bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biochemical modulation of cell energy by 2-deoxyglucose and malonate in 7,12-dimethylbenz(a)anthracene-induced carcinogenesis in rats
Authors: Moselhy Said S , Kumosani TA , Al-Malki AL , Naif Almalki A 
Published: January 2013

The goal of this study was to explore the impact of 2-deoxglucose or malonate individually or in combination on the level of cell energy (adenosine-5′-triphosphate) and oxidative stress in 7,12-dimethylbenz( a)anthracene (DMBA)-induced mammary proliferation in rats. A total of 60 adult female Sprague Dawley rats were randomly divided into five groups (12 rats each): group I serves as the control group. Rats in groups (II–V) were administrated intragastrically a single dose of 50 mg/kg body weight (bw) of DMBA. A day after DMBA administration, rats in group III were injected intraperitoneally (ip) with 100 mg 2-deoxyglucose (2-DG)/kg bw daily. Rats in group IV were injected ip with 10 mg sodium malonate/kg bw daily. Rats in group V were injected ip with 100 mg 2-DG/kg bw and 10 mg sodium malonate/kg bw (treatment for 90 days). The results obtained showed that DMBA induced oxidative stress by decreasing the activities of glutathione reductase (GRase) and superoxide dismutase (SOD), glutathione peroxidase (GPx) and elevating the levels of malondialdehyde (MDA) and nitric oxide (NO) in mammary tissues when compared with control. The combined treatment protected against the previous deleterious changes by a significant elevation in the activities of GRase and SOD, GPx and lowering the levels of MDA and NO more potentially when compared with individual treatment. Apoptosis, as indicated by a significant release of cytochrome c from mitochondria into the cytosol, observed in DMBA-injected rats was positively significantly correlated with the elevation of the level of NO. These data explained the possible additive effect of 2-DG and malonate by depleting the cell energy by their protective effects against the earlier stages of carcinogenesis.
Medical undergraduates’ use of behaviour change talk: the example of facilitating weight management
Authors: Peters Sarah , Bird Louisa , Ashraf Hamaira , Ahmed Sehar , McNamee Philip , Ng Cassandra , Hart Jo 
Published: January 2013

Abstract

Background
Obesity, an increasing problem worldwide, is a leading cause of morbidity and mortality. Management principally requires lifestyle (i.e. behavioural) changes. An evidence-base exists of behaviour change techniques for weight loss; however, in routine practice doctors are often unsure about effective treatments and commonly use theoretically-unfounded communication strategies (e.g. information-giving). It is not known if communication skills teaching during undergraduate training adequately prepares future doctors to engage in effective behaviour change talk with patients. The aim of the study was to examine which behaviour change techniques medical undergraduates use to facilitate lifestyle adjustments in obese patients.

Methods
Forty-eight medical trainees in their clinical years of a UK medical school conducted two simulated consultations each. Both consultations involved an obese patient scenario where weight loss was indicated. Use of simulated patients (SPs) ensured standardisation of key variables (e.g. barriers to behaviour change). Presentation of scenario order was counterbalanced. Following each consultation, students assessed the techniques they perceived themselves to have used. SPs rated the extent to which they intended to make behavioural changes and why. Anonymised transcripts of the audiotaped consultations were coded by independent assessors, blind to student and SP ratings, using a validated behaviour change taxonomy.

Results
Students reported using a wide range of evidence-based techniques. In contrast, codings of observed communication behaviours were limited. SPs behavioural intention varied and a range of helpful elements of student’s communication were revealed.

Conclusions
Current skills-based communication programmes do not adequately prepare future doctors for the growing task of facilitating weight management. Students are able to generalise some communication skills to these encounters, but are over confident and have limited ability to use evidence-based theoretically informed techniques. They recognise this as a learning need. Educators will need to tackle the challenges of integrating theoretically informed and evidence based behaviour change talk within medical training.
Induction without methanol: novel regulated promoters enable high-level expression in Pichia pastoris
Authors: Prielhofer Roland , Maurer Michael , Klein Joachim , Wenger Jana , Kiziak Christoph , Gasser Brigitte , Mattanovich Diethard 
Published: January 2013

Abstract

Background
Inducible high-level expression is favoured for recombinant protein production in Pichia pastoris. Therefore, novel regulated promoters are desired, ideally repressing heterologous gene expression during initial growth and enabling it in the production phase. In a typical large scale fed-batch culture repression is desired during the batch phase where cells grow on a surplus of e.g. glycerol, while heterologous gene expression should be active in the feed phase under carbon (e.g. glucose) limitation.

