bluuebunny/crossref_metadata_2025_split huggingface dataset:
Binding immunoglobulin protein resolves rheumatoid synovitis: a xenogeneic study using rheumatoid arthritis synovial membrane transplants in SCID mice
Authors: Yoshida Kaoru , Ochiai Akira , Matsuno Hiroaki , Panayi Gabriel S , Corrigall Valerie M 
Published: September 2011

Abstract
Introduction

Binding immunoglobulin protein (BiP) has previously shown powerful anti-inflammatory properties in the collagen-induced arthritis (CIA) model, where a single dose of BiP has proved to be both a long-term prophylactic and therapeutic. In both CIA and human in vitro studies, BiP induced regulatory T cells. The present investigation looked at the anti-inflammatory effect of BiP on inflamed human synovial tissue transplanted into severe combined immunodeficient mice (SCID), a chimaeric in vivo model previously used to test the efficacy of biologic therapies.

Methods

Rheumatoid arthritis synovial membrane (RASM) was engrafted into SCID mice. Following successful engraftment, mice were intravenously injected with BiP or human serum albumin in the presence or absence of anti-IL-10 mAb. Twelve days later the grafts were removed for analysis and human cytokines in the sera were quantified by ELISA. The extent of residual inflammatory cellular infiltrate in the synovial explants was determined by weight of the explants.

Results

The RASM transplants from mice treated with BiP showed visual reduction in cellular infiltrate and downregulation of all quantifiable features of inflammation as assessed by the Koizumi or Rooney histological criteria. Also downregulated were HLA-DR, CD86, IL-6 and TNFα expression as assessed by immunohistology. ELISA detected significantly less human IL-6 circulating in the BiP-treated mouse serum. After removal of transplanted tissue 12 days post administration of BiP, the RASM explants from the BiP-treated SCID mice weighed significantly less, indicating a suppression of tissue inflammation. Mice given concomitant neutralising anti-IL-10 antibody and BiP showed no such suppression.

Conclusions

BiP has anti-inflammatory properties partially dependent on the downregulation of HLA-DR and co-stimulatory molecules and the predominant production of IL-10.
Suppression of apoptosis inhibitor c-FLIP selectively eliminates breast cancer stem cell activity in response to the anti-cancer agent, TRAIL
Authors: Piggott Luke , Omidvar Nader , Pérez Salvador Martí , Eberl Matthias , Clarkson Richard WE 
Published: September 2011

Abstract
Introduction
It is postulated that breast cancer stem cells (bCSCs) mediate disease recurrence and drive formation of distant metastases - the principal cause of mortality in breast cancer patients. Therapeutic targeting of bCSCs, however, is hampered by their heterogeneity and resistance to existing therapeutics. In order to identify strategies to selectively remove bCSCs from breast cancers, irrespective of their clinical subtype, we sought an apoptosis mechanism that would target bCSCs yet would not kill normal cells. Suppression of the apoptosis inhibitor cellular FLICE-Like Inhibitory Protein (c-FLIP) partially sensitizes breast cancer cells to the anti-cancer agent Tumour Necrosis Factor-Related Apoptosis Inducing Ligand (TRAIL). Here we demonstrate in breast cancer cell lines that bCSCs are exquisitely sensitive to the de-repression of this pro-apoptotic pathway, resulting in a dramatic reduction in experimental metastases and the loss of bCSC self-renewal.

Methods
Suppression c-FLIP was performed by siRNA (FLIPi) in four breast cancer cell lines and by conditional gene-knockout in murine mammary glands. Sensitivity of these cells to TRAIL was determined by complementary cell apoptosis assays, including a novel heterotypic cell assay, while tumour-initiating potential of cancer stem cell subpopulations was determined by mammosphere cultures, aldefluor assay and in vivo transplantation.

Results
Genetic suppression of c-FLIP resulted in the partial sensitization of TRAIL-resistant cancer lines to the pro-apoptotic effects of TRAIL, irrespective of their cellular phenotype, yet normal mammary epithelial cells remained refractory to killing. While 10% to 30% of the cancer cell populations remained viable after TRAIL/FLIPi treatment, subsequent mammosphere and aldefluor assays demonstrated that this pro-apoptotic stimulus selectively targeted the functional bCSC pool, eliminating stem cell renewal. This culminated in an 80% reduction in primary tumours and a 98% reduction in metastases following transplantation. The recurrence of residual tumour initiating capacity was consistent with the observation that post-treated adherent cultures re-acquired bCSC-like properties in vitro. Importantly however this recurrent bCSC activity was attenuated following repeated TRAIL/FLIPi treatment.

