bluuebunny/crossref_metadata_2025 huggingface dataset:
Complete Genome Sequence of Providencia stuartii Clinical Isolate MRSN 2154
Authors: Clifford Robert J. , Hang Jun , Riley Matthew C. , Onmus-Leone Fatma , Kuschner Robert A. , Lesho Emil P. , Waterman Paige E.
Published: June 2012

Here we present the complete genome sequence of
Providencia stuartii
MRSN 2154, isolated from an Afghan national.
P. stuartii
is a Gram-negative bacillus capable of causing infections in a wide variety of human tissues. Because
Providencia
readily acquires plasmids bearing drug resistance loci, it is of growing clinical significance.
Complete Genome Sequence of Helicobacter cinaedi Strain PAGU611, Isolated in a Case of Human Bacteremia
Authors: Goto Takatsugu , Ogura Yoshitoshi , Hirakawa Hideki , Tomida Junko , Morita Yuji , Akaike Takaaki , Hayashi Tetsuya , Kawamura Yoshiaki
Published: June 2012

We report the complete genome sequence of
Helicobacter cinaedi
strain PAGU611, isolated in a case of human bacteremia. The PAGU611 genome comprises a 2,078,348-bp chromosome and a 23,054-bp plasmid. The chromosome contains a unique genomic island, encoding a type VI secretion system and clustered regularly interspaced short palindromic repeat (CRISPR) loci.
Genome Sequence of the Hemolytic-Uremic Syndrome-Causing Strain Escherichia coli NCCP15647
Authors: Jeong Haeyoung , Zhao Fumei , Igori Davaajargal , Oh Kyung-Hwan , Kim Seon-Young , Kang Sung Gyun , Kim Byung Kwon , Kwon Soon-Kyeong , Lee Choong Hoon , Song Ju Yeon , Yu Dong Su , Park Mi-Sun , Cho Seung-Hak , Kim Jihyun F.
Published: June 2012

Enterohemorrhagic
Escherichia coli
(EHEC) causes a disease involving diarrhea, hemorrhagic colitis, and hemolytic-uremic syndrome (HUS). Here we present the draft genome sequence of NCCP15647, an EHEC isolate from an HUS patient. Its genome exhibits features of EHEC, such as genes for verotoxins, a type III secretion system, and prophages.
The Forgotten Forefather: Joseph James Kinyoun and the Founding of the National Institutes of Health
Authors: Morens David M. , Fauci Anthony S.
Published: June 2012

In celebrating the 125th anniversary of the National Institutes of Health (NIH) in August 2012, NIH has been examining its origins, its history, and the visionary men and women whose research have contributed to the saving and/or improving the quality of life of millions of people throughout the world. This minireview examines Joseph James Kinyoun (1860 to 1919), the 1887 founder of a federal Hygienic Laboratory that is considered the direct ancestor of the modern NIH, and explores the development of NIH as it was shaped by, and in turn shaped, the new field of microbiology.
Screening and identification of the mimic epitope of the adhesion protein ofMycoplasma genitalium
Authors: Zeng Yanhua , Liu Liangzhuan , He Jun , Liu Yan , Zhu Cuiming , You Xiaoxing , Wu Yimou
Published: June 2012

Mycoplasma genitalium adhesion protein (MgPa) is the major adhesion protein of M. genitalium, and its C-terminal domain (amino acid 1075–1444) is the most immunogenic region. However, the exact epitopes of the adhesion protein of M. genitalium are still unclear. We used the purified polyclonal antibody against the recombinant adhesion protein to screen the mimic epitopes of MgPa using a random 12-peptide phage display library. Immunoscreening via the phage display peptide library revealed that 3 motifs (P-S-A-A/V-X-R-F/W-E/S-L-S-P, A-K-I/L-T/Q-X-T-L-X-L, and K-S-L-S-R-X-D-X-I) may represent 3 different mimotopes of MgPa. Results of bioinformatics analysis by MIMOX demonstrated that the key consensus amino acid residues in the aligned mimotopes may be S, A, and F for cluster 1; A, K, I, T, and L for cluster 2; and K, S, L, R, D, and I for cluster 3. Three representative phages could recognize sera from M. genitalium-positive patients to varying degrees, whereas they could not recognize the sera from Mycoplasma pneumoniae -positive patients or the sera from healthy people. These findings will help to clarify the mimic epitopes of MgPa to facilitate diagnosis of the antigen and to understand the antigenic structure of MgPa.
Microbial diversity, tolerance, and biodegradation potential of urban wetlands with different input regimes
Authors: Gilbert Nicolas , Fulthorpe Roberta , Kirkwood Andrea E.
Published: June 2012

