bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of mammography in the triple assessment of single-quadrant breast symptoms
Authors: Donnelly J , Iqbal M , Devaraj S , Marriott P J , Corder A P 
Published: April 2011

Abstract

Background
Most women over the age of 35 years referred to a breast clinic have single-quadrant symptoms and undergo mammography (MMG) as part of the triple assessment of these. A proportion of these women has no abnormality clinically or on ultrasonography (P1 U1). The aim of this study was to assess the additional contribution of MMG in diagnosing cancer in patients with P1 U1 findings and to consider whether it is safe to be more selective when requesting MMG.

Methods
Over a 2-year interval the clinical and radiological details of women whose single-quadrant breast symptoms were assessed as P1 U1, and who were then sent for MMG, were entered into a database. The results of further investigations initiated by a non-benign MMG report were recorded, and the patients reviewed to establish how many cancers were diagnosed purely by MMG and whether these were located at the site of symptoms.

Results
There were 454 women in the study group, representing 17·5 per cent of all new referrals. Twenty-one patients (4·6 per cent) were recalled following a non-benign MMG result, ten of whom required image-guided biopsy. Cancer was diagnosed in three patients (0·7 per cent of the study group), located in the contralateral breast in two women and a different ipsilateral quadrant in one.

Conclusion
MMG in this subset of patients did not increase the cancer detection rate at the site of symptoms and therefore constituted screening. The rationale for requesting MMG in these patients, and indeed for applying the triple assessment rule, should be reconsidered.
Clinical and cellular effects of hypothermia, acidosis and coagulopathy in major injury
Authors: Thorsen K , Ringdal K G , Strand K , Søreide E , Hagemo J , Søreide K 
Published: April 2011

Abstract

Background
Hypothermia, acidosis and coagulopathy have long been considered critical combinations after severe injury. The aim of this review was to give a clinical update on this triad in severely injured patients.

Methods
A non-systematic literature search on hypothermia, acidosis and coagulopathy after major injury was undertaken, with a focus on clinical data from the past 5 years.

Results
Hypothermia (less than 35 °C) is reported in 1·6–13·3 per cent of injured patients. The occurrence of acidosis is difficult to estimate, but usually follows other physiological disturbances. Trauma-induced coagulopathy (TIC) has both endogenous and exogenous components. Endogenous acute traumatic coagulopathy is associated with shock and hypoperfusion. Exogenous effects of dilution from fluid resuscitation and consumption through bleeding and loss of coagulation factors further add to TIC. TIC is present in 10–34 per cent of injured patients, depending on injury severity, acidosis, hypothermia and hypoperfusion. More expedient detection of coagulopathy is needed. Thromboelastography may be a useful point-of-care measurement. Management of TIC is controversial, with conflicting reports on blood component therapy in terms of both outcome and ratios of blood products to other fluids, particularly in the context of civilian trauma.

Conclusion
The triad of hypothermia, acidosis and coagulopathy after severe trauma appears to be fairly rare but does carry a poor prognosis. Future research should define modes of early detection and targeted therapy.
Synthesis, biophysical properties, and oxygenation potential of variable molecular weight glutaraldehyde‐polymerized bovine hemoglobins with low and high oxygen affinity
Authors: Zhou Yipin , Jia Yiping , Buehler Paul W. , Chen Guo , Cabrales Pedro , Palmer Andre F. 
Published: April 2011

