bluuebunny/crossref_metadata_2025_split huggingface dataset:
Syndromic Panel-Based Testing in Clinical Microbiology
Authors: Ramanan Poornima , Bryson Alexandra L. , Binnicker Matthew J. , Pritt Bobbi S. , Patel Robin 
Published: November 2017

SUMMARY
The recent development of commercial panel-based molecular diagnostics for the rapid detection of pathogens in positive blood culture bottles, respiratory specimens, stool, and cerebrospinal fluid has resulted in a paradigm shift in clinical microbiology and clinical practice. This review focuses on U.S. Food and Drug Administration (FDA)-approved/cleared multiplex molecular panels with more than five targets designed to assist in the diagnosis of bloodstream, respiratory tract, gastrointestinal, or central nervous system infections. While these panel-based assays have the clear advantages of a rapid turnaround time and the detection of a large number of microorganisms and promise to improve health care, they present certain challenges, including cost and the definition of ideal test utilization strategies (i.e., optimal ordering) and test interpretation.
Quantitative Analysis of Gamma Interferon Release Assay Response in Children with Latent and Active Tuberculosis
Authors: Lombardi Giulia , Petrucci Roberta , Corsini Ilaria , Bacchi Reggiani Maria Letizia , Visciotti Francesca , Bernardi Filippo , Landini Maria Paola , Cazzato Salvatore , Dal Monte Paola 
Published: November 2017

ABSTRACT

The use of interferon gamma (IFN-γ) release assays (IGRAs) for the diagnosis of tuberculosis (TB) infection in children is still under debate because of concerns about the immature immune response in children. The aim of this study was to investigate quantitative values of the QuantiFERON-TB Gold In-Tube (QFT-IT) test, a commercially available IGRA, in a large cohort of children screened for TB infection. A retrospective analysis was conducted on samples from 517 children aged 0 to 14 years old at the Pediatric Unit of S. Orsola-Malpighi University Hospital of Bologna (Italy); quantitative responses to QFT-IT stimuli were analyzed according to diagnosis and age. Elevated IFN-γ values in the QFT-IT nil (background) tube were statistically associated with diagnosis of active TB. Quantitative IFN-γ response to
Mycobacterium tuberculosis
-specific antigens (TB Ag) was not significantly different in children with active TB compared to those with latent TB infection (LTBI), even though the median values were higher in the first group. When children were grouped by age, those less than 5 years old produced significantly higher levels of IFN-γ in response to TB Ag if they had active TB (median 10 IU/ml) than those with LTBI (median 1.96 IU/ml). IFN-γ response to mitogen increased with age. The overall rate of indeterminate results was low (3.9%), and no indeterminate QFT-IT values were observed in active or latent TB patients. In conclusion, quantitative QFT-IT values could provide further information to clinicians to manage TB in children, and these observations could be transferred to the new version of the test, QuantiFERON-TB Gold Plus, which to date lacks data from the pediatric population.
Single-Dose Trivalent VesiculoVax Vaccine Protects Macaques from Lethal Ebolavirus and Marburgvirus Challenge
Authors: Matassov Demetrius , Mire Chad E. , Latham Theresa , Geisbert Joan B. , Xu Rong , Ota-Setlik Ayuko , Agans Krystle N. , Kobs Dean J. , Wendling Morgan Q. S. , Burnaugh Amanda , Rudge Thomas L. , Sabourin Carol L. , Egan Michael A. , Clarke David K. , Geisbert Thomas W. , Eldridge John H. 
Published: November 2017

