bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Genomic Day in the Life of a Clinical Microbiology Laboratory
Authors: Long S. Wesley , Williams Dawn , Valson Chandni , Cantu Concepcion C. , Cernoch Patricia , Musser James M. , Olsen Randall J. 
Published: January 2013

ABSTRACT
Next-generation sequencing technology is available to many clinical laboratories; however, it is not yet widely used in routine microbiology practice. To demonstrate the feasibility of using whole-genome sequencing in a routine clinical microbiology workflow, we sequenced the genome of every organism isolated in our laboratory for 1 day.
Evaluation of the Sensitivity of a pLDH-Based and an Aldolase-Based Rapid Diagnostic Test for Diagnosis of Uncomplicated and Severe Malaria Caused by PCR-Confirmed Plasmodium knowlesi, Plasmodium falciparum, and Plasmodium vivax
Authors: Barber Bridget E. , William Timothy , Grigg Matthew J. , Piera Kim , Yeo Tsin W. , Anstey Nicholas M. 
Published: January 2013

ABSTRACT

Plasmodium knowlesi
can cause severe and fatal human malaria in Southeast Asia. Rapid diagnosis of all
Plasmodium
species is essential for initiation of effective treatment. Rapid diagnostic tests (RDTs) are sensitive for detection of uncomplicated and severe falciparum malaria but have not been systematically evaluated in knowlesi malaria. At a tertiary referral hospital in Sabah, Malaysia, we prospectively evaluated the sensitivity of two combination RDTs for the diagnosis of uncomplicated and severe malaria from all three potentially fatal
Plasmodium
species, using a pan-
Plasmodium
lactate dehydrogenase (pLDH)-
P. falciparum
histidine-rich protein 2 (PfHRP2) RDT (First Response) and a pan-
Plasmodium
aldolase-PfHRP2 RDT (ParaHIT). Among 293 hospitalized adults with PCR-confirmed
Plasmodium
monoinfection, the sensitivity of the pLDH component of the pLDH-PfHRP2 RDT was 74% (95/129; 95% confidence interval [CI], 65 to 80%), 91% (110/121; 95% CI, 84 to 95%), and 95% (41/43; 95% CI, 85 to 99%) for PCR-confirmed
P. knowlesi
,
P. falciparum
, and
P. vivax
infections, respectively, and 88% (30/34; 95% CI, 73 to 95%), 90% (38/42; 95% CI, 78 to 96%), and 100% (12/12; 95% CI, 76 to 100%) among patients tested before antimalarial treatment was begun. Sensitivity in severe malaria was 95% (36/38; 95% CI, 83 to 99), 100% (13/13; 95% CI, 77 to 100), and 100% (7/7; 95% CI, 65 to 100%), respectively. The aldolase component of the aldolase-PfHRP2 RDT performed poorly in all
Plasmodium
species. The pLDH-based RDT was highly sensitive for the diagnosis of severe malaria from all species; however, neither the pLDH- nor aldolase-based RDT demonstrated sufficiently high overall sensitivity for
P. knowlesi
. More sensitive RDTs are needed in regions of
P. knowlesi
endemicity.
Identification of a Hydrophobic Domain in Varicella-Zoster Virus ORF61 Necessary for ORF61 Self-Interaction, Viral Replication, and Skin Pathogenesis
Authors: Wang Li , Rajamani Jaya , Sommer Marvin , Zerboni Leigh , Arvin Ann M. 
Published: January 2013

ABSTRACT

The varicella-zoster virus (VZV) ORF61 protein is necessary for normal replication
in vitro
and virulence in human skin xenografts in the severe combined immunodeficiency mouse model
in vivo
. These experiments identify a hydrophobic domain that mediates ORF61 self-interaction. While not needed to inhibit host cell defenses, disruption of this domain (residues 250 to 320) severely impairs VZV growth, transactivation of the immediate early 63 and glycoprotein E genes, and the pathogenesis of VZV skin infection
in vivo
.
Characteristics of Viruses Derived from Nude Mice with Persistent Measles Virus Infection
Authors: Abe Yusaku , Hashimoto Koichi , Watanabe Masahiro , Ohara Shinichiro , Sato Masatoki , Kawasaki Yukihiko , Hashimoto Yuko , Hosoya Mitsuaki 
Published: January 2013

