bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncogenic PIK3CA mutations in lobular breast cancer progression
Authors: Christgen Matthias , Noskowicz Monika , Schipper Elisa , Christgen Henriette , Heil Charlotte , Krech Till , Länger Florian , Kreipe Hans , Lehmann Ulrich 
Published: September 2012

AbstractInfiltrating lobular breast cancer (ILBC) is a tumor‐biologically distinct breast cancer subtype. A high frequency of oncogenic PIK3CA mutations has been reported in ILBC, which may allow for targeted therapy with newly developed PI3K inhibitors. This is of particular clinical relevance for ILBC patients, who have failed to respond to current treatment regimes and suffer from tumor recurrence or dissemination. In anticipation of this therapeutic strategy, we investigated PIK3CA mutations in ILBC with special reference to late stage tumor progression. A total of 88 ILBCs from 73 patients, including primary tumors (PTs, n = 43), ipsilateral locally recurrent tumors (LRTs, n = 15), and distant organ metastases (DOMs, n = 30), were compiled on tissue microarrays. Established ILBC marker proteins were evaluated by immunohistochemistry and PIK3CA hot spot mutations in exons 9 and 20 by direct sequencing. Matched PT/LRT, PT/DOM, and DOM/DOM cases were characterized on a patient‐by‐patient basis. Following correction for redundant patient representations, mutation frequencies were compared in PTs versus LRTs or DOMs. Nearly all specimens were E‐cadherin‐negative (99%), estrogen receptor (ER)‐positive (91%), and lacked basal epithelial markers (100%), demonstrating correct ILBC classification. PIK3CA mutations were detected in 32/88 (36%) specimens. The mutation rate was similar in PTs (33%) and DOMs (26%, P = 0.769), but approximately two‐fold increased in LRTs (69%, P = 0.022). Consistently, matched PT/LRT and LRT/DOM cases showed additional PIK3CA mutations in LRTs. Intriguingly, these findings imply that PIK3CA mutations are positively selected for during ILBC progression to local recurrence but not distant metastasis, which may have clinical implications for PI3K inhibitor‐based therapy. © 2012 Wiley Periodicals, Inc.
Activation of KCNN3/SK3/KCa2.3 channels attenuates enhanced calcium influx and inflammatory cytokine production in activated microglia
Authors: Dolga Amalia M. , Letsche Till , Gold Maike , Doti Nunzianna , Bacher Michael , Chiamvimonvat Nipavan , Dodel Richard , Culmsee Carsten 
Published: September 2012

AbstractIn neurons, small‐conductance calcium‐activated potassium (KCNN/SK/KCa2) channels maintain calcium homeostasis after N‐methyl‐D‐aspartate (NMDA) receptor activation, thereby preventing excitotoxic neuronal death. So far, little is known about the function of KCNN/SK/KCa2 channels in non‐neuronal cells, such as microglial cells. In this study, we addressed the question whether KCNN/SK/KCa2 channels activation affected inflammatory responses of primary mouse microglial cells upon lipopolysaccharide (LPS) stimulation. We found that N‐cyclohexyl‐N‐[2‐(3,5‐dimethyl‐pyrazol‐1‐yl)‐6‐methyl‐4‐pyrimidinamine (CyPPA), a positive pharmacological activator of KCNN/SK/KCa2 channels, significantly reduced LPS‐stimulated activation of microglia in a concentration‐dependent manner. The general KCNN/SK/KCa2 channel blocker apamin reverted these effects of CyPPA on microglial proliferation. Since calcium plays a central role in microglial activation, we further addressed whether KCNN/SK/KCa2 channel activation affected the changes of intracellular calcium levels, [Ca2+]i,, in microglial cells. Our data show that LPS‐induced elevation of [Ca2+]i was attenuated following activation of KCNN2/3/KCa2.2/KCa2.3 channels by CyPPA. Furthermore, CyPPA reduced downstream events including tumor necrosis factor alpha and interleukin 6 cytokine production and nitric oxide release in activated microglia. Further, we applied specific peptide inhibitors of the KCNN/SK/KCa2 channel subtypes to identify which particular channel subtype mediated the observed anti‐inflammatory effects. Only inhibitory peptides targeting KCNN3/SK3/KCa2.3 channels, but not KCNN2/SK2/KCa2.2 channel inhibition, reversed the CyPPA‐effects on LPS‐induced microglial proliferation. These findings revealed that KCNN3/SK3/KCa2.3 channels can modulate the LPS‐induced inflammatory responses in microglial cells. Thus, KCNN3/SK3/KCa2.3 channels may serve as a therapeutic target for reducing microglial activity and related inflammatory responses in the central nervous system. © 2012 Wiley Periodicals, Inc.
Complex invasion pattern of the cerebral cortex bymicroglial cells during development of the mouse embryo
Authors: Swinnen Nina , Smolders Sophie , Avila Ariel , Notelaers Kristof , Paesen Rik , Ameloot Marcel , Brône Bert , Legendre Pascal , Rigo Jean‐Michel 
Published: September 2012