Though microbial transformations are the primary mechanism of contaminant attenuation in wetlands, much remains to be known about microbial communities in urban wetlands. In this study, the microbial communities from urban wetlands with different runoff regimes (i.e., a contaminated remnant wetland, a constructed wetland, and a remnant wetland) were assessed for their capacity to attenuate and tolerate typical urban runoff pollutants. Results from denaturing gradient gel electrophoresis of 16S rRNA genes showed relatively high similarity in community composition among the wetlands. Community-level physiological profiles had similar results but exhibited within-site variation in both the contaminated remnant and remnant wetlands. All wetland communities were less tolerant to copper than 2,4-dichlorophenoxyacetic acid; however, the contaminated remnant wetland had the highest tolerance. All study wetlands had a limited capacity to biodegrade model chlorinated aromatic compounds (e.g., 2,4-dichlorophenoxyacetic acid and 3-chlorobenzoate). Though having different input regimes and contaminant exposure histories, the study wetlands were generally similar with respect to microbial community diversity and function. Additionally, the generally low capacity for these wetlands to biodegrade mobile chlorinated organic contaminants offers preliminary insight into the limited ecosystem services these wetlands may provide in urban environments.
SCALAR CASIMIR EFFECT BETWEEN TWO CONCENTRIC D-DIMENSIONAL SPHERES
Authors: ÖZCAN MUSTAFA
Published: June 2012

The Casimir energy for a massless scalar field between the closely spaced two concentric D-dimensional (for D>3) spheres is calculated by using the mode summation with contour integration in the complex plane of eigenfrequencies and the generalized Abel–Plana formula for evenly spaced eigenfrequency at large argument. The sign of the Casimir energy between closely spaced two concentric D-dimensional spheres for a massless scalar field satisfying the Dirichlet boundary conditions is strictly negative. The Casimir energy between (D-1)-dimensional surfaces, close to each other is regarded as interesting both by itself and as the key to describing of stability of the attractive Casimir force.
UNIFICATION AND DIVERSITY OF COMPUTATION MODELS FOR GENERALIZED SWARM INTELLIGENCE
Authors: KANG QI , AN JING , WANG LEI , WU QIDI
Published: June 2012

Swarm intelligence is a kind of nature-inspired heuristic optimization technique. Different computation models usually take on relative uniform characteristic though they usually have distinct extrinsic forms. These intelligent algorithms are coupling with deterministic and stochastic, the contradiction between necessity and accidental unity, which promotes the "evolution" of the inheritance and the creative process: "stochastic" is adopted to give creative ability to the implemented "intelligent system", and a succession of "certainty" is acted to ensure the system is converging. In this paper, a computing framework of generalized swarm intelligence is proposed based on the unifying idea. The unified hiberarchy model and formalization description for swarm intelligence are represented. Several typical swarm intelligence algorithms, such as ant colony system (ACS), particle swarm optimization (PSO), estimation of distribution algorithms (EDA) and artificial immune algorithms (AIA) are addressed to validate the uniform idea of swarm intelligence, respectively.
INCOMPARABLE TREEABLE EQUIVALENCE RELATIONS
Authors: MILLER BENJAMIN
Published: June 2012

We establish Hjorth's theorem that there is a family of continuum-many pairwise strongly incomparable free actions of free groups, and therefore a family of continuum-many pairwise incomparable treeable equivalence relations.
Firm-Specific Factors as Determinants of Capital Structure: Evidence From Indonesia
Authors: Moosa Imad , Li Larry
Published: June 2012

The cross-sectional technique of extreme bounds analysis (EBA) is used to identify the determinants of capital structure in a sample of Indonesian shareholding companies. Additional results are presented based on variable deletion and nonnested model selection tests. The results of traditional EBA show that the only robust variable is liquidity, but the results of restricted EBA add three more robust variables: profitability, tangibility, and income variability. However, variable deletion and nonnested model selection tests lend support only to size and liquidity. The conclusion is that most of the variables that appear important in studies of capital structure may not be important at all. From a policy perspective, the finding that some firm-specific factors are relevant to corporate capital structure confirms that financial reform has eliminated the distortions of corporate financial policies and financial markets caused by the previously dominant role of state banks.
USING THE ASPIRATION CORE TO PREDICT COALITION FORMATION
Authors: BEJAN CAMELIA , GÓMEZ JUAN CAMILO
Published: June 2012

This work uses the defining principles of the core solution concept to determine not only payoffs but also coalition formation. Given a cooperative transferable utility (TU) game, we propose two noncooperative procedures that in equilibrium deliver a natural and nonempty core extension, the aspiration core, together with the supporting coalitions it implies. As expected, if the cooperative game is balanced, the grand coalition forms. However, if the core is empty, other coalitions arise. Following the aspiration literature, not only partitions but also overlapping coalition configurations are allowed. Our procedures interpret this fact in different ways. The first game allows players to participate with a fraction of their time in more than one coalition, while the second assigns probabilities to the formation of potentially overlapping coalitions. We use the strong Nash and subgame perfect Nash equilibrium concepts.
SEISMIC PROTECTION OF EXISTING RC BUILDINGS USING FUSE ELEMENTS
Authors: MOWRTAGE (VAIL KARAKALE) WAIEL
Published: June 2012