ABSTRACT

Previous studies demonstrated that a single intramuscular (i.m.) dose of an attenuated recombinant vesicular stomatitis virus (rVSV) vector (VesiculoVax vector platform; rVSV-N4CT1) expressing the glycoprotein (GP) from the Mayinga strain of
Zaire ebolavirus
(EBOV) protected nonhuman primates (NHPs) from lethal challenge with EBOV strains Kikwit and Makona. Here, we studied the immunogenicities of an expanded range of attenuated rVSV vectors expressing filovirus GP in mice. Based on data from those studies, an optimal attenuated trivalent rVSV vector formulation was identified that included rVSV vectors expressing EBOV,
Sudan ebolavirus
(SUDV), and the Angola strain of
Marburg marburgvirus
(MARV) GPs. NHPs were vaccinated with a single dose of the trivalent formulation, followed by lethal challenge 28 days later with each of the three corresponding filoviruses. At day 14 postvaccination, a serum IgG response specific for all three GPs was detected in all the vaccinated macaques. A modest and balanced cell-mediated immune response specific for each GP was also detected in a majority of the vaccinated macaques. No matter the level of total GP-specific immune response detected postvaccination, all the vaccinated macaques were protected from disease and death following lethal challenge with each of the three filoviruses. These findings indicate that vaccination with a single dose of attenuated rVSV-N4CT1 vectors each expressing a single filovirus GP may provide protection against the filoviruses most commonly responsible for outbreaks of hemorrhagic fever in sub-Saharan Africa.

IMPORTANCE
The West African Ebola virus Zaire outbreak in 2013 showed that the disease was not only a regional concern, but a worldwide problem, and highlighted the need for a safe and efficacious vaccine to be administered to the populace. However, other endemic pathogens, like Ebola virus Sudan and Marburg, also pose an important health risk to the public and therefore require development of a vaccine prior to the occurrence of an outbreak. The significance of our research was the development of a blended trivalent filovirus vaccine that elicited a balanced immune response when administered as a single dose and provided complete protection against a lethal challenge with all three filovirus pathogens.
Adaptive Immune Responses following Senecavirus A Infection in Pigs
Authors: Maggioli Mayara F. , Lawson Steve , de Lima Marcelo , Joshi Lok R. , Faccin Tatiane C. , Bauermann Fernando V. , Diel Diego G. 
Published: November 2017

ABSTRACT

Senecavirus A (SVA), an emerging picornavirus of swine, causes vesicular disease (VD) that is clinically indistinguishable from foot-and-mouth disease (FMD) in pigs. Many aspects of SVA interactions with the host and the host immune responses to infection, however, remain unknown. In the present study, humoral and cellular immune responses to SVA were evaluated following infection in pigs. We show that SVA infection elicited an early and robust virus-neutralizing (VN) antibody response, which coincided and was strongly correlated with VP2- and VP3-specific IgM responses. Notably, the neutralizing antibody (NA) responses paralleled the reduction of viremia and resolution of the disease. Analysis of the major porcine T-cell subsets revealed that during the acute/clinical phase of SVA infection (14 days postinfection [p.i.]), T-cell responses were characterized by an increased frequency of αβ T cells, especially CD4
+
T cells, which were first detected by day 7 p.i. and increased in frequency until day 14 p.i. Additionally, the frequency of CD8
+
and double-positive CD4
+
CD8
+
T cells (effector/memory T cells) expressing interferon gamma (IFN-γ) or proliferating in response to SVA antigen stimulation increased after day 10 p.i. Results presented here show that SVA elicits B- and T-cell activation early upon infection, with IgM antibody levels being correlated with early neutralizing activity against the virus and peak B- and T-cell responses paralleling clinical resolution of the disease. The work provides important insights into the immunological events that follow SVA infection in the natural host.

IMPORTANCE
Senecavirus A (SVA) has recently emerged in swine, causing outbreaks of vesicular disease (VD) in major swine-producing countries around the world, including the United States, Brazil, China, Thailand, and Colombia. Notably, SVA-induced disease is clinically indistinguishable from other high-consequence VDs of swine, such as FMD, swine vesicular disease, vesicular stomatitis, and vesicular exanthema of swine. Despite the clinical relevance of SVA-induced VD, many aspects of the virus infection biology remain unknown. Here, we assessed host immune responses to SVA infection. The results show that SVA infection elicits early B- and T-cell responses, with the levels of VN antibody and CD4
+
T-cell responses paralleling the reduction of viremia and resolution of the disease. SVA-specific CD8
+
T cells are detected later during infection. A better understanding of SVA interactions with the host immune system may allow the design and implementation of improved control strategies for this important pathogen of swine.
Interaction between a Unique Minor Protein and a Major Capsid Protein of Bluetongue Virus Controls Virus Infectivity
Authors: Matsuo Eiko , Yamazaki Kiyoshi , Tsuruta Hiroki , Roy Polly 
Published: November 2017

