bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and Characterization ofRe-Citrate Synthase in Syntrophus aciditrophicus
Authors: Kim Marie , Le Huynh , McInerney Michael J. , Buckel Wolfgang 
Published: February 2013

ABSTRACTGlutamate is usually synthesized from acetyl coenzyme A (acetyl-CoA) via citrate, isocitrate, and 2-oxoglutarate. Genome analysis revealed that inSyntrophus aciditrophicus, the gene forSi-citrate synthase is lacking. An alternative pathway starting from the catabolic intermediate glutaconyl-CoA via 2-hydroxyglutarate could be excluded by genomic analysis. On the other hand, a putative gene (SYN_02536; NCBI gene accession no.CP000252.1) annotated as coding for isopropylmalate/citramalate/homocitrate synthase has been shown to share 49% deduced amino acid sequence identity with the gene encodingRe-citrate synthase ofClostridium kluyveri. We cloned and overexpressed this gene inEscherichia colitogether with the genes encoding the chaperone GroEL. The recombinant homotetrameric enzyme with a C-terminal Strep-tag (4 × 72,892 Da) was separated from GroEL on a Strep-Tactin column by incubation with ATP, K+, and Mg2+. The pureRe-citrate synthase used only acetyl-CoA and oxaloacetate as the substrates. As isolated, the enzyme contained stoichiometric amounts of Ca2+(0.9 Ca/73 kDa) but achieved higher specific activities in the presence of Mn2+(1.2 U/mg) or Co2+(2.0 U/mg). To determine the stereospecificity of the enzyme, [14C]citrate was enzymatically synthesized from oxaloacetate and [1-14C]acetyl-CoA; the subsequent cleavage bySi-citrate lyase yielded unlabeled acetate and labeled oxaloacetate, demonstrating that the enzyme is aRe-citrate synthase. The production ofRe-citrate synthase byS. aciditrophicusgrown axenically on crotonate was revealed by synthesis of [14C]citrate in a cell extract followed by stereochemical analysis. This result was supported by detection of transcripts of theRe-citrate synthase gene in axenic as well as in syntrophic cultures using quantitative reverse transcriptase PCR (qRT-PCR).
Effects of Acupuncture on the Outcome of in Vitro Fertilisation and Intracytoplasmic Sperm Injection in Women with Polycystic Ovarian Syndrome
Authors: Rashidi Batool Hossein , Tehrani Ensieh Shahrokh , Hamedani Navid Alhosseini , Pirzadeh Leila 
Published: February 2013

Background Different mechanisms have been described for the effects of acupuncture on fertility. Acupuncture may mediate neurotransmitter release, which results in the stimulation of gonadotrophin-releasing hormone secretion. The production of neurotransmitters such as endogenous opioids may also inhibit central nervous system outflow and biological stress response. Acupuncture may also stimulate blood flow to the uterus by inhibiting uterine central sympathetic nerve activity. Despite some evidence suggesting beneficial effects of acupuncture on in vitro fertilisation (IVF) success rates, recent clinical trials could not duplicate these effects, especially in patients who are infertile with polycystic ovarian syndrome (PCOS) who are undergoing IVF. Methods A total of 62 women with PCOS undergoing IVF/intracytoplasmic sperm injection (ICSI) at Shayamehr IVF Clinic in Tehran (Iran) participated in a randomised, controlled trial. Participants were randomly allocated to one of two groups: there were 31 women each in the acupuncture (group I) and control groups (group II). Acupuncture based on traditional Chinese medicine was performed in group I versus no adjunctive treatment in group II. All acupuncture procedures were performed in five sessions: start of downregulation, start of stimulation, 2 days before ovum pick-up, and immediately before and after embryo transfer. We measured the rate of oocytes in metaphase II, the fertilisation rate and the quality of embryos. Results Our results showed a statistically higher mean of good quality embryos in group I compared with group II (p=0.044). However, the mean number of metaphase II oocytes retrieved and fertilisation rate were similar between the two groups. We also could not find any significant differences among clinical, biochemical or ongoing pregnancy rates. Conclusions Acupuncture at an early stage of oocyte recruitment may have a beneficial effect on embryo quality. However, it seems to have no significant effect on other IVF/ICSI outcomes of women with PCOS. Trial Registration Number (IRCT ID: 201011275181N4)
Intrapleural fibrinolytic therapy (IPFT) in loculated pleural effusions—analysis of predictors for failure of therapy and bleeding: a cohort study
Authors: Abu-Daff Saleh , Maziak Donna E , Alshehab Derar , Threader Jennifer , Ivanovic Jelena , Deslaurier Valerie , Villeneuve Patrick-James , Gilbert Sebastian , Sundaresan Sudhir , Shamji Farid , Lougheed Colleen , Seely Jean M , Seely Andrew J E 
Published: February 2013