AbstractMicroglia are the immune cells of the central nervous system. They are suspected to play important roles in adult synaptogenesis and in the development of the neuronal network. Microglial cells originate from progenitors in the yolk sac. Although it was suggested that they invade the cortex at early developmental stages in the embryo, their invasion pattern remains largely unknown. To address this issue we analyzed the pattern of cortical invasion by microglial cells in mouse embryos at the onset of neuronal cell migration using in vivo immunohistochemistry and ex vivo time‐lapse analysis of microglial cells. Microglial cells begin to invade the cortex at 11.5 days of embryonic age (E11.5). They first accumulate at the pial surface and within the lateral ventricles, after which they spread throughout the cortical wall, avoiding the cortical plate region in later embryonic ages. The invasion of the cortical parenchyma occurs in different phases. First, there is a gradual increase of microglial cells between E10.5 and E14.5. From E14.5 to E15.5 there is a rapid phase with a massive increase in microglia, followed by a slow phase again from E15.5 until E17.5. At early stages, many peripheral microglia are actively proliferating before entering the parenchyma. Remarkably, activated microglia accumulate in the choroid plexus primordium, where they are in the proximity of dying cells. Time‐lapse analysis shows that embryonic microglia are highly dynamic cells. © 2012 Wiley Periodicals, Inc.
Hippocampal involvement in retrieval of odor vs. object memories
Authors: Lehn Hanne , Kjønigsen Lisa J. , Kjelvik Grete , Håberg Asta K. 
Published: September 2012

AbstractThe aim of this study was to investigate the role of the human hippocampus in episodic retrieval of odors, in comparison with episodic retrieval of visual objects. Subjects encoded a set of unique odors and objects, and retrieval was tested the next day during functional magnetic resonance imaging (fMRI). Subjects were shown the names of old (studied) and new (unstudied) odors and objects, and asked to indicate which of these stimuli had been presented the previous day. The results showed that brain activation was weaker and more restricted during retrieval of odors than during retrieval of objects, which possibly reflects a general visual dominance effect. Yet, retrieval of odors and objects yielded overlapping clusters of activation the bilateral hippocampi, and the left‐sided activation was specifically increased during successful retrieval (hits > correct rejections) in both modalities. Moreover, retrieval of odors uniquely activated olfactory cortical regions, likely to reflect cortical reinstatement of sensory details. Our fMRI study is the first to make a direct comparison between olfactory and visual episodic memory, and the results provide clear evidence for modality‐independent functions of the hippocampus. © 2012 Wiley Periodicals, Inc.
Introduction of a high‐throughput double‐stent animal model for the evaluation of biodegradable vascular stents
Authors: Borinski Mauricio , Flege Christian , Schreiber Fabian , Krott Nicole , Gries Thomas , Liehn Elisa , Blindt Rüdiger , Marx Nikolaus , Vogt Felix 
Published: September 2012

AbstractCurrent stent system efficacy for the treatment of coronary artery disease is hampered by in‐stent restenosis (ISR) rates of up to 20% in certain high‐risk settings and by the risk of stent thrombosis, which is characterized by a high mortality rate. In theory, biodegradable vascular devices exhibit crucial advantages. Most absorbable implant materials are based on poly‐L‐lactic acid (PLLA) owing to its mechanical properties; however, PLLA might induce an inflammatory reaction in the vessel wall. Evaluation of biodegradable implant efficacy includes a long‐term examination of tissue response; therefore, a simplein vivotool for thorough biocompatibility and biodegradation evaluation would facilitate future stent system development. Rats have been used for the study ofin vivodegradation processes, and stent implantation into the abdominal aorta of rats is a proven model for stent evaluation. Here, we report the transformation of the porcine double‐stent animal model into the high‐throughput rat abdominal aorta model. As genetic manipulation of rats was introduced recently, this novel method presents a powerful tool for futurein vivobiodegradable candidate stent biocompatibility and biodegradation characterization in a reliable simple model of coronary ISR. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
Mathematical modeling of cross‐linking monomer elution from resin‐based dental composites
Authors: Manojlovic Dragica , Radisic Marina , Lausevic Mila , Zivkovic Slavoljub , Miletic Vesna 
Published: September 2012