ABSTRACT

Among the
Reoviridae
family of double-stranded RNA viruses, only members of the
Orbivirus
genus possess a unique structural protein, termed VP6, within their particles. Bluetongue virus (BTV), an important livestock pathogen, is the prototype
Orbivirus
. BTV VP6 is an ATP-dependent RNA helicase, and it is indispensable for virus replication. In the study described in this report, we investigated how VP6 might be recruited to the virus capsid and whether the BTV structural protein VP3, which forms the internal layer of the virus capsid core, is involved in VP6 recruitment. We first demonstrated that VP6 interacts with VP3 and colocalizes with VP3 during capsid assembly. A series of VP6 mutants was then generated, and in combination with immunoprecipitation and size exclusion chromatographic analyses, we demonstrated that VP6 directly interacts with VP3 via a specific region of the C-terminal portion of VP6. Finally, using our reverse genetics system, mutant VP6 proteins were introduced into the BTV genome and interactions between VP6 and VP3 were shown in a live cell system. We demonstrate that BTV strains possessing a mutant VP6 are replication deficient in wild-type BSR cells and fail to recruit the viral replicase complex into the virus particle core. Taken together, these data suggest that the interaction between VP3 and VP6 could be important in the packaging of the viral genome and early stages of particle formation.

IMPORTANCE
The orbivirus bluetongue virus (BTV) is the causative agent of bluetongue disease of livestock, often causing significant economic and agricultural impacts in the livestock industry. In the study described in this report, we identified the essential region and residues of the unique orbivirus capsid protein VP6 which are responsible for its interaction with other BTV proteins and its subsequent recruitment into the virus particle. The nature and mechanism of these interactions suggest that VP6 has a key role in packaging of the BTV genome into the virus particle. As such, this is a highly significant finding, as this new understanding of BTV assembly could be exploited to design novel vaccines and antivirals against bluetongue disease.
Antenatal Bartter syndrome presenting with vomiting and constipation mimicking subacute intestinal obstruction in a 20-day-old neonate
Authors: Abdelgadir Ibtihal Siddiq , Elgharbawy Fawzia , Salameh Khalil Mohamad , Juma Baha Eldin 
Published: November 2017

Antenatal Bartter syndrome is a rare condition that can present with different clinical features. These features include early onset maternal polyhydramnios, failure to thrive, prematurity and nephrocalcinosis.We are presenting this 20-day-old girl who had an antenatal history of polyhydramnios. She developed persistent non-bilious vomiting that was associated with constipation soon after birth. She presented with failure to thrive and features suggestive of intestinal obstruction. On the initial evaluation, she was noted to have hypokalaemic, hyponatraemic metabolic alkalosis. The initial work-up was done to exclude surgical and renal causes of her presentation, and the diagnosis was confirmed by gene analysis to be type III—classic Bartter syndrome. She was closely monitored for her growth and development with the appropriate salt replacement therapy.
Effects of health and social care spending constraints on mortality in England: a time trend analysis
Authors: Watkins Johnathan , Wulaningsih Wahyu , Da Zhou Charlie , Marshall Dominic C , Sylianteng Guia D C , Dela Rosa Phyllis G , Miguel Viveka A , Raine Rosalind , King Lawrence P , Maruthappu Mahiben 
Published: November 2017