This paper presents a new concept on collapse prevention of existing RC buildings during a seismic event. The idea is to install steel panels in specified locations in the structure to reduce inter-story drifts. The panels are expected to work as a fuse in an electric circuit when a major earthquake occurs; the panels will attract the seismic forces and they may totally damaged but they will prevent severe damage in the main structural system. The proposed panels are light-weight, easy to handle, and can be constructed very quickly. Moreover, they are cheap and do not need formwork or skilled workers. To test the concept, a half-scale, single-story 3D reinforced concrete frame specimen was constructed at the shake-table laboratories of the Kandilli Observatory and Earthquake Research Institute of Bogazici University, and subjected to recorded real earthquake base accelerations. The amplitudes of base accelerations were increased until a moderate damage level is reached. Then, the damaged RC frames was retrofitted by means of steel panels and tested under the same earthquake. The seismic performance of the specimen before and after the retrofit was evaluated using FEMA356 standards, and the results were compared in terms of stiffness, strength, and deformability. The results have confirmed effectiveness of the proposed retrofit scheme.
Synergistic effects of prenatal hypoxia and postnatal high-fat diet in the development of cardiovascular pathology in young rats
Authors: Rueda-Clausen Christian F. , Morton Jude S. , Dolinsky Vernon W. , Dyck Jason R. B. , Davidge Sandra T.
Published: June 2012

We have previously shown that adult offspring exposed to a prenatal hypoxic insult leading to intrauterine growth restriction (IUGR) are more susceptible to cardiovascular pathologies. Our objectives were to evaluate the interaction between hypoxia-induced IUGR and postnatal diet in the early development of cardiovascular pathologies. Furthermore, we sought to determine whether the postnatal administration of resveratrol could prevent the development of cardiovascular disorders associated with hypoxia-induced IUGR. On day 15 of pregnancy, Sprague-Dawley rats were randomly assigned to hypoxia (11.5% oxygen), to induce IUGR, or normal oxygen (control) groups. For study A, male offspring (3 wk of age) were randomly assigned a low-fat (LF, <10% fat) or a high-fat (HF, 45% fat) diet. For study B, offspring were randomized to either HF or HF+resveratrol diets. After 9 wk, cardiac and vascular functions were evaluated. Prenatal hypoxia and HF diet were associated with an increased myocardial susceptibility to ischemia. Blood pressure, in vivo cardiac function, and ex vivo vascular function were not different among experimental groups; however, hypoxia-induced IUGR offspring had lower resting heart rates. Our results suggest that prenatal insults can enhance the susceptibility to a second hit such as myocardial ischemia, and that this phenomenon is exacerbated, in the early stages of life by nutritional stressors such as a HF diet. Supplementing HF diets with resveratrol improved cardiac tolerance to ischemia in offspring born IUGR but not in controls. Thus we conclude that the additive effect of prenatal (hypoxia-induced IUGR) and postnatal (HF diet) factors can lead to the earlier development of cardiovascular pathology in rats, and postnatal resveratrol supplementation prevented the deleterious cardiovascular effects of HF diet in offspring exposed to prenatal hypoxia.
Effects of Statins on Cardiorenal Syndrome
Authors: Yagi Shusuke , Aihara Ken-ichi , Ikeda Yasumasa , Akaike Masashi , Sata Masataka , Matsumoto Toshio
Published: June 2012

Cardiovascular disease and renal disease have a close relationship that forms a vicious cycle as a cardiorenal syndrome (CRS). Oxidative stress, endothelial dysfunction, and vascular inflammation could be therapeutic targets when the renin-angiotensin-aldosterone system is activated by accumulation of conventional cardiovascular risk factors; however, a strategy for management of CRS has not been established yet. Statins, HMG-CoA reductase inhibitors, have not only cholesterol-lowering effects but also pleiotropic effects on cardiovascular systems, including anti-inflammatory and antioxidant effects and improvement of nitric oxide bioavailability. Since recent studies have indicated that statins have beneficial effects on chronic kidney disease and heart failure as well as coronary artery disease in cholesterol-lowering-dependent/independent manners, treatment with statins might be a successful strategy for preventing deterioration of CRS.
Development of Brainstem-Evoked Responses in Congenital Auditory Deprivation
Authors: Tillein J. , Heid S. , Lang E. , Hartmann R. , Kral A.
Published: June 2012

To compare the development of the auditory system in hearing and completely acoustically deprived animals, naive congenitally deaf white cats (CDCs) and hearing controls (HCs) were investigated at different developmental stages from birth till adulthood. The CDCs had no hearing experience before the acute experiment. In both groups of animals, responses to cochlear implant stimulation were acutely assessed. Electrically evoked auditory brainstem responses (E-ABRs) were recorded with monopolar stimulation at different current levels. CDCs demonstrated extensive development of E-ABRs, from first signs of responses at postnatal (p.n.) day 3 through appearance of all waves of brainstem response at day 8 p.n. to mature responses around day 90 p.n.. Wave I of E-ABRs could not be distinguished from the artifact in majority of CDCs, whereas in HCs, it was clearly separated from the stimulus artifact. Waves II, III, and IV demonstrated higher thresholds in CDCs, whereas this difference was not found for wave V. Amplitudes of wave III were significantly higher in HCs, whereas wave V amplitudes were significantly higher in CDCs. No differences in latencies were observed between the animal groups. These data demonstrate significant postnatal subcortical development in absence of hearing, and also divergent effects of deafness on early waves II–IV and wave V of the E-ABR.
The Relationship between Beliefs about Pain and Functioning with Rheumatologic Conditions
Authors: Pons Tracey , Shipton Edward , Mulder Rodger
Published: June 2012

