bluuebunny/crossref_metadata_2025_split huggingface dataset:
TIde: a software for the systematic scanning of drug targets in kinetic network models
Authors: Schulz Marvin , Bakker Barbara M , Klipp Edda 
Published: October 2009

Abstract

Background
During the stages of the development of a potent drug candidate compounds can fail for several reasons. One of them, the efficacy of a candidate, can be estimated in silico if an appropriate ordinary differential equation model of the affected pathway is available. With such a model at hand it is also possible to detect reactions having a large effect on a certain variable such as a substance concentration.

Results
We show an algorithm that systematically tests the influence of activators and inhibitors of different type and strength acting at different positions in the network. The effect on a quantity to be selected (e.g. a steady state flux or concentration) is calculated. Moreover, combinations of two inhibitors or one inhibitor and one activator targeting different network positions are analysed. Furthermore, we present TIde (Target Identification), an open source, platform independent tool to investigate ordinary differential equation models in the common systems biology markup language format. It automatically assigns the respectively altered kinetics to the inhibited or activated reactions, performs the necessary calculations, and provides a graphical output of the analysis results. For illustration, TIde is used to detect optimal inhibitor positions in simple branched networks, a signalling pathway, and a well studied model of glycolysis in Trypanosoma brucei.

Conclusion
Using TIde, we show in the branched models under which conditions inhibitions in a certain pathway can affect a molecule concentrations in a different. In the signalling pathway we illuminate which inhibitions have an effect on the signalling characteristics of the last active kinase. Finally, we compare our set of best targets in the glycolysis model with a similar analysis showing the applicability of our tool.
Ras promotes cell survival by antagonizing both JNK and Hid signals in the Drosophilaeye
Authors: Wu Yue , Zhuang Yuan , Han Min , Xu Tian , Deng Kejing 
Published: October 2009

Abstract

Background
Programmed cell death, or apoptosis, is a fundamental physiological process during normal development or in pathological conditions. The activation of apoptosis can be elicited by numerous signalling pathways. Ras is known to mediate anti-apoptotic signals by inhibiting Hid activity in the Drosophila eye. Here we report the isolation of a new loss-of-function ras allele, ras

KP
, which causes excessive apoptosis in the Drosophila eye.

Results
This new function is likely to be mediated through the JNK pathway since the inhibition of JNK signalling can significantly suppress ras

KP
-induced apoptosis, whereas the removal of hid only weakly suppresses the phenotype. Furthermore, the reduction of JNK signalling together with the expression of the baculovirus caspase inhibitor p35, which blocks Hid activity, strongly suppresses the ras

KP
cell death. In addition, we find a strong correlation between ras

KP
-induced apoptosis in the eye disc and the activation of JNK signalling.

Conclusion
In the Drosophila eye, Ras may protect cells from apoptosis by inhibiting both JNK and Hid activities. Surprisingly, reducing Ras activity in the wing, however, does not cause apoptosis but rather affects cell and organ size. Thus, in addition to its requirement for cell viability, Ras appears to mediate different biological roles depending on the developmental context and on the level of its expression.
Widespread variation in transcript abundance within and across developmental stages of Trypanosoma brucei
Authors: Jensen Bryan C , Sivam Dhileep , Kifer Charles T , Myler Peter J , Parsons Marilyn 
Published: October 2009

AbstractBackgroundTrypanosoma brucei, the causative agent of African sleeping sickness, undergoes a complex developmental cycle that takes place in mammalian and insect hosts and is accompanied by changes in metabolism and cellular morphology. While differences in mRNA expression have been described for many genes, genome-wide expression analyses have been largely lacking. Trypanosomatids represent a unique case in eukaryotes in that they transcribe protein-coding genes as large polycistronic units, and rarely regulate gene expression at the level of transcription initiation.ResultsHere we present a comprehensive analysis of mRNA expression in several stages of parasite development. Utilizing microarrays that have multiple copies of multiple probes for each gene, we were able to demonstrate with a high degree of statistical confidence that approximately one-fourth of genes show differences in mRNA expression levels in the stages examined. These include complex patterns of gene expression within gene families, including the large family of variant surface glycoproteins (VSGs) and their relatives, where we have identified a number of constitutively expressed family members. Furthermore, we were able to assess the relative abundance of all transcripts in each stage, identifying the genes that are either weakly or highly expressed. Very few genes show no evidence of expression.ConclusionDespite the lack of gene regulation at the level of transcription initiation, our results reveal extensive regulation of mRNA abundance associated with different life cycle and growth stages. In addition, analysis of variant surface glycoprotein gene expression reveals a more complex picture than previously thought. These data provide a valuable resource to the community of researchers studying this lethal agent.
Regulation of phenylacetic acid degradation genes of Burkholderia cenocepacia K56-2
Authors: Hamlin Jason NR , Bloodworth Ruhi AM , Cardona Silvia T 
Published: October 2009