Conclusions
We describe an apoptotic mechanism that selectively and repeatedly removes bCSC activity from breast cancer cell lines and suggest that a combined TRAIL/FLIPi therapy could prevent metastatic disease progression in a broad range of breast cancer subtypes.
Improved ICU design reduces acquisition of antibiotic-resistant bacteria: a quasi-experimental observational study
Authors: Levin Phillip D , Golovanevski Mila , Moses Allon E , Sprung Charles L , Benenson Shmuel 
Published: September 2011

Abstract
Introduction
The role of ICU design and particularly single-patient rooms in decreasing bacterial transmission between ICU patients has been debated. A recent change in our ICU allowed further investigation.

Methods
Pre-move ICU-A and pre-move ICU-B were open-plan units. In March 2007, ICU-A moved to single-patient rooms (post-move ICU-A). ICU-B remained unchanged (post-move ICU-B). The same physicians cover both ICUs. Cultures of specified resistant organisms in surveillance or clinical cultures from consecutive patients staying >48 hours were compared for the different ICUs and periods to assess the effect of ICU design on acquisition of resistant organisms.

Results
Data were collected for 62, 62, 44 and 39 patients from pre-move ICU-A, post-move ICU-A, pre-move ICU-B and post-move ICU-B, respectively. Fewer post-move ICU-A patients acquired resistant organisms (3/62, 5%) compared with post-move ICU-B patients (7/39, 18%; P = 0.043, P = 0.011 using survival analysis) or pre-move ICU-A patients (14/62, 23%; P = 0.004, P = 0.012 on survival analysis). Only the admission period was significant for acquisition of resistant organisms comparing pre-move ICU-A with post-move ICU-A (hazard ratio = 5.18, 95% confidence interval = 1.03 to 16.06; P = 0.025). More antibiotic-free days were recorded in post-move ICU-A (median = 3, interquartile range = 0 to 5) versus post-move ICU-B (median = 0, interquartile range = 0 to 4; P = 0.070) or pre-move ICU-A (median = 0, interquartile range = 0 to 4; P = 0.017). Adequate hand hygiene was observed on 140/242 (58%) occasions in post-move ICU-A versus 23/66 (35%) occasions in post-move ICU-B (P < 0.001).

Conclusions
Improved ICU design, and particularly use of single-patient rooms, decreases acquisition of resistant bacteria and antibiotic use. This observation should be considered in future ICU design.
High-Throughput Simultaneous Analysis of RNA, Protein, and Lipid Biomarkers in Heterogeneous Tissue Samples
Authors: Reiser Vladimír , Smith Ryan C , Xue Jiyan , Kurtz Marc M , Liu Rong , LeGrand Cheryl , He Xuanmin , Yu Xiang , Wong Peggy , Hinchcliffe John S , Tanen Michael R , Lazar Gloria , Zieba Renata , Ichetovkin Marina , Chen Zhu , O'Neill Edward A , Tanaka Wesley K , Marton Matthew J , Liao Jason , Morris Mark , Hailman Eric , Tokiwa George Y , Plump Andrew S 
Published: September 2011

