bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiology and cost analysis for patients with oral cancer in a university hospital in China
Authors: Han Sheng , Chen Yan , Ge Xu , Zhang Ming , Wang Jinwei , Zhao Qingbo , He Jianjun , Wang Zhenghong
Published: April 2010

Background

Although several studies have reported the direct cost of oral cancer (OC), little research has invested the factors that could influence the costs of OC patient. This study analyzes the epidemiological characteristics and the direct cost of OC. More specifically, the study examines the relationship between patients' medical costs and influencing factors of epidemiology.

Methods

All patients encountered from January 2007 to December 2007 at the School of Stomatology of the Fourth Military Medical University (FMMU) in China with diagnosis of oral cancer have been selected. Medical hospitalization days (MHD) and cost per patient (CPP) of the samples have been calculated for different patient groups, and the results have been compared using statistical methods.

Results

A total of 456 oral cancer patients have been selected in this study. The epidemical characteristics are as follows: female/male 176/280; squamous cell carcinoma (SCC)/adenocarcinoma/sarcoma/lymphoma/other types 246/127/40/27/16; stage I/II/III/IV 90/148/103/115; smoker/non-smoker 136/320; rural/urban patients 82/374. Of all the patients, 82.24% were over 40 years of age. Rural patients were significantly younger than urban patients. SCC was the majority histology in older patients, while sarcoma was more common in younger patients. 372 of the patients received treatment and 84 gave up any treatment after diagnosis. Treatment cost accounted for majority of the payment. The CPP and MHD of patients in late clinical stage were higher than that of patient in early stage.

Conclusion

Gender, smoking habit and age older than 40 years are the epidemiological risk factors for oral cancer. Lack of medicare, smoking habit, late clinical stage and SCC are the high economic factors for patient medical cost.
Epidermal growth factor receptor gene copy number in 101 advanced colorectal cancer patients treated with chemotherapy plus cetuximab
Authors: Campanella Carla , Mottolese Marcella , Cianciulli Anna , Torsello Angela , Merola Roberta , Sperduti Isabella , Melucci Elisa , Conti Salvatore , Diodoro Maria Grazia , Zeuli Massimo , Paoletti Giancarlo , Cognetti Francesco , Garufi Carlo
Published: April 2010

Background

Responsiveness to Cetuximab alone can be mediated by an increase of Epidermal Growth factor Receptor (EGFR) Gene Copy Number (GCN). Aim of this study was to assess the role of EGFR-GCN in advanced colorectal cancer (CRC) patients receiving chemotherapy plus Cetuximab.

Methods

One hundred and one advanced CRC patients (43 untreated- and 58 pre-treated) were retrospectively studied by fluorescence in situ hybridization (FISH) to assess EGFR-GCN and by immunohistochemistry (IHC) to determine EGFR expression. Sixty-one out of 101 patients were evaluated also for k-ras status by direct sequencing. Clinical end-points were response rate (RR), progression-free survival (PFS) and overall survival (OS).

Results

Increased EGFR-GCN was found in 60/101 (59%) tumor samples. There was no correlation between intensity of EGFR-IHC and EGFR-GCN (p = 0.43). Patients receiving chemotherapy plus Cetuximab as first line treatment had a RR of 70% (30/43) while it was 18% (10/56) in the group with previous lines of therapy (p < 0.0001). RR was observed in 29/60 (48%) of patients with increased EGFR-GCN and in 6/28 (21%) in those without (p = 0.02). At multivariate analyses, number of chemotherapy lines and increased EGFR-GCN were predictive of response; EGFR-IHC score, increased EGFR-GCN and number of chemotherapy lines were significantly associated with a significant better PFS. Response to therapy was the only prognostic predictive factor for OS. In the 60 patients analyzed for k-ras mutations, number of chemotherapy lines, increased EGFR-GCN and k-ras wild type status predicted a better PFS.

Conclusion

In metastatic CRC patients treated with chemotherapy plus Cetuximab number of chemotherapy lines and increased EGFR-GCN were significantly associated with a better clinical outcome, independent of k-ras status.
Oxidative stress in NSC-741909-induced apoptosis of cancer cells
Authors: Wei Xiaoli , Guo Wei , Wu Shuhong , Wang Li , Huang Peng , Liu Jinsong , Fang Bingliang
Published: April 2010

Background

NSC-741909 is a novel anticancer agent that can effectively suppress the growth of several cell lines derived from lung, colon, breast, ovarian, and kidney cancers. We recently showed that NSC-741909-induced antitumor activity is associated with sustained Jun N-terminal kinase (JNK) activation, resulting from suppression of JNK dephosphorylation associated with decreased protein levels of MAPK phosphatase-1. However, the mechanisms of NSC-741909-induced antitumor activity remain unclear. Because JNK is frequently activated by oxidative stress in cells, we hypothesized that reactive oxygen species (ROS) may be involved in the suppression of JNK dephosphorylation and the cytotoxicity of NSC-741909.

Methods

The generation of ROS was measured by using the cell-permeable nonfluorescent compound H2DCF-DA and flow cytometry analysis. Cell viability was determined by sulforhodamine B assay. Western blot analysis, immunofluorescent staining and flow cytometry assays were used to determine apoptosis and molecular changes induced by NSC-741909.

Results

Treatment with NSC-741909 induced robust ROS generation and marked MAPK phosphatase-1 and -7 clustering in NSC-741909-sensitive, but not resistant cell lines, in a dose- and time-dependent manner. The generation of ROS was detectable as early as 30 min and ROS levels were as high as 6- to 8-fold above basal levels after treatment. Moreover, the NSC-741909-induced ROS generation could be blocked by pretreatment with antioxidants, such as nordihydroguaiaretic acid, aesculetin, baicalein, and caffeic acid, which in turn, inhibited the NSC-741909-induced JNK activation and apoptosis.

Conclusion

Our results demonstrate that the increased ROS production was associated with NSC-741909-induced antitumor activity and that ROS generation and subsequent JNK activation is one of the primary mechanisms of NSC-741909-mediated antitumor cell activity.
In vivo trans-specific gene silencing in fungal cells by in planta expression of a double-stranded RNA
Authors: Tinoco Maria Laine P , Dias Bárbara BA , Dall'Astta Rebeca C , Pamphile João A , Aragão Francisco JL
Published: April 2010

Background

Self-complementary RNA transcripts form a double-stranded RNA (dsRNA) that triggers a sequence-specific mRNA degradation, in a process known as RNA interference (RNAi), leading to gene silencing. In vascular plants, RNAi molecules trafficking occur between cells and systemically throughout the plant. RNAi signals can spread systemically throughout a plant, even across graft junctions from transgenic to non-transgenic stocks. There is also a great interest in applying RNAi to pathogenic fungi. Specific inhibition of gene expression by RNAi has been shown to be suitable for a multitude of phytopathogenic filamentous fungi. However, double-stranded (ds)RNA/small interfering (si)RNA silencing effect has not been observed in vivo.

Results

This study demonstrates for the first time the in vivo interference phenomenon in the pathogenic fungus Fusarium verticillioides, in which expression of an individual fungal transgene was specifically abolished by inoculating mycelial cells in transgenic tobacco plants engineered to express siRNAs from a dsRNA corresponding to the particular transgene.

Conclusion

The results provide a powerful tool for further studies on molecular plant-microbe and symbiotic interactions. From a biotechnological perspective, silencing of fungal genes by generating siRNAs in the host provides a novel strategy for the development of broad fungi-resistance strategies in plants and other organisms.
Ultra-Low Dose Naltrexone Attenuates Chronic Morphine-Induced Gliosis in Rats
Authors: Mattioli Theresa-Alexandra M , Milne Brian , Cahill Catherine M
Published: April 2010

Background:

The development of analgesic tolerance following chronic morphine administration can be a significant clinical problem. Preclinical studies demonstrate that chronic morphine administration induces spinal gliosis and that inhibition of gliosis prevents the development of analgesic tolerance to opioids. Many studies have also demonstrated that ultra-low doses of naltrexone inhibit the development of spinal morphine antinociceptive tolerance and clinical studies demonstrate that it has opioid sparing effects. In this study we demonstrate that ultra-low dose naltrexone attenuates glial activation, which may contribute to its effects on attenuating tolerance.

Results:

Spinal cord sections from rats administered chronic morphine showed significantly increased immunolabelling of astrocytes and microglia compared to saline controls, consistent with activation. 3-D images of astrocytes from animals administered chronic morphine had significantly larger volumes compared to saline controls. Co-injection of ultra-low dose naltrexone attenuated this increase in volume, but the mean volume differed from saline-treated and naltrexone-treated controls. Astrocyte and microglial immuno-labelling was attenuated in rats co-administered ultra-low dose naltrexone compared to morphine-treated rats and did not differ from controls. Glial activation, as characterized by immunohistochemical labelling and cell size, was positively correlated with the extent of tolerance developed. Morphine-induced glial activation was not due to cell proliferation as there was no difference observed in the total number of glial cells following chronic morphine treatment compared to controls. Furthermore, using 5-bromo-2-deoxyuridine, no increase in spinal cord cell proliferation was observed following chronic morphine administration.

Conclusion:

Taken together, we demonstrate a positive correlation between the prevention of analgesic tolerance and the inhibition of spinal gliosis by treatment with ultra-low dose naltrexone. This research provides further validation for using ultra-low dose opioid receptor antagonists in the treatment of various pain syndromes.
The Health Informatics Trial Enhancement Project (HITE): Using routinely collected primary care data to identify potential participants for a depression trial
Authors: McGregor Joanna , Brooks Caroline , Chalasani Padmaja , Chukwuma Jude , Hutchings Hayley , Lyons Ronan A , Lloyd Keith
Published: April 2010

Background

Recruitment to clinical trials can be challenging. We identified anonymous potential participants to an existing pragmatic randomised controlled depression trial to assess the feasibility of using routinely collected data to identify potential trial participants. We discuss the strengths and limitations of this approach, assess its potential value, report challenges and ethical issues encountered.

Methods

Swansea University's Health Information Research Unit's Secure Anonymised Information Linkage (SAIL) database of routinely collected health records was interrogated, using Structured Query Language (SQL). Read codes were used to create an algorithm of inclusion/exclusion criteria with which to identify suitable anonymous participants. Two independent clinicians rated the eligibility of the potential participants' identified. Inter-rater reliability was assessed using the kappa statistic and inter-class correlation.

Results

The study population (N = 37263) comprised all adults registered at five general practices in Swansea UK. Using the algorithm 867 anonymous potential participants were identified. The sensitivity and specificity results > 0.9 suggested a high degree of accuracy from the algorithm. The inter-rater reliability results indicated strong agreement between the confirming raters. The Intra Class Correlation Coefficient (Cronbach's Alpha) > 0.9, suggested excellent agreement and Kappa coefficient > 0.8; almost perfect agreement.

