bluuebunny/crossref_metadata_2025_split huggingface dataset:
A proposal for a computer-based framework of support for public health in the management of biological incidents: the Czech Republic experience
Authors: Bureš Vladimír , Otčenášková Tereza , Čech Pavel , Antoš Karel 
Published: May 2012

Aims: Biological incidents jeopardising public health require decision-making that consists of one dominant feature: complexity. Therefore, public health decision-makers necessitate appropriate support. Methods: Based on the analogy with business intelligence (BI) principles, the contextual analysis of the environment and available data resources, and conceptual modelling within systems and knowledge engineering, this paper proposes a general framework for computer-based decision support in the case of a biological incident. At the outset, the analysis of potential inputs to the framework is conducted and several resources such as demographic information, strategic documents, environmental characteristics, agent descriptors and surveillance systems are considered. Results: Consequently, three prototypes were developed, tested and evaluated by a group of experts. Their selection was based on the overall framework scheme. Subsequently, an ontology prototype linked with an inference engine, multi-agent-based model focusing on the simulation of an environment, and expert-system prototypes were created. Conclusions: All prototypes proved to be utilisable support tools for decision-making in the field of public health. Nevertheless, the research revealed further issues and challenges that might be investigated by both public health focused researchers and practitioners.
The Safety of Lacosamide for Treatment of Seizures and Seizure Prophylaxis in Adult Hospitalized Patients
Authors: Luk Marilyn E. , Tatum William O. , Patel Alden V. , Nau Karen M. , Freeman William D. 
Published: May 2012

Background: Lacosamide (LCM) is a newer antiepileptic drug (AED) with favorable properties for hospitalized patients including intravenous formulation, minimal hepatic metabolism, and no adverse respiratory effects. We sought to determine the safety profile of LCM in hospitalized patients. Methods: We performed a retrospective medical record review of patients who received LCM between July 1, 2009, and January 31, 2010, at Mayo Clinic Hospital. Data included demographics, LCM dosing, concomitant AED therapy, documented seizure activity, hemodynamic variables, electrocardiogram (ECG), and laboratory data. Adverse drug reaction and drug–drug interactions were reviewed. Results: Thirty-two patients were identified. No major hypotension or serious cardiac arrhythmias occurred. Heart rate increased, however, in seizure group compared with the prophylaxis group 2 hours postdrug infusion (median heart rate = 86 vs 164). The ECGs demonstrated a mean PR interval prolongation of about 6 milliseconds (ms) after LCM initiation (mean PR 185.5 ms, compared with baseline ECG mean of 179.3 ms). Laboratory data revealed no clinically significant changes 24 hours after LCM initiation. Three patients developed adverse events (9.4%): One with altered mental state and exceptionally prolonged ECG PR interval (212 vs 178 ms baseline); One with unexplained thrombocytopenia; and a third patient with dizziness, all of which resolved after drug discontinuation. Conclusion: The LCM demonstrated ECG PR prolongation as previously reported without systemic hypotension, with no discernable drug–drug interactions in hospitalized patients. About 9% of patients had transient adverse drug reactions after LCM, namely alteration in mental state, unexplained thrombocytopenia, and dizziness, which stopped after discontinuation of the drug.
Critical role of P1-Runx1 in mouse basophil development
Authors: Mukai Kaori , BenBarak Maya J. , Tachibana Masashi , Nishida Keigo , Karasuyama Hajime , Taniuchi Ichiro , Galli Stephen J. 
Published: May 2012

AbstractRunx1 P1N/P1N mice are deficient in the transcription factor distal promoter-derived Runt-related transcription factor 1 (P1-Runx1) and have a > 90% reduction in the numbers of basophils in the BM, spleen, and blood. In contrast, Runx1P1N/P1N mice have normal numbers of the other granulocytes (neutrophils and eosinophils). Although basophils and mast cells share some common features, Runx1P1N/P1N mice have normal numbers of mast cells in multiple tissues. Runx1P1N/P1N mice fail to develop a basophil-dependent reaction, IgE-mediated chronic allergic inflammation of the skin, but respond normally when tested for IgE- and mast cell–dependent passive cutaneous anaphylaxis in vivo or IgE-dependent mast cell degranulation in vitro. These results demonstrate that Runx1P1N/P1N mice exhibit markedly impaired function of basophils, but not mast cells. Infection with the parasite Strongyloides venezuelensis and injections of IL-3, each of which induces marked basophilia in wild-type mice, also induce modest expansions of the very small populations of basophils in Runx1P1N/P1N mice. Finally, Runx1P1N/P1N mice have normal numbers of the granulocyte progenitor cells, SN-Flk2+/−, which can give rise to all granulocytes, but exhibit a > 95% reduction in basophil progenitors. The results of the present study suggest that P1-Runx1 is critical for a stage of basophil development between SN-Flk2+/− cells and basophil progenitors.
Induction of activin B by inflammatory stimuli up-regulates expression of the iron-regulatory peptide hepcidin through Smad1/5/8 signaling
Authors: Besson-Fournier Céline , Latour Chloé , Kautz Léon , Bertrand Jessica , Ganz Tomas , Roth Marie-Paule , Coppin Hélène 
Published: May 2012