ABSTRACTMeasles virus (MV) isolates from patients with subacute sclerosing panencephalitis (SSPE) differ from wild-type MV virologically. However, few animal models have reported viruses with characteristics of the SSPE virus. The MV Edmonston strain was inoculated into the subarachnoid space of nude mice. All nude mice displayed weight loss and required euthanasia, with a mean survival duration of 73.2 days. The viral load in the brain was 4- to 400-fold higher than the inoculated load, and brain infection was confirmed by immunostaining. Gene sequencing of the viruses revealed that amino acid mutations occurred more frequently in matrix proteins. The most common mutation was a uridine-to-cytosine transition. The virus exhibited lower free virus particle formation ability than the Edmonston strain. When nude mice were challenged with 2 × 102PFU of the brain-derived virus, the mean survival duration was 34.7 days, which was significantly shorter than that of the mice challenged with 4 × 104PFU of the Edmonston strain (P< 0.01). This study indicated that MV in a nude mouse model of persistent infection exhibited characteristics of the SSPE virus. This model may prove useful in elucidating the pathogenic mechanism of SSPE and developing potential therapeutics.
Do open label blinded outcome studies of novel anticoagulants versus warfarin have equivalent validity to those carried out under double-blind conditions?
Authors: O’Neil William , Welner Sharon , Lip Gregory 
Published: January 2013

SummaryRecent anticoagulants for stroke prevention in AF have been tested in active comparator controlled studies versus warfarin using two designs: double-blind, double-dummy and prospective randomised, open blinded endpoint (PROBE). The former requires elaborate procedures to maintain blinding, while PROBE does not. Outcomes of double-blind and PROBE designed studies of novel anticoagulants for AF, focusing on warfarin controls, were explored. Major, Phase III warfarin-controlled trials for stroke prevention in AF were identified. Odds ratios (ORs) of key outcomes for active comparators versus VKA and event rates for VKA arms were compared between designs, in context of baseline demographics and inclusion criteria. Identified trials studied five novel anticoagulants in three each of PROBE and double-blind design. For ORs of results across studies and outcomes, there was little pattern differentiating the two designs. Among VKA-control subjects, event rates for the primary outcome (stroke or systemic embolism) in PROBE trials at 1.74 %/year (95% confidence interval: 1.54–1.95) was not significantly different from that in double-blind trials, at 1.88 (1.73–2.03). Among other outcomes, VKA-treated subjects in both trial designs had similar event rates, apart from higher all-cause mortality in ROCKET AF, and lower myocardial infarction rates among the PROBE study patients. Although there are differences in outcome between PROBE and double blind trials, they do not appear to be design-related. The exacting requirements of double-blinding in AF trials may not be necessary.
The endothelial protein C receptor and activated protein C play a limited role in host defense during experimental tuberculosis
Authors: Roelofs Joris J. T. H. , de Vos Alex F. , Wieland Catharina W. , Schouten Marcel , Meijers Joost C. M. , Isermann Berend , van’t Veer Cornelis , Esmon Charles T. , van der Poll Tom , Kager Liesbeth M. 
Published: January 2013

SummaryThe protein C (PC) system is an important regulator of both coagulation and inflammation. Activated PC (APC), together with its receptor the endothelial protein C receptor (EPCR), has anticoagulant and anti-inflammatory properties. During tuberculosis (TB), a devastating chronic pulmonary disease caused by Mycobacterium (M.) tuberculosis, both a local inflammatory reaction characterised by the recruitment of mainly mononuclear cells and the formation of pulmonary granulomas as well as activation of coagulation occurs as part of the host immune response. We investigated the role of EPCR and APC in a mouse model of TB using mice overexpressing EPCR (Tie2-EPCR), mice deficient for EPCR (EPCR−/−), mice treated with APC-inhibiting antibodies and mice overexpressing APC (APChigh) and compared them with wild-type (WT) mice. Blood and organs were harvested to quantify bacterial loads, cellular influxes, cytokines, histopathology and coagulation parameters. Additionally observation studies were performed. Lung EPCR expression was upregulated during experimental TB. No significant differences in bacterial growth were seen between WT and Tie2-EPCR mice. However, Tie2-EPCR mice had decreased pulmonary coagulation activation, displayed an increased influx of macro-phages 2 and 6 weeks after infection, but no increase in other proin-flammatory markers. On the other hand, in EPCR−/−-mice coagulation activation was decreased 6 weeks post-infection, with little impact on other inflammation markers. APC-overexpression or treatment with anti-(A)PC antibodies displayed minimal effects during experimental TB. In conclusion, EPCR and APC play a limited role in the host response during experimental pulmonary TB.
The Biblical Prohibition Against Tattooing
Authors: Huehnergard John , Liebowitz Harold 
Published: January 2013