Conclusions

This proof of concept study showed that routinely collected primary care data can be used to identify potential participants for a pragmatic randomised controlled trial of folate augmentation of antidepressant therapy for the treatment of depression. Further work will be needed to assess generalisability to other conditions and settings and the inclusion of this approach to support Electronic Enhanced Recruitment (EER).
Cell-matrix interactions in dermal repair and scarring
Authors: Eckes Beate , Nischt Roswitha , Krieg Thomas
Published: April 2010

Regulation of cellular functions during dermal repair following injury is complex and critically dependent on the interaction of cells with the surrounding extracellular matrix (ECM). The ECM comprises various families of macromolecules that form the structural scaffold of the tissue, but also carry distinct biological activities. After injury to the skin, the defect is filled by a provisional matrix that is invaded by inflammatory cells, sprouting blood vessels and fibroblasts. In a later phase, the wound contracts, the tissue is replaced by mature connective tissue produced by activated fibroblasts, and a scar is formed. All cells involved communicate directly with the ECM by integrins and other matrix receptors. These transmit signals and induce adaptive responses to the environment by the embedded cells. The ECM or proteolytic fragments of individual ECM constituents exert defined biological activities influencing cell survival, differentiation of myofibroblasts, ECM synthesis and turnover, wound angiogenesis and scar remodeling. Extensive crosstalk exists between ECM and growth factors, and between growth factors and integrins. ECM-cell contact also enables direct transmission of mechanical tension, which then modulates many activities of all cellular players. Understanding this complex interplay is important to provide a basis for designing effective wound therapy and for strategic interference with mechanisms that have gone out of control in fibrotic conditions.
Management of anastrozole-induced bone loss in breast cancer patients with oral risedronate: results from the ARBI prospective clinical trial
Authors: Markopoulos Christos , Tzoracoleftherakis Evagelos , Polychronis Athanassios , Venizelos Basileios , Dafni Urania , Xepapadakis Grigorios , Papadiamantis John , Zobolas Vasilios , Misitzis John , Kalogerakos Kyriakos , Sarantopoulou Angeliki , Siasos Nikolaos , Koukouras Dimitrios , Antonopoulou Zoh , Lazarou Spyros , Gogas Helen
Published: April 2010

Introduction

The aim of this multicenter, phase III, prospective open label clinical trial was to investigate the effect of risedronate (R) on bone mineral density (BMD) in postmenopausal, early breast cancer (BC) patients scheduled to receive anastrozole (A).

Methods

Pre-treatment BMD of 213 patients with hormone receptor-positive BC was evaluated at lumbar spine (LS) and hip (HP). Patients were categorized according to their baseline BMD T-score as being at low, moderate and high risk of osteoporosis. Low risk patients received anastrozole only (A), moderate risk were randomized to anastrozole +/- risedronate (A+/-R) administration and high risk patients received anastrozole + risedronate (A+R). Anastrozole was given at a dosage of 1 mg/day while oral risedronate was given at 35 mg/week. BMD was then assessed at 12 and 24 months. All patients received daily supplements of calcium (1000 mg/day) and vitamin D (400 IU/day).

Results

At 24 months, in the moderate risk group, treatment with A+R resulted in a significant increase in BMD at LS and HP compared to treatment with A only (5.7% v -1.5%, Wilcoxon test P = 0.006, and 1.6% v -3.9% Wilcoxon test P = 0.037, respectively), while no significant difference was found at 12 months; 24.3% of the patients moved to normal BMD region. In the high risk group, a significant increase for LS was detected both at 12 and 24 months (6.3% and 6.6%, P < 0.001) but not for HP; BMD in 14% of patients improved to the osteopenic region. In the low risk group, a significant decrease of BMD was detected at 12 months for LS and HP (-5.3% P < 0.001 and -2.4% P < 0.001, respectively,); at 24 months, a significant decrease of BMD was detected only for LS (-2.5%, P < 0.001). However, 22% of patients became osteopenic and only 4% became osteoporotic.

Conclusions

The addition of oral risedronate in post-menopausal breast cancer patients receiving anastrozole has a favorable effect on BMD. Patients with pre-treatment osteopenic to osteoporotic status should be treated with a combination of both therapies in order to avoid bone loss induced by aromatase inhibition. Patients with normal BMD before starting treatment with anastrozole have a very low risk to develop osteoporosis.

Trial registration

ClinicalTrials.gov Identifier NCT00809484.
Monovalent and unpoised status of most genes in undifferentiated cell-enriched Drosophilatestis
Authors: Gan Qiang , Schones Dustin E , Ho Eun Suk , Wei Gang , Cui Kairong , Zhao Keji , Chen Xin
Published: April 2010

Background

Increasing evidence demonstrates that stem cells maintain their identities by a unique transcription network and chromatin structure. Opposing epigenetic modifications H3K27me3 and H3K4me3 have been proposed to label differentiation-associated genes in stem cells, progenitor and precursor cells. In addition, many differentiation-associated genes are maintained at a poised status by recruitment of the initiative RNA Polymerase II (Pol II) at their promoter regions, in preparation for lineage-specific expression upon differentiation. Previous studies have been performed using cultured mammalian embryonic stem cells. To a lesser extent, chromatin structure has been delineated in other model organisms, such as Drosophila, to open new avenues for genetic analyses.

Results

Here we use testes isolated from a Drosophila bag of marbles mutant strain, from which germ cells are in their undifferentiated status. We use these testes to study the endogenous chromatin structure of undifferentiated cells using ChIP-seq. We integrate the ChIP-seq with RNA-seq data, which measures the digital transcriptome. Our genome-wide analyses indicate that most differentiation-associated genes in undifferentiated cells lack an active chromatin mark and initiative Pol II; instead, they are associated with either the repressive H3K27me3 mark or no detectable mark.