AbstractIn a recent study, ultrahigh molecular weight (Mw) glutaraldehyde‐polymerized bovine hemoglobins (PolybHbs) were synthesized with low O2 affinity and exhibited no vasoactivity and a slight degree of hypertension in a 10% top‐load model.1 In this work, we systematically investigated the effect of varying the glutaraldehyde to hemoglobin (G:Hb) molar ratio on the biophysical properties of PolybHb polymerized in either the low or high O2 affinity state. Our results showed that the Mw of the resulting PolybHbs increased with increasing G:Hb molar ratio. For low O2 affinity PolybHbs, increasing the G:Hb molar ratio reduced the O2 affinity and CO association rate constants in comparison to bovine hemoglobin (bHb). In contrast for high O2 affinity PolybHbs, increasing the G:Hb molar ratio led to increased O2 affinity and significantly increased the CO association rate constants compared to unmodified bHb and low O2 affinity PolybHbs. The methemoglobin level and NO dioxygenation rate constants were insensitive to the G:Hb molar ratio. However, all PolybHbs displayed higher viscosities compared to unmodified bHb and whole blood, which also increased with increasing G:Hb molar ratio. In contrast, the colloid osmotic pressure of PolybHbs decreased with increasing G:Hb molar ratio. To preliminarily evaluate the ability of low and high O2 affinity PolybHbs to potentially oxygenate tissues in vivo, an O2 transport model was used to simulate O2 transport in a hepatic hollow fiber (HF) bioreactor. It was observed that low O2 affinity PolybHbs oxygenated the bioreactor better than high O2 affinity PolybHbs. This result points to the suitability of low O2 affinity PolybHbs for use in tissue engineering and transfusion medicine. Taken together, our results show the quantitative effect of varying the oxygen saturation of bHb and G:Hb molar ratio on the biophysical properties of PolybHbs and their ability to oxygenate a hepatic HF bioreactor. We suggest that the information gained from this study can be used to guide the design of the next generation of hemoglobin‐based oxygen carriers (HBOCs) for use in tissue engineering and transfusion medicine applications. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Automated live cell imaging systems reveal dynamic cell behavior
Authors: Chirieleison Steven M. , Bissell Taylor A. , Scelfo Christopher C. , Anderson Jordan E. , Li Yong , Koebler Doug J. , Deasy Bridget M. 
Published: April 2011

AbstractAutomated time‐lapsed microscopy provides unique research opportunities to visualize cells and subcellular components in experiments with time‐dependent parameters. As accessibility to these systems is increasing, we review here their use in cell science with a focus on stem cell research. Although the use of time‐lapsed imaging to answer biological questions dates back nearly 150 years, only recently have the use of an environmentally controlled chamber and robotic stage controllers allowed for high‐throughput continuous imaging over long periods at the cell and subcellular levels. Numerous automated imaging systems are now available from both companies that specialize in live cell imaging and from major microscope manufacturers. We discuss the key components of robots used for time‐lapsed live microscopic imaging, and the unique data that can be obtained from image analysis. We show how automated features enhance experimentation by providing examples of uniquely quantified proliferation and migration live cell imaging data. In addition to providing an efficient system that drastically reduces man‐hours and consumes fewer laboratory resources, this technology greatly enhances cell science by providing a unique dataset of temporal changes in cell activity. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Cell culture and gene transcription effects of copper sulfate on Chinese hamster ovary cells
Authors: Qian Yueming , Khattak Sarwat F. , Xing Zizhuo , He Aiqing , Kayne Paul S. , Qian Nan‐Xin , Pan Shih‐Hsie , Li Zheng Jian 
Published: April 2011

AbstractThis study reports the effects of varying concentrations of copper sulfate on the metabolic and gene transcriptional profile of a recombinant Chinese hamster ovary (CHO) cell line producing an immunoglobulin G (IgG)‐fusion protein (B0). Addition of 50 μM copper sulfate significantly decreased lactate accumulation in the cultures while increasing viable cell density and protein titer. These changes could be seen from day 6 and became increasingly evident with culture duration. Reducing the copper sulfate concentration to 5 μM retained all the above beneficial effects, but with the added benefit of reduced levels of the aggregated form of the B0 protein. To profile the cellular changes due to copper sulfate addition at the transcriptional level, Affymetrix® CHO microarrays were used to identify differentially expressed genes related to reduced cellular stresses and facilitated cell cycling. Based on the microarray results, down‐regulation of the transferrin receptor and lactate dehydrogenase, and up‐regulation of a cytochrome P450 family‐2 polypeptide were then confirmed by Western blotting. These results showed that copper played a critical role in cell metabolism and productivity on recombinant CHO cells and highlighted the usefulness of microarray data for better understanding biological responses on medium modification. © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
A numerical simulation model to facilitate the understanding of the properties of a diffraction grating
Authors: Zurek Eduardo E. , Moreno Wilfrido A. , García‐Rubio Luis H. 
Published: April 2011