Abstract
Lev 19:28 prohibits tattooing, but no reason for the prohibition is given. Since it appears in a context of pagan mourning practices (Lev 19:27,28) it is assumed that the reason for the prohibition lay in its association with such mourning practices. In this paper we explore the broader context of the law in biblical times, and how it was understood in subsequent rabbinic times. We propose that in the biblical period the prohibition was associated with the marking of slaves, and that in the subsequent rabbinic period it was associated with paganism.
Plante Absalom eine Reform der Gerichtsordnung in Israel? (2 Sam 15:2-4)
Authors: Wagner Volker 
Published: January 2013

AbstractA detailed reexamination of the text of 2 Sam 15:2-4 and the inclusion of today’s knowledge of the legal system of pre-exilic Israel deprive the usual criticism of Absalom’s behavior of much of its justification. Absalom probably planned a judicial reform with the goal to extend the judicial authority of the king.
The Impact of Assimilating Dropwindsonde Data Deployed at Different Sites on Typhoon Track Forecasts
Authors: Chen Boyu , Mu Mu , Xiaohao Qin 
Published: January 2013

AbstractThis study investigates the impacts on typhoon track forecasting by the fifth-generation Pennsylvania State University–National Center for Atmospheric Research Mesoscale Model (MM5) and its three-dimensional variational data assimilation (3DVAR) system of assimilating dropwindsonde observational data acquired from different sites. All of the sonde data were obtained between 2004 and 2009 in the typhoon surveillance program Dropwindsonde Observations for Typhoon Surveillance near the Taiwan Region (DOTSTAR). Experiments were conducted to test the model's response to five scenarios involving differing dropwindsonde data inputs: 1) no dropwindsonde data, 2) all available dropwindsonde data, 3) data gathered in sensitive regions identified by the conditional nonlinear optimal perturbation (CNOP) approach, 4) data gathered in sensitive regions identified by the first singular vector (FSV) approach, and 5) several sondes selected at random. The results show that using dropwindsonde data based on CNOP sensitivity can lead to improvements in typhoon track forecasting similar to, and occasionally better than, those achieved by assimilating all of the available data. Both approaches offered greater benefits than the other three alternatives averagely. It is proposed that CNOP provides a suitable approach to determining sensitive regions during adaptive observation of typhoons. Similar results may be obtained if the sensitivity products developed using MM5 are employed in the Weather Research and Forecasting Model (WRF), suggesting that it is applicable to utilize sensitivity produced by MM5 in WRF.
Pelvic floor muscle exercise for chronic low back pain
Authors: Bi Xia , Zhao Jiangxia , Zhao Lei , Liu Zhihao , Zhang Jinming , Sun Dan , Song Lei , Xia Yun 
Published: January 2013

Objective To assess the effect of pelvic floor muscle exercise in patients with chronic low back pain. Methods Adults (aged ≥18 years) with chronic low back pain (with or without radiculopathy) were randomized to undergo either routine treatment (ultrasonography, short wave diathermy and lumbar strengthening exercises; control group) or routine treatment with pelvic floor exercises (intervention group) for 24 weeks. Pain, disability (Oswestry Disability Index [ODI] score) and trunk muscle function were assessed at baseline and after completion of treatment. Results The study included 47 patients (control group n = 24; intervention group n = 23). Pain severity and ODI scores were significantly lower in the intervention group than in the control group after 24 weeks. There were no significant between-group differences in trunk muscle function. Conclusion Pelvic floor exercise in combination with routine treatment provides significant benefits in terms of pain relief and disability over routine treatment alone.
Clinical significance of protocadherin-8 (PCDH8) promoter methylation in bladder cancer
Authors: Lin Ying-Li , Ma Jian-Hua , Luo Xiang-Li , Guan Tong-Yu , Li Zhi-Gang 
Published: January 2013