Abstract
Anemia is very common in patients suffering from infections or chronic inflammation and can add substantially to the morbidity of the underlying disease. It is mediated by excessive production of the iron-regulatory peptide hepcidin, but the signaling pathway responsible for hepcidin up-regulation in the inflammatory context is still not understood completely. In the present study, we show that activin B has an unexpected but crucial role in the induction of hepcidin by inflammation. There is a dramatic induction of Inhbb mRNA, encoding the activin βB-subunit, in the livers of mice challenged with lipopolysaccharide, slightly preceding an increase in Smad1/5/8 phosphorylation and Hamp mRNA. Activin B also induces Smad1/5/8 phosphorylation in human hepatoma–derived cells and, synergistically with IL-6 and STAT-3 signaling, up-regulates hepcidin expression markedly, an observation confirmed in mouse primary hepatocytes. Pretreatment with a bone morphogenic protein type I receptor inhibitor showed that the effect of activin B on hepcidin expression is entirely attributable to its effect on bone morphogenetic protein signaling, most likely via activin receptor-like kinase 3. Activin B is therefore a novel and specific target for the treatment of anemia of inflammation.
Long-term outcomes after autologous stem cell transplantation for patients with POEMS syndrome (osteosclerotic myeloma): a single-center experience
Authors: D'Souza Anita , Lacy Martha , Gertz Morie , Kumar Shaji , Buadi Francis , Hayman Suzanne , Dingli David , Zeldenrust Steven , Kyle Robert , Ansell Stephen , Inwards David , Johnston Patrick , Micallef Ivana , Porrata Luis , Litzow Mark , Gastineau Dennis , Hogan William , Dispenzieri Angela 
Published: May 2012

AbstractThe POEMS syndrome (polyradiculoneuropathy, organomegaly, multiple endocrinopathies, monoclonal protein, skin changes) is a rare disease associated with a plasma cell dyscrasia. Patients with disseminated POEMS can be treated with high-dose therapy and autologous stem cell transplantation (ASCT). While clinical improvement is nearly universal in these patients, the long-term outcomes after transplantation are unclear. We therefore assessed the long-term clinical outcomes of 59 POEMS patients treated with ASCT at our institution. With a median follow-up of 45 months, 14 patients have progressed with a progression-free survival of 98% and 75% at 1 and 5 years, respectively. Factors associated with progression have included an IgG-λ monoclonal component (hazard ratio [HR] 7.5; 95% confidence interval [CI], 2.3-28.3; P = .0008), fluorodeoxyglucose-avid lesions on baseline positron emission tomography (HR 6.4; 95% CI, 1.2-120; P = .03), lack of complete hematologic response (HR 5.4; 95% CI, 1.8-16.7; P = .003), and patients aged 50 years or younger at transplantation (HR 4.4; 95% CI, 1.3-20; P = .01). The most common progression events have been radiologic followed by rising VEGF. Symptomatic progression has been rare. Most patients could be salvaged with immunomodulatory drugs or radiation. The 5-year survival is 94%. Herein, we describe a system of monitoring response and progression among patients with POEMS after ASCT.
Treatment of erythropoietin deficiency in mice with systemically administered siRNA
Authors: Querbes William , Bogorad Roman L. , Moslehi Javid , Wong Jamie , Chan Amy Y. , Bulgakova Elena , Kuchimanchi Satya , Akinc Akin , Fitzgerald Kevin , Koteliansky Victor , Kaelin William G. 
Published: May 2012

AbstractAnemia linked to a relative deficiency of renal erythropoietin production is a significant cause of morbidity and medical expenditures in the developed world. Recombinant erythropoietin is expensive and has been linked to excess cardiovascular events. Moreover, some patients become refractory to erythropoietin because of increased production of factors such as hepcidin. During fetal life, the liver, rather than the kidney, is the major source of erythropoietin. In the present study, we show that it is feasible to reactivate hepatic erythropoietin production and suppress hepcidin levels using systemically delivered siRNAs targeting the EglN prolyl hydroxylases specifically in the liver, leading to improved RBC production in models of anemia caused by either renal insufficiency or chronic inflammation with enhanced hepcidin production.
Characterization of Shigella sonnei in Malaysia, an increasingly prevalent etiologic agent of local shigellosis cases
Authors: Koh Xiu Pei , Chiou Chien Shun , Ajam Noni , Watanabe Haruo , Ahmad Norazah , Thong Kwai Lin 
Published: May 2012

Abstract

Background
Shigellosis is a major public health concern worldwide, especially in developing countries. It is an acute intestinal infection caused by bacteria of the genus Shigella, with a minimum infective dose as low as 10–100 bacterial cells. Increasing prevalence of Shigella sonnei as the etiologic agent of shigellosis in Malaysia has been reported. As there is limited information on the genetic background of S. sonnei in Malaysia, this study aimed to characterize Malaysian S. sonnei and to evaluate the prospect of using multilocus variable-number tandem-repeat (VNTR) analysis (MLVA) for subtyping of local S. sonnei.

Methods
Forty non-repeat clinical strains of S. sonnei isolated during the years 1997–2000, and 2007–2009 were studied. The strains were isolated from stools of patients in different hospitals from different regions in Malaysia. These epidemiologically unrelated strains were characterized using biotyping, antimicrobial susceptibility testing, pulsed-field gel electrophoresis (PFGE) and MLVA.

Results
The two biotypes identified in this study were biotype a (n = 29, 73%) and biotype g (n = 11, 27%). All the 40 strains were sensitive to kanamycin, ceftriaxone and ciprofloxacin. Highest resistance rate was observed for streptomycin (67.5%), followed by tetracycline (40%) and trimethoprim-sulfamethoxazole (37.5%). All the S. sonnei biotype g strains had a core resistance type of streptomycin - trimethoprim-sulfamethoxazole - tetracycline whereas the 29 biotype a strains were subtyped into eight resistotypes. All the strains were equally distinguishable by PFGE and MLVA. Overall, PFGE analysis indicated that S. sonnei biotype a strains were genetically more diverse than biotype g strains. Cluster analysis by MLVA was better in grouping the strains according to biotypes, was reflective of the epidemiological information and was equally discriminative as PFGE.

Conclusions
The S. sonnei strains circulating in Malaysia throughout the period studied were derived from different clones given their heterogeneous nature. MLVA based on seven selected VNTR loci was rapid, reproducible and highly discriminative and therefore may complement PFGE for routine subtyping of S. sonnei.
The German fibromyalgia consumer reports – a cross-sectional survey
Authors: Häuser Winfried , Jung Eva , Erbslöh-Möller Brigitte , Gesmann Mechthild , Kühn-Becker Hedi , Petermann Franz , Langhorst Jost , Thoma Reinhard , Weiss Thomas , Wolfe Frederick , Winkelmann Andreas 
Published: May 2012

Abstract

Background
Consumer surveys provide information on effectiveness and side effects of medical interventions in routine clinical care. A report of fibromyalgia syndrome (FMS) consumers has not been carried out in Europe.

Methods
The study was carried out from November 2010 to April 2011. Participants diagnosed with FMS rated the effectiveness and side effects of pharmacological and non-pharmacological FMS interventions on a 0 to 10 scale, with 10 being most efficacious (harmful). The questionnaire was distributed by the German League for people with Arthritis and Rheumatism and the German Fibromyalgia Association to their members and to all consecutive FMS patients of nine clinical centers of different levels of care.

Results
1661 questionnaires (95% women, mean age 54 years, mean duration since FMS diagnosis 6.8 years) were analysed. The most frequently used therapies were self-management strategies, prescription pain medication and aerobic exercise. The highest average effectiveness was attributed to whole body and local warmth therapies, thermal bathes, FMS education and resting. The highest average side effects were attributed to strong opioids, local cold therapy, gamma-amino-butyric acid analogues (pregabalin and gabapentin), tramadol and opioid transdermal systems.

Conclusion
The German fibromyalgia consumer reports highlight the importance of non-pharmcological therapies in the long-term management of FMS, and challenges the strong recommendations for drug therapies given by FMS-guidelines.
Hepatitis B assays in serum, plasma and whole blood on filter paper
Authors: Mayer Theodor K , Vargas Roberto L , Knebel Ann E , Williams Scott A , Culver Sean P , Clark Daniel M , King Louise R 
Published: May 2012

Abstract

Background
Screening and determining the immune status of individuals for hepatitis B is usually done by detecting hepatitis B surface antigen (HBsAg) and hepatitis B surface antigen-specific antibodies (HBsAb). In some countries with the highest viral burden, performing these assays is currently impractical. This paper explores the use of filter paper as a blood specimen transport medium.

Methods
Samples, chosen from routine clinical laboratory pool, were applied and dried onto filter paper. Eluates, from the paper samples, were analyzed as routine clinical specimens on ADVIA Centaur 5634® immunoassay analyzers using the standard HBsAg and HBsAb kits. Dried blood samples were subjected to a range of environmental conditions in order to assess stability.

Results
After drying and elution the assays showed linearity and precision comparable to clinical assays performed on fresh serum. Elutions at various times during a 149 day incubation period showed very little variability in the Index numbers. All analytes were temperature stable except for a decrease in the HBsAg signal at 42°C.

Conclusions
Filter paper is an acceptable storage and transport medium for serum to be used in the detection of hepatitis B markers if atmospheric variability can be controlled. HBsAg, HBsAb and HBcAb are all stable for at least five months under storage conditions below room temperature. Drying specimens, particularly serum, on filter paper at remote locations, offers a reasonable solution to the problem of hepatitis surveillance in underdeveloped regions, although some attempt at temperature control might be desirable.
Optimization of fatty alcohol biosynthesis pathway for selectively enhanced production of C12/14 and C16/18 fatty alcohols in engineered Escherichia coli
Authors: Zheng Yan-Ning , Li Ling-Ling , Liu Qiang , Yang Jian-Ming , Wang Xiang-Wei , Liu Wei , Xu Xin , Liu Hui , Zhao Guang , Xian Mo 
Published: May 2012

Abstract

Background
With the increasing stress from oil price and environmental pollution, aroused attention has been paid to the microbial production of chemicals from renewable sources. The C12/14 and C16/18 alcohols are important feedstocks for the production of surfactants and detergents, which are widely used in the most respected consumer detergents, cleaning products and personal care products worldwide. Though bioproduction of fatty alcohols has been carried out in engineered E. coli, several key problems have not been solved in earlier studies, such as the quite low production of C16/18 alcohol, the lack of optimization of the fatty alcohol biosynthesis pathway, and the uncharacterized performance of the engineered strains in scaled-up system.

Results
We improved the fatty alcohol production by systematically optimizing the fatty alcohol biosynthesis pathway, mainly targeting three key steps from fatty acyl-acyl carrier proteins (ACPs) to fatty alcohols, which are sequentially catalyzed by thioesterase, acyl-coenzyme A (CoA) synthase and fatty acyl-CoA reductase. By coexpression of thioesterase gene BTE, acyl-CoA synthase gene fadD and fatty acyl-CoA reductase gene acr1, 210.1 mg/L C12/14 alcohol was obtained. A further optimization of expression level of BTE, fadD and acr1 increased the C12/14 alcohol production to 449.2 mg/L, accounting for 75.0% of the total fatty alcohol production (598.6 mg/L). In addition, by coexpression of thioesterase gene ‘tesA, acyl-CoA synthase gene fadD and fatty acyl-CoA reductase gene FAR, 101.5 mg/L C16/18 alcohol was obtained, with C16/18 alcohol accounting for 89.2% of the total fatty alcohol production.

Conclusions
To our knowledge, this is the first report on selective production of C12/14 and C16/18 alcohols by microbial fermentation. This work achieved high-specificity production of both C12/14 and C16/18 alcohols. The encouraging 598.6 mg/L of fatty alcohols represents the highest titer reported so far. In addition, the 101.5 mg/L 89.2% C16/18 alcohol suggests an important breakthrough in C16/18 alcohol production. A more detailed optimization of the expression level of fatty alcohol biosynthesis pathway may contribute to a further improvement of fatty alcohol production.
Optimal compressed sensing reconstructions of fMRI using 2D deterministic and stochastic sampling geometries
Authors: Jeromin Oliver , Pattichis Marios S , Calhoun Vince D 
Published: May 2012

Abstract

Background
Compressive sensing can provide a promising framework for accelerating fMRI image acquisition by allowing reconstructions from a limited number of frequency-domain samples. Unfortunately, the majority of compressive sensing studies are based on stochastic sampling geometries that cannot guarantee fast acquisitions that are needed for fMRI. The purpose of this study is to provide a comprehensive optimization framework that can be used to determine the optimal 2D stochastic or deterministic sampling geometry, as well as to provide optimal reconstruction parameter values for guaranteeing image quality in the reconstructed images.