Abstract

Background
Metabolically versatile soil bacteria Burkholderia cepacia complex (Bcc) have emerged as opportunistic pathogens, especially of cystic fibrosis (CF). Previously, we initiated the characterization of the phenylacetic acid (PA) degradation pathway in B. cenocepacia, a member of the Bcc, and demonstrated the necessity of a functional PA catabolic pathway for full virulence in Caenorhabditis elegans. In this study, we aimed to characterize regulatory elements and nutritional requirements that control the PA catabolic genes in B. cenocepacia K56-2.

Results
Translational fusions of the PA degradation gene promoters with eGFP were constructed and introduced in B. cenocepacia K56-2. eGFP expression was observed when the reporter strains were grown in minimal media containing glycerol and PA or other compounds expected to proceed through the PA pathway, and in synthetic CF medium (SCFM). Addition of succinate or glucose to the PA containing medium repressed eGFP expression. To show that BCAL0210, a putative TetR-type regulator gene encodes a regulator for the PA genes in B. cenocepacia, we developed a BCAL0210 insertional mutant reporter strain. Results show that these strains exhibit fluorescence regardless of the presence of PA in the culture.

Conclusion
The PA catabolic genes of B. cenocepacia K56-2 are induced by PA and other related compounds, are negatively regulated by PaaR (named herein), a TetR-type regulator, and are subjected to catabolic repression by glucose and succinate. As the PA catabolic pathway of B. cenocepacia appears to be induced during growth in synthetic cystic fibrosis medium (SCFM), further research is necessary to determine the relevance of this pathway in CF-like conditions and in other host-pathogen interactions.
Protective measures and H5N1-seroprevalence among personnel tasked with bird collection during an outbreak of avian influenza A/H5N1 in wild birds, Ruegen, Germany, 2006
Authors: Cai Wei , Schweiger Brunhilde , Buchholz Udo , Buda Silke , Littmann Martina , Heusler Jörg , Haas Walter 
Published: October 2009

Abstract

Background
In Germany, the first outbreak of highly pathogenic avian influenza A/H5N1 occurred among wild birds on the island of Ruegen between February and April 2006. The aim of this study was to investigate the use of recommended protective measures and to measure H5N1-seroprevalence among personnel tasked with bird collection.

Methods
Inclusion criteria of our study were participation in collecting wild birds on Ruegen between February and March 2006. Study participants were asked to complete a questionnaire, and to provide blood samples. For evaluation of the use of protective measures, we developed a personal protective equipment (PPE)-score ranging between 0 and 9, where 9 corresponds to a consistent and complete use of PPE. Sera were tested by plaque neutralization (PN) and microneutralization (MN) assays. Reactive sera were reanalysed in the World Health Organization-Collaborating Centre (WHO-CC) using MN assay.

Results
Of the eligible personnel, consisting of firemen, government workers and veterinarians, 61% (97/154) participated in the study. Of those, 13% reported having always worn all PPE-devices during bird collection (PPE-score: 9). Adherence differed between firemen (mean PPE-score: 6.6) and government workers (mean PPE-score: 4.5; p = 0.006). The proportion of personnel always adherent to wearing PPE was lowest for masks (19%). Of the participants, 18% had received seasonal influenza vaccination prior to the outbreak. There were no reports of influenza-like illness. Five sera initially H5-reactive by PN assay were negative by WHO-CC confirmatory testing.