Results
DNA microarray analysis of P. pastoris wild type cells growing in glycerol-based batch and glucose-based fed batch was used for the identification of genes with both, strong repression on glycerol and high-level expression in the feed phase. Six novel glucose-limit inducible promoters were successfully applied to express the intracellular reporter eGFP. The highest expression levels together with strong repression in pre-culture were achieved with the novel promoters PG1 and PG6.
Human serum albumin (HSA) was used to characterize the promoters with an industrially relevant secreted protein. A PG1 clone with two gene copies reached about 230% of the biomass specific HSA titer in glucose-based fed batch fermentation compared to a PGAP clone with identical gene copy number, while PG6 only achieved 39%. Two clones each carrying eleven gene copies, expressing HSA under control of PG1 and PG6 respectively were generated by post-transformational vector amplification. They produced about 1.0 and 0.7 g L-1 HSA respectively in equal fed batch processes. The suitability in production processes was also verified with HyHEL antibody Fab fragment for PG1 and with porcine carboxypeptidase B for PG6. Moreover, the molecular function of the gene under the control of PG1 was determined to encode a high-affinity glucose transporter and named GTH1.

Conclusions
A set of novel regulated promoters, enabling induction without methanol, was successfully identified by using DNA microarrays and shown to be suitable for high level expression of recombinant proteins in glucose-based protein production processes.
Repressible promoters – A novel tool to generate conditional mutants in Pichia pastoris
Authors: Delic Marizela , Mattanovich Diethard , Gasser Brigitte 
Published: January 2013

Abstract

Background
Repressible promoters are a useful tool for down-regulating the expression of genes, especially those that affect cell viability, in order to study cell physiology. They are also popular in biotechnological processes, like heterologous protein production.

Results
Here we present five novel repressible Pichia pastoris promoters of different strength: P
SER1
, P
MET3
, P
THR1
, P
PIS1
and P
THI11
. eGFP was expressed under the control of each of these promoters and its fluorescence could be successfully decreased in liquid culture by adding different supplements. We also expressed the essential genes with different native promoter strength, ERO1 and PDI1, under the control of two of the novel promoters. In our experiments, a clear down-regulation of both repressible promoters on transcriptional level could be achieved. Compared to the transcript levels of these two genes when expressed under the control of their native promoters, only ERO1 was significantly down-regulated.

Conclusion
Our results show that all of the novel promoters can be used for repression of genes in liquid culture. We also came to the conclusion that the choice of the repressible promoter is of particular importance. For a successful repression experiment it is crucial that the native promoter of a gene and the repressible promoter in its non-repressed state are of similar strength.
Cerebral inflammation and mobilization of the peripheral immune system following global hypoxia-ischemia in preterm sheep
Authors: Jellema Reint K , Lima Passos Valéria , Zwanenburg Alex , Ophelders Daan RMG , De Munter Stephanie , Vanderlocht Joris , Germeraad Wilfred TV , Kuypers Elke , Collins Jennifer JP , Cleutjens Jack PM , Jennekens Ward , Gavilanes Antonio WD , Seehase Matthias , Vles Hans J , Steinbusch Harry , Andriessen Peter , Wolfs Tim GAM , Kramer Boris W 
Published: January 2013

Abstract

Background
Hypoxic-ischemic encephalopathy (HIE) is one of the most important causes of brain injury in preterm infants. Preterm HIE is predominantly caused by global hypoxia-ischemia (HI). In contrast, focal ischemia is most common in the adult brain and known to result in cerebral inflammation and activation of the peripheral immune system. These inflammatory responses are considered to play an important role in the adverse outcomes following brain ischemia. In this study, we hypothesize that cerebral and peripheral immune activation is also involved in preterm brain injury after global HI.

Methods
Preterm instrumented fetal sheep were exposed to 25 minutes of umbilical cord occlusion (UCO) (n = 8) at 0.7 gestation. Sham-treated animals (n = 8) were used as a control group. Brain sections were stained for ionized calcium binding adaptor molecule 1 (IBA-1) to investigate microglial proliferation and activation. The peripheral immune system was studied by assessment of circulating white blood cell counts, cellular changes of the spleen and influx of peripheral immune cells (MPO-positive neutrophils) into the brain. Pre-oligodendrocytes (preOLs) and myelin basic protein (MBP) were detected to determine white matter injury. Electro-encephalography (EEG) was recorded to assess functional impairment by interburst interval (IBI) length analysis.