Objective To investigate the clinical significance of protocadherin-8 ( PCDH8) promoter methylation in bladder cancer. Methods Methylation-specific polymerase chain reaction was used to examine the promoter methylation status of PCDH8 in tumour tissue samples obtained from patients with bladder cancer, and in normal bladder epithelial tissue samples obtained from age- and sex-matched control subjects. Methylation status was correlated with demographic, clinical and pathological parameters and disease outcome. Results PCDH8 promoter methylation was detected in 76/135 (56.3%) patients with bladder cancer and none of 34 (0%) control subjects. Methylation was significantly associated with advanced stage (T2–T4), high grade (G3), tumour recurrence, larger tumour diameter (>3 cm) and nonpapillary morphology. In addition, methylation was associated with significantly shorter survival time and was an independent predictor of overall survival. Conclusions PCDH8 promoter methylation is a common occurrence in bladder cancer, and is associated with malignant behaviour and poor prognosis. Determination of PCDH8 promoter methylation status in tumour tissue may assist in the identification of patients who require aggressive postoperative intervention in order to improve prognosis.
Identification of neutrophil extracellular traps in the blood of patients with systemic inflammatory response syndrome
Authors: Hamaguchi Shigeto , Hirose Tomoya , Akeda Yukihiro , Matsumoto Naoya , Irisawa Taro , Seki Masafumi , Hosotsubo Hideo , Tasaki Osamu , Oishi Kazunori , Shimazu Takeshi , Tomono Kazunori 
Published: January 2013

Objective Neutrophils are able to form ‘neutrophil extracellular traps’ (NETs), which they use to trap and kill pathogens such as bacteria and fungi at the foci of infection. This observational study investigated the presence of NETs in the blood from critically ill patients and healthy volunteers. Methods Fluorescent triple-colour immunocytochemical analysis of blood smears collected from patients with systemic inflammatory response syndrome (SIRS; associated with various clinical conditions) who had been hospitalized in the intensive care unit, and healthy volunteers, was undertaken to identify NETs in the blood. Blood smears were stained for DNA, histone H1 and neutrophil elastase. Results NETs were identified in 10 of 21 (47.6%) blood samples from the study group compared with none of the blood samples from eight healthy volunteers. Conclusion These data suggest that fluorescent triple-colour immunocytochemical staining of NETs in the blood could be used to simplify the early identification of critically ill patients with SIRS. Larger studies are required to clarify the pathophysiological role of NETs in this specific patient population.
Interleukin-10 involvement in exposure to low dose of benzene
Authors: Spatari Giovanna , Saitta Salvatore , Giorgianni Concetto , Cristani Maria Teresa , Quattrocchi Paolina , Abbate Adriana , Carrieri Mariella , Ferraro Giorgia , Saija Antonella , Gangemi Sebastiano 
Published: January 2013

Objective: To establish if serum levels of interleukin-10 (IL-10) in subjects exposed to benzene are connected with age, working years, and employment age. Methods: We evaluated serum levels of IL-10 in 51 employees working in oil refinery (group A) and in 16 office workers who resided in the same area (group B). Results: There was no statistically significant difference between serum concentrations of IL-10 in groups A and B. There was a statistically significant dependent relationship in group A between age, working years, and serum concentration of IL-10. There was a statistically significant and positive dependent relationship in group A between serum concentration of IL-10 and employment age. Conclusions: The role played by IL-10 in benzene immune suppression may be relevant and attention should be directed toward assessment of age, working years, and employment age in benzene-exposed populations.
Relation of Neutrophil to Lymphocyte Ratio With the Presence and Severity of Stable Coronary Artery Disease
Authors: Kaya Ahmet , Kurt Mustafa , Tanboga Ibrahim Halil , Işık Turgay , Günaydın Zeki Yüksel , Kaya Yasemin , Topçu Selim , Sevimli Serdar 
Published: January 2013

Objectives: We examined the association between neutrophil to lymphocyte ratio (NLR) and the complexity of coronary artery disease assessed by SYNTAX score (SS). Methods: The study population included patients with chest pain who had undergone coronary angiography for stable angina pectoris. Patients were classified depending on whether the SS was 0 or SS > 0. Results: Left ventricular ejection fraction, estimated glomerular filtration rate, and NLR were found to be the independent predictors of high SS in multivariate analysis. The area under the receiver–operating curve of NLR was 0.72 (0.65-0.80, P < .001) for predicting high SS. The optimal cutoff value of NLR to predict high SS was 2.7 (sensitivity of 72% and a specificity of 61%). There was a significant correlation between NLR ratio and continuous SS ( r = .552, P < .001). Conclusion: The NLR is a readily measurable systemic inflammatory marker and is associated with both the presence and the complexity of coronary artery disease.
A mixed exercise training programme is feasible and safe and may improve quality of life and muscle strength in multiple myeloma survivors
Authors: Groeneveldt Lara , Mein Gill , Garrod Rachel , Jewell Andrew P , Someren Ken Van , Stephens Richard , D’Sa Shirley P , Yong Kwee L 
Published: January 2013