ObjectivesTo assess risk factors associated with failure and bleeding in intrapleural fibrinolytic therapy (IPFT) for pleural effusions.DesignRetrospective case series.SettingTwo tertiary-care centres in North America.ParticipantsWe identified 237 cases that received IPFT for the treatment of pleural effusions.Data for 227 patients were compiled including demographics, investigations, radiological findings pretherapy and post-therapy and outcomes.InterventionFibrinolytic therapy in the form of tissue plasminogen activator (t-PA) or streptokinase.Primary and secondary outcomesSuccess of therapy is defined as the presence of both clinical and radiological improvement leading to resolution. Failure was defined as persistence (ie, ineffective treatment) or complications requiring intervention from IPFT. Incidence of bleeding post-IPFT, identifying factors related to failure of therapy and bleeding.ResultsIPFT was used in 237 patients with pleural effusions; 163 with empyema/complicated parapneumonic effusions, 32 malignant effusions and 23 with haemothorax. Overall, resolution was achieved in 80% of our cases. Failure occurred in 46 (20%) cases. Multivariate analysis revealed that failure was associated with the presence of pleural thickening (>2 mm) on CT scan (p=0.0031, OR 3, 95% CI 1.46 to 6.57). Bleeding was not associated with any specific variable in our study (antiplatelet medications, p=0.08).ConclusionsPleural thickening on a CT scan was found to be associated with failure of IPFT.
Suicidal feelings in the twilight of life: a cross-sectional population-based study of 97-year-olds
Authors: Fässberg Madeleine Mellqvist , Östling Svante , Börjesson-Hanson Anne , Skoog Ingmar , Wærn Margda 
Published: February 2013

ObjectiveTo examine the occurrence of past month suicidal feelings in extreme old age. Further, to identify factors associated with such feelings.DesignCross-sectional population-based study.SettingGothenburg, Sweden.Participants269 adults (197 women, 72 men) without dementia born in 1901–1909 who participated in a psychiatric examination.Main outcome measuresDeath thoughts and suicidal feelings. The latter were rated in accordance with the Paykel questions (life not worth living, death wishes, thoughts of taking own life, seriously considered taking own life, attempted suicide) during the past month.ResultsOne quarter of the sample (26.7%) reported that they thought about their own death at least once a month. Past month thoughts that life was not worth living were acknowledged by 7.9% of the total sample, death wishes by 10.5% and thoughts of taking life by 3.8%. Few had serious thoughts of taking own life (0.8%) and none had attempted suicide. In all, 11.5% acknowledged some level of suicidal feelings. Most (77.4%) of those who reported such feelings fulfilled criteria for neither major nor minor depression. Neither poor perceived health nor disability (hearing, vision and motor function) was associated with suicidal feelings. Problematic sleep and deficient social contacts were also related to suicidal feelings after adjustment for depression.ConclusionsSuicidal feelings may occur outside the context of depression and disability in this age group. Results can inform clinicians who care for persons who reach extreme old age.
A cross-sectional study on socioeconomic status and health-related quality of life among elderly Chinese
Authors: Ma Xiaoguang , McGhee Sarah M 
Published: February 2013