Pain beliefs influence understanding of pain mechanisms and outcomes. This study in rheumatologic conditions sought to determine a relationship between beliefs about pain and functioning. Participants in Arthritis New Zealand’s (ANZ) exercise and education programmes were used. Demographic data and validated instruments used included the Arthritis Impact Measurement Scale 2nd version-Short Form (AIMS2-SF) to measure functioning, and two scales of organic and psychological beliefs in Pain Beliefs Questionnaires (PBQ) to measure pain beliefs. 236 Members of ANZ were surveyed anonymously with AIMS2-SF and PBQ, with a 61% response rate; 144 responses were entered into the database. This study used α of 0.05 and a 1-β of 0.8 to detect for significant effect size estimated to ber=0.25. Analysis revealed a significant relationship between organic beliefs scale of PBQ and functioning of AIMS2-SF, with anrvalue of 0.32 andPvalue of 0.00008. No relationship was found between psychological beliefs scale of PBQ and AIMS2-SF. Organic pain beliefs are associated with poorer functioning. Psychological pain beliefs are not. Beliefs might have been modified by ANZ programmes. Clinicians should address organic pain beliefs early in consultation. Causal links between organic pain beliefs and functioning should be clarified.
Etiopathogenesis of Nonalcoholic Steatohepatitis: Role of Obesity, Insulin Resistance and Mechanisms of Hepatotoxicity
Authors: Guturu Praveen , Duchini Andrea
Published: June 2012

Incidence of nonalcoholic fatty liver disease is increasing with an estimated prevalence of 20–30% in developed nations. This is leading to increased incidence of chronic liver disease, cirrhosis, and hepatocellular cancer. It is critical to understand the etiology and pathogenesis of any disease to create therapeutic targets and develop new treatments. In this paper we discuss the etiology and pathogenesis of nonalcoholic steatohepatitis with special focus on obesity, role of insulin resistance, and molecular mechanisms of hepatotoxicity.
Estimation of National Colorectal-Cancer Incidence Using Claims Databases
Authors: Quantin C. , Benzenine E. , Hägi M. , Auverlot B. , Abrahamowicz M. , Cottenet J. , Fournier E. , Binquet C. , Compain D. , Monnet E. , Bouvier A. M. , Danzon A.
Published: June 2012

Background.The aim of the study was to assess the accuracy of the colorectal-cancer incidence estimated from administrative data.Methods.We selected potential incident colorectal-cancer cases in 2004-2005 French administrative data, using two alternative algorithms. The first was based only on diagnostic and procedure codes, whereas the second considered the past history of the patient. Results of both methods were assessed against two corresponding local cancer registries, acting as “gold standards.” We then constructed a multivariable regression model to estimate the corrected total number of incident colorectal-cancer cases from the whole national administrative database.Results.The first algorithm provided an estimated local incidence very close to that given by the regional registries (646 versus 645 incident cases) and had good sensitivity and positive predictive values (about 75% for both). The second algorithm overestimated the incidence by about 50% and had a poor positive predictive value of about 60%. The estimation of national incidence obtained by the first algorithm differed from that observed in 14 registries by only 2.34%.Conclusion.This study shows the usefulness of administrative databases for countries with no national cancer registry and suggests a method for correcting the estimates provided by these data.
Calciphylaxis: Temporal Artery Calcification Preceding Widespread Skin Lesions and Penile Necrosis
Authors: Shah Manzoor A. , Roppolo Michael W.
Published: June 2012

Temporal artery calciphylaxis has rarely been described in chronic kidney disease patients on dialysis. We report a case of 72-year-old Caucasian man with multiple comorbidities and end-stage renal disease on dialysis who presented with temporal artery calcification leading to bilateral loss of vision followed by extensive skin lesions including one on glans penis. While on peritoneal dialysis, he developed anterior ischemic optic neuropathy, had no improvement on high dose steroids, and temporal artery biopsy showed marked calcification without any evidence of vasculitis. Few weeks later on hemodialysis, he developed widespread cutaneous lesions on extremities and penile necrosis with skin biopsy revealing calciphylaxis. On literature review of calciphylaxis in chronic kidney disease, we found only four cases of temporal artery calciphylaxis leading to anterior ischemic optic neuropathy and blindness. We believe this is the first case in which the rare temporal artery calciphylaxis and the uncommon penile necrosis are being described together. The objective is to emphasize the need to recognize this condition early in the CKD patients on dialysis presenting with visual symptoms as the different treatment strategies may help prevent complete loss of vision and also modify or prevent a full blown calciphylaxis.
Morphology and Developmental Rate of the Blow Fly,Hemipyrellia ligurriens(Diptera: Calliphoridae): Forensic Entomology Applications
Authors: Bunchu Nophawan , Thaipakdee Chinnapat , Vitta Apichat , Sanit Sangob , Sukontason Kom , Sukontason Kabkaew L.
Published: June 2012

Hemipyrellia ligurriens(Diptera: Calliphoridae) is a forensically important blow fly species presented in many countries. In this study, we determined the morphology of all stages and the developmental rate ofH. ligurriensreared under natural ambient conditions in Phitsanulok province, northern Thailand. Morphological features of all stages based on observing under a light microscope were described and demonstrated in order to use for identification purpose. Moreover, development time in each stage was given. The developmental time ofH. ligurriensto complete metamorphosis; from egg, larva, pupa to adult, took 270.71 h for 1 cycle of development. The results from this study may be useful not only for application in forensic investigation, but also for study in its biology in the future.
Potential Impacts of the Introduction of Low-Sulfur Fuel on Concentrations at Breathing Level in a Subarctic City
Authors: Leelasakultum Ketsiri , Mölders Nicole , Tran Huy N. Q. , Grell Georg A.
Published: June 2012

