bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isolation of a Highly Thermal Stable Lama Single Domain Antibody Specific for Staphylococcus aureusEnterotoxin B
Authors: Graef Russell R , Anderson George P , Doyle Katherine A , Zabetakis Dan , Sutton Felicia N , Liu Jinny L , Serrano-González Joseline , Goldman Ellen R , Cooper Lynn A 
Published: September 2011

Abstract

Background
Camelids and sharks possess a unique subclass of antibodies comprised of only heavy chains. The antigen binding fragments of these unique antibodies can be cloned and expressed as single domain antibodies (sdAbs). The ability of these small antigen-binding molecules to refold after heating to achieve their original structure, as well as their diminutive size, makes them attractive candidates for diagnostic assays.

Results
Here we describe the isolation of an sdAb against Staphyloccocus aureus enterotoxin B (SEB). The clone, A3, was found to have high affinity (Kd = 75 pM) and good specificity for SEB, showing no cross reactivity to related molecules such as Staphylococcal enterotoxin A (SEA), Staphylococcal enterotoxin D (SED), and Shiga toxin. Most remarkably, this anti-SEB sdAb had an extremely high Tm of 85°C and an ability to refold after heating to 95°C. The sharp Tm determined by circular dichroism, was found to contrast with the gradual decrease observed in intrinsic fluorescence. We demonstrated the utility of this sdAb as a capture and detector molecule in Luminex based assays providing limits of detection (LODs) of at least 64 pg/mL.

Conclusion
The anti-SEB sdAb A3 was found to have a high affinity and an extraordinarily high Tm and could still refold to recover activity after heat denaturation. This combination of heat resilience and strong, specific binding make this sdAb a good candidate for use in antibody-based toxin detection technologies.
The effect on survival of continuing chemotherapy to near death
Authors: Saito Akiko M , Landrum Mary Beth , Neville Bridget A , Ayanian John Z , Earle Craig C 
Published: September 2011

Abstract

Background
Overuse of anti-cancer therapy is an important quality-of-care issue. An aggressive approach to treatment can have negative effects on quality of life and cost, but its effect on survival is not well-defined.

Methods
Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified 7,879 Medicare-enrolled patients aged 65 or older who died after having survived at least 3 months after diagnosis of advanced non-small cell lung cancer (NSCLC) between 1991 and 1999. We used Cox proportional hazards regression analysis, propensity scores, and instrumental variable analysis (IVA) to compare survival among patients who never received chemotherapy (n = 4,345), those who received standard chemotherapy but not within two weeks prior to death (n = 3,235), and those who were still receiving chemotherapy within 14 days of death (n = 299). Geographic variation in the application of chemotherapy was used as the instrument for IVA.

Results
Receipt of chemotherapy was associated with a 2-month improvement in overall survival. However, based on three different statistical approaches, no additional survival benefit was evident from continuing chemotherapy within 14 days of death. Moreover, patients receiving chemotherapy near the end of life were much less likely to enter hospice (81% versus 51% with no chemotherapy and 52% with standard chemotherapy, P < 0.001), or were more likely to be admitted within only 3 days of death.

Conclusions
Continuing chemotherapy for advanced NSCLC until very near death is associated with a decreased likelihood of receiving hospice care but not prolonged survival. Oncologists should strive to discontinue chemotherapy as death approaches and encourage patients to enroll in hospice for better end-of-life palliative care.
Effects of amodiaquine and artesunate on sulphadoxine-pyrimethamine pharmacokinetic parameters in children under five in Mali
Authors: Tekete Mamadou M , Toure Sékou , Fredericks Alfia , Beavogui Abdoul H , Sangare Cheick PO , Evans Alicia , Smith Peter , Maiga Hamma , Traore Zoumana I , Doumbo Ogobara K , Barnes Karen I , Djimde Abdoulaye A 
Published: September 2011

Abstract

Background
Sulphadoxine-pyrimethamine, in combination with artesunate or amodiaquine, is recommended for the treatment of uncomplicated malaria and is being evaluated for intermittent preventive treatment. Yet, limited data is available on pharmacokinetic interactions between these drugs.

Methods
In a randomized controlled trial, children aged 6-59 months with uncomplicated falciparum malaria, received either one dose of sulphadoxine-pyrimethamine alone (SP), one dose of SP plus three daily doses of amodiaquine (SP+AQ) or one dose of SP plus 3 daily doses of artesunate (SP+AS). Exactly 100 μl of capillary blood was collected onto filter paper before drug administration at day 0 and at days 1, 3, 7, 14, 21 and 28 after drug administration for analysis of sulphadoxine and pyrimethamine pharmacokinetic parameters.

Results
Fourty, 38 and 31 patients in the SP, SP+AQ and SP+AS arms, respectively were included in this study. The concentrations on day 7 (that are associated with therapeutic efficacy) were similar between the SP, SP+AQ and SP+AS treatment arms for sulphadoxine (median [IQR] 35.25 [27.38-41.70], 34.95 [28.60-40.85] and 33.40 [24.63-44.05] μg/mL) and for pyrimethamine (56.75 [46.40-92.95], 58.75 [43.60-98.60] and 59.60 [42.45-86.63] ng/mL). There were statistically significant differences between the pyrimethamine volumes of distribution (4.65 [3.93-6.40], 4.00 [3.03-5.43] and 5.60 [4.40-7.20] L/kg; p = 0.001) and thus elimination half-life (3.26 [2.74 -3.82], 2.78 [2.24-3.65] and 4.02 [3.05-4.85] days; p < 0.001). This study confirmed the lower SP concentrations previously reported for young children when compared with adult malaria patients.

Conclusion
Despite slight differences in pyrimethamine volumes of distribution and elimination half-life, these data show similar exposure to SP over the critical initial seven days of treatment and support the current use of SP in combination with either AQ or AS for uncomplicated falciparum malaria treatment in young Malian children.
The in-vitro evaluation of antibacterial, antifungal and cytotoxic properties of Marrubium vulgare L. essential oil grown in Tunisia
Authors: Zarai Zied , Kadri Adel , Ben Chobba Ines , Ben Mansour Riadh , Bekir Ahmed , Mejdoub Hafedh , Gharsallah Néji 
Published: September 2011

Abstract

Background
In order to validate its antiseptic and anticancer properties with respect to traditional uses, we have screened for the first time the antimicrobial activity of aerial parts of M. vulgare L. essential oil against different pathogenic microorganisms and the cytotoxic activity against HeLa cell lines.

Methods
The agar disk diffusion method was used to study the antibacterial activity of M. vulgare essential oil against 12 bacterial and 4 fungi strains. The disc diameters of zone of inhibition (DD), the minimum inhibitory concentrations (MIC) and the concentration inhibiting 50% (IC50) were investigated to characterize the antimicrobial activities of this essential oil. The in vitro cytotoxicity of M. vulgare essential oil was examined using a modified MTT assay; the viability and the IC50 were used to evaluate this test.

Results
The antimicrobial activity of the essential oil was investigated in order to evaluate its efficacy against the different tested microorganisms. The present results results showed a significant activity against microorganisms especially Gram (+) bacteria with inhibition zones and minimal inhibitory concentration values in the range of 6.6-25.2 mm and 1120-2600 μg/ml, respectively, whereas Gram (-) bacteria exhibited a higher resistance. As far as the antifungal activity, among four strains tested, Botrytis cinerea exhibited the strongest activity with inhibition zones of 12.6 mm. However, Fusarium solani, Penicillium digitatum and Aspergillus niger were less sensitive to M. vulgare essential oil. About the citotoxicity assay, this finding indicate the capability of this essential oil to inhibited the proliferation of HeLa cell lines under some conditions with IC50 value of 0.258 μg/ml.

Conclusion
This investigation showed that the M. vulgare essential oil has a potent antimicrobial activity against some Gram (+) pathogenic bacteria and Botrytis cinerea fungi. The present studies confirm the use of this essential oil as anticancer agent. Further research is required to evaluate the practical values of therapeutic applications.
Noise reduction for periodic signals using high-resolution frequency analysis
Authors: Yoshizawa Toshio , Hirobayashi Shigeki , Misawa Tadanobu 
Published: September 2011

Abstract
The spectrum subtraction method is one of the most common methods by which to remove noise from a spectrum. Like many noise reduction methods, the spectrum subtraction method uses discrete Fourier transform (DFT) for frequency analysis. There is generally a trade-off between frequency and time resolution in DFT. If the frequency resolution is low, then the noise spectrum can overlap with the signal source spectrum, which makes it difficult to extract the latter signal. Similarly, if the time resolution is low, rapid frequency variations cannot be detected. In order to solve this problem, as a frequency analysis method, we have applied non-harmonic analysis (NHA), which has high accuracy for detached frequency components and is only slightly affected by the frame length. Therefore, we examined the effect of the frequency resolution on noise reduction using NHA rather than DFT as the preprocessing step of the noise reduction process. The accuracy in extracting single sinusoidal waves from a noisy environment was first investigated. The accuracy of NHA was found to be higher than the theoretical upper limit of DFT. The effectiveness of NHA and DFT in extracting music from a noisy environment was then investigated. In this case, NHA was found to be superior to DFT, providing an approximately 2 dB improvement in SNR.
Complementary tensor-driven image coherence diffusion for oriented structure enhancement
Authors: Hong-mei Zhang , Ming-xi Wan , Zheng-zhong Bian 
Published: September 2011

Abstract
Oriented structure enhancement plays important role in computer vision tasks, where the diffusion is encouraged along the preferred direction instead of perpendicular to it. By analyzing the differential geometric property of the oriented structure, a complementary tensor is proposed by combining the first and the second-order structure tensors as complementary descriptors, which can precisely analyze not only the step edges, but also the weak edges such as narrow peak or ridge-like structures. Complementary diffusion tensor is constructed from the new structure tensor, which steers coherence diffusion for oriented structure enhancement. Furthermore, fast algorithm based on additive operator splitting scheme is used for numerical solution, which is much faster than usual approach. The experimental results on several images are provided. Experiments show that the image diffusion process steered by the new complementary tensor can strengthen the oriented structures and also close the interrupted lines as well. Both strong and weak edges are enhanced while noise is removed. Our approach is very promising and could be applied to many other images.
Optimization of adefovir therapy in chronic hepatitis B according to baseline predictors and on-treatment HBV DNA: a 5-Year prospective study
Authors: Lu Hui , Geng Da Ying , Shen Fei , Zhang Jing Yao , Lu Bing , Ma Li Xian 
Published: September 2011

AbstractBackgroundAdefovir Dipivoxil (ADV) is an important agent to suppress hepatitis B virus (HBV) replication with suboptimal effect on virological and serological response. To optimize Adefovir therapy in chronic hepatitis B (CHB) patients with hepatitis B e antigen (HBeAg) positive, we studied the baseline parameters and on-treatment HBV DNA for favorable outcomes.Methods48 patients were enrolled in the study and followed up for 5 years prospectively. Baseline characteristics, virological, serological and biochemical parameters as well as on treatment HBV DNA were assessed in prediction of favorable outcomes.Results1. The patients with baseline alanine aminotransferase (ALT) ≥5 × the upper limit of normal (ULN, 40 IU/L) had higher rates of viral response (VR), HBeAg loss and HBeAg seroconversion at year 5 compared to the patients with ALT < 5 × ULN (VR: 75% vs 43.8%, p = 0.035; HBeAg loss: 43.9% vs 13.8%, p = 0.017; HBeAg seroconversion: 37.9% vs 13.8%, p = 0.035); Patients with baseline HBV DNA < 109copies/ml and ALT ≥3 × ULN had more chance of HBeAg seroconversion (40.9% vs 8.7%, p = 0.012), while in patients with HBeAg < 800 s/co or HBsAg < 5000 IU/ml higher rates of HBeAg loss were achieved. 2. HBV DNA level < 104copies/ml at week 24 was predictive for VR (96.0% vs 40.9%, P < 0.001), HBeAg loss (84.0% vs 36.3%, P = 0.001) and HBeAg seroconversion (36.0% vs 9.1%, P = 0.030).ConclusionsADV treatment should be started for patients with baseline ALT≥5 × ULN or patients with ALT≥3 × ULN and HBV DNA < 109copies/ml. Lower level of HBeAg(< 800 s/co) and HBsAg(< 5000 IU/ml) may be regarded as referenced factors. In patients with serum HBV DNA < 104copies/ml at week 24 the therapy should continue, and a favorable outcome may be achieved in 5 years or longer.
Expression of an IRF-3 fusion protein and mouse estrogen receptor, inhibits hepatitis C viral replication in RIG-I-deficient Huh 7.5 cells
Authors: Yao Luyu , Yan Xiaobo , Dong Huijia , Nelson David R , Liu Chen , Li Xiaoyu 
Published: September 2011

