bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protease IV, a quorum sensing‐dependent protease of Pseudomonas aeruginosa modulates insect innate immunity
Authors: Park Su‐Jin , Kim Soo‐Kyoung , So Yong‐In , Park Ha‐Young , Li Xi‐Hui , Yeom Doo Hwan , Lee Mi‐Nan , Lee Bok‐Luel , Lee Joon‐Hee 
Published: October 2014

SummaryIn Pseudomonas aeruginosa, quorum sensing (QS) plays an essential role in pathogenesis and the QS response controls many virulence factors. Using a mealworm, Tenebrio molitor as a host model, we found that Protease IV, a QS‐regulated exoprotease of P. aeruginosa functions as a key virulence effector causing the melanization and death of T. molitor larvae. Protease IV was able to degrade zymogens of spätzle processing enzyme (SPE) and SPE‐activating enzyme (SAE) without the activation of the antimicrobial peptide (AMP) production. Since SPE and SAE function to activate spätzle, a ligand of Toll receptor in the innate immune system of T. molitor, we suggest that Protease IV may interfere with the activation of the Toll signaling. Independently of the Toll pathway, the melanization response, another innate immunity was still generated, since Protease IV directly converted Tenebrio prophenoloxidase into active phenoloxidase. Protease IV also worked as an important factor in the virulence to brine shrimp and nematode. These results suggest that Protease IV provides P. aeruginosa with a sophisticated way to escape the immune attack of host by interfering with the production of AMPs.
PhoR autokinase activity is controlled by an intermediate in wall teichoic acid metabolism that is sensed by the intracellular PAS domain during the PhoPR‐mediated phosphate limitation response of Bacillus subtilis
Authors: Botella Eric , Devine Susanne Krogh , Hubner Sebastian , Salzberg Letal I. , Gale Robert T. , Brown Eric D. , Link Hannes , Sauer Uwe , Codée Jeroen D. , Noone David , Devine Kevin M. 
Published: October 2014

SummaryThe PhoPR two‐component signal transduction system controls one of the major responses to phosphate limitation in Bacillus subtilis. When activated it directs expression of phosphate scavenging enzymes, lowers synthesis of the phosphate‐rich wall teichoic acid (WTA) and initiates synthesis of teichuronic acid, a non‐phosphate containing replacement anionic polymer. Despite extensive knowledge of this response, the signal to which PhoR responds has not been identified. Here we report that one of the main functions of the PhoPR two‐component system in B. subtilis is to monitor WTA metabolism. PhoR autokinase activity is controlled by the level of an intermediate in WTA synthesis that is sensed through the intracellular PAS domain. The pool of this intermediate generated by WTA synthesis in cells growing under phosphate‐replete conditions is sufficient to inhibit PhoR autokinase activity. However WTA synthesis is lowered upon phosphate limitation by the combined effects of PhoP∼P‐mediated activation of tuaA–H transcription and repression of tagAB. These transcriptional changes combine to lower the level of the inhibitory WTA metabolite thereby increasing PhoR autokinase activity. This amplifies the PHO response with full induction being achieved ∼ 90 min after the onset of phosphate limitation.
Influence of a new 5‐HT4 receptor partial agonist, YKP10811, on visceral hypersensitivity in rats triggered by stress and inflammation
Authors: Gilet M. , Eutamene H. , Han H. , Kim H. W. , Bueno L. 
Published: October 2014