Conclusions

Our results reveal that most of the differentiation-associated genes in undifferentiated-cell-enriched Drosophila testes are associated with monovalent but not bivalent modifications, a chromatin signature that is distinct from the data reported in mammalian stem or precursor cells, which may reflect cell type specificity, species specificity, or both.
Two complementary rat NK cell subsets, Ly49s3+ and NKR-P1B+, differ in phenotypic characteristics and responsiveness to cytokines
Authors: Kveberg Lise , Jiménez-Royo Pilar , Naper Christian , Rolstad Bent , Butcher Geoffrey W , Vaage John T , Inngjerdingen Marit
Published: April 2010

NKR-P1B+ and Ly49s3+ NK cells display divergent phenotypic profiles, indicating distinct tasks in vivo.

Two major subsets of rat NK cells can be distinguished based on their expression of the Ly49s3 or the NKR-P1B lectin-like receptor. Ly49s3+ NK cells, but not NKR-P1B+ NK cells, express a wide range of Ly49 receptors. Here, we have examined differences between these two subsets in their expression of certain NK cell-associated molecules as well as their responses to cytokines. A microarray analysis suggested several differentially expressed genes, including preferential expression of NKG2A/C receptors by NKR-P1B+ NK cells. This was confirmed by staining with tetramers of RT.BM1, the putative ligand of CD94/NKG2, indicating that Ly49 and CD94/NKG2 receptors separate into distinct NK cell compartments. Further, expression of CD25 by Ly49s3+ NK cells was associated with more rapid proliferation in response to IL-2 as compared with NKR-P1B+ NK cells. Thus, certain inflammatory situations may preferentially expand the Ly49s3+ NK cells. Moreover, freshly isolated Ly49s3+ and NKR-P1B+ NK cells produce similar amounts of cytokines, and a minor Ly49s3–NKR-P1B– double-negative NK subset appears to be hyporesponsive based on its significantly lower IFN-γ production. Collectively, our data demonstrate divergent profiles of NKR-P1B+ and Ly49s3+ NK cells, indicating distinct tasks in vivo.
Elucidation of Mechanisms of the Reciprocal Cross Talk between Gonadotropin-Releasing Hormone and Prostaglandin Receptors
Authors: Naidich Michal , Shterntal Boris , Furman Ran , Pawson Adam J. , Jabbour Henry N. , Morgan Kevin , Millar Robert P. , Jia Jingjing , Tomic Melanija , Stojilkovic Stanko , Stern Naftali , Naor Zvi
Published: April 2010

We recently described a novel GnRH receptor signaling pathway mediated by the prostaglandins (PGs) F2α and PGI2, which acts through an autocrine/paracrine modality to limit autoregulation of the GnRH receptor and inhibit LH but not FSH release. Here we further explore the cross talk between GnRH and the PG receptors. GnRH stimulates arachidonic acid (AA) release from LβT2 gonadotrope cells via the Ca2+-independent phospholipase A2 (iPLA2) and not via the more common Ca2+-dependent cytosolic phospholipase A2α (cPLA2α). AA release was followed by a marked induction of cyclooxygenase (COX)-1 and COX-2 by GnRH via the protein kinase C/c-Src/phosphatidylinositol 3-kinase/MAPK pathway. COX-2 transcription by GnRH is mediated by the two nuclear factor-κB sites and the CCAAT/enhancer-binding protein site within its promoter. Indeed, GnRH stimulates p65/RelA phosphorylation (22-fold) in LβT2 cells and the two nuclear factor-κB sites apparently act as a composite response element. Although GnRH stimulates cAMP formation in LβT2 cells, we found no role for cAMP acting via the cAMP response element site in the COX-2 promoter. PGF2α, PGI2, or PGE2 had no effect on GnRH-stimulated ERK, c-Jun N-terminal kinase, and p38MAPK activation or on GnRH- and high K+-stimulated intracellular Ca2+ elevation in LβT2 and gonadotropes in primary culture. Although, PGF2α, PGI2, and PGE2 reduced GnRH-stimulated cAMP formation, we could not correlate it to the inhibition of GnRH receptor expression, which is exerted only by PGF2α and PGI2. Hence, the inhibition by PGF2α and PGI2 of the autoregulation of GnRH receptor expression is most likely mediated via inhibition of GnRH-stimulated phosphoinositide turnover and not by inhibition of Ca2+ elevation and MAPK activation.
Interdependence of macrophage migration and ventral nerve cord development in Drosophila embryos
Authors: Evans Iwan R. , Hu Nan , Skaer Helen , Wood Will
Published: April 2010

During embryonic development, Drosophila macrophages (haemocytes) undergo a series of stereotypical migrations to disperse throughout the embryo. One major migratory route is along the ventral nerve cord (VNC), where haemocytes are required for the correct development of this tissue. We show, for the first time, that a reciprocal relationship exists between haemocytes and the VNC and that defects in nerve cord development prevent haemocyte migration along this structure. Using live imaging, we demonstrate that the axonal guidance cue Slit and its receptor Robo are both required for haemocyte migration, but signalling is not autonomously required in haemocytes. We show that the failure of haemocyte migration along the VNC in slit mutants is not due to a lack of chemotactic signals within this structure, but rather to a failure in its detachment from the overlying epithelium, creating a physical barrier to haemocyte migration. This block of haemocyte migration in turn disrupts the formation of the dorsoventral channels within the VNC, further highlighting the importance of haemocyte migration for correct neural development. This study illustrates the important role played by the three-dimensional environment in directing cell migration in vivo and reveals an intriguing interplay between the developing nervous system and the blood cells within the fly, demonstrating that their development is both closely coupled and interdependent.
Opposing Fgf and Bmp activities regulate the specification of olfactory sensory and respiratory epithelial cell fates
Authors: Maier Esther , von Hofsten Jonas , Nord Hanna , Fernandes Marie , Paek Hunki , Hébert Jean M. , Gunhaga Lena
Published: April 2010