ObjectivesTo examine the association between socioeconomic status (SES) and health-related quality of life (HRQOL) in a sample of elderly Chinese people in Hong Kong.Study DesignCross-sectional study.Setting18 elderly health centers in Hong Kong.ParticipantsThis study was based on a cohort aged 65 years or above who were enrolled in the Elderly Health Services from 1998 to 2005 in Hong Kong. Initially, 3324 individuals were randomly sampled from the baseline database. In the end, 2441 successful cases were obtained for the telephone survey. After excluding cases with missing SES or HRQOL information and the cases whose questionnaires were answered by their family members, 2347 individuals were included in the final analysis.ResultsElderly Chinese with less subjective economic hardship reported much better self-rated health (SRH) (OR 1.57–4.70, all p<0.01)< and higher Medical Outcomes Study short form (SF)12 scores (β 2.56–10.26, all p<0.01) than those with economic hardship. Male individuals in the highest education and occupation subgroup reported better HRQOL comparing with the baseline subgroup (OR for SRH 1.91–3.26, p<0.01; β 2.63–4.96, p<0.05). Two economic indicators, income and expenditure, only showed significant positive associations with physical SF12 scores for men (β 2.91–5.42, all p<0.05). Housing tenure was associated with SRH (OR 1.34 for men and 1.27 for women, p<0.05) but not SF12 scores.ConclusionsEconomic hardship showed the strongest association with HRQOL among all SES indicators. Educational level, occupational level and economic indicators tended to associate with physical HRQOL only among elderly Chinese men. More attention should be placed on subjective SES indicators when investigating influences on HRQOL among elderly Chinese people.
Improvement in the quality of molecular analysis ofEGFRin non-small-cell lung cancer detected by three rounds of external quality assessment
Authors: Deans Zandra C , Bilbe Neil , O'Sullivan Brendan , Lazarou Lazarus P , de Castro David Gonzalez , Parry Suzanne , Dodson Andrew , Taniere Philippe , Clark Caroline , Butler Rachel 
Published: February 2013

BackgroundThe clinical need to determine the presence of epidermal growth factor receptor (EGFR) gene mutations in non-small-cell lung cancers (NSCLC) in order to make informed decisions for patient treatment has seen the widespread introduction of EGFR molecular testing in many laboratories. To ensure high-quality molecular testing and allow laboratories to externally measure the standard of the service, an external quality assessment (EQA) scheme was provided to assess the whole testing process.MethodsFormalin-fixed paraffin-embedded NSCLC tumour sections were distributed to laboratories for routine EGFR molecular testing, and the genotyping accuracy, interpretation of the result and clerical accuracy of the report were independently assessed.ResultsThree rounds of assessment have identified many genotyping errors and have highlighted the need for external assessment and education in many testing laboratories. The main issues raised were the importance of accurate genotyping, including the use of common mutation nomenclature, clear unambiguous interpretation of the result, the impact of tumour sample assessment regarding amount of tumour being analysed and the heterogeneity of the sample on the molecular test result.ConclusionsImprovements in all these areas were observed during the progression of the three EQA rounds, however, continuous unacceptably high genotyping error rates demonstrate the clear need for continual external assessment and education in this field.
Breast cancerdiagnosis in aresource poorenvironment through a collaborativemultidisciplinaryapproach: the Kenyan experience
Authors: Sayed Shahin , Moloo Zahir , Bird Peter , Wasike Ronald , Njoroge Wambui , Karanu Joseph , Nzioka Ancent , Sherman Omar , Prasad Satya , Mariwa Costa , Otieno James Obondi , Chumba David , Koech David , Mbinga Daniel , Mohammed Musa , Njoroge Richard , Chauhan Rajendra , Vinayak Sudhir , Kyobutungi Catherine , Saleh Mansoor 
Published: February 2013

INTRODUCTIONThe majority of women with breast cancer in Kenya present with node-positive (stage II) or locally advanced Q7 disease (stage IIIB). Diagnosis is made on fine needle aspirate cytology and treatment is with surgery if resectable. Diagnostic core biopsy is available only at subspecialty hospitals. Processing and reporting of biopsy tissue are not standardised. Hormone receptor and HER2 analyses are rarely done preoperatively.METHODSAs part of a larger study investigating the prevalence of triple negative breast cancer in Kenya, a multidisciplinary workshop of collaborators from 10 healthcare facilities was held. Process gaps were identified, preanalytic variables impacting on ER/PR/HER2 discussed and training in core biopsy provided. Local remedial strategies were deliberated.CONCLUSIONWe describe our experience and outcome from the workshop, which can be modelled for other resource poor settings.
An investigation of the cost and benefit of mechanical thrombectomy for endovascular treatment of acute ischemic stroke
Authors: Turk Aquilla S , Campbell John M , Spiotta Alejandro , Vargas Jan , Turner Raymond D , Chaudry M Imran , Battenhouse Holly , Holmstedt Christine A , Jauch Edward 
Published: February 2013

IntroductionThe use of mechanical thrombectomy for the treatment of acute ischemic stroke has significantly advanced over the past 5 years, with few available data. The aim of this study was to analyze the cost and benefit of mechanical thrombectomy devices utilized during endovascular therapy of ischemic stroke patients.MethodsA retrospective chart review of patients that underwent intra-arterial stroke interventions was conducted. Clinical, angiographic, all devices used, procedural and postprocedural event and outcome data were collected. Thrombectomy devices were categorized as Penumbra aspiration system thrombectomy (group P) or stent retriever (group S). Statistical analysis of outcomes and costs for each group was performed.Results171 patients underwent mechanical thrombectomy. The Penumbra aspiration system was able to primarily achieve recanalization in 41.7% and the stent retriever in 70.4% of the time (p=0.006). The average cost was $11 159 and $16 022 (p=0.0002) in groups P and S, respectively. Average time to recanalization for group P was 85.1 min and for group S, 51.6 min (p<0.0001). Procedural complications were more frequent with the stent retriever (11.1% vs 9.0%; p=0.72) as were periprocedural significant complications (14.8 v 3%; p=0.04). Successful recanalization rates (Thrombolysis in Cerebral Infarction score 2b-3) were the same in groups P and S (78.5 vs. 77.8%). Similar rates of good neurologic outcomes were seen in group P (36.4%) and group S (50.0%) (p=0.19).ConclusionsFor the treatment of acute stroke patients, the use of aspiration appears to be the most cost effective method to achieve acceptable recanalization rates and low complication rates. Stent retriever with local aspiration, despite higher costs and complication rates, yielded better overall outcome.
Plastin3 Is a Novel Marker for Circulating Tumor Cells Undergoing the Epithelial–Mesenchymal Transition and Is Associated with Colorectal Cancer Prognosis
Authors: Yokobori Takehiko , Iinuma Hisae , Shimamura Teppei , Imoto Seiya , Sugimachi Keishi , Ishii Hideshi , Iwatsuki Masaaki , Ota Daisuke , Ohkuma Masahisa , Iwaya Takeshi , Nishida Naohiro , Kogo Ryunosuke , Sudo Tomoya , Tanaka Fumiaki , Shibata Kohei , Toh Hiroyuki , Sato Tetsuya , Barnard Graham F. , Fukagawa Takeo , Yamamoto Seiichiro , Nakanishi Hayao , Sasaki Shin , Miyano Satoru , Watanabe Toshiaki , Kuwano Hiroyuki , Mimori Koshi , Pantel Klaus , Mori Masaki 
Published: February 2013

Abstract
Circulating tumor cells (CTC) in blood have attracted attention both as potential seeds for metastasis and as biomarkers. However, most CTC detection systems might miss epithelial–mesenchymal transition (EMT)-induced metastatic cells because detection is based on epithelial markers. First, to discover novel markers capable of detecting CTCs in which EMT has not been repressed, microarray analysis of 132 colorectal cancers (CRC) from Japanese patients was conducted, and 2,969 genes were detected that were overexpressed relative to normal colon mucosa. From the detected genes, we selected those that were overexpressed CRC with distant metastasis. Then, we analyzed the CRC metastasis-specific genes (n = 22) to determine whether they were expressed in normal circulation. As a result, PLS3 was discovered as a CTC marker that was expressed in metastatic CRC cells but not in normal circulation. Using fluorescent immunocytochemistry, we validated that PLS3 was expressed in EMT-induced CTC in peripheral blood from patients with CRC with distant metastasis. PLS3-expressing cells were detected in the peripheral blood of approximately one-third of an independent set of 711 Japanese patients with CRC. Multivariate analysis showed that PLS3-positive CTC was independently associated with prognosis in the training set (n = 381) and the validation set [n = 330; HR = 2.17; 95% confidence interval (CI) = 1.38–3.40 and HR = 3.92; 95% CI = 2.27–6.85]. The association between PLS3-positive CTC and prognosis was particularly strong in patients with Dukes B (HR = 4.07; 95% CI = 1.50–11.57) and Dukes C (HR = 2.57; 95% CI = 1.42–4.63). PLS3 is a novel marker for metastatic CRC cells, and it possesses significant prognostic value. Cancer Res; 73(7); 2059–69. ©2012 AACR.
Cholesterol Loading and Ultrastable Protein Interactions Determine the Level of Tumor Marker Required for Optimal Isolation of Cancer Cells
Authors: Jain Jayati , Veggiani Gianluca , Howarth Mark 
Published: February 2013