The effects of using low-sulfur fuel for oil-heating and oil-burning facilities on the concentrations at breathing level in an Alaska city surrounded by vast areas were examined with the Weather Research and Forecasting model coupled with chemistry packages that was modified for the subarctic. Simulations were performed in forecast mode for a cold season using the National Emission Inventory 2008 and alternatively emissions that represent the use of low-sulfur fuel for oil-heating and oil-burning facilities while keeping the emissions of other sources the same as in the reference simulation. The simulations suggest that introducing low-sulfur fuel would decrease the monthly mean 24 h-averaged concentrations over the city’s nonattainment area by 4%, 9%, 8%, 6%, 5%, and 7% in October, November, December, January, February, and March, respectively. The quarterly mean relative response factors for of 0.96 indicate that with a design value of 44.7 μg/m3introducing low-sulfur fuel would lead to a new design value of 42.9 μg/m3that still exceeds the US National Ambient Air Quality Standard of 35 μg/m3. The magnitude of the relation between the relative response of sulfate and nitrate changes differs with temperature. The simulations suggest that, in the city, concentrations would decrease stronger on days with low atmospheric boundary layer heights, low hydrometeor mixing ratio, low downward shortwave radiation, and low temperatures.
Acute Intestinal Obstruction: A Rare Aetiology
Authors: Chatterjee Shamita , Chatterjee Souvik , Kumar Sanjeev , Gupta Shahana
Published: June 2012

Internal herniation of small intestine is a very rare entity, and it poses a real diagnostic challenge clinically. Recurrent entrapment of the bowel may lead to partial to complete intestinal obstruction and eventually strangulation of the small bowel. Of this rare clinical entity, left paraduodenal hernia is more common. High index of suspicion with prompt management may prevent bowel strangulation and gangrene. We present a case of acute intestinal obstruction due to left paraduodenal hernia with malrotation of midgut in a 55-year-old male patient.
A Paraneoplastic Syndrome Characterized by Extremity Swelling with Associated Inflammatory Infiltrate Heralds Aggressive Transformation of Myelodysplastic Syndromes/Myeloproliferative Neoplasms to Acute Myeloid Leukemia: A Case Series
Authors: Mangan James K. , Luger Selina M.
Published: June 2012

There has been a long history of reports describing a variety of paraneoplastic phenomena associated with myelodysplastic syndromes, particularly those with autoimmune manifestations. We report here a series of patients with an antecedent myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) that underwent aggressive transformation to acute myeloid leukemia (AML). In each case, the transformation to AML was preceded by an inflammatory syndrome characterized by unilateral extremity swelling and an associated inflammatory skin infiltrate, as well as other signs of inflammation, including profound hyperferritinemia without evidence of a hemophagocytic syndrome. We suggest that such an inflammatory syndrome may herald aggressive transformation of MDS/MPN to AML. Patients with known MDS/MPN who present with these features may benefit from early bone marrow examination to assess disease status. Early intervention with corticosteroids in select patients may result in improvement or resolution of the symptoms and permit intensive therapy for AML to be delivered.
Criminal Genomic Pragmatism: Prisoners' Representations of DNA Technology and Biosecurity
Authors: Machado Helena , Silva Susana
Published: June 2012

Background. Within the context of the use of DNA technology in crime investigation, biosecurity is perceived by different stakeholders according to their particular rationalities and interests. Very little is known about prisoners’ perceptions and assessments of the uses of DNA technology in solving crime.Aim. To propose a conceptual model that serves to analyse and interpret prisoners’ representations of DNA technology and biosecurity.Methods. A qualitative study using an interpretative approach based on 31 semi-structured tape-recorded interviews was carried out between May and September 2009, involving male inmates in three prisons located in the north of Portugal. The content analysis focused on the following topics: the meanings attributed to DNA and assessments of the risks and benefits of the uses of DNA technology and databasing in forensic applications.Results. DNA was described as a record of identity, an exceptional material, and a powerful biometric identifier. The interviewees believed that DNA can be planted to incriminate suspects. Convicted offenders argued for the need to extend the criteria for the inclusion of DNA profiles in forensic databases and to restrict the removal of profiles.Conclusions. The conceptual model entitledcriminal genomic pragmatismallows for an understanding of the views of prison inmates regarding DNA technology and biosecurity.
Human Amniotic Fluid Cells Form Functional Gap Junctions with Cortical Cells
Authors: Jezierski Anna , Rennie Kerry , Tremblay Roger , Zurakowski Bogdan , Gruslin Andreé , Sikorska Marianna , Bani-Yaghoub Mahmud
Published: June 2012