The olfactory sensory epithelium and the respiratory epithelium are derived from the olfactory placode. However, the molecular mechanisms regulating the differential specification of the sensory and the respiratory epithelium have remained undefined. To address this issue, we first identified Msx1/2 and Id3 as markers for respiratory epithelial cells by performing quail chick transplantation studies. Next, we established chick explant and intact chick embryo assays of sensory/respiratory epithelial cell differentiation and analyzed two mice mutants deleted of Bmpr1a;Bmpr1b or Fgfr1;Fgfr2 in the olfactory placode. In this study, we provide evidence that in both chick and mouse, Bmp signals promote respiratory epithelial character, whereas Fgf signals are required for the generation of sensory epithelial cells. Moreover, olfactory placodal cells can switch between sensory and respiratory epithelial cell fates in response to Fgf and Bmp activity, respectively. Our results provide evidence that Fgf activity suppresses and restricts the ability of Bmp signals to induce respiratory cell fate in the nasal epithelium. In addition, we show that in both chick and mouse the lack of Bmp or Fgf activity results in disturbed placodal invagination; however, the fate of cells in the remaining olfactory epithelium is independent of morphological movements related to invagination. In summary, we present a conserved mechanism in amniotes in which Bmp and Fgf signals act in an opposing manner to regulate the respiratory versus sensory epithelial cell fate decision.
Use it or lose it? Sablefish,Anoplopoma fimbria, a species representing a fifth teleostean group where the βNHE associated with the red blood cell adrenergic stress response has been secondarily lost
Authors: Rummer Jodie L. , Roshan-Moniri Mani , Balfry Shannon K. , Brauner Colin J.
Published: April 2010

Like most teleosts, sablefish (Anoplopoma fimbria Pallas 1814) blood exhibits a moderate Root effect (~35% maximal desaturation), where a reduction in blood pH dramatically reduces O2 carrying capacity, a mechanism important for oxygenating the eye and filling the swim bladder (SB) in teleosts. Although sablefish lack a SB, we observed a well-defined choroid rete at the eye. The adrenergically mediated cell swelling typically associated with a functional red blood cell (RBC) β-adrenergic Na+/H+ exchanger (βNHE), which would normally protect RBC pH, and thus O2 transport, during a generalized acidosis, was not observed in sablefish blood. Neither isoproterenol (a β-agonist) nor 8-bromo cAMP could elicit this response. Furthermore, RBC osmotic shrinkage, known to stimulate NHEs in general and βNHE in other teleosts such as trout and flounder, resulted in no significant regulatory volume increase (RVI), further supporting the absence of a functional RBC βNHE. The onset of the Root effect occurs at a much lower RBC pH (6.83–6.92) than in other teleosts, and thus RBC βNHE may not be required to protect O2 transport during a generalized acidosis in vivo. Phylogenetically, sablefish may represent a fifth group of teleosts exhibiting a secondary reduction or loss of βNHE activity. However, sablefish have not lost the choroid rete at the eye (unlike in the other four groups), which may still function with the Root effect to oxygenate the retina, but the low pH onset of the Root effect may ensure haemoglobin (Hb)-O2 binding is not compromised at the respiratory surface during a general acidosis in the absence of RBC βNHE. The sablefish may represent an anomaly within the framework of Root effect evolution, in that they possess a moderate Root effect and a choroid rete at the eye, but lack the RBC βNHE and the SB system.
Function of the epaxial muscles in walking, trotting and galloping dogs: implications for the evolution of epaxial muscle function in tetrapods
Authors: Schilling Nadja , Carrier David R.
Published: April 2010

The body axis plays a central role in tetrapod locomotion. It contributes to the work of locomotion, provides the foundation for the production of mechanical work by the limbs, is central to the control of body posture, and integrates limb and trunk actions. The epaxial muscles of mammals have been suggested to mobilize and globally stabilize the trunk, but the timing and the degree to which they serve a particular function likely depend on the gait and the vertebral level. To increase our understanding of their function, we recorded the activity of the m. multifidus lumborum and the m. longissimus thoracis et lumborum at three cranio-caudal levels in dogs while they walked, trotted and galloped. The level of muscle recruitment was significantly higher during trotting than during walking, but was similar during trotting and galloping. During walking, epaxial muscle activity is appropriate to produce lateral bending and resist long-axis torsion of the trunk and forces produced by extrinsic limb muscles. During trotting, they also stabilize the trunk in the sagittal plane against the inertia of the center of mass. Muscle recruitment during galloping is consistent with the production of sagittal extension. The sequential activation along the trunk during walking and galloping is in accord with the previously observed traveling waves of lateral and sagittal bending, respectively, while synchronized activity during trotting is consistent with a standing wave of trunk bending. Thus, the cranio-caudal recruitment patterns observed in dogs resemble plesiomorphic motor patterns of tetrapods. In contrast to other tetrapods, mammals display bilateral activity during symmetrical gaits that provides increased sagittal stability and is related to the evolution of a parasagittal limb posture and greater sagittal mobility.
A multi-stage anti-predator response increases information on predation risk
Authors: Hemmi Jan M. , Pfeil Andreas
Published: April 2010