BACKGROUNDWith expanding biomarker discovery efforts and increasing costs of drug development, it is critical to maximize the value of mass-limited clinical samples. The main limitation of available methods is the inability to isolate and analyze, from a single sample, molecules requiring incompatible extraction methods. Thus, we developed a novel semiautomated method for tissue processing and tissue milling and division (TMAD).METHODSWe used a SilverHawk atherectomy catheter to collect atherosclerotic plaques from patients requiring peripheral atherectomy. Tissue preservation by flash freezing was compared with immersion in RNAlater®, and tissue grinding by traditional mortar and pestle was compared with TMAD. Comparators were protein, RNA, and lipid yield and quality. Reproducibility of analyte yield from aliquots of the same tissue sample processed by TMAD was also measured.RESULTSThe quantity and quality of biomarkers extracted from tissue prepared by TMAD was at least as good as that extracted from tissue stored and prepared by traditional means. TMAD enabled parallel analysis of gene expression (quantitative reverse-transcription PCR, microarray), protein composition (ELISA), and lipid content (biochemical assay) from as little as 20 mg of tissue. The mean correlation was r = 0.97 in molecular composition (RNA, protein, or lipid) between aliquots of individual samples generated by TMAD. We also demonstrated that it is feasible to use TMAD in a large-scale clinical study setting.CONCLUSIONSThe TMAD methodology described here enables semiautomated, high-throughput sampling of small amounts of heterogeneous tissue specimens by multiple analytical techniques with generally improved quality of recovered biomolecules.
The estimation of selected endogenous anticoagulation system parameters in patients with subclinical Cushing's syndrome
Authors: Świątkowska-Stodulska Renata , Kaniuka-Jakubowska Sonia , Wiśniewski Piotr , Skibowska-Bielińska Anna , Sworczak Krzysztof 
Published: September 2011

ObjectiveAn increased tendency towards thromboembolic events is observed in patients with Cushing's syndrome. There are much fewer publications available about thromboembolic complications in patients with subclinical Cushing's syndrome (SCS). Therefore, a question arises whether hemostatic disturbances appear in this particular disease phase.Aim of studyEstimation of protein C (PC), free protein S (FPS), antithrombin (AT) activity, thrombomodulin (TM) concentration and activated PC resistance (APCR) in patients with SCS.Materials and methodsWe studied 35 patients with SCS. The control group consisted of 33 healthy volunteers. The activity of PC, AT, FPS, APCR and the concentration of TM was estimated in all representatives.ResultsThe comparison of the examined coagulation parameters between the patients with SCS and the healthy individuals revealed significantly higher mean PC activity and mean FPS activity in the SCS group. Mean TM concentration was significantly lower in patients with SCS compared with the control group. The differences in APCR and AT activity were not significant. We did not prove any statistically significant correlations between the examined coagulation parameters and hormonal parameters. We did not find any correlation between the concentration of cortisol and basic coagulation parameters such as international normalized ratio, activated partial thromboplastin time or fibrinogen in the group with SCS either.ConclusionsThe patients with SCS present disturbances in endogenous anticoagulation system defined as PC, FPS activity and TM concentration. This finding suggests an impact of mild autonomic cortisol overproduction on coagulation system.
Product Market Competition and Investments in Cooperative R&D
Authors: Hinloopen Jeroen , Vandekerckhove Jan 
Published: September 2011

Abstract
Building on the framework developed by Qiu (1997) we investigate the influence of product market competition on incentives to invest in cooperative R&D. For that we disentangle the three components that make up the combined-profits externality. The strategic component is always negative and the size component is always positive. The spillover component is negative (positive) with Bertrand (Cournot) competition. Cournot competition thus yields more cooperative R&D, which could drive the Cournot-Nash price below the Bertrand-Nash price. Our decomposition also explains why, under Cournot competition, cooperative R&D exceeds non-cooperative R&D only if spillovers are “high enough.”
John Ray, physico-theology and afterwards
Authors: Berry R. J. 
Published: September 2011

Ray's most widely read book was his Wisdom of God manifested in the works of creation (1691), probably based on addresses given in the chapel of Trinity College Cambridge 20 years previously. In it he forswore the use of allegory in biblical interpretation, just as he had done in his (and Francis Willughby's) Ornithology (1678). His discipline seeped into theology, complementing the influence of the Reformers and weakening Enlightenment assumptions about teleology, thus softening the hammer-blows of Darwinism on Deism. The physico-theology of the eighteenth century and the popularity of Gilbert White and the like survived the squeezing of natural theology by Paley and the Bridgewater Treatises a century after Wisdom … , and contributed to a peculiarly British understanding of natural theology. This undergirded the subsequent impact of the results of the voyagers and geologists and prepared the way for a modern reading of God's “Book of Works” (“Darwinism … under the disguise of a foe, did the work of a friend”).Natural theology is often assumed to have been completely discredited by Darwin (as well as condemned by Barth and ridiculed by Dawkins). Notwithstanding, and despite the vapours of vitalism (ironically urged – among others – by Ray's biographer, Charles Raven) and the current fashion for “intelligent design”, the attitudes encouraged by Wisdom … still seem to be robust, albeit needing constant re-tuning (as in all understandings influenced by science).
A Generic Method to Monitor Completeness and Speed of Medical Documentation Processes
Authors: Dugas-Breit S. , Dugas M. 
Published: September 2011