ObjectiveSince 2010, England has experienced relative constraints in public expenditure on healthcare (PEH) and social care (PES). We sought to determine whether these constraints have affected mortality rates.MethodsWe collected data on health and social care resources and finances for England from 2001 to 2014. Time trend analyses were conducted to compare the actual mortality rates in 2011–2014 with the counterfactual rates expected based on trends before spending constraints. Fixed-effects regression analyses were conducted using annual data on PES and PEH with mortality as the outcome, with further adjustments for macroeconomic factors and resources. Analyses were stratified by age group, place of death and lower-tier local authority (n=325). Mortality rates to 2020 were projected based on recent trends.ResultsSpending constraints between 2010 and 2014 were associated with an estimated 45 368 (95% CI 34 530 to 56 206) higher than expected number of deaths compared with pre-2010 trends. Deaths in those aged ≥60 and in care homes accounted for the majority. PES was more strongly linked with care home and home mortality than PEH, with each £10 per capita decline in real PES associated with an increase of 5.10 (3.65–6.54) (p<0.001) care home deaths per 100 000. These associations persisted in lag analyses and after adjustment for macroeconomic factors. Furthermore, we found that changes in real PES per capita may be linked to mortality mostly via changes in nurse numbers. Projections to 2020 based on 2009-2014 trend was cumulatively linked to an estimated 152 141 (95% CI 134 597 and 169 685) additional deaths.ConclusionsSpending constraints, especially PES, are associated with a substantial mortality gap. We suggest that spending should be targeted on improving care delivered in care homes and at home; and maintaining or increasing nurse numbers.
Emergency versus standard response: time efficacy of London’s Air Ambulance rapid response vehicle
Authors: Rehn Marius , Davies Gareth , Smith Paul , Lockey David 
Published: November 2017

ObjectiveThe potential increased risk of an emergency response using a rapid response vehicle (RRV) should only be accepted when it allows a clinically significant time saving for management of patients who are critically injured or sick. Air ambulance services often use an RRV to maintain operational resilience. We compared the RRV response time on emergency versus standard driving to inform emergency services of time efficacy of emergency response in an urban environment.MethodsProspective observational controlled study of response data of emergency and standard driving. An identical RRV shadowed the medical team until the team was dispatched to a job (emergency driving). The shadow RRV then drove to the same given location from the same origin location in equal traffic conditions being compliant with all traffic signals, road signs and speed limits (standard driving).ResultsThe emergency response resulted in an estimated reduction in median response time of 14 min (95% CI 9 to 19) which represented a time saving of 54.9%. The estimated difference in distance travelled (0.6 km) was not statistically significant. Median speed was significantly higher when using an emergency response (46.1 IQR 39–53.4 km/hour) versus standard response (20.1 IQR 16.3–24.7 km/hour), with an estimated difference of −24.5 km/hour (95% CI −28.8 to −20.5).ConclusionsThe current study found RRVs to be significantly quicker when responding with lights, sirens and traffic rule exemptions compared with a response being compliant with all traffic signals, road signs and speed limits.
Evaluation of a single‐administration ototopical treatment for canine otitis externa: a randomised trial
Authors: Blake John , Keil Daniel , Kwochka Kenneth , Palma Kathleen , Schofield Jennifer 
Published: November 2017

ObjectiveTo evaluate the efficacy and safety of a new, single‐administration Otic Solution containing florfenicol, terbinafine and mometasone furoate for the treatment of canine otitis externa (OE).DesignThe clinical efficacy and safety study was a multicentre, controlled, masked and randomised field study conducted over 30 days. Two hundred and twenty‐one (221) client‐owned dogs of varying breeds with diagnosed bacterial and/or fungal OE were enrolled.ProcedureDogs were randomised to either Otic Solution or control groups. Evaluations were conducted over a minimum period of 30 days with a primary effectiveness endpoint based on the improvement in a clinical severity score at the final visit (day 30). Safety analyses were based on clinical and laboratory parameters and the occurrence of adverse events.ResultsThe Otic Solution group demonstrated a significantly higher treatment success rate compared with that observed for the control group (72.5 per cent v 11.1 per cent, P value=0.0001) for cases of OE caused by Staphylococcus pseudintermedius and Malassezia pachydermatis. No significant safety findings were reported.Conclusions/clinical relevanceThis new ototopical formulation provides safe and effective treatment of canine OE and is an important alternative antimicrobial for this indication. The single‐administration dosage regimen eliminates opportunities for client dosage administration errors and medication stockpiling.
Short note on the number of 1-ascents in dispersed Dyck paths
Authors: Kangro Kairi , Pourmoradnasseri Mozhgan , Theis Dirk Oliver 
Published: November 2017