Abstract

Background
Exercise programmes are beneficial for cancer patients however evidence is limited in patients with multiple myeloma (MM), a cancer that is characterised by osteolytic bone disease, giving rise to high levels of bone morbidity including fractures and bone pain.

Methods
We conducted a single arm phase 2 study of an exercise programme (EP) as rehabilitation for treated MM patients, to evaluate feasibility, effects on QOL and physiological parameters. Patients were given individualised programmes, comprising stretching, aerobic and resistance exercises, carried out under supervision for 3 months then at home for a further 3 months.

Results
Study uptake was high, 60 of 75 (80%) patients approached consented to the study. Screen failures (11, due to fracture risk and disease relapse) and patient withdrawals (12) resulted in a final 37 patients enrolling on the programme. These 37 patients demonstrated high attendance rates in the supervised classes (87%), and high levels of adherence in home exercising (73%). Patients reported better QOL following the EP, with improvement in FACT-G and Fatigue scores over time from baseline (p<0.01 for both, one-way repeated measures ANOVA) to 6 months. Upper and lower limb strength also improved on the EP, from baseline to 6 months (p<0.01 for both). There were no adverse reactions.

Conclusions
An EP in MM patients is feasible and safe, with high attendance and adherence. Benefits in QOL, fatigue and muscle strength await confirmation in randomized studies, prompting urgent evaluation of the benefits of EP in the rehabilitation of MM patients.
Analysis of antibody induction upon immunization with distinct NTS-DBL1α-domains of PfEMP1 from rosetting Plasmodium falciparum parasites
Authors: Angeletti Davide , Albrecht Letusa , Wahlgren Mats , Moll Kirsten 
Published: January 2013

Abstract

Background
Rosette-formation of Plasmodium falciparum parasitized erythrocytes is of importance in the development of severe malaria. The parasite-derived molecule PfEMP1 (Plasmodium falciparum erythrocyte membrane protein 1), central to rosetting, is suggested to be included in a multimeric vaccine targeting severe disease.

Methods
Three recombinant NTS-DBL1α-domains of PfEMP1 were generated in Escherichia coli, purified and used for immunization of rats and goats. Antibody titres were determined in ELISA assays and responses were compared in-between different individual animals and species. Reactivity with the parasites was tested in live pRBC using FACS. B-cell epitopes prediction was carried out in silico and compared to the results obtained by peptide microarray. Screening for serological cross-reactivity with heterologous NTS-DBL1α variants was carried out by ELISA, peptide array and FACS on pRBC of different laboratory strains and patient isolates.

Results
All three NTS-DBL1α-domains induced high titres of antibodies that were biologically active with no apparent difference between constructs covering slightly different parts of the DBL1α-sequence. The different animal species showed comparable titres of antibodies, while variations within individuals of the species could be observed.
Mapping of the recognized epitopes revealed that most parts of the molecule were able to induce an antibody response with a tendency for the N and C terminal parts of the molecule for slightly higher recognition. Important differences to the epitopes predicted were found as some of the most conserved parts of the DBL1α-domain contained the main epitopes for antibody reactivity. ELISA assays and peptide microarray demonstrated substantial cross-reactivity to heterologous variants, while binding to native PfEMP1 was observed only in few combinations on the pRBC surface, underlining that mainly internal, conserved and not surface exposed parts of the DBL1α-domain are responsible for this observation.

Conclusion
Biologically active antibodies can be induced consistently, with high titres, in different animal species and the antibodies elicited by different constructs react with similar epitopes. Induced antibodies recognize epitopes localized in all subdomains of the DBL1α-sequence. Cross-reactivity between NTS-DBL1α-variants is common in ELISA, but rare with live pRBC emphasizing that also internal, conserved areas of PfEMP1 carry important highly immunogenic epitopes of the molecule.