AbstractElution of potentially toxic substances, including monomers, from resin‐based dental composites may affect the biocompatibility of these materials in clinical conditions. In addition to the amounts of eluted monomers, mathematical modeling of elution kinetics reveals composite restorations as potential chronic sources of leachable monomers. The aim of this work was to experimentally quantify elution of main cross‐linking monomers from four commercial composites and offer a mathematical model of elution kinetics. Composite samples (n = 7 per group) of Filtek Supreme XT (3M ESPE), Tetric EvoCeram (Ivoclar Vivadent), Admira (Voco), and Filtek Z250 (3M ESPE) were prepared in 2‐mm thick Teflon moulds and cured with halogen or light‐emitting diode light. Monomer elution in ethanol and water was analyzed using high‐performance liquid chromatography up to 28 days postimmersion. The mathematical model was expressed as a sum of two exponential regression functions representing the first‐order kinetics law. Elution kinetics in all cases followed the same mathematical model though differences in rate constants as well as the extent of monomer elution were material‐, LCU‐, medium‐dependent. The proposed mechanisms of elution indicate fast elution from surface and subsurface layers and up to 100 times slower monomer extraction from the bulk polymer. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 101B: 61–67, 2013.
Physical plugging does not account for attenuation of capillary leakage by hydroxyethyl starch 130/0.4: A synthetic gel layer model
Authors: Tatara Tsuneo , Itani Motoi , Sugi Takashi , Fujita Kimihiko 
Published: September 2012

AbstractHydroxyethyl starch (HES) solutions, widely used plasma substitutes, reportedly attenuate capillary leakage via physical plugging of capillary defects. We investigated how 2% HES solutions of different molecular weights (HES70: 70 kDa, HES130: 130 kDa, HES200: 200 kDa, and HES670: 670 kDa) affect dye release from polyacrylamide gels (PAGs) as a model of endothelial glycocalyx. We assessed dye release from 4% PAG with varying concentrations of albumin [0, 1, 2, 4, and 8% (w/v)] by measuring the change in dye absorbance (ΔAbs) at 5 h for each HES solution. For PAG containing no albumin, ΔAbs for HES130 was 30% lower than that for HES70 and HES200, and 50% lower than that for HES670. At concentrations of 1–8% albumin, ΔAbs at 5 h with HES70, HES130, and HES200 solutions were almost half that with the HES670 solution, but no significant differences were noted in ΔAbs at 5 h among HES70, HES130, and HES200 solutions. The inhibition of dye release by HES670 is likely due to the hindering effect of HES molecules partitioned into gel pores. However, a unique property of HES130, including the heavy hydroxyethylation at the C2 position, may promote specific interactions with PAG and thereby inhibit solute release. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 101B: 85–90, 2013.
Preliminary investigation of crosslinked chitosan sponges for tailorable drug delivery and infection control
Authors: Parker Ashley C. , Jennings Jessica A. , Bumgardner Joel D. , Courtney Harry S. , Lindner Ernö , Haggard Warren O. 
Published: September 2012

AbstractLocal versus systemic antibiotic delivery may be an effective strategy for treating musculoskeletal infections, especially when antibiotic‐resistant bacteria are present. Lyophilized uncrosslinked, genipin crosslinked, and genipin crosslinked with poly(N‐isopropylacrylamide) (PNIPAM) chitosan sponges were analyzed for theirin vitrodegradation rate, chemical crosslinking, antibiotic uptake, elution, biologic activity, and cytotoxicity. These evaluations were pursued to determine if crosslinking with genipin could be used to create a tailorable point of care loaded sponge for local infection control. Crosslinking the chitosan sponges decreased degradation in phosphate‐buffered saline from 4.48 ± 2.28 wt % remaining of the uncrosslinked sponges to 78.82 ± 1.15 and 73.87 ± 1.27 wt % remaining at week 1 for the genipin and PNIPAM/genipin crosslinked sponges, respectively. The PNIPAM/genipin crosslinked sponges exhibited the most sustained release of biologically active antibiotics, with an average antibiotic release 63% higher than uncrosslinked and 37% higher than genipin crosslinked sponges, after 96 h. No significant cytotoxic effects from sponges or eluates were exhibited with NIH 3T3 fibroblasts. These preliminary results indicate that genipin crosslinked chitosan sponges, with or without PNIPAM, have potential as local delivery systems for adjunctive therapy for infection control, especially when longer degradation periods and higher antibiotic elutions are desired. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 101B: 110–123, 2013.
Alterations of Dendritic Cell Subsets and Th1/Th2 Cytokines in the Peripheral Circulation of Patients With Superficial Transitional Cell Carcinoma of the Bladder
Authors: Lang Feng , Linlin Ma , Ye Tian , Yuhai Zhang 
Published: September 2012