Optimal escape theory generally assumes that animals have accurate information about predator distance and direction of approach. To what degree such information is available depends not only on the prey's sensory capabilities but also on its behaviour. The structure of behaviour can strongly constrain or support the gathering of information. The ability of animals to collect and process information is therefore an important factor shaping predator avoidance strategies. Fiddler crabs, like many prey animals, escape predators in a multi-step sequence. In their initial response, they do not have accurate information about a predator's distance and approach trajectory and are forced to base their response decision on incomplete information that is not strictly correlated with risk. We show here that fiddler crabs gather qualitatively different visual information during successive stages of their escape sequence. This suggests that multi-stage anti-predator behaviours serve not only to successively reduce risk but also to increase the quality of information with regards to the actual risk. There are countless reasons why prey animals are not able to accurately assess risk. By concentrating on sensory limitations, we can quantify such information deficits and investigate how improving risk assessment helps prey optimise the balance between predation risk and escape costs.
Diapause termination and development of encystedArtemiaembryos: roles for nitric oxide and hydrogen peroxide
Authors: Robbins Heather M. , Van Stappen Gilbert , Sorgeloos Patrick , Sung Yeong Yik , MacRae Thomas H. , Bossier Peter
Published: April 2010

Encysted embryos (cysts) of the brine shrimp Artemia undergo diapause, a state of profound dormancy and enhanced stress tolerance. Upon exposure to the appropriate physical stimulus diapause terminates and embryos resume development. The regulation of diapause termination and post-diapause development is poorly understood at the molecular level, prompting this study on the capacity of hydrogen peroxide (H2O2) and nitric oxide (NO) to control these processes. Exposure to H2O2 and NO, the latter generated by the use of three NO generators, promoted cyst development, emergence and hatching, effects nullified by catalase and the NO scavenger 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl 3-oxide (PTIO). The maximal effect of NO and H2O2 on cyst development was achieved by 4 h of exposure to either chemical. NO was effective at a lower concentration than H2O2 but more cysts developed in response to H2O2. Promotion of development varied with incubation conditions, indicating for the first time a population of Artemia cysts potentially arrested in post-diapause and whose development was activated by either H2O2 or NO. A second cyst sub-population, refractory to hatching after prolonged incubation, was considered to be in diapause, a condition broken by H2O2 but not NO. These observations provide clues to the molecular mechanisms of diapause termination and development in Artemia, while enhancing the organism's value in aquaculture by affording a greater understanding of its growth and physiology.
Structural and Spectroscopic Characteristics of a Proton-Conductive Ionic Liquid Diethylmethylammonium Trifluoromethanesulfonate [dema][TfOH]
Authors: Mori Kazuki , Hashimoto Syu , Yuzuri Tomoaki , Sakakibara Kazuhisa
Published: April 2010

Structural specificity including dynamic behavior and stable conformations in the bulk phase of diethylmethylammonium trifluoromethanesulfonate [dema][TfOH], which is assumed to be a prominent ionic liquid electrolyte for non-humidified intermediate temperature fuel cells, have been investigated by 1H NMR, IR spectroscopic analyses, and molecular dynamics (MD) simulation. It is found that an N–H proton in [dema][TfOH] is an exchangeable mobile proton which can be substituted by D2O, and free rotation around the N–C bond in the ethyl side chain of the ammonium cation is retarded by ionic interactions between the cations and anions, therefore the methylene protons in the ethyl side chain are unisochronous. In addition, the rotational barrier of this N–C bond was observed to be 71 kJ mol−1, comparable to the barrier height of the amide N–C bond (which is well-known to have partial double bond character) from temperature-dependent NMR experiments by monitoring the peak-shape changes of methylene protons in the ethyl side chain of the ammonium cation. The bulk-phase structure of [dema][TfOH] was calculated by MD simulations on the basis of the OPLS-AA force field, and the evaluated structure was consistent with those of experimental results. Thus, IR spectrum frequency of the N–H proton, and the 1H NMR chemical shift values could be rationally assigned on the basis of the theoretically evaluated structures in the bulk phase.
Correlation of serum-adjusted calcium with ionized calcium over a 24-h period in patients with adult growth hormone deficiency before and after growth hormone replacement
Authors: White Helen D , Joshi A A , Ahmad A M , Durham B H , Vora J P , Fraser W D
Published: April 2010

Background

Difficulties associated with measuring ionized calcium in clinical practice have led to the use of total calcium, with or without adjustment for albumin concentration, as an estimate of calcium metabolism. We examined the correlation between ionized and total/adjusted calcium over a 24-h period in patients with adult growth hormone deficiency (AGHD), a group of patients with previously reported alterations in calcium metabolism.

Methods

Four patients with AGHD were consented to the study. They were hospitalized for 24 h where half-hourly blood samples were collected for ionized calcium, total calcium, albumin and creatinine, before and one month after the commencement of growth hormone replacement. Total calcium concentration was adjusted for serum albumin.