Conclusion
Gaps and variability in adherence demonstrate the risk of exposure to avian influenza under conditions of wild bird collection, and justify serological testing and regular training of task personnel.
The incidence and risk of developing a second primary esophageal cancer in patients with oral and pharyngeal carcinoma: a population-based study in Taiwan over a 25 year period
Authors: Lee Kuan-Der , Lu Chang-Hsien , Chen Ping-Tsung , Chan Chunghuang Hubert , Lin Jen-Tsun , Huang Cih-En , Chen Chih-Cheng , Chen Min-Chi 
Published: October 2009

Abstract

Background
The incidence of oral and pharyngeal (including oral cavity, oropharynx and hypopharynx) carcinoma increases rapidly in Asia and South Pacific because of betel quid chewing. Thus far, large-scale epidemiological studies are not available yet to stratify these patients by their risks of developing a second primary cancer in the digestive tract including esophagus, stomach, colon, and rectum.

Methods
A population-based study was conducted using the database from the Taiwan National Cancer Registry for the period 1979-2003. We quantified standardized incidence ratios (SIRs) and cumulative incidence of second primary cancers among 33,787 patients with initial diagnoses of oral and pharyngeal carcinoma.

Results
Among these four digestive tract organs, the esophagus was the only site of second cancer with excess risk in patients with oral and pharyngeal carcinoma. The incidence and risk of developing a second primary esophageal cancer differed by the site of the primary index tumor, most frequently seen in hypopharyngeal cancer (71/4,218 = 1.68%, SIR = 22.76, 95% CI 17.77-28.70), followed by oropharyngeal cancer (30/3,403 = 0.88%, SIR = 14.29, 95% CI 9.64-20.39) and the least in oral cavity cancer (99/26,166 = 0.38%, SIR = 5.57, 95% CI 4.53-6.78). In addition, the risk was extraordinarily high for patients with a follow-up interval ≤ 1 year and those with first primary cancer diagnosed at age ≤50. These patients may justify more close surveillance.

Conclusion
The present study represents the first population-based study in Asia attempting to stratify the patients of oral and pharyngeal carcinoma by their risk of developing a second esophageal cancer. It helps identify patients at high risk and tailor the application of intense follow-up surveillance to the estimated risk in each individual case.
Dietary supplementation by older adults in southern China: a hospital outpatient clinic study
Authors: Liang Wenbin , Lee Andy H , Binns Colin W 
Published: October 2009

Abstract

Background
There has been little knowledge about dietary supplementation by the Chinese elderly. The aim of this cross-sectional study was to investigate the usage of dietary supplements by older adults in southern China.

Methods
A total of 600 community-dwelling older adults were recruited from the outpatient clinics of three major hospitals in Foshan city between July 2007 and July 2008. Face-to-face interviews of participants were conducted to obtain information on demographics, lifestyle and dietary supplements use. Frequency and duration of usage were recorded for six categories of dietary supplements.

Results
Among the 446 consented participants (241 men and 205 women) who were over 55 years of age, 19.1% consumed one or more types of dietary supplements. The prevalence of usage was significantly higher (p = 0.008) for females (24.4%) than for males (14.5%). Dietary supplements were more likely to be consumed by non-smokers (p = 0.021) and those with hyperlipidemia (p = 0.003). The most popular supplement among users was calcium (53%). The majority (71%) of the users consumed supplements on a regular basis at one or more times per day, with an average duration of 2.95 (SD 4.80) years.

Conclusion
The overall prevalence of dietary supplementation in this older Chinese population was considerably lower than those in other Asia-Pacific countries.
An EIAV field isolate reveals much higher levels of subtype variability than currently reported for the equine lentivirus family
Authors: Craigo Jodi K , Barnes Shannon , Zhang Baoshan , Cook Sheila J , Howe Laryssa , Issel Charles J , Montelaro Ronald C 
Published: October 2009

