bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ghost marker detection and elimination in marker‐based optical tracking systems for real‐time tracking in stereotactic body radiotherapy
Authors: Yan Guanghua , Li Jonathan , Huang Yin , Mittauer Kathryn , Lu Bo , Liu Chihray 
Published: October 2014

Purpose:To propose a simple model to explain the origin of ghost markers in marker‐based optical tracking systems (OTS) and to develop retrospective strategies to detect and eliminate ghost markers.Methods:In marker‐based OTS, ghost markers are virtual markers created due to the cross‐talk between the two camera sensors, which can lead to system execution failure or inaccuracy in patient tracking. As a result, the users have to limit the number of markers and avoid certain marker configurations to reduce the chances of ghost markers. In this work, the authors propose retrospective strategies to detect and eliminate ghost markers. The two camera sensors were treated as mathematical points in space. The authors identified the coplanar within limit (CWL) condition as the necessary condition for ghost marker occurrence. A simple ghost marker detection method was proposed based on the model. Ghost marker elimination was achieved through pattern matching: a ghost marker‐free reference set was matched with the optical marker set observed by the OTS; unmatched optical markers were eliminated as either ghost markers or misplaced markers. The pattern matching problem was formulated as a constraint satisfaction problem (using pairwise distances as constraints) and solved with an iterative backtracking algorithm. Wildcard markers were introduced to address missing or misplaced markers. An experiment was designed to measure the sensor positions and the limit for the CWL condition. The ghost marker detection and elimination algorithms were verified with samples collected from a five‐marker jig and a nine‐marker anthropomorphic phantom, rotated with the treatment couch from −60° to +60°. The accuracy of the pattern matching algorithm was further validated with marker patterns from 40 patients who underwent stereotactic body radiotherapy (SBRT). For this purpose, a synthetic optical marker pattern was created for each patient by introducing ghost markers, marker position uncertainties, and marker displacement.Results:The sensor positions and the limit for the CWL condition were measured with excellent reproducibility (standard deviation ≤ 0.39 mm). The ghost marker detection algorithm had perfect detection accuracy for both the jig (1544 samples) and the anthropomorphic phantom (2045 samples). Pattern matching was successful for all samples from both phantoms as well as the 40 patient marker patterns.Conclusions:The authors proposed a simple model to explain the origin of ghost markers and identified the CWL condition as the necessary condition for ghost marker occurrence. The retrospective ghost marker detection and elimination algorithms guarantee complete ghost marker elimination while providing the users with maximum flexibility in selecting the number of markers and their configuration to meet their clinic needs.
Tracking cancer drugs in living cells by thermal profiling of the proteome
Authors: Savitski Mikhail M. , Reinhard Friedrich B. M. , Franken Holger , Werner Thilo , Savitski Maria Fälth , Eberhard Dirk , Molina Daniel Martinez , Jafari Rozbeh , Dovega Rebecca Bakszt , Klaeger Susan , Kuster Bernhard , Nordlund Pär , Bantscheff Marcus , Drewes Gerard 
Published: October 2014

Mapping human drug targets in the cellTo understand both the beneficial and the side effects of a drug, one would need to know its full binding profile to all cellular proteins. Savitskiet al.take significant steps toward meeting this daunting challenge. They monitored the unfolding or “melting” of over 7000 human proteins and measured how small-molecule binding changes individual melting profiles. As a proof of principle, over 50 targets were identified for an inhibitor known to bind a broad spectrum of kinases. Two cancer drugs, vemurafib and Alectinib, are known to have a side effect of photosensitivity. The thermal profiling approach identified drug-protein interactions responsible for these side effects.Science, this issue10.1126/science.1255784
Emerging Technologies for the Clinical Microbiology Laboratory
Authors: Buchan Blake W. , Ledeboer Nathan A. 
Published: October 2014

SUMMARYIn this review we examine the literature related to emerging technologies that will help to reshape the clinical microbiology laboratory. These topics include nucleic acid amplification tests such as isothermal and point-of-care molecular diagnostics, multiplexed panels for syndromic diagnosis, digital PCR, next-generation sequencing, and automation of molecular tests. We also review matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) and electrospray ionization (ESI) mass spectrometry methods and their role in identification of microorganisms. Lastly, we review the shift to liquid-based microbiology and the integration of partial and full laboratory automation that are beginning to impact the clinical microbiology laboratory.
Pharmacokinetics and Pharmacodynamics of Aerosolized Antibacterial Agents in Chronically Infected Cystic Fibrosis Patients
Authors: Dalhoff Axel 
Published: October 2014