Results

Strong correlations were found between ionized calcium and adjusted calcium ( r2 = 0.840 and 0.766 for visits 1 and 2, respectively, P < 0.001), and between ionized calcium and total calcium ( r2 = 0.828 and 0.731 for visits 1 and 2, respectively, P < 0.001). Correlations remained significant during the day (ionized versus adjusted calcium: r2 = 0.847 and 0.780 for visits 1 and 2, respectively; ionized versus total calcium: r2 = 0.860 and 0.792 for visits 1 and 2, respectively, all P < 0.001) and at night (ionized versus adjusted calcium: r2 = 0.831 and 0.802 for visits 1 and 2, respectively; ionized versus total calcium: r2 = 0.767 and 0.722 for visits 1 and 2, respectively, all P < 0.001).

Conclusion

The results of our study suggest that total calcium and serum-adjusted calcium can be used in place of ionized calcium as a reliable indicator of calcium metabolism over a 24-h period in patients with AGHD.
An Automated Intensity-Modulated Radiation Therapy Planning System
Authors: Ahmed Shabbir , Gozbasi Ozan , Savelsbergh Martin , Crocker Ian , Fox Tim , Schreibmann Eduard
Published: April 2010

We design and implement an intensity-modulated radiation therapy plan generation technology that effectively and efficiently optimizes beam geometry as well as beam intensities. Our approach is based on an existing linear programming-based fluence map optimization model that approximates dose-volume requirements using conditional value-at-risk (C-VaR) constraints. We show how the parameters of the C-VaR constraints can be used to control various metrics of treatment plan quality. Next, we develop an automated search strategy for parameter tuning. Finally, beam angle selection is integrated with fluence map optimization. The beam angle selection scheme employs a bicriteria scoring of beam angle geometries and a selection mechanism to choose from among the set of nondominated geometries. The overall technology is automated and generates several high-quality treatment plans satisfying dose prescription requirements in a single invocation and without human guidance. The technology has been tested on various real-patient cases with uniform success.
Why Does Collaborative Filtering Work? Transaction-Based Recommendation Model Validation and Selection by Analyzing Bipartite Random Graphs
Authors: Huang Zan , Zeng Daniel Dajun
Published: April 2010

A large number of collaborative filtering algorithms have been proposed in the literature as the foundation of automated recommender systems. However, the underlying justification for these algorithms is lacking, and their relative performances are typically domain and data dependent. In this paper, we aim to develop initial understanding of the recommendation model/algorithm validation and selection issues based on the graph topological modeling methodology. By representing the input data in the form of consumer–product interactions as a bipartite graph, the consumer–product graph, we develop bipartite graph topological measures to capture patterns that exist in the input data relevant to the transaction-based recommendation task. We observe the deviations of these topological measures of real-world consumer–product graphs from the expected values for simulated random bipartite graphs. These deviations help explain why certain collaborative filtering algorithms work for particular recommendation data sets. They can also serve as the basis for a comprehensive model selection framework that “recommends” appropriate collaborative filtering algorithms given characteristics of the data set under study. We validate our approach using three real-world recommendation data sets and demonstrate the effectiveness of the proposed bipartite graph topological measures in selection and validation of commonly used heuristic-based recommendation algorithms, the user-based, item-based, and graph-based algorithms.
MRSA Transmission Reduction Using Agent-Based Modeling and Simulation
Authors: Barnes Sean , Golden Bruce , Wasil Edward
Published: April 2010

Methicillin-resistant Staphylococcus aureus (MRSA) is a significant ongoing problem in health care, posing a substantial threat to hospitals and communities as well. Its spread among patients causes many downstream effects, such as a longer length of stay for patients, higher costs for hospitals and insurance companies, and fatalities. An agent-based simulation model is developed to investigate the dynamics of MRSA transmission within a hospital. The simulation model is used to examine the effectiveness of various infection control procedures and explore more specific questions relevant to hospital administrators and policy makers. Simulation experiments are performed to examine the effects of hand-hygiene compliance and efficacy, patient screening, decolonization, patient isolation, and health-care worker-to-patient ratios on the incidence of MRSA transmission and other relevant metrics. Experiments are conducted to investigate the dynamic between the number of colonizations directly attributable to nurses and physicians, including rogue health-care workers who practice poor hygiene. We begin to explore the most likely threats to trigger an outbreak in hospitals that practice high hand-hygiene compliance and additional preventive measures.
Error Bounds for Approximations from Projected Linear Equations
Authors: Yu Huizhen , Bertsekas Dimitri P.
Published: April 2010

We consider linear fixed point equations and their approximations by projection on a low dimensional subspace. We derive new bounds on the approximation error of the solution, which are expressed in terms of low dimensional matrices and can be computed by simulation. When the fixed point mapping is a contraction, as is typically the case in Markov decision processes (MDP), one of our bounds is always sharper than the standard contraction-based bounds, and another one is often sharper. The former bound is also tight in a worst-case sense. Our bounds also apply to the noncontraction case, including policy evaluation in MDP with nonstandard projections that enhance exploration. There are no error bounds currently available for this case to our knowledge.
Prognostic Significance of the 2004 WHO/ISUP Classification for Prediction of Recurrence, Progression, and Cancer-Specific Mortality of Non–Muscle-Invasive Urothelial Tumors of the Urinary Bladder
Authors: Pan Chin-Chen , Chang Yen-Hwa , Chen Kuang-Kuo , Yu Hui-Jung , Sun Chih-Hao , Ho Donald M. T.
Published: April 2010