AbstractBackgroundAdverse effects of previously developed 5‐HT4 receptor agonists to treat functional constipation (FC) and constipation IBS (IBS‐C) patients have limited their use but have given rise to new and more selective 5‐HT4 receptor agonists. This work was aimed to evaluate the influence of YKP10811, a new potent 5‐HT4 receptor partial agonist, on rat models of colorectal hypersensitivity to distension.MethodsMale and female rats were submitted to colorectal distension (CRD) before and after trinitrobenzene sulfonic acid (TNBS) infusion, acute (PRS) or chronic (water avoidance ‐10 days – WAS) stress. Electromyographic (EMG) response of abdominal muscles to CRD (15–60 mmHg) was used to measure pain. Changes of colonic tone were also evaluated. The influence of YKP10811 was compared to that of tegaserod with or without exposure of rats to a 5‐HT4 receptor antagonist in TNBS treated rats and to both tegaserod and CP‐154,526, a corticotropine releasing factor‐R1 antagonist in WAS. We tested a possible pharmacological tachyphylaxis of YKP10811 in TNBS‐induced hypersensitivity.Key ResultsYKP10811 (30 mg/kg) had no effect on basal sensitivity and tone in male and female rats but suppressed TNBS‐induced hypersensitivity, an effect blocked by the 5‐HT4 receptor antagonist GR113808 (10 mg/kg, SC). YKP10811 attenuated acute PRS‐induced but not chronic WAS‐induced colonic hypersensitivity. In addition, YKP10811 but not tegaserod reduced TNBS‐induced colorectal hypersensitivity after 7 days of treatment.Conclusions & InferencesYKP10811exhibits antinociceptive activity in inflammation and acute stress‐induced colonic hypersensitivity through 5‐HT4 receptors but unlike tegaserod, YKP10811 maintains its activity after repeated administrations and may represent a new candidate to treat IBS‐C patients.
Utility of a multiple serum biomarker test to monitor remission status and relapse in dogs with lymphoma undergoing treatment with chemotherapy
Authors: Alexandrakis I. , Tuli R. , Ractliffe S. C. , Tappin S. W. , Foale R. D. , Roos A. , Slater K. J. 
Published: October 2014

AbstractA blinded retrospective study was conducted to investigate remission and recurrence of lymphoma in dogs receiving chemotherapy. The objective was to compare clinicians' assessment using palpation and cytology to the results of serum biochemical tests for haptoglobin (Hapt) and C‐reactive protein (C‐RP). These biochemical test results were combined using a diagnostic algorithm developed using data from 344 individual dogs. This multivariate approach, termed the canine lymphoma blood test (cLBT), was used to follow 57 dogs during and after treatment. cLBT of remission and recurrence compared well with clinicians' assessment and differentiated dogs in remission and those with recurring disease before appearance of lymphadenopathy (P < 0.001). The cLBT demonstrated prognostic potential based on pre‐treatment values on dogs with shorter survival times and on those achieving the lowest cLBT score during treatment that showed longer survival times. The test, therefore, demonstrates potential to assist in monitoring treatment of canine lymphoma.
Real‐time out‐of‐plane artifact subtraction tomosynthesis imaging using prior CT for scanning beam digital x‐ray system
Authors: Wu Meng , Fahrig Rebecca 
Published: October 2014

Purpose:The scanning beam digital x‐ray system (SBDX) is an inverse geometry fluoroscopic system with high dose efficiency and the ability to perform continuous real‐time tomosynthesis in multiple planes. This system could be used for image guidance during lung nodule biopsy. However, the reconstructed images suffer from strong out‐of‐plane artifact due to the small tomographic angle of the system.Methods:The authors propose an out‐of‐plane artifact subtraction tomosynthesis (OPAST) algorithm that utilizes a prior CT volume to augment the run‐time image processing. A blur‐and‐add (BAA) analytical model, derived from the project‐to‐backproject physical model, permits the generation of tomosynthesis images that are a good approximation to the shift‐and‐add (SAA) reconstructed image. A computationally practical algorithm is proposed to simulate images and out‐of‐plane artifacts from patient‐specific prior CT volumes using the BAA model. A 3D image registration algorithm to align the simulated and reconstructed images is described. The accuracy of the BAA analytical model and the OPAST algorithm was evaluated using three lung cancer patients’ CT data. The OPAST and image registration algorithms were also tested with added nonrigid respiratory motions.Results:Image similarity measurements, including the correlation coefficient, mean squared error, and structural similarity index, indicated that the BAA model is very accurate in simulating the SAA images from the prior CT for the SBDX system. The shift‐variant effect of the BAA model can be ignored when the shifts between SBDX images and CT volumes are within ±10 mm in the x and y directions. The nodule visibility and depth resolution are improved by subtracting simulated artifacts from the reconstructions. The image registration and OPAST are robust in the presence of added respiratory motions. The dominant artifacts in the subtraction images are caused by the mismatches between the real object and the prior CT volume.Conclusions:Their proposed prior CT‐augmented OPAST reconstruction algorithm improves lung nodule visibility and depth resolution for the SBDX system.
Multipinhole collimator with 20 apertures for a brain SPECT application
Authors: Lee Tzu‐Cheng , Ellin Justin R. , Huang Qiu , Shrestha Uttam , Gullberg Grant T. , Seo Youngho 
Published: October 2014