AbstractBackgroundEquine infectious anemia virus (EIAV), a lentivirus that infects horses, has been utilized as an animal model for the study of HIV. Furthermore, the disease associated with the equine lentivirus poses a significant challenge to veterinary medicine around the world. As with all lentiviruses, EIAV has been shown to have a high propensity for genomic sequence and antigenic variation, especially in its envelope (Env) proteins. Recent studies have demonstrated Env variation to be a major determinant of vaccine efficacy, emphasizing the importance of defining natural variation among field isolates of EIAV. To date, however, published EIAV sequences have been reported only for cell-adapted strains of virus, predominantly derived from a single primary virus isolate, EIAVWyoming(EIAVWY).ResultsWe present here the first characterization of the Env protein of a natural primary isolate from Pennsylvania (EIAVPA) since the widely utilized and referenced EIAVWYstrain. The data demonstrated that the level of EIAVPAEnv amino acid sequence variation, approximately 40% as compared to EIAVWY, is much greater than current perceptions or published reports of natural EIAV variation between field isolates. This variation did not appear to give rise to changes in the predicted secondary structure of the proteins. While the EIAVPAEnv was serologically cross reactive with the Env proteins of the cell-adapted reference strain, EIAVPV(derivative of EIAVWY), the two variant Envs were shown to lack any cross neutralization by immune serum from horses infected with the respective virus strains.ConclusionTaking into account the significance of serum neutralization to universal vaccine efficacy, these findings are crucial considerations towards successful EIAV vaccine development and the potential inclusion of field isolate Envs in vaccine candidates.
A rare clinic presentation of abdominal pain: rupture of splenic artery aneurysm: a case report
Authors: Sarikaya Sezgin , Ekci Baki , Aktas Can , Cetin Asli , Ay Didem , Demirag Alp 
Published: October 2009

Abstract

Background
Splenic artery aneurysms (SAA) are uncommon but the most common visceral artery aneurysm. Splenic artery aneurysms are important to recognize because up to 25% may be complicated by rupture and the mortality rate after rupture is between 25% and 70%.

Case report
We present a patient who have abdominal pain. Previously healthy 22-year-old female admitted to emergency department with abdominal pain. Her physical examination reveals only left upper quadrant tenderness. Suddenly she developed hypovolemic shock. On emergent laparotomy massive blood collection within peritoneal cavity and retroperitoneal space at the left upper quadrant was detected. The source of bleeding was evident as rupture of splenic artery aneurysm. Splenectomy was performed following the ligation of splenic artery proximal to lesion. On the tenth day she was discharged from the hospital with complete recovery.

Conclusion
It is important to remember rupture of splenic artery aneurysm in patients with abdominal pain and hypovolemic shock status.
Animal models for clinical and gestational diabetes: maternal and fetal outcomes
Authors: Kiss Ana CI , Lima Paula HO , Sinzato Yuri K , Takaku Mariana , Takeno Marisa A , Rudge Marilza VC , Damasceno Débora C 
Published: October 2009

AbstractBackgroundDiabetes in pregnant women is associated with an increased risk of maternal and neonatal morbidity and remains a significant medical challenge. Diabetes during pregnancy may be divided into clinical diabetes and gestational diabetes. Experimental models are developed with the purpose of enhancing understanding of the pathophysiological mechanisms of diseases that affect humans. With regard to diabetes in pregnancy, experimental findings from models will lead to the development of treatment strategies to maintain a normal metabolic intrauterine milieu, improving perinatal development by preventing fetal growth restriction or macrosomia. Based on animal models of diabetes during pregnancy previously reported in the medical literature, the present study aimed to compare the impact of streptozotocin-induced severe (glycemia >300 mg/dl) and mild diabetes (glycemia between 120 and 300 mg/dl) on glycemia and maternal reproductive and fetal outcomes ofWistarrats to evaluate whether the animal model reproduces the maternal and perinatal results of clinical and gestational diabetes in humans.MethodsOn day 5 of life, 96 femaleWistarrats were assigned to three experimental groups: control (n = 16), severe (n = 50) and mild diabetes (n = 30). At day 90 of life, rats were mated. On day 21 of pregnancy, rats were killed and their uterine horns were exposed to count implantation and fetus numbers to determine pre- and post-implantation loss rates. The fetuses were classified according to their birth weight.ResultsSevere and mild diabetic dams showed different glycemic responses during pregnancy, impairing fetal glycemia and weight, confirming that maternal glycemia is directly associated with fetal development. Newborns from severe diabetic mothers presented growth restriction, but mild diabetic mothers were not associated with an increased rate of macrosomic fetuses.ConclusionExperimental models of severe diabetes during pregnancy reproduced maternal and fetal outcomes of pregnant women presenting uncontrolled clinical diabetes. On the other hand, the mild diabetes model caused mild hyperglycemia during pregnancy, although it was not enough to reproduce the increased rate of macrosomic fetuses seen in women with gestational diabetes.
Randomized Phase III Trial on Gemcitabine Versus Mytomicin in Recurrent Superficial Bladder Cancer: Evaluation of Efficacy and Tolerance
Authors: Addeo Raffaele , Caraglia Michele , Bellini Sergio , Abbruzzese Alberto , Vincenzi Bruno , Montella Liliana , Miragliuolo Antonio , Guarrasi Rosario , Lanna Michele , Cennamo Gregorio , Faiola Vincenzo , Del Prete Salvatore 
Published: October 2009