Methods
We investigate the use of frequency-space (k-space) sampling based on: (i) 2D deterministic geometries of dyadic phase encoding (DPE) and spiral low pass (SLP) geometries, and (ii) 2D stochastic geometries based on random phase encoding (RPE) and random samples on a PDF (RSP). Overall, we consider over 36 frequency-sampling geometries at different sampling rates. For each geometry, we compute optimal reconstructions of single BOLD fMRI ON & OFF images, as well as BOLD fMRI activity maps based on the difference between the ON and OFF images. We also provide an optimization framework for determining the optimal parameters and sampling geometry prior to scanning.

Results
For each geometry, we show that reconstruction parameter optimization converged after just a few iterations. Parameter optimization led to significant image quality improvements. For activity detection, retaining only 20.3% of the samples using SLP gave a mean PSNR value of 57.58 dB. We also validated this result with the use of the Structural Similarity Index Matrix (SSIM) image quality metric. SSIM gave an excellent mean value of 0.9747 (max = 1). This indicates that excellent reconstruction results can be achieved. Median parameter values also gave excellent reconstruction results for the ON/OFF images using the SLP sampling geometry (mean SSIM > =0.93). Here, median parameter values were obtained using mean-SSIM optimization. This approach was also validated using leave-one-out.

Conclusions
We have found that compressive sensing parameter optimization can dramatically improve fMRI image reconstruction quality. Furthermore, 2D MRI scanning based on the SLP geometries consistently gave the best image reconstruction results. The implication of this result is that less complex sampling geometries will suffice over random sampling. We have also found that we can obtain stable parameter regions that can be used to achieve specific levels of image reconstruction quality when combined with specific k-space sampling geometries. Furthermore, median parameter values can be used to obtain excellent reconstruction results.
Up-regulation of microglial cathepsin C expression and activity in lipopolysaccharide-induced neuroinflammation
Authors: Fan Kai , Wu Xuefei , Fan Bin , Li Ning , Lin Yongzhong , Yao Yiwen , Ma Jianmei 
Published: May 2012

Abstract

Background
Cathepsin C (Cat C) functions as a central coordinator for activation of many serine proteases in inflammatory cells. It has been recognized that Cat C is responsible for neutrophil recruitment and production of chemokines and cytokines in many inflammatory diseases. However, Cat C expression and its functional role in the brain under normal conditions or in neuroinflammatory processes remain unclear. Our previous study showed that Cat C promoted the progress of brain demyelination in cuprizone-treated mice. The present study further investigated the Cat C expression and activity in lipopolysaccharide (LPS)-induced neuroinflammation in vivo and in vitro.

Methods
C57BL/6 J mice were intraperitoneally injected with either 0.9% saline or lipopolysaccharide (LPS, 5 mg/kg). Immunohistochemistry (IHC) and in situ hybridization (ISH) were used to analyze microglial activation, TNF-α, IL-1β, IL-6, iNOS mRNAs expressions and cellular localization of Cat C in the brain. Nitrite assay was used to examine microglial activation in vitro; RT-PCR and ELISA were used to determine the expression and release of Cat C. Cat C activity was analyzed by cellular Cat C assay kit. Data were evaluated for statistical significance with paired t test.

Results
Cat C was predominantly expressed in hippocampal CA2 neurons in C57BL/6 J mice under normal conditions. Six hours after LPS injection, Cat C expression was detected in cerebral cortical neurons; whereas, twenty-four hours later, Cat C expression was captured in activated microglial cells throughout the entire brain. The duration of induced Cat C expression in neurons and in microglial cells was ten days and three days, respectively. In vitro, LPS, IL-1β and IL-6 treatments increased microglial Cat C expression in a dose-dependent manner and upregulated Cat C secretion and its activity.

Conclusions
Taken together, these data indicate that LPS and proinflammatory cytokines IL-1β, IL-6 induce the expression, release and upregulate enzymatic activity of Cat C in microglial cells. Further investigation is required to determine the functional role of Cat C in the progression of neuroinflammation, which may have implications for therapeutics for the prevention of neuroinflammation-involved neurological disorders in the future.