SUMMARY
Bacteria adapt to growth in lungs of patients with cystic fibrosis (CF) by selection of heterogeneously resistant variants that are not detected by conventional susceptibility testing but are selected for rapidly during antibacterial treatment. Therefore, total bacterial counts and antibiotic susceptibilities are misleading indicators of infection and are not helpful as guides for therapy decisions or efficacy endpoints. High drug concentrations delivered by aerosol may maximize efficacy, as decreased drug susceptibilities of the pathogens are compensated for by high target site concentrations. However, reductions of the bacterial load in sputum and improvements in lung function were within the same ranges following aerosolized and conventional therapies. Furthermore, the use of conventional pharmacokinetic/pharmacodynamic (PK/PD) surrogates correlating pharmacokinetics in serum with clinical cure and presumed or proven eradication of the pathogen as a basis for PK/PD investigations in CF patients is irrelevant, as minimization of systemic exposure is one of the main objectives of aerosolized therapy; in addition, bacterial pathogens cannot be eradicated, and chronic infection cannot be cured. Consequently, conventional PK/PD surrogates are not applicable to CF patients. It is nonetheless obvious that systemic exposure of patients, with all its sequelae, is minimized and that the burden of oral treatment for CF patients suffering from chronic infections is reduced.
Microbiology, Genomics, and Clinical Significance of the Pseudomonas fluorescens Species Complex, an Unappreciated Colonizer of Humans
Authors: Scales Brittan S. , Dickson Robert P. , LiPuma John J. , Huffnagle Gary B. 
Published: October 2014

SUMMARYPseudomonas fluorescensis not generally considered a bacterial pathogen in humans; however, multiple culture-based and culture-independent studies have identified it at low levels in the indigenous microbiota of various body sites. With recent advances in comparative genomics, many isolates originally identified as the “species”P. fluorescensare now being reclassified as novelPseudomonasspecies within theP. fluorescens“species complex.” Although most widely studied for its role in the soil and the rhizosphere,P. fluorescenspossesses a number of functional traits that provide it with the capability to grow and thrive in mammalian hosts. While significantly less virulent thanP. aeruginosa,P. fluorescenscan cause bacteremia in humans, with most reported cases being attributable either to transfusion of contaminated blood products or to use of contaminated equipment associated with intravenous infusions. Although not suspected of being an etiologic agent of pulmonary disease, there are a number of reports identifying it in respiratory samples. There is also an intriguing association betweenP. fluorescensand human disease, in that approximately 50% of Crohn's disease patients develop serum antibodies toP. fluorescens. Altogether, these reports are beginning to highlight a far more common, intriguing, and potentially complex association between humans andP. fluorescensduring health and disease.
Coagulase-Negative Staphylococci
Authors: Becker Karsten , Heilmann Christine , Peters Georg 
Published: October 2014

SUMMARYThe definition of the heterogeneous group of coagulase-negative staphylococci (CoNS) is still based on diagnostic procedures that fulfill the clinical need to differentiate betweenStaphylococcus aureusand those staphylococci classified historically as being less or nonpathogenic. Due to patient- and procedure-related changes, CoNS now represent one of the major nosocomial pathogens, withS. epidermidisandS. haemolyticusbeing the most significant species. They account substantially for foreign body-related infections and infections in preterm newborns. WhileS. saprophyticushas been associated with acute urethritis,S. lugdunensishas a unique status, in some aspects resemblingS. aureusin causing infectious endocarditis. In addition to CoNS found as food-associated saprophytes, many other CoNS species colonize the skin and mucous membranes of humans and animals and are less frequently involved in clinically manifested infections. This blurred gradation in terms of pathogenicity is reflected by species- and strain-specific virulence factors and the development of different host-defending strategies. Clearly, CoNS possess fewer virulence properties thanS. aureus, with a respectively different disease spectrum. In this regard, host susceptibility is much more important. Therapeutically, CoNS are challenging due to the large proportion of methicillin-resistant strains and increasing numbers of isolates with less susceptibility to glycopeptides.
Effectiveness of the E2-Classical Swine Fever Virus Recombinant Vaccine Produced and Formulated within Whey from Genetically Transformed Goats
Authors: Sánchez O. , Barrera M. , Farnós O. , Parra N. C. , Salgado E. R. , Saavedra P. A. , Meza C. D. , Rivas C. I. , Cortez-San Martín M. , Toledo J. R. 
Published: October 2014