The usage of stem cells is a promising strategy for the repair of damaged tissue in the injured brain. Recently, amniotic fluid (AF) cells have received a lot of attention as an alternative source of stem cells for cell-based therapies. However, the success of this approach relies significantly on proper interactions between graft and host tissue. In particular, the reestablishment of functional brain networks requires formation of gap junctions, as a key step to provide sufficient intercellular communication. In this study, we show that AF cells express high levels of CX43 (GJA1) and are able to establish functional gap junctions with cortical cultures. Furthermore, we report an induction of Cx43 expression in astrocytes following injury to the mouse motor cortex and demonstrate for the first time CX43 expression at the interface between implanted AF cells and host brain cells. These findings suggest that CX43-mediated intercellular communication between AF cells and cortical astrocytes may contribute to the reconstruction of damaged tissue by mediating modulatory, homeostatic, and protective factors in the injured brain and hence warrants further investigation.
Ethanol Production from Nondetoxified Dilute-Acid Lignocellulosic Hydrolysate by Cocultures of Saccharomyces cerevisiae Y5 and Pichia stipitis CBS6054
Authors: Wan Ping , Zhai Dongmei , Wang Zhen , Yang Xiushan , Tian Shen
Published: June 2012

Saccharomyces cerevisiae Y5 (CGMCC no. 2660) and Issatchenkia orientalis Y4 (CGMCC no. 2159) were combined individually with Pichia stipitis CBS6054 to establish the cocultures of Y5 + CBS6054 and Y4 + CBS6054. The coculture Y5 + CBS6054 effectively metabolized furfural and HMF and converted xylose and glucose mixture to ethanol with ethanol concentration of 16.6 g/L and ethanol yield of 0.46 g ethanol/g sugar, corresponding to 91.2% of the maximal theoretical value in synthetic medium. Accordingly, the nondetoxified dilute-acid hydrolysate was used to produce ethanol by co-culture Y5 + CBS6054. The co-culture consumed glucose along with furfural and HMF completely in 12 h, and all xylose within 96 h, resulting in a final ethanol concentration of 27.4 g/L and ethanol yield of 0.43 g ethanol/g sugar, corresponding to 85.1% of the maximal theoretical value. The results indicated that the co-culture of Y5 + CBS6054 was a satisfying combination for ethanol production from non-detoxified dilute-acid lignocellulosic hydrolysates. This co-culture showed a promising prospect for industrial application.
Assessment of Referrals into the Soft Tissue Sarcoma Service: Evaluation of Imaging Early in the Pathway Process
Authors: Rowbotham Emma , Bhuva Shaheel , Gupta Harun , Robinson Philip
Published: June 2012

Purpose. To prospectively evaluate regional referrals into a soft tissue sarcoma service from outside the tertiary centre with local hospital imaging.Materials and Methods. Consecutive referrals were prospectively assessed for: patient demographics, source, referral date, date received by Multidisciplinary Team (MDT), lesion size, local radiology, MDT radiology and final diagnoses. Radiology diagnosis was categorised benign, indeterminate or malignant by consensus. Delays were defined as >10 days.Results. 112 patients were included with high correlation between local and MDT radiology categrorisation and histology (P=0.54andP=0.49, resp.). There was only a trend for MDT radiology diagnosis to downgrade local imaging diagnosis (n=15,P>0.05). 48 cases (43%) had ultrasound and MRI at referral and 20 (18%) ultrasound only. 85% of cases were benign (lipoma most common), 15% malignant (sarcoma most common). Delay occurred in 34% of cases.Discussion. In comparison to previous series these results show a reduction in benign lesions, increased biopsy and malignancy rate for lesions referred to a tertiary centre when imaging is performed and reviewed by local radiologists.Advances in Knowledge. Imaging triage of soft tissue masses can decrease benign referral rates and increase the proportion of indeterminate and malignant lesions referred to specialist centres.
Adaptive Neuroplastic Responses in Early and Late Hemispherectomized Monkeys
Authors: Burke Mark W. , Kupers Ron , Ptito Maurice
Published: June 2012

Behavioural recovery in children who undergo medically required hemispherectomy showcase the remarkable ability of the cerebral cortex to adapt and reorganize following insult early in life. Case study data suggest that lesions sustained early in childhood lead to better recovery compared to those that occur later in life. In these children, it is possible that neural reorganization had begun prior to surgery but was masked by the dysfunctional hemisphere. The degree of neural reorganization has been difficult to study systematically in human infants. Here we present a 20-year culmination of data on our nonhuman primate model (Chlorocebus sabeus) of early-life hemispherectomy in which behavioral recovery is interpreted in light of plastic processes that lead to the anatomical reorganization of the early-damaged brain. The model presented here suggests that significant functional recovery occurs after the removal of one hemisphere in monkeys with no preexisting neurological dysfunctions. Human and primate studies suggest a critical role for subcortical and brainstem structures as well as corticospinal tracts in the neuroanatomical reorganization which result in the remarkable behavioral recovery following hemispherectomy. The non-human primate model presented here offers a unique opportunity for studying the behavioral and functional neuroanatomical reorganization that underlies developmental plasticity.
MS1-2: Tumor Entrained Neutrophils Inhibit Seeding in the Pre-Metastatic Lung.
Authors: Granot Z , Heneke E , Comen EA , King TA , Norton L , Benezra R
Published: June 2012