Abstract
Cell isolation via antibody-targeted magnetic beads is a powerful tool for research and clinical applications, most recently for isolating circulating tumor cells (CTC). Nonetheless fundamental features of the cell–bead interface are still unknown. Here we apply a clinically relevant antibody against the cancer target HER2 (ErbB2) for magnetic cell isolation. We investigate how many target proteins per cell are sufficient for a cell to be isolated. To understand the importance of primary antibody affinity, we compared a series of point mutants with known affinities and show that even starting with subnanomolar affinity, improving antibody affinity improved cell isolation. To test the importance of the connection between the primary antibody and the magnetic bead, we compared bridging the antibody to the beads with Protein L, secondary antibody, or streptavidin: the high-stability streptavidin–biotin linkage improved sensitivity by an order of magnitude. Cytoskeletal polymerization did not have a major effect on cell isolation, but isolation was inhibited by cholesterol depletion and enhanced by cholesterol loading of cells. Analyzing a panel of human cancer cell lines spanning a wide range of expression showed that the standard approach could only isolate the highest expressing cells. However, our optimization of cholesterol level, primary antibody affinity, and antibody–bead linkage allowed efficient and specific isolation of cells expressing low levels of HER2 or epithelial cell adhesion molecule. These insights should guide future approaches to cell isolation, either magnetically or using other means, and extend the range of cellular antigens and biomarkers that can be targeted for CTC isolation in cancer research and diagnosis. Cancer Res; 73(7); 2310–21. ©2013 AACR.
FOXO3a Is a Major Target of Inactivation by PI3K/AKT Signaling in Aggressive Neuroblastoma
Authors: Santo Evan E. , Stroeken Peter , Sluis Peter V. , Koster Jan , Versteeg Rogier , Westerhout Ellen M. 
Published: February 2013

Abstract
Neuroblastoma is a pediatric tumor of the peripheral sympathetic nervous system with a highly variable prognosis. Activation of the phosphoinositide 3-kinase (PI3K)/AKT pathway in neuroblastoma is correlated with poor patient prognosis, but the precise downstream effectors mediating this effect have not been determined. Here we identify the forkhead transcription factor FOXO3a as a key target of the PI3K/AKT pathway in neuroblastoma. FOXO3a expression was elevated in low-stage neuroblastoma tumors and normal embryonal neuroblasts, but reduced in late-stage neuroblastoma. Inactivation of FOXO3a by AKT was essential for neuroblastoma cell survival. Treatment of neuroblastoma cells with the dual PI3K/mTOR inhibitor PI-103 activated FOXO3a and triggered apoptosis. This effect was rescued by FOXO3a silencing. Conversely, apoptosis induced by PI-103 or the AKT inhibitor MK-2206 was potentiated by FOXO3a overexpression. Furthermore, levels of total or phosphorylated FOXO3a correlated closely with apoptotic sensitivity to MK-2206. In clinical specimens, there was an inverse relationship between gene expression signatures regulated by PI3K signaling and FOXO3a transcriptional activity. Moreover, high PI3K activity and low FOXO3a activity were each associated with an extremely poor prognosis. Our work indicates that expression of FOXO3a and its targets offer useful prognostic markers as well as biomarkers for PI3K/AKT inhibitor efficacy in neuroblastoma. Cancer Res; 73(7); 2189–98. ©2013 AACR.
Autoimmune Gastritis Mediated by CD4+ T Cells Promotes the Development of Gastric Cancer
Authors: Nguyen Thanh-Long M. , Khurana Shradha S. , Bellone Clifford J. , Capoccia Benjamin J. , Sagartz John E. , Kesman Russell A. , Mills Jason C. , DiPaolo Richard J. 
Published: February 2013

AbstractChronic inflammation is a major risk factor for cancer, including gastric cancers and other gastrointestinal cancers. For example, chronic inflammation caused by autoimmune gastritis (AIG) is associated with an increased risk of gastric polyps, gastric carcinoid tumors, and possibly adenocarcinomas. In this study, we characterized the progression of gastric cancer in a novel mouse model of AIG. In this model, disease was caused by CD4+ T cells expressing a transgenic T-cell receptor specific for a peptide from the H+/K+ ATPase proton pump, a protein expressed by parietal cells in the stomach. AIG caused epithelial cell aberrations that mimicked most of those seen in progression of human gastric cancers, including chronic gastritis followed by oxyntic atrophy, mucous neck cell hyperplasia, spasmolytic polypeptide-expressing metaplasia, dysplasia, and ultimately gastric intraepithelial neoplasias. Our work provides the first direct evidence that AIG supports the development of gastric neoplasia and provides a useful model to study how inflammation drives gastric cancer. Cancer Res; 73(7); 2117–26. ©2013 AACR.