SummaryBackground: Physicians dedicate approximately a quarter of daily work to documentation. Completeness and speed of medical documentation processes are important parameters, because they can affect quality of healthcare.Objectives: A generic method to monitor these quality parameters is proposed and its utility is demonstrated in two examples.Methods: Based on a generic event-driven process chain of a medical documentation process, completeness functions for created and finalized documents (available versus required documents by time) are defined. The 95%-quantile of process time is applied as performance indicator of documentation speed. A plotting function for these parameters is provided: completeness and speed of medical documentation (CSMD)-plot. Open source code and a sample data set are available in the Supplement.Results: This methodology is applied to analyze the effect of an electronic dictation system on discharge letter documents. CSMD-plot detects significant differences regarding speed and completeness of the process before and after implementation of electronic dictation; in addition, it pinpoints differences regarding these quality parameters in documentation processes between different clinical departments. In a second example, CSMD-plot is used to analyze follow-up documentation of a clinical trial. Due to its generic design, CSMD-plots can be applied to other medical documentation processes such as order-entry processes.Conclusions: Monitoring of completeness and speed of medical documentation is feasible and can provide quantitative information on these processes.
Respiratory Variability during Different Auditory Stimulation Periods in Schizophrenia Patients
Authors: Kara S. , Bilgiç V. , Akar S. A. 
Published: September 2011

SummaryBackground: Schizophrenic patients are known to have difficulty processing emotions and to exhibit impairment in stimuli discrimination. However, there is limited knowledge regarding their physiological responsivity to auditory stimuli.Objectives: The purpose of this study was to compare the respiratory effects of two types of auditory stimuli with emotional content, classical Turkish music (CTM) and white noise (WN), on schizophrenia patients and healthy control subjects.Methods: Forty-six individuals participated in the experiment, and respiratory signals derived from a strain-gauge were recorded. Two important respiratory patterns, respiration rate and depth, were analyzed.Results: The results indicated that the patients presented a significantly higher respiration rate than control subjects during the initial baseline and WN exposure periods. Although CTM evoked an increase in respiration rates and a decrease in respiration depths in the control group, no significant differences were found during the stimulation periods in the patient group. The respiration rate was lower in the post-stimulation period than during the initial baseline period, and no respiration depth differences were found for the WN, music or post-stimulation periods in the schizophrenia group. Patients exhibited a greater respiration depth than the control subjects over all periods; however, a significant difference between the patient and control groups was obtained in the second resting condition and CTM exposure period. Furthermore, to analyze the effect of symptom severity on respiratory patterns, patients were divided into two classes according to their Positive and Negative Syndrome Scale score.Conclusions: Further studies are needed to correlate respiratory differences with emotionally evocative stimuli and to refine our understanding of the dynamics of these types of stimuli in relation to clinical state and medication effects.
Investigation on structural, thermal, optical and sensing properties of meta-stable hexagonal MoO3 nanocrystals of one dimensional structure
Authors: Chithambararaj Angamuthuraj , Bose Arumugam Chandra 
Published: September 2011