ABSTRACTThis paper introduces a new tool to approach the effects of a diffraction grating and its interaction with other optical and electronic components in a light wavelength analysis system. The model's theoretical background is described. This model is intended for educational purposes and it is referred to a miniaturized spectrophotometer. © 2011 Wiley Periodicals, Inc. Comput Appl Eng Educ 22:187–194, 2014; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.20544
Effect of pH on Hydride Transfer by Escherichia coli Dihydrofolate Reductase
Authors: Loveridge E. Joel , Allemann Rudolf K. 
Published: April 2011

AbstractThe kinetic isotope effect (KIE) on hydride transfer in the reaction catalysed by dihydrofolate reductase from Escherichia coli (EcDHFR) is known to be temperature dependent at pH 7, but essentially independent of temperature at elevated pH. Here, we show that the transition from the temperature‐dependent regime to the temperature‐independent regime occurs sharply between pH 7.5 and 8. The activation energy for hydride transfer is independent of pH. The mechanism leading to the change in behaviour of the KIEs is not clear, but probably involves a conformational change in the enzyme brought about by deprotonation of a key residue (or residues) at high pH. The KIE on hydride transfer at low pH suggests that the rate constant for the reaction is not limited by a conformational change to the enzyme under these conditions. The effect of pH on the temperature dependence of the rate constants and KIEs for hydride transfer catalysed by EcDHFR suggests that enzyme motions and conformational changes do not directly influence the chemistry, but that the reaction conditions affect the conformational ensemble of the enzyme prior to reaction and control the reaction though this route.
Mechanism‐Based Inhibition of Quinone Reductase 2 (NQO2): Selectivity for NQO2 over NQO1 and Structural Basis for Flavoprotein Inhibition
Authors: Dufour Marine , Yan Chao , Siegel David , Colucci Marie A. , Jenner Matthew , Oldham Neil J. , Gomez Joe , Reigan Philip , Li Yazhuo , De Matteis Cristina I. , Ross David , Moody Christopher J. 
Published: April 2011

AbstractA role for the flavoprotein NRH:quinone oxidoreductase 2 (NQO2, QR2) in human diseases such as malaria, leukemia and neurodegeneration has been proposed. In order to explore the potential of NQO2 as a therapeutic target, we have developed potent and selective mechanism‐based inhibitors centered on the indolequinone pharmacophore. The compounds show remarkable selectivity for NQO2 over the closely related flavoprotein NQO1, with small structural changes defining selectivity. Biochemical studies confirmed the mechanism‐based inhibition, whereas X‐ray crystallography and mass spectrometry revealed the nature of the inhibitor interaction with the protein. These indolequinones represent the first mechanism‐based inhibitors of NQO2, and their novel mode of action involving alkylation of the flavin cofactor, provides significant advantages over existing competitive inhibitors in terms of potency and irreversibility, and will open new opportunities to define the role of NQO2 in disease.
Diverse Clinical Compounds Alter the Quaternary Structure and Inhibit the Activity of an Essential Enzyme
Authors: Lawrence Sarah H. , Selwood Trevor , Jaffe Eileen K. 
Published: April 2011

AbstractAn in vitro evaluation of the Johns Hopkins Clinical Compound Library demonstrates that certain drugs can alter the quaternary structure of an essential human protein. Human porphobilinogen synthase (HsPBGS) is an essential enzyme involved in heme biosynthesis; it exists as an equilibrium of high‐activity octamers, low‐activity hexamers, and alternate dimer configurations that dictate the stoichiometry and architecture of further assembly. Decreased HsPBGS activity is implicated in toxicities associated with lead poisoning and 5‐aminolevulinate dehydratase (ALAD) porphyria, the latter of which involves hexamer‐favoring HsPBGS variants. A medium‐throughput native PAGE mobility‐shift screen coupled with evaluation of hits as HsPBGS inhibitors revealed 12 drugs that stabilize the HsPBGS hexamer and inhibit HsPBGS activity in vitro. A detailed characterization of these effects is presented. Drug inhibition of HsPBGS in vivo by inducing hexamer formation would constitute an unprecedented mechanism for side effects. We suggest that small‐molecule perturbation of quaternary structure equilibria be considered as a general mechanism for drug action and side effects.
Design and Stereoselective Synthesis of Retinoids with Ferrocene or N‐Butylcarbazole Pharmacophores that Induce Post‐Differentiation Apoptosis in Acute Promyelocytic Leukemia Cells
Authors: Ivanova Diana , Gronemeyer Hinrich , de Lera Angel R. 
Published: April 2011