A dispersed Dyck path (DDP) of length [Formula: see text] is a lattice path on [Formula: see text] from [Formula: see text] to [Formula: see text] in which the following steps are allowed: “up” [Formula: see text]; “down” [Formula: see text]; and “right” [Formula: see text]. An ascent in a DDP is an inclusion-wise maximal sequence of consecutive up steps. A 1-ascent is an ascent consisting of exactly 1 up step. We give a closed formula for the total number of 1-ascents in all dispersed Dyck paths of length [Formula: see text], #A191386 in Sloane’s OEIS. Previously, only implicit generating function relations and asymptotics were known.
Developmental changes in spinal neuronal properties, motor network configuration, and neuromodulation at free-swimming stages ofXenopustadpoles
Authors: Currie Stephen P. , Sillar Keith T. 
Published: November 2017

We describe a novel preparation of the isolated brain stem and spinal cord from prometamorphic tadpole stages of the South African clawed frog ( Xenopus laevis) that permits whole cell patch-clamp recordings from neurons in the ventral spinal cord. Previous research on earlier stages of the same species has provided one of the most detailed understandings of the design and operation of a central pattern generator circuit. Here we have addressed how development sculpts complexity from this more basic circuit. The preparation generates bouts of fictive swimming activity either spontaneously or in response to electrical stimulation of the optic tectum, allowing an investigation into how the neuronal properties, activity patterns, and neuromodulation of locomotor rhythm generation change during development. We describe an increased repertoire of cellular responses compared with younger larval stages and investigate the cellular-level effects of nitrergic neuromodulation as well as the development of a sodium pump-mediated ultraslow afterhyperpolarization (usAHP) in these free-swimming larval animals.NEW & NOTEWORTHY A novel in vitro brain stem-spinal cord preparation is described that enables whole cell patch-clamp recordings from spinal neurons in prometamorphic Xenopus tadpoles. Compared with the well-characterized earlier stages of development, spinal neurons display a wider range of firing properties during swimming and have developed novel cellular properties. This preparation now makes it feasible to investigate in detail spinal central pattern generator maturation during the dramatic switch between undulatory and limb-based locomotion strategies during amphibian metamorphosis.
Standardized automated training of rhesus monkeys for neuroscience research in their housing environment
Authors: Berger M. , Calapai A. , Stephan V. , Niessing M. , Burchardt L. , Gail A. , Treue S. 
Published: November 2017

Teaching nonhuman primates the complex cognitive behavioral tasks that are central to cognitive neuroscience research is an essential and challenging endeavor. It is crucial for the scientific success that the animals learn to interpret the often complex task rules and reliably and enduringly act accordingly. To achieve consistent behavior and comparable learning histories across animals, it is desirable to standardize training protocols. Automatizing the training can significantly reduce the time invested by the person training the animal. In addition, self-paced training schedules with individualized learning speeds based on automatic updating of task conditions could enhance the animals’ motivation and welfare. We developed a training paradigm for across-task unsupervised training (AUT) of successively more complex cognitive tasks to be administered through a stand-alone housing-based system optimized for rhesus monkeys in neuroscience research settings (Calapai A, Berger M, Niessing M, Heisig K, Brockhausen R, Treue S, Gail A. Behav Res Methods 5: 1–11, 2016). The AUT revealed interindividual differences in long-term learning progress between animals, helping to characterize learning personalities, and commonalities, helping to identify easier and more difficult learning steps in the training protocol. Our results demonstrate that 1) rhesus monkeys stay engaged with the AUT over months despite access to water and food outside the experimental sessions but with lower numbers of interaction compared with conventional fluid-controlled training; 2) with unsupervised training across sessions and task levels, rhesus monkeys can learn tasks of sufficient complexity for state-of-the-art cognitive neuroscience in their housing environment; and 3) AUT learning progress is primarily determined by the number of interactions with the system rather than the mere exposure time. NEW & NOTEWORTHY We demonstrate that highly structured training of behavioral tasks, as used in neuroscience research, can be achieved in an unsupervised fashion over many sessions and task difficulties in a monkey housing environment. Employing a predefined training strategy allows for an observer-independent comparison of learning between animals and of training approaches. We believe that self-paced standardized training can be utilized for pretraining and animal selection and can contribute to animal welfare in a neuroscience research environment.