Primary tumors have been shown to prepare distal organs for later colonization of metastatic cells by stimulating organ-specific infiltration of bone marrow derived cells. We have recently demonstrated that neutrophils are mobilized by the primary tumor and accumulate in the lung prior to the arrival of metastatic cells in mouse models of breast cancer. Tumor-entrained neutrophils (TENs) inhibit metastatic seeding in the lungs by generating H2O2 and tumor secreted CCL2 is both required and sufficient for optimal anti-metastatic entrainment of G-CSF-mobilized neutrophils. TENs are present in the peripheral blood of breast cancer patients prior to surgical resection but not in healthy individuals. Thus, while tumor-secreted factors contribute to tumor progression at the primary site, they concomitantly induce a neutrophil-mediated inhibitory process at the metastatic site.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr MS1-2.
OT1-02-08: The PERSEPHONE Trial: Duration of Trastuzumab with Chemotherapy in Women with HER2 Positive Early Breast Cancer. Changing the Randomisation Point To Address Potential Barriers to Recruitment.
Authors: Earl HM , Loi S , Vallier A-L , Hiller L , Ogburn-Storey E , Higgins H , Dunn J
Published: June 2012

Background

Persephone is a phase III randomised controlled trial comparing six months of trastuzumab (9 doses) to the standard 12 month duration (18 doses) in patients with HER2 positive early breast cancer in respect of disease free survival, safety and cost-effectiveness. The trial opened to recruitment in October 2007 but soon showed that meeting recruitment targets was challenging, reaching only 20–30 patients per month. A key issue seemed to be the mandatory requirement to randomise before patients started trastuzumab treatment. Successful accrual of patients in the PHARE trial, a Persephone sister study, run by the National Institute for Cancer, Paris had not incorporated this criteria.

Method: In September 2009, following accrual of 316 patients, this potential barrier to recruitment was addressed by a major protocol amendment which relaxed the eligibility criteria to allow randomisation of patients who had received up to 9 doses of trastuzumab.

Results: To date, 1334 patients have been randomised into PERSEPHONE. After the amendment, monthly recruitment increased to 40–50 patients and, more recently, to 60–70 patients. Of the 1018 patients recruited since September 2009, 450 (44%) patients had received at least 1 dose of trastuzumab pre-randomisation (see Table).

Retrospective collection of pre-randomisation trastuzumab dose and toxicity information has proved successful, allowing analyses of dose intensity, toxicity and compliance to be carried out on all patients.

Conclusion: Relaxing the eligibility criteria has considerably improved recruitment into the PERSEPHONE trial without compromising the important endpoints the trial sets out to assess.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-02-08.
OT1-02-09: A Phase II Randomized Trial of Lapatinib with Either Vinorelbine or Capecitabine as First- and Second-Line Therapy for HER2−Overexpressing Metastatic Breast Cancer.
Authors: Janni W , Pikiel J , Sarosiek T , Karaszewska B , Papadimitriou CA , Schwedler K , Alavarez Gallego J , Caruso M , Herve RA , Lau MR , Williams LS , Briggs K , Sapunar FJ
Published: June 2012

Background: Lapatinib, a dual kinase inhibitor of epidermal growth factor receptor (EGFR) and the human epidermal growth factor receptor-2 (HER2/ErbB2), is approved for the treatment of HER2−overexpressing (HER2+) metastatic breast cancer (MBC) in combination with capecitabine following progression after trastuzumab, anthracyclines, and taxanes. Vinorelbine is an important chemotherapy option in MBC, and multiple phase II trials in combination with trastuzumab have been conducted.

Methods: This randomized, open-label, multicenter, phase II study (VITAL, LAP112620, NCT01013740) is evaluating the efficacy and safety of lapatinib with either vinorelbine or capecitabine in women with HER2+ MBC. A total of 105 stage IV breast cancer patients with disease progression who have received ≤1 chemotherapy regimen in the metastatic setting with an ECOG performance status of ≤1 are randomized 2:1 to either: lapatinib 1250 mg orally once daily (QD) continuously plus vinorelbine 20 mg/m2 intravenously on days 1 and 8 every third week; or lapatinib 1250 mg orally QD continuously plus capecitabine 2000 mg/m2/d orally in 2 doses 12 hours apart on days 1 to 14 every third week. Following progression in the randomized phase, patients will be given the option to cross over to the other arm. The primary endpoint is progression-free survival and will be analyzed with a descriptive intent since the study is not powered to detect differences between treatment arms. Secondary endpoints include overall response rate, overall survival, duration of response, time to response, and clinical benefit rate.

The study is currently recruiting in 8 countries in Europe (Bulgaria, France, Germany, Greece, Italy, Poland, Serbia, Spain) and 2 in Latin America (Chile, Mexico).

Funding Source: GlaxoSmithKline

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-02-09.
OT2-03-01: Incidence of Mastalgia as a Presenting Complaint in Iranian Population with Regard to Age, BMI, Education, Residency (City or Rural), State of Marriage and Compare with Western Countries.
Authors: Razavi S
Published: June 2012

As it is has usually been stated, breast pain (mastalgia) is among the most common (or the commonest) cause of women referring to a breast clinic. The incidence has been reported in different ranges, and some studies (e.g. Canadian groups) have stated that mastalgia has its lowest incidence in middle east (compared to western countries). Based on this information, I have recently planned a study to investigate this issue.

To evaluate this data, I planned a questionnaire for every new patient coming to my breast clinic randomly. Every questionnaire was double checked & if still incomplete, was completed by phone communication.