ABSTRACTSubunit recombinant vaccines against classical swine fever virus (CSFV) are a promising alternative to overcome practical and biosafety issues with inactivated vaccines. One of the strategies in evaluation under field conditions is the use of a new marker E2-based vaccine produced in the milk of adenovirally transduced goats. Previously we had demonstrated the efficacy of this antigen, which conferred early protection and long-lasting immunity in swine against CSFV infection. Here, we have used a simpler downstream process to obtain and formulate the recombinant E2 glycoprotein expressed in the mammary gland. The expression levels reached approximately 1.7 mg/ml, and instead of chromatographic separation of the antigen, we utilized a clarification process that eliminates the fat content, retains a minor amount of caseins, and includes an adenoviral inactivation step that improves the biosafety of the final formulation. In a vaccination and challenge experiment in swine, different doses of the E2 antigen contained within the clarified whey generated an effective immune response of neutralizing antibodies that protected all of the animals against a lethal challenge with CSFV. During the immunization and after challenge, the swine were monitored for adverse reactions related to the vaccine or symptoms of CSF, respectively. No adverse reactions or clinical signs of disease were observed in vaccinated animals, in which no replication of CSFV could be detected after challenge. Overall, we consider that the simplicity of the procedures proposed here is a further step toward the introduction and implementation of a commercial subunit vaccine against CSF.
Multiple Low-Dose Challenges in a Rhesus Macaque AIDS Vaccine Trial Result in an Evolving Host Response That Affects Protective Outcome
Authors: Selinger Christian , Strbo Natasa , Gonzalez Louis , Aicher Lauri , Weiss Jeffrey M. , Law G. Lynn , Palermo Robert E. , Vaccari Monica , Franchini Genoveffa , Podack Eckhard R. , Katze Michael G. 
Published: October 2014

ABSTRACTUsing whole-blood transcriptional profiling, we investigated differences in the host response to vaccination and challenge in a rhesus macaque AIDS vaccine trial. Samples were collected from animals prior to and after vaccination with live, irradiated vaccine cells secreting the modified endoplasmic reticulum chaperone gp96-Ig loaded with simian immunodeficiency virus (SIV) peptides, either alone or in combination with a SIV-gp120 protein boost. Additional samples were collected following multiple low-dose rectal challenges with SIVmac251. Animals in the boosted group had a 73% reduced risk of infection. Surprisingly, few changes in gene expression were observed during the vaccination phase. Focusing on postchallenge comparisons, in particular for protected animals, we identified a host response signature of protection comprised of strong interferon signaling after the first challenge, which then largely abated after further challenges. We also identified a host response signature, comprised of early macrophage-mediated inflammatory responses, in animals with undetectable viral loads 5 days after the first challenge but with unusually high viral titers after subsequent challenges. Statistical analysis showed that prime-boost vaccination significantly lowered the probability of infection in a time-consistent manner throughout several challenges. Given that humoral responses in the prime-boost group were highly significant prechallenge correlates of protection, the strong innate signaling after the first challenge suggests that interferon signaling may enhance vaccine-induced antibody responses and is an important contributor to protection from infection during repeated low-dose exposure to SIV.
Field Evaluation of the InBios Chagas Detect Plus Rapid Test in Serum and Whole-Blood Specimens in Bolivia
Authors: Shah Vishal , Ferrufino Lisbeth , Gilman Robert H. , Ramirez Margot , Saenza Eliana , Malaga Edith , Sanchez Gerardo , Okamoto Emi E. , Sherbuck Jacqueline E. , Clark Eva H. , Galdos-Cardenas Gerson , Bozo Ricardo , Flores-Franco Jorge Luis , Colanzi Rony , Verastegui Manuela , Bern Caryn 
Published: October 2014

ABSTRACTTrypanosoma cruzicauses Chagas disease, which affects an estimated 7 million to 8 million people. Chagas disease is endemic throughout Latin America, with the highest prevalence in Bolivia. Conventional diagnosis requires a well-equipped laboratory with experienced personnel. We evaluated the Chagas Detect Plus (CDP) (InBios, Seattle, WA), a rapid immunochromatographic assay for IgG antibodies toT. cruzi. CDP performance was compared to infection status based on results obtained by indirect hemagglutination assay, immunofluorescent-antibody test, and enzyme-linked immunosorbent assay. Confirmed infection required positive results by at least 2 conventional assays. We used specimens from adults of both sexes in a general hospital in the city of Santa Cruz and from pregnant women in a hospital and children in villages in the Bolivian Chaco, an area of hyperendemicity. CDP was performed in paired whole-blood and serum specimens from 385 individuals in the two hospital studies and in 200 serum specimens from the community study. CDP showed sensitivities/specificities of 96.2% (95% confidence interval, 92.7 to 98.4)/98.8% (95.9 to 99.9) in whole blood and 99.3% (97.5 to 99.9)/96.9% (94.2 to 98.6) in serum, with no differences by sex, age group, or study site. CDP showed excellent sensitivity and specificity in our study population, comparable to those of conventional serology. The test is reliable for field surveys, requires no laboratory equipment, and performed well in serum and whole blood. The CDP could also be used for accurate maternal screening to identify neonates at risk of congenital transmission. CDP performance data in diverse geographic areas are needed to strengthen the evidence base for its use.
Acidovorax oryzae Catheter-Associated Bloodstream Infection
Authors: Orsborne Christopher , Hardy Alison , Isalska Barbara , Williams Simon G. , Muldoon Eavan G. 
Published: October 2014