Abstract
Interferon Regulatory Factor-3 (IRF-3) plays a central role in the induction of interferon (IFN) production and succeeding interferon-stimulated genes (ISG) expression en route for restraining hepatitis C virus (HCV) infection. Here, we established a stable Huh7.5-IRF3ER cell line expressing a fusion protein of IRF-3 and mouse estrogen receptor (ER) to examine IFN production and anti-HCV effects of IRF-3 in retinoic acid inducible-gene-I (RIG-I) deficient Huh 7.5 cells. Homodimerization of the IRF-3ER fusion protein was detected by Western blotting after treatment with the estrogen receptor agonist 4-hydrotamoxifen (4-HT) in Huh7.5-IRF3ER cells. Expression of IFN-α, IFN-β, and their inhibitory effects on HCV replication were demonstrated by real-time polymerase chain reaction (PCR). Peak expression of IFN-α and IFN-β was achieved 24-hours post 4-HT treatment, coinciding with the appearance of phosphorylated signal transducer and activator of transcription (STAT) proteins. Additionally, HCV viral replication declined in time-dependent fashion. In previous studies, a novel IFN-mediated pathway regulating expression of 1-8U and heterogeneous nuclear ribonucleoprotein M (hnRNP M) inhibited HCV internal ribosomal entry site (IRES)-dependent translation. When expression of ISGs such as 1-8U and hnRNP M were measured in 4-HT-treated Huh7.5-IRF3ER cells, both genes were positively regulated by activation of the IRF-3ER fusion protein. In conclusion, the anti-HCV effects of IRF-3ER homodimerization inhibited HCV RNA replication as well as HCV IRES-dependent translation in Huh7.5-IRF3ER cells. The results of this study indicate that IRF-3ER homodimerization is a key step to restore IFN expression in Huh7.5-IRF3ER cells and in achieving its anti-HCV effects.
Migraine Attacks the Basal Ganglia
Authors: Maleki Nasim , Becerra Lino , Nutile Lauren , Pendse Gautam , Brawn Jennifer , Bigal Marcelo , Burstein Rami , Borsook David 
Published: September 2011

Background: With time, episodes of migraine headache afflict patients with increased frequency, longer duration and more intense pain. While episodic migraine may be defined as 1-14 attacks per month, there are no clear-cut phases defined, and those patients with low frequency may progress to high frequency episodic migraine and the latter may progress into chronic daily headache (> 15 attacks per month). The pathophysiology of this progression is completely unknown. Attempting to unravel this phenomenon, we used high field (human) brain imaging to compare functional responses, functional connectivity and brain morphology in patients whose migraine episodes did not progress (LF) to a matched (gender, age, age of onset and type of medication) group of patients whose migraine episodes progressed (HF). Results: In comparison to LF patients, responses to pain in HF patients were significantly lower in the caudate, putamen and pallidum. Paradoxically, associated with these lower responses in HF patients, gray matter volume of the right and left caudate nuclei were significantly larger than in the LF patients. Functional connectivity analysis revealed additional differences between the two groups in regard to response to pain. Conclusions: Supported by current understanding of basal ganglia role in pain processing, the findings suggest a significant role of the basal ganglia in the pathophysiology of the episodic migraine.
Red blood cell transfusion and outcomes in patients with acute lung injury, sepsis and shock
Authors: Parsons Elizabeth C , Hough Catherine L , Seymour Christopher W , Cooke Colin R , Rubenfeld Gordon D , Watkins Timothy R ,   the NHLBI ARDS Network
Published: September 2011

Abstract
Introduction
In this study, we sought to determine the association between red blood cell (RBC) transfusion and outcomes in patients with acute lung injury (ALI), sepsis and shock.

Methods
We performed a secondary analysis of new-onset ALI patients enrolled in the Acute Respiratory Distress Syndrome Network Fluid and Catheter Treatment Trial (2000 to 2005) who had a documented ALI risk factor of sepsis or pneumonia and met shock criteria (mean arterial pressure (MAP) < 60 mmHg or vasopressor use) within 24 hours of randomization. Using multivariable logistic regression, we examined the association between RBC transfusion and 28-day mortality after adjustment for age, sex, race, randomization arm and Acute Physiology and Chronic Health Evaluation III score. Secondary end points included 90-day mortality and ventilator-free days (VFDs). Finally, we examined these end points among the subset of subjects meeting prespecified transfusion criteria defined by five simultaneous indicators: hemoglobin < 10.2 g/dL, central or mixed venous oxygen saturation < 70%, central venous pressure ≥ 8 mmHg, MAP ≥ 65 mmHg, and vasopressor use.

Results
We identified 285 subjects with ALI, sepsis, shock and transfusion data. Of these, 85 also met the above prespecified transfusion criteria. Fifty-three (19%) of the two hundred eighty-five subjects with shock and twenty (24%) of the subset meeting the transfusion criteria received RBC transfusion within twenty-four hours of randomization. We found no independent association between RBC transfusion and 28-day mortality (odds ratio = 1.49, 95% CI (95% confidence interval) = 0.77 to 2.90; P = 0.23) or VFDs (mean difference = -0.35, 95% CI = -4.03 to 3.32; P = 0.85). Likewise, 90-day mortality and VFDs did not differ by transfusion status. Among the subset of patients meeting the transfusion criteria, we found no independent association between transfusion and mortality or VFDs.