To verify prognostic significance of the 2004 World Health Organization (WHO)/International Society of Urological Pathology (ISUP) grading systems, we retrospectively studied the tumors of 1,515 patients who underwent transurethral resection of primary non–muscle-invasive urothelial tumors (pTa, 1,006 patients; pT1, 509 patients) confined to the bladder. Cases were classified according to the 2004 WHO/ISUP systems as 212 cases of papillary urothelial neoplasm of low malignant potential (PUNLMP), 706 low-grade papillary urothelial carcinomas (LPUCs), and 597 high-grade papillary urothelial carcinomas (HPUCs). PUNLMP showed the statistically significantly lowest recurrence cumulative incidence compared with the other tumor types. There were significant differences and trends for higher progression and cancer-specific mortality cumulative incidence in the following order: PUNLMP, LPUC, pTa HPUC, and pT1 HPUC. No differences of progression and cancer-specific mortality cumulative incidence were found between pTa and pT1 LPUC. Our study validates the usefulness of the 2004 WHO/ISUP system to classify urothelial tumors into prognostically distinct categories that would contribute to the design of therapeutic and monitoring strategies for patients with non–muscle-invasive bladder urothelial tumors.
Oxidized-LDL/β2-Glycoprotein I Complexes Are Associated With Disease Severity and Increased Risk for Adverse Outcomes in Patients With Acute Coronary Syndromes
Authors: Greco Thomas P. , Conti-Kelly Ann Marie , Anthony J. Robert , Greco Thomas , Doyle Robin , Boisen Matt , Kojima Kazuo , Matsuura Eiji , Lopez Luis R.
Published: April 2010

Oxidized low-density lipoprotein (oxLDL)/β2-glycoprotein I (β2GPI) complexes have been implicated in atherogenesis. oxLDL/β2GPI complexes were measured in 339 patients with suspected acute coronary syndromes. Approximately 68% had angiographically documented coronary artery disease (CAD) and significantly higher mean ± SD levels of oxLDL/β2GPI (3.75 ± 6.31 U/mL) than patients with normal coronary arteries (2.21 ± 3.03 U/mL; P = .0026). Patients with severe CAD had significantly higher mean ± SD levels of oxLDL/β2GPI (8.71 ± 12.87 U/mL) compared with the overall mean of 3.25 U/mL (P < .05) and a significantly higher rate (28.9%) of adverse events than the overall rate of 11.2% (P < .05). Patients with adverse events had higher mean ± SD levels of oxLDL/β2GPI (4.05 ± 5.38 U/mL) than patients without adverse events (3.15 ± 5.53; P = .029). The relative risk for adverse events in higher oxLDL/β2GPI quartiles was 3.1 (95% confidence interval, 1.0–9.1; P = .06) for quartile 3 and 3.5 (95% confidence interval, 1.2–10.4; P = .02) for quartile 4. Our results support the concept that oxLDL/β2GPI complexes are associated with severity of CAD and a 3.5-fold increased risk for adverse outcomes.
Acute Myeloid Leukemia With t(9;11)(p21–22;q23)
Authors: Chandra Pranil , Luthra Rajyalakshmi , Zuo Zhuang , Yao Hui , Ravandi Farhad , Reddy Neeli , Garcia-Manero Guillermo , Kantarjian Hagop , Jones Dan
Published: April 2010

We compared pathogenetic features of 32 de novo and 29 therapy-related (t) t(9;11)(p21-22;q23)/MLLT3-MLL acute myeloid leukemia (AML) cases to identify progression factors and to assess whether distinction between these manifestations is warranted. MLLT3-MLL rearrangement was commonly the sole karyotypic abnormality at diagnosis, with many secondary chromosomal changes emerging at relapse in both subgroups. Ras point mutations were common in both groups (overall, 18/50 [36%]) and associated with monocytic phenotype and aneuploid progression. Expression patterns of 675 microRNAs profiled in 7 cases were also similar, with let-7 species linked to Ras down-modulation expressed at low levels. Outcome for both groups was poor (relapsed or refractory in 49/61 [80%] cases); however, patients with t-AML were generally older and female, with worse outcome (P = .03), likely secondary to t-AML mostly arising in patients with breast cancer following topoisomerase inhibitor–containing chemotherapy. Ras activation seems to complement the MLLT3-MLL oncogene in transformation with features of de novo and t-AML with MLLT3-MLL being similar.
Plasma MicroRNA 499 as a Biomarker of Acute Myocardial Infarction
Authors: Adachi Taichi , Nakanishi Michio , Otsuka Yoritaka , Nishimura Kunihiro , Hirokawa Gou , Goto Yoichi , Nonogi Hiroshi , Iwai Naoharu
Published: April 2010

Background: MicroRNAs (miRNAs) are endogenous small RNAs 21–25 nucleotides in length. Recently, we reported that miRNA 208 (miR-208) is produced exclusively in the rat myocardium and that plasma miR-208 is a biomarker of myocardial injury in rats. In the present study, we assessed the hypothesis that plasma concentrations of myocardial-specific miRNAs can be used to diagnose myocardial injury in humans.

Methods: We used array analysis of miRNA production in various human tissues to identify heart-specific miRNAs. We assessed the plasma concentrations of miR-499 in 14 individuals with acute coronary syndromes, 15 individuals with congestive heart failure, and 10 individuals without cardiovascular diseases. Plasma miR-499 concentrations were measured with a real-time reverse-transcription PCR method that used an artificial small RNA as an internal calibrator.

Results: The miRNA array analysis of various human tissues indicated that miR-499 was produced almost exclusively in the heart. Plasma miR-499 concentrations were measurably increased in all individuals with acute myocardial infarction but were below the limit of detection for all individuals in the other patient groups.

Conclusions: The plasma concentration of miR-499 may be a useful biomarker of myocardial infarction in humans.