Results
Global HI resulted in profound activation and proliferation of microglia in the hippocampus, periventricular and subcortical white matter. In addition, non-preferential mobilization of white blood cells into the circulation was observed within 1 day after global HI and a significant influx of neutrophils into the brain was detected 7 days after the global HI insult. Furthermore, global HI resulted in marked involution of the spleen, which could not be explained by increased splenic apoptosis. In concordance with cerebral inflammation, global HI induced severe brain atrophy, region-specific preOL vulnerability, hypomyelination and persistent suppressed brain function.

Conclusions
Our data provided evidence that global HI in preterm ovine fetuses resulted in profound cerebral inflammation and mobilization of the peripheral innate immune system. These inflammatory responses were paralleled by marked injury and functional loss of the preterm brain. Further understanding of the interplay between preterm brain inflammation and activation of the peripheral immune system following global HI will contribute to the development of future therapeutic interventions in preterm HIE.
The effect of flexor tenotomy on healing and prevention of neuropathic diabetic foot ulcers on the distal end of the toe
Authors: van Netten Jaap J , Bril Adriaan , van Baal Jeff G 
Published: January 2013

AbstractBackgroundFlexor tenotomy is a minimally invasive surgical alternative for the treatment of neuropathic diabetic foot ulcers on the distal end of the toe. The influence of infection on healing and time to heal after flexor tenotomy is unknown. Flexor tenotomy can also be used as a prophylactic treatment. The effectiveness as a prophylactic treatment has not been described before.MethodsA retrospective study was performed with the inclusion of all consecutive flexor tenotomies from one hospital between January 2005 and December 2011.ResultsFrom 38 ulcers, 35 healed (92%), with a mean time to heal of 22 ± 26 days. The longest duration for healing was found for infected ulcers that were penetrating to bone (35 days; p =. 042). Cases of prophylactic flexor tenotomies (n=9) did not result in any ulcer or other complications during follow‐up.ConclusionsThe results of this study suggest that flexor tenotomy may be beneficial for neuropathic diabetic foot ulcers on the distal end of the toe, with a high healing percentage and a short mean time to heal. Infected ulcers that penetrated to bone took a significantly longer time to heal. Prospective research, to confirm the results of this retrospective study, should be performed.
Peering into peer-review at GigaScience
Authors: Edmunds Scott C 
Published: January 2013

Abstract
Fostering and promoting more open and transparent science is one of the goals of GigaScience. One of the ways we have been doing this is by throwing light on the peer-review process and carrying out open peer-review as standard. In this editorial, we provide our rationale for undertaking this policy, give examples of our positive experiences to date, and encourage others to open up the normally opaque publication process.
The Shc family protein adaptor, Rai, acts as a negative regulator of Th17 and Th1 cell development
Authors: Savino Maria Teresa , Ulivieri Cristina , Emmi Giacomo , Prisco Domenico , De Falco Giulia , Ortensi Barbara , Beccastrini Enrico , Emmi Lorenzo , Pelicci Giuliana , DˈElios Mario M , Baldari Cosima T 
Published: January 2013

Abstract
Rai prevents lupus nephritis by impairing the development and expansion of both proinflammatory Th17 and Th1 cells.
Rai, a Shc adapter family member, acts as a negative regulator of antigen receptor signaling in T and B cells. Rai−/− mice develop lupus-like autoimmunity associated to the spontaneous activation of self-reactive lymphocytes. Here, we have addressed the potential role of Rai in the development of the proinflammatory Th1 and Th17 subsets, which are centrally implicated in the pathogenesis of a number of autoimmune diseases, including lupus. We show that Rai−/− mice display a spontaneous Th1/Th17 bias. In vitro polarization experiments on naive and effector/memory CD4+ T cells demonstrate that Rai−/− favors the development and expansion of Th17 but not Th1 cells, indicating that Rai modulates TCR signaling to antagonize the pathways driving naive CD4+ T cell differentiation to the Th17 lineage, while indirectly limiting Th1 cell development in vivo. Th1 and Th17 cell infiltrates were found in the kidneys of Rai−/− mice, providing evidence that Rai−/− contributes to the development of lupus nephritis, not only by enhancing lymphocyte activation but also by promoting the development and expansion of proinflammatory effector T cells. Interestingly, T cells from SLE patients were found to have a defect in Rai expression, suggesting a role for Rai in disease pathogenesis.
Increased Serum and Urinary MicroRNAs in Children with Idiopathic Nephrotic Syndrome
Authors: Luo Yang , Wang Cheng , Chen Xi , Zhong Tianying , Cai Xiaoyi , Chen Sidi , Shi Yonghui , Hu Jing , Guan Xiaocui , Xia Zhengkun , Wang Junjun , Zen Ke , Zhang Chen-Yu , Zhang Chunni 
Published: January 2013