BackgroundDendritic cells (DCs) and cytokines play an important role in the tumor growth and recurrence.MethodsSixty‐six patients with superficial transitional cell carcinoma of the bladder (STCCB) and 38 healthy controls were studied to investigate the percentages of DC subsets, monocyte‐derived DC (MoDC) function, and alterations of Th1 and Th2 cytokines. MoDCs were generated and three‐color flow cytometry was used for determining the phenotype of MoDCs and DC subsets. The ability to stimulate autologous T cells was tested in mixed leukocyte reaction (MLR). The levels of various cytokines were measured using commercially available sandwich enzyme linked immunosorbent assay (ELISA) kit.ResultsThe myeloid DC (mDC) counts, MoDC surface molecular expression, and stimulatory capacity to T cells were impaired in STCCB patients than in controls. The percentage of mDC and the expression of CD80, CD83, and CD86 were lower in patients showing recurrence. The serum levels of IL‐2 and IFN‐γ were found to be significantly lower while IL‐4, IL‐6, and IL‐10 were significantly higher in STCCB patients than in controls. IL‐6 was found to be significantly higher in recurrent patients.ConclusionThe impairment of mDC counts and MoDC function with imbalance of Th1/Th2 cytokines was closely associated with proliferation and recurrence of STCCB. J. Clin. Lab. Anal. 26:365‐371, 2012. © 2012 Wiley Periodicals, Inc.
External Evaluation of the Dimension Vista 1500® Intelligent Lab System
Authors: Bruneel Arnaud , Dehoux Monique , Barnier Anne , Boutten Anne 
Published: September 2012

BackgroundDimension Vista® analyzer combines four technologies (photometry, nephelometry, V‐LYTE® integrated multisensor potentiometry, and LOCI® chemiluminescence) into one high‐throughput system.MethodsWe assessed analytical performance of assays routinely performed in our emergency laboratory according to the VALTEC protocol, and practicability.ResultsPrecision was good for most parameters. Analytical domain was large and suitable for undiluted analysis in most clinical settings encountered in our hospital. Data were comparable and correlated to our routine analyzers (Roche Modular DP®, Abbott AXSYM®, Siemens Dimension® RxL, and BN ProSpec®). Performance of nephelometric and LOCI modules was excellent. Functional sensitivity of high‐sensitivity C‑reactive protein and cardiac troponin I were 0.165 mg/l and 0.03 ng/ml, respectively (coefficient of variation; CV < 10%). The influence of interfering substances (i.e., hemoglobin, bilirubin, or lipids) was moderate, and Dimension Vista® specifically alerted for interference according to HIL (hemolysis, icterus, lipemia) indices. Good instrument performance and full functionality (no reagent or sample carryover in the conditions evaluated, effective sample‐volume detection, and clot detection) were confirmed. Simulated routine testing demonstrated excellent practicability, throughput, ease of use of software and security.ConclusionPerformance and practicability of Dimension Vista® are highly suitable for both routine and emergency use. Since no volume detection and thus no warning is available on limited sample racks, pediatric samples require special caution to the Siemens protocol to be analyzed in secured conditions. Our experience in routine practice is also discussed, i.e., the impact of daily workload, “manual” steps resulting from dilutions and pediatric samples, maintenances, flex hydration on instrument's performance on throughput and turnaround time. J. Clin. Lab. Anal. 26:384‐397, 2012. © 2012 Wiley Periodicals, Inc.
Inhibition of NF‐κB activity by HIV‐1 Vpr is dependent on Vpr binding protein
Authors: Kogan Michael , Deshmane Satish , Sawaya Bassel E. , Gracely Edward J. , Khalili Kamel , Rappaport Jay 
Published: September 2012