Conclusions
In patients with new-onset ALI, sepsis and shock, we found no independent association between RBC transfusion and mortality or VFDs. The physiological criteria did not identify patients more likely to be transfused or to benefit from transfusion.
Effects of changes in arterial pressure on organ perfusion during septic shock
Authors: Thooft Aurélie , Favory Raphaël , Salgado Diamantino Ribeiro , Taccone Fabio S , Donadello Katia , De Backer Daniel , Creteur Jacques , Vincent Jean-Louis 
Published: September 2011

Abstract
Introduction
Septic shock is characterized by altered tissue perfusion associated with persistent arterial hypotension. Vasopressor therapy is generally required to restore organ perfusion but the optimal mean arterial pressure (MAP) that should be targeted is uncertain. The aim of this study was to assess the effects of increasing MAP using norepinephrine (NE) on hemodynamic and metabolic variables and on microvascular reactivity in patients with septic shock.

Methods
This was a single center, prospective, interventional study conducted in the medico-surgical intensive care unit of a university hospital. Thirteen patients in septic shock for less than 48 hours who required NE administration were included. NE doses were adjusted to obtain MAPs of 65, 75, 85 and (back to) 65 mmHg. In addition to hemodynamic and metabolic variables, we measured thenar muscle oxygen saturation (StO2), using near infrared spectroscopy (NIRS), with serial vaso-occlusive tests (VOTs) on the upper arm. We also evaluated the sublingual microcirculation using sidestream dark field (SDF) imaging in 6 of the patients.

Results
Increasing NE dose was associated with an increase in cardiac output (from 6.1 to 6.7 l/min, P<0.05) and mixed venous oxygen saturation (SvO2, from 70.6 to 75.9%, P<0.05). Oxygen consumption (VO2) remained stable, but blood lactate levels decreased. There was a significant increase in the ascending slope of StO2 (from 111 to 177%/min, P<0.05) after VOTs. SDF imaging showed an increase in perfused vessel density (PVD, from 11.0 to 13.2 n/mm, P<0.05) and in microvascular flow index (MFI, from 2.4 to 2.9, P<0.05).

Conclusions
In this series of patients with septic shock, increasing MAP above 65 mmHg with NE was associated with increased cardiac output, improved microvascular function, and decreased blood lactate concentrations. The microvascular response varied among patients suggesting that individualization of blood pressure targets may be warranted.
Investigation of the differential potentials of TLR agonists to elicit uveitis in mice
Authors: Allensworth Jordan J , Planck Stephen R , Rosenbaum James T , Rosenzweig Holly L 
Published: September 2011

ABSTRACTTLRs are critical for host defense and innate immunity. Emerging evidence also supports a role for TLRs in many chronic inflammatory diseases, including inflammatory eye disease, known as uveitis. The activation of TLR4 by endotoxin induces a standard model of murine uveitis. How activation of additional TLRs influences the onset and/or severity of anterior uveitis has not been examined. We sought to elucidate the potential of TLRs (TLR1/2, TLR2/6, TLR3, TLR4, TLR5, TLR7/8, and TLR9) to trigger uveitis in mice. Directly stimulated iris/ciliary body explants demonstrated a marked increase in production of inflammatory cytokines TNF-α, IL-6, IP-10/CXCL10, MCP-1, and KC with relatively little production of IFN-γ, IL-10, IL-12p40, IL-12p70, IL-17, IL-1β, IL-4, or RANTES. The cytokine-response profiles were comparable amongst the TLR agonists, albeit some differences were noted, such as greater IP-10 production following TLR3 activation. Intra-ocular injection of TLR agonists increased leukocyte interactions with the endothelium of the iris vasculature and resulted in chemotaxis into the iris tissue. Assessment of leukocytic responses by ivt videomicroscopy and histology revealed quantitative differences amongst responses to the TLR agonists with respect to the timing and numbers of rolling, adhering, iris-infiltrating, and aqueous humor-infiltrating cells, along with cytokine levels in vivo. Our data demonstrate the eye's responsiveness to a diverse array of microbial products, which activates TLRs, and reveal differences in relative cellular response among the various TLR agonists in vivo.