BACKGROUNDMicroRNAs (miRNAs) are present in body fluids and may have the potential to serve as disease biomarkers. This study explored the clinical value of miRNAs in serum and urine as biomarkers for idiopathic childhood nephrotic syndrome (NS).METHODSWe obtained serum samples from 159 NS children (24 steroid resistant and 135 steroid sensitive), 109 age/sex-matched healthy controls and 44 children with other kidney diseases. Serum miRNAs were analyzed with the TaqMan Low Density Array and then validated with a quantitative reverse-transcription PCR assay with 126 individual samples. Moreover, we collected paired serum samples from 50 patients before and after treatment to determine the value of these miRNAs for condition assessment. In addition, urine samples from these patients were examined for candidate miRNAs.RESULTSThe concentrations of serum miR-30a-5p, miR-151-3p, miR-150, miR-191, and miR-19b were highly increased in NS children compared with controls (P &lt; 0.0001). The urinary miR-30a-5p concentration was also increased in NS (P = 0.001). The area under the ROC curve and the odds ratio for the combined 5 serum miRNAs were 0.90 (95% CI, 0.86–0.94; P &lt; 0.0001) and 40.7 (95% CI, 6.06–103; P &lt; 0.0001), respectively. Moreover, the concentrations of the 5 serum miRNAs and urinary miR-30a-5p markedly declined with the clinical improvement of the patients.CONCLUSIONSWe determined that 5 distinct serum miRNAs and urinary miR-30a-5p were increased in NS children. These circulating or urinary miRNAs may represent potential diagnostic and prognostic biomarkers for idiopathic pediatric NS.
Crystal structure of 1-(7-methoxy-1-methyl-9H-pyrido[3,4-b]indol-9-yl) ethanone monohydrate, C15H14N2O2·H2O, C15H16N2O3
Authors: Du Hong-Tao , Ma Fang , Zhang Ge-Chao , Liu Bing-Rui , Wang Jun-Ru 
Published: January 2013

Abstract C15H16N2O3, tetragonal, I41/a (no. 88), a = 14.646(2) Å, c = 26.028(2) Å, V = 5583.4 Å3, Z = 16, Rgt(F) = 0.0497, wRref(F2) = 0.1680, T = 298 K.
Frequency Selective Surfaces Enable Mems Gas Sensor
Authors: Puscasu Irina , Pralle Martin U. , McNeal Mark P. , Moelders Nicholas , Last Lisa , Ho William , Greenwald Anton C. , Daly James T. , Johnson Edward A. , El-Kady Ihab , Biswas Rana 
Published: January 2013

AbstractWe have developed a thermally stimulated narrow-band infrared source for sensing, spectroscopy and thermophotovoltaic applications by combining the unique advantages of two different structures: a photonic crystal that consists of an array of holes etched into a dielectric substrate and a periodically perforated metallic thin film. The dielectric photonic crystal structure is passive and exhibits a strong absorption at resonance. This acts as a radiation reservoir for the conductive array, which plays an active role through plasmon interactions and is opaque at all wavelengths except those at which coupling occurs. We have fabricated the arrays on silicon, silicon dioxide and silicon nitride substrates using MEMS-based processing methods. Infrared spectroscopic studies were used to characterize reflection, absorption and emission in the 2 to 14 micron range showing narrow band resonance. Spectral tuning was accomplished by controlling symmetry and lattice spacing of the arrays. The effects of the etch depth, metal and dielectric properties have been studied experimentally and theoretically. These structures have been used as an emitter/detector sensor chip to selectively detect industrial pollutants like carbon dioxide.
Treatment of Splenic Marginal Zone Lymphoma With Rituximab Monotherapy: Progress Report and Comparison With Splenectomy
Authors: Kalpadakis Christina , Pangalis Gerassimos A. , Angelopoulou Maria K. , Sachanas Sotirios , Kontopidou Flora N. , Yiakoumis Xanthi , Kokoris Stella I. , Dimitriadou Evagelia M. , Dimopoulou Maria N. , Moschogiannis Maria , Korkolopoulou Penelope , Kyrtsonis Marie-Christine , Siakantaris Marina P. , Papadaki Theodora , Tsaftaridis Panayiotis , Plata Eleni , Papadaki Helen E. , Vassilakopoulos Theodoros P. 
Published: January 2013