AbstractNew ferrocene and N‐alkylcarbazole retinoids were designed and synthesized stereoselectively in good yields. A number of these synthesized ligands, in particular 2, 3, and 11, were found to exhibit a high RARα activation potential and to effectively induce post‐differentiation apoptosis in NB4 acute promyelocytic leukemia (APL) cells. Increasing the length of the side chain attached to the heterocycle of the carbazole arotinoids creates new opportunities for altered compound catabolism and for fine‐tuning of the apoptosis‐inducing potential of the ligand. In the carbazole series of new retinoids, maximal activity was established for N‐butylcarbazole analogue 11 in all assays (i.e., RARα activation, differentiation induction, and apoptosis induction). Study of the mechanism of apoptosis revealed an activation of initiator caspases‐8 and ‐9, followed by efficient cleavage of effector caspase‐3 on day 6 of treatment. Subsequent induction of a caspase cascade in NB4 cells triggered ultimate leukemic cell death. The selected ligands 2, 3, and 11 may provide alternate options for the treatment of APL in cases of life‐threatening ATRA syndrome, resistance, and high toxicity to conventionally used retinoids.
From critical values to critical diagnoses
Authors: Chapman Christopher N. , Otis Christopher N. 
Published: April 2011

AbstractThe concept of critical values in the medical laboratory found its roots in clinical pathology nearly 40 years ago. The goal of this review was to trace the evolution of the critical value concept from clinical into anatomic pathology with specific emphasis on cytopathology. Difficulties in the meaningful application of the critical value concept in the practice of cytopathology are reviewed along with ambiguities that have yet to be fully resolved. Suggestions that may enhance the operational success of critical value policies in cytopathology and a central role for the cytotechnologist are presented. Cooperation between key pathology and clinical organizations is essential for improvement in the critical value process. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.
The Reaction Microscope: Imaging and Pulse Shaping Control in Photodynamics
Authors: Vredenborg Arno , Lehmann C. Stefan , Irimia Daniel , Roeterdink Wim G. , Janssen Maurice H. M. 
Published: April 2011

AbstractHerein, we review the current capabilities and potential of advanced single‐particle imaging techniques to study photodynamics in isolated molecules. These reaction microscopes are able to measure the full three‐dimensional energy and angular distribution of (correlated) particles such as electrons and molecular fragments ejected after photoexcitation of molecules. In particular, we discuss the performance and capabilities of a novel photoelectron–photoion coincidence imaging spectrometer constructed at LaserLaB Amsterdam. This microscope was developed for the study of nonadiabatic effects in ultrafast time‐resolved experiments. It is specifically targeted at optimal control studies of photodynamics to foster and advance our understanding of mechanisms in optimal control with shaped ultrafast laser pulses. We review a few recent experimental results illustrating the wealth of detailed information that can be obtained in such imaging experiments about the interplay between (shaped) laser fields, molecular dynamics, ionization processes and competing multichannel pathways. Furthermore, the recently developed photoelectron–circular‐dichroism imaging technique to detect enantiomers and to study chirality effects will be discussed, as a further illustration of the potential of modern reaction microscopes in stereochemistry.
Regulative patterning in limb bud transplants is induced by distalizing activity of apical ectodermal ridge signals on host limb cells
Authors: Roselló‐Díez Alberto , Torres Miguel 
Published: April 2011

AbstractWe have used the chick limb as a model to gain insight into the longstanding question of regulative vs. mosaic development. To test the influence of signals on limb proximodistal development, distal limb bud tips of several stages were grafted to regions of the embryo known to provide different signaling environments. Of interest, thin grafts (100‐micron thick) formed elements more proximal in character when grafted to the proximal limb region than when grafted to other regions. The extra elements were derived from host tissue, presumably distalized and recruited by the graft's apical ectodermal ridge signals. The results of classic and recent experiments have been reinterpreted in light of our conclusions. Developmental Dynamics 240:1203–1211, 2011. © 2011 Wiley‐Liss, Inc.
Cochrane Review: One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates
Authors: Rao Shripada C , Srinivasjois Ravisha , Hagan Ronald , Ahmed Mohmed 
Published: April 2011