Purpose:Several new technologies for single photon emission computed tomography (SPECT) instrumentation with parallel‐hole collimation have been proposed to improve detector sensitivity and signal collection efficiency. Benefits from improved signal efficiency include shorter acquisition times and lower dose requirements. In this paper, the authors show a possibility of over an order of magnitude enhancement in photon detection efficiency (from 7.6 × 10−5 to 1.6 × 10−3) for dopamine transporter (DaT) imaging of the striatum over the conventional SPECT parallel‐hole collimators by use of custom‐designed 20 multipinhole (20‐MPH) collimators with apertures of 0.75 cm diameter.Methods:Quantifying specific binding ratio (SBR) of 123I‐ioflupane or 123I‐iometopane's signal at the striatal region is a common brain imaging method to confirm the diagnosis of the Parkinson's disease. The authors performed imaging of a striatal phantom filled with aqueous solution of I‐123 and compared camera recovery ratios of SBR acquired between low‐energy high‐resolution (LEHR) parallel‐hole collimators and 20‐MPH collimators.Results:With only two‐thirds of total acquisition time (20 min against 30 min), a comparable camera recovery ratio of SBR was achieved using 20‐MPH collimators in comparison to that from the LEHR collimator study.Conclusions:Their systematic analyses showed that the 20‐MPH collimator could be a promising alternative for the DaT SPECT imaging for brain over the traditional LEHR collimator, which could give both shorter scan time and improved diagnostic accuracy.
Temporal and Stochastic Control of Staphylococcus aureus Biofilm Development
Authors: Moormeier Derek E. , Bose Jeffrey L. , Horswill Alexander R. , Bayles Kenneth W. 
Published: October 2014

ABSTRACT

Biofilm communities contain distinct microniches that result in metabolic heterogeneity and variability in gene expression. Previously, these niches were visualized within
Staphylococcus aureus
biofilms by observing differential expression of the
cid
and
lrg
operons during tower formation. In the present study, we examined early biofilm development and identified two new stages (designated “multiplication” and “exodus”) that were associated with changes in matrix composition and a distinct reorganization of the cells as the biofilm matured. The initial attachment and multiplication stages were shown to be protease sensitive but independent of most cell surface-associated proteins. Interestingly, after 6 h of growth, an exodus of the biofilm population that followed the transition of the biofilm to DNase I sensitivity was demonstrated. Furthermore, disruption of the gene encoding staphylococcal nuclease (
nuc
) abrogated this exodus event, causing hyperproliferation of the biofilm and disrupting normal tower development. Immediately prior to the exodus event,
S. aureus
cells carrying a
nuc
::
gfp
promoter fusion demonstrated Sae-dependent expression but only in an apparently random subpopulation of cells. In contrast to the existing model for tower development in
S. aureus
, the results of this study suggest the presence of a Sae-controlled nuclease-mediated exodus of biofilm cells that is required for the development of tower structures. Furthermore, these studies indicate that the differential expression of
nuc
during biofilm development is subject to stochastic regulatory mechanisms that are independent of the formation of metabolic microniches.