AbstractNumerous studies have reported that Vpr alters NF‐κB signaling in various cell types, however, the findings have been largely conflicting with reports of both stimulatory and inhibitory effects of Vpr. Our aim was to investigate the role of Vpr signaling in myeloid cells using an adenovirus based expression and indicator system. Our results show that Vpr is inhibitory to NF‐κB, however, this effect is dependent on the particular manner of NF‐κB stimulation. Consistent with this notion, we report that Vpr has inhibitory effects that are specific to the TNF‐α pathway, but not affecting the LPS pathway, suggesting that differential targets of Vpr may exist for NF‐κB regulation. Further, we identify VprBP as one possible cellular component of Vpr's regulation of IκBα in response to TNF‐α stimulation. We did not identify such a role for HSP27, which instead seems to inhibit Vpr functions. Chronically HIV‐1 infected U1 cells with knockdown constructs for Vpr were unexpectedly less responsive to TNF‐α mediated viral replication, perhaps suggesting that other HIV‐1 components may antagonize these anti‐NF‐κB effects in infected cells. We hypothesize that Vpr may serve an important role in the context of viral infection and immune function in vivo, through its selective inhibition of NF‐κB pathways. J. Cell. Physiol. 228: 781–790, 2013. © 2012 Wiley Periodicals, Inc.
Comparing the Predictive Accuracy of Case Linkage Methods in Serious Sexual Assaults
Authors: Winter Jan Martin , Lemeire Jan , Meganck Stijn , Geboers Jo , Rossi Gina , Mokros Andreas 
Published: September 2012

AbstractThe empirical support for linkage analysis is steadily increasing, but the question remains as to what method of linking is the most effective. We compared a more theory‐based, dimensional behavioural approach with a rather pragmatic, multivariate behavioural approach with regard to their accuracy in linking serial sexual assaults in a UK sample of serial sexual assaults (n = 90) and one‐off sexual assaults (n = 129). Their respective linkage accuracy was assessed by (1) using seven dimensions derived by non‐parametric Mokken scale analysis (MSA) as predictors in discriminant function analysis (DFA) and (2) 46 crime scene characteristics simultaneously in a naive Bayesian classifier (NBC). The dimensional scales predicted 28.9% of the series correctly, whereas the NBC correctly identified 34.5% of the series. However, a subsequent inclusion of non‐serial offences in the target group decreased the amount of correct links in the dimensional approach (MSA–DFA: 8.9%; NBC: 32.2%). Receiver operating characteristic analysis was used as a more objective comparison of the two methods under both conditions, confirming that each achieved good accuracies (AUCs = .74–.89), but the NBC performed significantly better than the dimensional approach. The consequences for the practical implementation in behavioural case linkage are discussed. Copyright © 2012 John Wiley & Sons, Ltd.
Comparison of MRS and DWI in the diagnosis of prostate cancer based on sextant analysis
Authors: Li Bo , Cai Wenchao , Lv Dongjiao , Guo Xuemei , Zhang Jue , Wang Xiaoying , Fang Jing 
Published: September 2012

AbstractPurpose:To evaluate apparent diffusion coefficient (ADC) value, metabolic ratio ((Cho + Cr)/Cit) and the combination of the two in identifying prostate malignant regions.Materials and Methods:Fifty‐six consecutive patients with prostate biopsy results were retrospectively recruited in this study. Transrectal ultrasound‐guided (TRUS) systemic prostate biopsies were used as a standard of reference. Mean ADC value and mean metabolic ratio (MMR) were calculated within each benign sextant region or malignant region. The efficiency of these two indices in prostate cancer (PCa) diagnosis is estimated in Fisher linear discriminant analysis (FLDA). The area under the receiver operating characteristic (ROC) curve was used to evaluate the distinguishing capacity of mean ADC, MMR, and the combination of the two in differentiating between noncancerous and cancerous cases.Results:There were significant differences for mean ADC value and MMR between malignant and benign regions. Weights of mean ADC value obtained by FLDA were much higher than those of MMR. In differentiating malignant regions, both ADC alone and combined ADC and metabolic ratio performed significantly better than MMR alone. However, accuracy improvements were not significant by using combined ADC and MMR than ADC alone.Conclusion:DWI is more efficient than MR spectroscopic (MRS) in the detection of PCa in this study. Combined ADC and MMR performed significantly better than MMR alone in distinguishing malignant from benign region in prostate peripheral zone. J. Magn. Reson. Imaging 2013;37:194–200. © 2012 Wiley Periodicals, Inc.