Abstract

Background.
Treatment of splenic marginal zone lymphoma (SMZL) patients is not standardized. Recent data suggest that rituximab is highly effective and could be considered as initial therapy.

Aim.
To assess the efficacy of rituximab monotherapy in a large series of patients with SMZL and compare these results with splenectomy results.

Methods.
The studied population included 85 patients. Fifty-eight received rituximab at a dose of 375 mg/m2 per week for 6 weeks as induction followed by maintenance at the same dose every 2 months for 1–2 years, whereas 27 patients were treated using splenectomy only.

Results.
The overall response rate to rituximab 2 months after the end of induction was 95% (complete response [CR], 45%; unconfirmed CR, 26%; partial response, 24%). The median times to hematologic and clinical response were 2 weeks and 3 weeks, respectively. Forty-three of 55 patients already completed the maintenance phase: 28 sustained their initial response, 14 improved their response, and one progressed. Eighty-five percent of splenectomized patients responded, and two were treated with rituximab as consolidation after splenectomy and achieved a CR. The 5-year overall and progression-free survival (PFS) rates for rituximab-treated and splenectomized patients were 92% and 77% (p = .09) and 73% and 58% (p = .06), respectively. Furthermore, maintenance therapy with rituximab resulted in a longer duration of response (at 5 years, PFS was 84% for patients receiving maintenance and 36% for patients without maintenance, p &lt;.0001).

Conclusions.
Rituximab is a very effective and well-tolerated therapy and may be substituted for splenectomy as the first-line treatment of choice for patients with SMZL.
Cancer Risk for Patients Using Thiazolidinediones for Type 2 Diabetes: A Meta-Analysis
Authors: Bosetti Cristina , Rosato Valentina , Buniato Danilo , Zambon Antonella , La Vecchia Carlo , Corrao Giovanni 
Published: January 2013

Abstract

Learning Objectives
Evaluate the risk of cancer as well as cardiovascular and renal disease in the use of oral antidiabetics. Define and adequately quantify the effect of TZD on the risk of bladder cancer, other selected cancers, and all neoplasms.

Objective.
To clarify and quantify the effect of thiazolidinediones (TZDs; e.g., pioglitazone, rosiglitazone) on the risk of bladder cancer, other selected cancers, and overall cancer in patients with type 2 diabetes, we performed a systematic review and meta-analysis of observational studies.

Methods.
A PubMed/MEDLINE search was conducted for studies published in English up to June 30, 2012. Random-effect models were fitted to estimate summary relative risks (RR).

Results.
Seventeen studies satisfying inclusion criteria (3 case-control studies and 14 cohort studies) were considered. Use of TZDs was not associated to the risk of cancer overall (summary RR: 0.96; 95% confidence interval [CI]: 0.91–1.01). A modest excess risk of bladder cancer was reported in pioglitazone (RR: 1.20; 95% CI: 1.07–1.34 from six studies) but not in rosiglitazone (RR: 1.08; 95% CI: 0.95–1.23 from three studies) users. The RRs of bladder cancer were higher for longer duration (RR: 1.42 for &gt;2 years) and higher cumulative dose of pioglitazone (RR: 1.64 for &gt;28,000 mg). Inverse relations were observed with colorectal cancer (RR: 0.93; 95% CI: 0.90–0.97 from six cohort studies) and liver cancer (RR: 0.65; 95% CI: 0.48–0.89 from four studies), whereas there was no association with pancreatic, lung, breast, and prostate cancers.

Conclusions.
Adequate evidence excludes an overall excess cancer risk in TZD users within a few years after starting treatment. However, there is a modest excess risk of bladder cancer, particularly with reference to pioglitazone. Assuming that this association is real, the potential implications on the risk-benefit analysis of TZD use should be evaluated.