IMPORTANCE
In this study, we provide a novel view of four early stages of biofilm formation by the human pathogen
Staphylococcus aureus
. We identified an initial nucleoprotein matrix during biofilm development that is DNase I insensitive until a critical point when a nuclease-mediated exodus of the population is induced prior to tower formation. Unlike the previously described dispersal of cells that occurs after tower development, we found that the mechanism controlling this exodus event is dependent on the Sae regulatory system and independent of Agr. In addition, we revealed that the gene encoding the secreted staphylococcal nuclease was expressed in only a subpopulation of cells, consistent with a model in which biofilms exhibit multicellular characteristics, including the presence of specialized cells and a division of labor that imparts functional consequences to the remainder of the population.
Parathyroid adenoma in a patient with familial hypocalciuric hypercalcaemia
Authors: Forde Hannah Elizabeth , Hill Arnold D , Smith Diarmuid 
Published: October 2014

A 57-year-old man with symptoms of fatigue, joint pains and insomnia was found to have hypercalcaemia secondary to hyperparathyroidism with a corrected calcium of 2.61 mmol/L (2.2–2.6 mmol/L) and a serum parathyroid hormone (PTH) of 86 pg/mL (10–65 pg/mL). Preoperative workup demonstrated a parathyroid adenoma in the right upper position and he proceeded to surgery. Postoperatively, however, his symptoms remained unchanged and the corrected calcium remained elevated at 2.87 mmol/L with a PTH of 59 pg/mL. He had no family history of hypercalcaemia. Further investigations revealed low 24 h urinary calcium level and a low urine calcium to creatinine ratio. Genetic testing revealed a mutation in exon 4 of the calcium sensing receptor (CaSR) confirming a diagnosis of familial hypocalciuric hyercalcaemia (FHH).The case is an example of a rare phenomenon when a parathyroid adenoma develops in patients with FHH.
Term perinatal mortality audit in the Netherlands 2010–2012: a population-based cohort study
Authors: Eskes Martine , Waelput Adja J M , Erwich Jan Jaap H M , Brouwers Hens A A , Ravelli Anita C J , Achterberg Peter W , Merkus Hans (J) M W M , Bruinse Hein W 
Published: October 2014

ObjectiveTo assess the implementation and first results of a term perinatal internal audit by a standardised method.DesignPopulation-based cohort study.SettingAll 90 Dutch hospitals with obstetric/paediatric departments linked to community practices of midwives, general practitioners in their attachment areas, organised in perinatal cooperation groups (PCG).PopulationThe population consisted of 943 registered term perinatal deaths occurring in 2010–2012 with detailed information, including 707 cases with completed audit results.Main outcome measuresParticipation in the audit, perinatal death classification, identification of substandard factors (SSF), SSF in relation to death, conclusive recommendations for quality improvement in perinatal care and antepartum risk selection at the start of labour.ResultsAfter the introduction of the perinatal audit in 2010, all PCGs participated. They organised 645 audit sessions, with an average of 31 healthcare professionals per session. Of all 1102 term perinatal deaths (2.3/1000) data were registered for 86% (943) and standardised anonymised audit results for 64% (707). In 53% of the cases at least one SSF was identified. Non-compliance to guidelines (35%) and deviation from usual professional care (41%) were the most frequent SSF. There was a (very) probable relation between the SSF and perinatal death for 8% of all cases. This declined over the years: from 10% (n=23) in 2010 to 5% (n=10) in 2012 (p=0.060). Simultaneously term perinatal mortality decreased from 2.3 to 2.0/1000 births (p<0.00001). Possibilities for improvement were identified in the organisation of care (35%), guidelines or usual care (19%) and in documentation (15%). More pregnancies were antepartum selected as high risk, 70% in 2010 and 84% in 2012 (p=0.0001).ConclusionsThe perinatal audit is implemented nationwide in all obstetrical units in the Netherlands in a short time period. It is possible that the audit contributed to the decrease in term perinatal mortality.
Audiologists’ preferences for patient-centredness: a cross-sectional questionnaire study of cross-cultural differences and similarities among professionals in Portugal, India and Iran
Authors: Manchaiah Vinaya , Gomersall Philip A , Tomé David , Ahmadi Tayebeh , Krishna Rajalakshmi 
Published: October 2014

ObjectivePatient-centredness has become an important aspect of health service delivery; however, there are a limited number of studies that focus on this concept in the domain of hearing healthcare. The objective of this study was to examine and compare audiologists’ preferences for patient-centredness in Portugal, India and Iran.DesignThe study used a cross-sectional survey design with audiologists recruited from three different countries.ParticipantsA total of 191 fully-completed responses were included in the analysis (55 from Portugal, 78 from India and 58 from Iran).Main outcome measureThe Patient–Practitioner Orientation Scale (PPOS).ResultsPPOS mean scores suggest that audiologists have a preference for patient-centredness (ie, mean of 3.6 in a 5-point scale). However, marked differences were observed between specific PPOS items suggesting these preferences vary across clinical situations. A significant level of difference (p<0.001) was found between audiologists’ preferences for patient-centredness in three countries. Audiologists in Portugal had a greater preference for patient-centredness when compared to audiologists in India and Iran, although no significant differences were found in terms of age and duration of experience among these sample populations.ConclusionsThere are differences and similarities in audiologists’ preferences for patient-centredness among countries. These findings may have implications for the training of professionals and also for clinical practice in terms of optimising hearing healthcare across countries.
Doctors who pilot the GMC’s Tests of Competence: who volunteers and why?
Authors: Mehdizadeh Leila , Sturrock Alison , Myers Gil , Khatib Yasmin , Dacre Jane 
Published: October 2014

Abstract

Background
Doctors who are investigated by the General Medical Council for performance concerns may be required to take a Test of Competence (ToC). The tests are piloted on volunteer doctors before they are used in Fitness to Practise (FtP) investigations.

Objectives
To find out who volunteers to take a pilot ToC and why.

Methods
This was a retrospective cohort study. Between February 2011 and October 2012 we asked doctors who volunteered for a test to complete a questionnaire about their reasons for volunteering and recruitment. We analysed the data using descriptive statistics and Pearson’s χ2 test.

Results
301 doctors completed the questionnaire. Doctors who took a ToC voluntarily were mostly women, of white ethnicity, of junior grades, working in general practice and who held a Primary Medical Qualification (PMQ) from the UK. This was a different population to doctors under investigation and all registered doctors in the UK. Most volunteers heard about the General Medical Council’s pilot events through email from a colleague and used the experience to gain exam practice for forthcoming postgraduate exams.

Conclusions
The reference groups of volunteers are not representative of doctors under FtP investigation. Our findings will be used to inform future recruitment strategies with the aim to encourage better matching of groups who voluntarily pilot a ToC with those under FtP investigation.
Copper Signaling Axis as a Target for Prostate Cancer Therapeutics
Authors: Safi Rachid , Nelson Erik R. , Chitneni Satish K. , Franz Katherine J. , George Daniel J. , Zalutsky Michael R. , McDonnell Donald P. 
Published: October 2014

Abstract
Previously published reports indicate that serum copper levels are elevated in patients with prostate cancer and that increased copper uptake can be used as a means to image prostate tumors. It is unclear, however, to what extent copper is required for prostate cancer cell function as we observed only modest effects of chelation strategies on the growth of these cells in vitro. With the goal of exploiting prostate cancer cell proclivity for copper uptake, we developed a “conditional lethal” screen to identify compounds whose cytotoxic actions were manifested in a copper-dependent manner. Emerging from this screen was a series of dithiocarbamates, which, when complexed with copper, induced reactive oxygen species–dependent apoptosis of malignant, but not normal, prostate cells. One of the dithiocarbamates identified, disulfiram (DSF), is an FDA-approved drug that has previously yielded disappointing results in clinical trials in patients with recurrent prostate cancer. Similarly, in our studies, DSF alone had a minimal effect on the growth of prostate cancer tumors when propagated as xenografts. However, when DSF was coadministered with copper, a very dramatic inhibition of tumor growth in models of hormone-sensitive and of castrate-resistant disease was observed. Furthermore, we determined that prostate cancer cells express high levels of CTR1, the primary copper transporter, and additional chaperones that are required to maintain intracellular copper homeostasis. The expression levels of most of these proteins are increased further upon treatment of androgen receptor (AR)–positive prostate cancer cell lines with androgens. Not surprisingly, robust CTR1-dependent uptake of copper into prostate cancer cells was observed, an activity that was accentuated by activation of AR. Given these data linking AR to intracellular copper uptake, we believe that dithiocarbamate/copper complexes are likely to be effective for the treatment of patients with prostate cancer whose disease is resistant to classical androgen ablation therapies. Cancer Res; 74(20); 5819–31. ©2014 AACR.