PurposeApproximately 30% to 40% patients with a superficial bladder cancer treated with Bacille Calmette-Guerin (BCG) or epirubicin do not respond; of the initial responders, 35% have a relapse within 5 years. We compare the therapeutic efficacy and toxicity of intravescical infusions of gemcitabine (GEM) with mitomycin (MMC) in patients with a recurrent superficial bladder cancer.Patients and MethodsPatients with a history of a previously treated, recurrent Ta-T1, G1-G3 bladder transitional cell carcinoma were enrolled in the study. The patients received a 6-week course of GEM infusions or 4-week course of MMC. In both arms, for the initial responders who remained free of recurrences, maintenance therapy consisted of 10 monthly treatments during the first year.ResultsA total of 120 patients were enrolled and randomly assigned to either the MMC or GEM treatment arm. At the end of the study, 109 patients (55 in MMC and 54 in GEM) were assessable. The median duration of follow-up was 36 months for either arm. In the GEM arm, 39 (72%) of 54 patients remained free of recurrence versus 33 (61%) of 55 in MMC arm. Among patients with recurrences, 10 in the MMC arm and six in the GEM arm also had a progressive disease by stage. The incidence of chemical cystitis in the MMC arm was statistically higher than in the GEM arm (P = .012).ConclusionThis study demonstrates that GEM has better efficacy and lower toxicity than MMC; therefore, GEM appears as a logical candidate for intrabladder therapy in patients with refractory transitional cancer.
Clinically Driven Diagnostic Antifungal Approach in Neutropenic Patients: A Prospective Feasibility Study
Authors: Girmenia Corrado , Micozzi Alessandra , Gentile Giuseppe , Santilli Stefania , Arleo Eva , Cardarelli Luisa , Capria Saveria , Minotti Clara , Cartoni Claudio , Brocchieri Simonetta , Guerrisi Vito , Meloni Giovanna , Foà Robin , Martino Pietro 
Published: October 2009

Purpose Preemptive strategies in neutropenic patients based on serum galactomannan (GM) –guided triggering of diagnostic work-up may be time-consuming and expensive when applied to the entire population. We have assessed the feasibility of a clinically driven diagnostic strategy without GM screening. Patients and Methods Patients with neutropenic fever underwent a baseline diagnostic work-up (BDWU; three blood cultures and other examinations as indicated). An intensive diagnostic work-up (IDWU; GM for 3 days, chest computed tomography and other examinations as indicated) was reserved for patients with 4 days of persisting or relapsing fever or with other clinical findings possibly related to an invasive fungal diseaser (IFD). Antifungal therapy was administered to patients diagnosed with IFD and empirically (negative IDWU) only to those with persisting neutropenic fever and worsening clinical conditions. Results Of 220 neutropenia episodes, fever occurred in 159 cases and recurred in 28 cases. Overall, 49 IFDs were diagnosed (two by BDWU and 47 by IDWU) during 48 episodes (21.8%). Diagnostic-driven therapy was administered to 48 patients with IFDs; one patient with zygomycosis died without treatment. Only one patient received empirical therapy. IDWU was required in 40% of neutropenia episodes, and only 1.4 mean blood samples per neutropenia episode were tested for GM. Our strategy allowed a 43% reduction in antifungal treatments compared with a standard empirical approach. At 3-month follow-up, 63% of patients with IFD survived, and no undetected IFDs were found. Conclusion A clinically driven diagnostic approach in selected neutropenia episodes offered effective antifungal control and reduced the exposure to unnecessary antifungal treatment.