Hexagonal molybdenum oxide (h-MoO3) was synthesized by a solution based chemical precipitation technique. Analysis by X-ray diffraction (XRD) confirmed that the as-synthesized powder had a metastable hexagonal structure. The characteristic vibrational band of Mo–O was identified from Fourier transform infrared spectroscopy (FT-IR). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images clearly depicted the morphology and size of h-MoO3. The morphology study showed that the product comprises one-dimensional (1D) hexagonal rods. From the electron energy loss spectroscopy (EELS) measurement, the elemental composition was investigated and confirmed from the characteristic peaks of molybdenum and oxygen. Thermogravimetric (TG) analysis on metastable MoO3 revealed that the hexagonal phase was stable up to 430 °C and above this temperature complete transformation into a highly stable orthorhombic phase was achieved. The optical band gap energy was estimated from the Kubelka–Munk (K–M) function and was found to be 2.99 eV. Finally, the ethanol vapor-sensing behavior was investigated and the sensing response was found to vary linearly as a function of ethanol concentration in the parts per million (ppm) range.
In Vivo Measurements of Thermal Load During Ablation in High-speed Laser Corneal Refractive Surgery
Authors: de Ortueta Diego , Magnago Thomas , Triefenbach Nico , Arba Mosquera Samuel , Sauer Udo , Brunsmann Ulrich 
Published: September 2011

PURPOSE:
To evaluate the thermal load of ablation in high-speed laser corneal refractive surgery with the AMARIS excimer laser (SCHWIND eye-tech-solutions).

METHODS:

Thermal load from refractive corrections on human corneas using a 500-Hz laser system with a fluence of 500 mJ/cm
2
and aspheric ablation profiles was recorded with an infrared thermography camera. Each single in vivo measurement was analyzed and temperature values were evaluated.

RESULTS:
Overall, the maximum temperature change of the ocular surface induced by the refractive ablations was ≤4°C. The increase in the peak temperature of the ocular surface never exceeded 35°C in any case. This low thermal load was independent of the amount of correction the eye achieved.

CONCLUSIONS:
The thermal load of the ablation in high-speed laser corneal refractive surgery was minimized using a computer algorithm to control the peak temperature to avoid corneal collagen denaturation with minimal compromise on treatment duration.
Comparison of Blind Nasal Packing vs Endoscopic Control of Epistaxis in an Emergency Setting
Authors: Chhapola Sunita , Matta Inita , Marker Pratima 
Published: September 2011

ABSTRACTAim:To compare the precision and efficacy of endoscopic control versus nasal packing in epistaxis presenting to the emergency room.DesignOpen labelled randomized controlled trial for comparison of precision and efficacy of emergency blind nasal packing with primary endoscopic control of epistaxis.SubjectsA total of 160 consecutive patients of epistaxis in the age group of 40 to 70 years were randomized in two groups (A and B) of 80 patients each. Group A was subjected to blind nasal packing and group B to endoscopic procedure. About 48 (30%) patients were alcoholic, 64 (40%) were hypertensive and 48 (30%) patients did not have any overt predisposing factor. Bleeding time, clotting time, prothrombin time, partial thromboplastin time and international normalized ratio (INR) were done in all patients to rule out coagulation diseases.ResultsThe nasal pack of patients in group A was removed after 48 hours. The nose was endoscopically examined on 3rd day, 7th day and then 1 month after the epistaxis. A total of 44 (55%) patients of group A had nasal mucosal abrasions (p < 0.05), two (2.5%) patients had secretory otitis media (p > 0.05) and 10 (12.5%) had synechiae formation (p > 0.05). A total of 28 (35%) patients from group A had one episode of rebleed after nasal pack removal. Group B had no complications.ConclusionEpistaxis presenting to the emergency room can be precisely and effectively controlled endoscopically. Clumsy nasal packing, complications and subsequent hospitalization costs are thereby reduced.
Schwannomas along Different Segments of Facial Nerve: Case Series with Review of Literature
Authors: Nair Deepa , Pai Prathamesh S , Joseph Shawn T , Moiyadi Aliasgar V 
Published: September 2011

ABSTRACTFacial nerve schwannomas are rare conditions which can mimic many other conditions. A series of patients with facial nerve schwannomas were treated in our department, all of whom had a delay in diagnosis resulting in a significant morbidity. This prompted us to present this rare case series of schwannomas along different segments of facial nerve and also review the literature on such tumors—the different presentations, work-up issues in management and rehabilitation. A wide text and PubMed English literature-based search was done on the existing literature on facial nerve schwannomas and the summary presented. Facial nerve schwannomas can have multiple clinical presentations with or without a facial paresis. Only a high degree of clinical suspicion and early imaging can lead to this diagnosis. An early diagnosis of facial nerve schwannoma is important as the morbidity associated with the condition as well as the surgery increases with the delay in diagnosis.