The only inclusion criteria were to be a new patient. In this way over 550 questioners were completed during over 4 months. The aim is to find if there is any statistical difference in incidence rate and if there is any, evaluate any demographic difference that can be a cause.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-03-01.
OT2-05-01: An Open-Label Positron Emission Tomography Study To Investigate and Quantify Brain and Tumor Penetration of Carbon-11-Labeled Lapatinib in Patients with HER2−Overexpressing Advanced or Metastatic Breast Cancer.
Authors: Coombes RC , Reise JA , Lau MR , Carme SC , Searle GE , Huiban M , Burgess P , Noibi S , Koch K , Sapunar F , Saleem A
Published: June 2012

Background: Patients with HER2−overexpressing (HER2+) breast cancer tend to develop visceral metastases. About a third will develop brain metastases in the course of their disease. Several anticancer agents including trastuzumab are not believed to readily cross the blood-brain barrier (BBB); therefore, central nervous system (CNS) disease progression is emerging as an important clinical problem in this patient population. Although preclinical data indicate that lapatinib brain concentrations are low in healthy animals, probably due to the BBB efflux transporters, observations from clinical studies suggest lapatinib treatment might be associated with reduced CNS tumor growth. One hypothesis is that disruption of the BBB by tumors circumvents the usual protective function of transporters. Alternatively, inhibition of efflux transporters by lapatinib enhances its own accumulation with repeat dosing. The role of lapatinib in prevention of brain metastases is currently being explored in a phase III trial, EGF 111438 (CEREBEL).

Methods: To directly assess if lapatinib penetrates the brain and brain metastases, an open-label non-randomized study using carbon-11-labeled [11C] lapatinib is enrolling patients with HER2+ metastatic breast cancer. A minimum of 10 patients with an ECOG of <3 are grouped into 2 cohorts: with at least one 1-cm diameter brain metastasis or without brain metastases. Two positron emission tomography (PET) scans will be performed in each patient following intravenous administration of a microdose of [11C] lapatinib: in lapatinib-naïve patients and at steady-state lapatinib, after treatment with unlabelled oral lapatinib 1500 mg once daily for 8 days. [11C] lapatinib time-activity curves will be generated for normal brain and brain metastases, the PET volume of distribution in the brain calculated and penetration of [11C] lapatinib into the brain quantified. Analysis of brain PET data is explorative as [11C] lapatinib is a new tracer. Therefore, this study investigates both the difference in lapatinib brain penetration between patients with and without brain metastases, as well as the effect of low and high concentrations of lapatinib on the BBB efflux system.

The study is currently recruiting in one center in the United Kingdom.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-05-01.
OT2-05-04: ACRIN PA 4006: Comparison of Full-Field Digital Mammography with Digital Breast Tomosynthesis Image Acquisition in Relation to Screening Call-Back Rate.
Authors: Conant EF , Maidment A , Copit D , Olson CB , Heckel ML , Gatsonis C
Published: June 2012

Background

With competing parameters of specificity and sensitivity, breast cancer screening must limit both missed cancers and false-positive call-backs (with potential to biopsy) to reduce cost and unnecessary anxiety to patients. Full-field digital mammography (FFDM) has been shown to provide improved sensitivity over analog mammography in the detection of breast cancers, particularly in women with dense breasts. Unfortunately, call-back rates for both digital and analog screening mammography have similar, elevated rates of approximately 10% (E. Pisano et al, NEJM, 2005). Incorporation of digital breast tomosynthesis (DBT), a novel 3-D reconstruction of multiple low-dose digital mammographic images, may reduce the number of call-back visits needed by providing many of the benefits of diagnostic imaging at screening. This study will assess variations in DBT image acquisition while limiting radiation dose to women with varying breast sizes and densities, to define parameters to be used in a larger national screening tomosynthesis trial.

Eligibility: Asymptomatic women 25 years and older with no breast cancer history are eligible for Group A or B (see below). Pregnant women, women unable to tolerate compression of the breast associated with mammography, women with implants, and women with breasts too large for DBT are excluded from participation.

Trial design/target accrual: This multicenter trial uses Hologic digital mammography units at two institutions in Philadelphia, Pennsylvania. The timing of the study-related imaging visits are segregated into two cohorts, screening (Group A) and diagnostic (Group B). Group A comprises 500 women who will undergo both FFDM and DBT at screening. Initial independent interpretations of the FFDM and DBT from local readers will determine call back. Enriched Group B comprises 50 women who have been informed of abnormal findings from a FFDM screening within 30 days of enrollment. They will be recruited prior to their diagnostic imaging and consent to DBT of both breasts as part of their diagnostic imaging. Participants from both Groups will be followed or biopsied as recommended by their treating physician. Follow up includes medical record review and images collection at approximately 1-year. Follow-up data may be collected up to 18 months.

Specific aims and statistical methods: ACRIN PA 4006 will evaluate the specificity of 2-D FFDM versus a combination of 2-D and 3-D tomosynthesis imaging in breast cancer screening. Specificity will be measured by the participant call-back rate by each modality. Sensitivity and specificity by lesion-type characteristics, especially focused on DBT assessment of calcifications, will be compared.

Current accrual: Currently, the trial accrual has reached 259 of 550.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT2-05-04.