ABSTRACT

Acidovorax oryzae
is a bacterium that has never before been reported as pathogenic in human subjects. Here we describe the first case of a successfully treated
A. oryzae
catheter-associated bloodstream infection in an immunocompetent patient prior to heart transplantation.
Pattern of Circulation of Norovirus GII Strains during Natural Infection
Authors: Ayukekbong James Ayukepi , Fobisong Cajetan , Tah Ferdinand , Lindh Magnus , Nkuo-Akenji Theresia , Bergström Tomas 
Published: October 2014

ABSTRACT
Norovirus (NoV) is considered a major cause of nonbacterial gastroenteritis among people of all ages worldwide, but the natural course of infection is incompletely known. In this study, the pattern of circulation of NoVs was studied among 146 children and 137 adults in a small community in southwestern Cameroon. The participants provided monthly fecal samples during a year. NoV RNA was detected in at least one sample from 82 (29%) of the participants. The partial VP1 region could be sequenced in 36 NoV GII-positive samples. Three different genotypes were identified (GII.1, GII.4, and GII.17), with each genotype circulating within 2 to 3 months and reappearing after a relapse period of 2 to 3 months. Most infections occurred once, and 2 episodes at most within a year were detected. No difference in the frequency of NoV infection between children and adults was recorded. The same genotype was detected for a maximum of 2 consecutive months in 3 children only, suggesting that a less than 30-day duration of viral shedding in natural infection was common. Reinfection within a year with the same genotype was not observed, consistent with short-term homotypic immune protection. The study revealed that NoV strains are circulating with a limited duration of viral shedding both in the individuals and the population as part of their natural infection. The results also provide evidence of cross-protective immunity of limited duration between genotypes of the same genogroup.
Rapid Identification of Pathogens from Pediatric Blood Cultures by Use of the FilmArray Blood Culture Identification Panel
Authors: Zheng Xiaotian , Polanco Wanda , Carter Donna , Shulman Stanford 
Published: October 2014

ABSTRACT
The performance of the FilmArray blood culture identification (BCID) panel has been studied in adult patients. We describe here an evaluation of this assay for the rapid identification of pathogens in Bactec Peds Plus/F and Bactec standard anaerobic/F bottles that contained blood samples from pediatric patients at a tertiary care children's hospital.
Development and Optimization of a Real-Time PCR Assay for Detection of Herpes Simplex and Varicella-Zoster Viruses in Skin and Mucosal Lesions by Use of the BD Max Open System
Authors: Cárdenas Ana María , Edelstein Paul H. , Alby Kevin 
Published: October 2014

ABSTRACT
We transitioned laboratory-developed PCR assays for herpes simplex virus 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV) to the BD Max system by using BD Max open system reagents. After optimization, the agreement with the reference PCR assay was 100% (123/123) for HSV-1, 96.7% (119/123) for HSV-2, and 100% (60/60) for VZV using retrospective clinical samples.
Multiplex PCR for Detection of Seven Virulence Factors and K1/K2 Capsular Serotypes of Klebsiella pneumoniae
Authors: Compain Fabrice , Babosan Ana , Brisse Sylvain , Genel Nathalie , Audo Jennifer , Ailloud Florent , Kassis-Chikhani Najiby , Arlet Guillaume , Decré Dominique 
Published: October 2014

ABSTRACT

A single multiplex PCR assay targeting seven virulence factors and the
wzi
gene specific for the K1 and K2 capsular serotypes of
Klebsiella pneumoniae
was developed and tested on 65 clinical isolates, which included 45 isolates responsible for community-acquired severe human infections. The assay is useful for the surveillance of emerging highly virulent strains.
Direct Detection and Prediction of All Pneumococcal Serogroups by Target Enrichment-Based Next-Generation Sequencing
Authors: Ip Margaret , Liyanapathirana Veranja , Ang Irene , Fung Kitty S. C. , Ng T. K. , Zhou Haokui , Tsang Dominic N. C. 
Published: October 2014

ABSTRACT

Despite the availability of standard methods for pneumococcal serotyping, there is room for improvement in the available methods, in terms of throughput, multiplexing capacity, and the number of serotypes identified. We describe a target enrichment-based next-generation sequencing method applied to nasopharyngeal samples for direct detection and serogroup prediction of all known serotypes of
Streptococcus pneumoniae
, 32 to the serotype level and the rest to the closely related serogroup level. The method was applied to detect and to predict the serogroups of pneumococci directly in clinical samples and from sweeps of primary culture DNA, with increased detection rates versus culture-based identification and agreement with the serotypes/serogroups determined by conventional serotyping methods. We propose this method, in conjunction with traditional serotyping methods, as an alternative to rapid detection and serotyping of pneumococci.