. The overall mortality rate was 12%. Multivariate analysis showed that the mortality rate was significantly associated with a low mean arterial blood pressure (MAP) (odds ratio [OR] 0.91, 95% confidence interval [CI] 0.86-0.96), an intubation event (OR 6.12, 95% CI 1.24-30.87), and an elevated blood urea nitrogen (BUN) (OR 1.06, 95% CI 1.01-1.12) (p<0.05 for each factor). Conclusion: This study identified clinical parameters associated with increased mortality in patients with AECOPD admitted to an ICU. These factors include a low MAP, intubation, and a high BUN and are easily obtained during the initial evaluation of the patient. They reflect the severity of the acute exacerbation and complications in other organ systems.
Acute respiratory distress syndrome, metabolic acidosis, and respiratory acidosis associated with citalopram overdose
Authors: Edriss Hawa , Pfarr Marie 
Published: January 2017

We report a 53-year-old man who ingested 2400 mg of citalopram and presented to the emergency department three hours post-ingestion with altered mental status, somnolence, and a blood pressure of 67/45 mmHg. He failed to respond to three boluses of normal saline (1000 ml each) and required vasopressors. The patient developed serotonin syndrome with hyper-reflexia, rigidity, and ankle myoclonus. He had a tonic-clonic seizure in the ER requiring intravenous lorazepam and phenytoin. An ECG showed QT prolongation. Chest x-ray on presentation was normal. Within 32 hours the patient developed acute respiratory distress, hypoxemia, a wide A-a gradient, PaO2/FiO2< 200, and chest x-ray changes compatible with acute respiratory distress syndrome (ARDS). He had normal central venous pressures, normal cardiac biomarkers, normal systolic and diastolic functions on echocardiography, and no acute ST/T wave changes. His ABG showed a metabolic acidosis and a respiratory acidosis. The patient required intubation and ventilation. Citalopram has been associated with seizures and ECG abnormalities after overdoses. The respiratory complications and metabolic acidosis have been reported only a few times in the literature. We are reporting the second case of ARDS and the fifth case of metabolic acidosis due to citalopram overdose and suggest that the metabolic acidemia is explained by propionic acid. The respiratory acidosis seen in this patient has not been reported previously.