AbstractBackgroundAnimal studies and trials in older children and adults suggest that a one dose per day regimen of gentamicin is superior to a multiple doses per day regimen.ObjectivesTo compare the efficacy and safety of one dose per day compared to multiple doses per day of gentamicin in suspected or proven sepsis in neonates.Search strategyEligible studies were identified by searching MEDLINE (February 2010), EMBASE 1980 to 2009, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2010) and CINAHL (December 1982 to October 2009). Abstracts of the Society for Pediatric Research were searched from 1980 to 2009 inclusive.Selection criteriaAll randomised or quasi randomised controlled trials comparing one dose per day ( 'once a day') compared to multiple doses per day ( 'multiple doses a day') of gentamicin to newborn infants < 28 days of life.Data collection and analysisData collection and analysis was performed according to the standards of the Cochrane Neonatal Review Group.Main resultsEighteen studies were excluded and eleven studies (N = 574) included.All infants in both 'once a day' as well as 'multiple doses a day' regimen showed adequate clearance of sepsis [typical RD 0.00 (95% CI ‐ 0.19, 0.19); 3 trials; N = 36]. For the other primary outcome measures relating to gentamicin pharmacokinetics 'once a day' dosing of gentamicin was superior. 'Once a day' gentamicin regimen was associated with less failures to attain peak level of at least 5 µg/ml [Typical RR 0.22 (95% CI 0.11, 0.47); 9 trials; N = 422] and less failures to achieve trough levels of ≤ 2 µg/ml [Typical RR 0.38 (95% CI 0.27, 0.55); 11 trials N = 503] compared to 'multiple doses a day' regimen.Ototoxicity and nephrotoxicity were not noted with either of the treatment regimens.Authors' conclusionsThere is insufficient evidence from the currently available RCTs to conclude whether 'once a day' or 'multiple doses a day' regimen of gentamicin is superior in treating proven neonatal sepsis. However data suggests that pharmacokinetic properties of 'once a day' gentamicin regimen are superior to 'multiple doses a day' regimen in that it achieves higher peak levels while avoiding toxic trough levels. There is no change in nephrotoxicity or auditory toxicity. Based on this assessment of pharmacokinetics, 'once a day regimen' may be superior in treating neonatal sepsis in neonates greater than 32 weeks gestation.Plain Language SummaryGentamicin dosage in neonatesGentamicin is a commonly used antibiotic that is very effective in treating bacterial infections in neonates. However, gentamicin may cause adverse effects on auditory and renal functions that may be related to the dosage, interval and in turn the drug levels in plasma. Safer and potentially more effective levels of the drug were maintained using a one dose per day treatment schedule.
Summary of ‘One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates’
Authors: Canadian Editorial Office Evidence‐Based Child Health 
Published: April 2011

AbstractThis is a summary of a Cochrane review, published in this issue of EBCH, first published as: Rao SC, Srinivasjois R, Hagan R, Ahmed M. One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates. Cochrane Database of Systematic Reviews 2006, Issue 1. Art.No.: CD005091. DOI: 10.1002/14 651 858.CD005091.pub2. Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
WHO Calls for Targeted Research on the Pharmacological Treatment of Persisting Pain in Children with Medical Illnesses
Authors: Milani Barbara , Magrini Nicola , Gray Andy , Wiffen Phil , Scholten Willem 
Published: April 2011

AbstractThe WHO has undertaken an update of the 1998 WHO Cancer Pain Relief and Palliative Care in Children Guidelines, in extending the scope to persisting pain associated with other medical conditions. The new WHO Guidelines for Pharmacological Treatment of Persisting Pain in Children with Medical Illnesses, using the GRADE approach for evidence synthesis and grading of recommendations, are expected to help reduce the enormous treatment gap for pain in children. The WHO aims to update these guidelines within the next five years. Given the paucity of studies in the paediatric population with persisting pain, a meaningful revision of these guidelines will need the international scientific community to invest in research on the topics that were identified as evidence gaps during the development process For this reason, the WHO calls for a collaborative effort to cover the identified priority research areas and related systematic reviews of evidence. Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration