bluuebunny/crossref_metadata_2025_split huggingface dataset:
RhoA‐Mediated Inhibition of Vascular Endothelial Cell Mobility: Positive Feedback Through Reduced Cytosolic p21 and p27
Authors: Hsu Yung‐Ho , Chang Chih‐Cheng , Yang Nian‐Jie , Lee Yi‐Hsuan , Juan Shu‐Hui 
Published: February 2014

AbstractWe previously identified that activation of the aryl hydrocarbon receptor (AhR) by 3‐methylcholanthrene (3MC) exerts antiproliferative and antimigratory effects on human umbilical vein endothelial cells (HUVECs) through the upregulation of p21/p27 transcription and RhoA activation. In this study, we investigated the mechanisms of 3MC‐mediated downregulation of cytosolic p21/ p27, and the effects of 3MC on RhoA activation and cell migration, in mouse cerebral vascular endothelial cells (MCVECs). Our results indicated that 3MC reduced the phosphorylation of p21/p27 through AhR/RhoA/PTEN‐mediated PI3K/Akt inactivation, which reduced cytosolic p21/p27 retention, causing RhoA activation through positive feedback. Downregulation of p21/p27 by siRNA, and cytosolic p21/p27 by the nuclear export blocker leptomycin B, further reduced cell migration in the 3MC‐treated cells. Reduced cytosolic p21/p27 expression led to reduced interaction between RhoA and the RhoA inhibitor p190RhoGAP, causing RhoA activation. Treatment with YS‐49 activated PI3K/Akt, a downstream target of RhoA, to reduce RhoA/PTEN activation in the 3MC‐treated cells, whereas treatment with wortmannin, a PI3K inhibitor, activated RhoA/PTEN. Gain‐ and loss‐of‐function analyses revealed that constitutively active (CA) Akt1, but not CA Akt2, inactivated RhoA and stimulated migratory activity. Considering the essential role of RhoA activation in cell migration, we evaluated the potential use of simvastatin, a RhoA inhibitor, as a therapeutic intervention in vivo using matrigel plug formation assays. Our results provide a molecular basis for the therapeutic application of simvastatin to reduce RhoA/PTEN activation, restore cytosolic levels of phosphorylated p21/p27, and induce angiogenic processes. J. Cell. Physiol. 229: 1455–1465, 2014. © 2014 Wiley Periodicals, Inc.
Roles of universal three‐dimensional image analysis devices that assist surgical operations
Authors: Sakamoto Tsuyoshi 
Published: February 2014

Abstract The circumstances surrounding medical image analysis have undergone rapid evolution. In such a situation, it can be said that “imaging” obtained through medical imaging modality and the “analysis” that we employ have become amalgamated. Recently, we feel the distance between “imaging” and “analysis” has become closer regarding the imaging analysis of any organ system, as if both terms mentioned above have become integrated. The history of medical image analysis started with the appearance of the computer. The invention of multi‐planar reconstruction (MPR) used in the helical scan had a significant impact and became the basis for recent image analysis. Subsequently, curbed MPR (CPR) and other methods were developed, and the 3D diagnostic imaging and image analysis of the human body have started on a full scale. Volume rendering: the development of a new rendering algorithm and the significant improvement of memory and CPUs contributed to the development of “volume rendering,” which allows 3D views with retained internal information. A new value was created by this development; computed tomography (CT) images that used to be for “diagnosis” before that time have become “applicable to treatment.” In the past, before the development of volume rendering, a clinician had to mentally reconstruct an image reconfigured for diagnosis into a 3D image, but these developments have allowed the depiction of a 3D image on a monitor. Current technology: Currently, in Japan, the estimation of the liver volume and the perfusion area of the portal vein and hepatic vein are vigorously being adopted during preoperative planning for hepatectomy. Such a circumstance seems to be brought by the substantial improvement of said basic techniques and by upgrading the user interface, allowing doctors easy manipulation by themselves. The following describes the specific techniques. Future of post‐processing technology: It is expected, in terms of the role of image analysis, for better or worse, that computer‐aided diagnosis (CAD) will develop to a highly advanced level in every diagnostic field. Further, it is also expected in the treatment field that a technique coordinating various devices will be strongly required as a surgery navigator. Actually, surgery using an image navigator is being widely studied, and coordination with hardware, including robots, will also be developed.
Endoscopic removal technique of migrated pancreatic plastic stents
Authors: Matsumoto Kazuyuki , Katanuma Akio , Maguchi Hiroyuki 
Published: February 2014

Abstract Endoscopic pancreatic stenting (EPS) is used for various pancreatic conditions. With the increasing use of pancreatic stents, many complications have been observed. Especially, proximal stent migration presents a more serious condition because of the possibility of pancreatic duct (PD) damage. However, the removal of proximally migrated stents is technically challenging because of the small PD diameter, the bended PD course, the presence of PD strictures, and the lack of suitable devices for stent removal. Thus, few cases of surgical intervention have been encountered. In this study, we review the endoscopic treatment of proximally migrated pancreatic plastic stents. We classify migrated stent conditions into four types according to stent and PD conditions. In Type A, the main pancreatic duct (MPD) has no stricture. In Type B, the stent is positioned across the stricture on the MPD. In Type C, the stent is positioned further away from the stricture on the MPD. The tip of the proximal stent is located in the MPD in types A thru C. In Type D, the tip of the proximal stent is located in a branch duct. We introduced the strategy of endoscopic removal technique of each type of migrated plastic stents.
Followership in Leadership Studies: A Case of Leader–Follower Trade Approach
Authors: Malakyan Petros G. 
Published: February 2014

AbstractThe current article acknowledges the absence of followership from the leadership literature for many years. Major theories of leadership are reviewed to assert that (1) modern leadership studies have been developed strictly from the leader's perspective with little or no attention on followership, (2) leadership studies have primarily been based on the static understanding of leadership (leaders always remain leaders),1 and (3) there seems to be a need for a new paradigm for leader–follower relationships, which may result in organic relationships between leaders and followers through exchange of leadership and followership functions and roles. Thus, it is argued that the mutuality of relationships and influence between the follower and the leader exists. To address the need for a new paradigm for leadership, the leader–follower trade (LFT) approach is introduced, which may result in the nonstatic and organic approach to leadership–followership as two valuable human behavioral functions. In this case, leadership and followership functions and roles may be traded or exchanged by the positional leaders and followers in different situations or organizational settings toward mutual respect, empowerment, and effectiveness.
Fine morphology of the jaw apparatus of Puncturella noachina (Fissurellidae, Vetigastropoda)
Authors: Vortsepneva Elena , Ivanov Dmitry , Purschke Günter , Tzetlin Alexander 
Published: February 2014

ABSTRACTJaws of various kinds occur in virtually all groups of Mollusca, except for Polyplacophora and Bivalvia. Molluscan jaws are formed by the buccal epithelium and either constitute a single plate, a paired formation or a serial structure. Buccal ectodermal structures in gastropods are rather different. They can be nonrenewable or having final growth, like the hooks in Clione (Gastropoda, Gymnosomata). In this case, they are formed by a single cell. Conversely, they can be renewable during the entire life span and in this case they are formed by a set of cells, like the formation of the radula. The fine structure of the jaws was studied in the gastropod Puncturella noachina. The jaw is situated in the buccal cavity and consists of paired elongated cuticular plates. On the anterior edge of each cuticular plate there are numerous longitudinally oriented rodlets disposed over the entire jaw surface and immersed into a cuticular matrix. The jaw can be divided into four zones situated successively toward the anterior edge: 1) the posterior area: the zone of formation of the thick cuticle covering the entire jaw and forming the electron‐dense outer layer of the jaw plate; 2) the zone of rodlet formation; 3) the zone of rodlet arrangement; and 4) the anterior zone: the free scraping edge of the plate, or the erosion zone. In the general pattern of jaw formation, Puncturella noachina resembles Testudinalia tessulata (Patellogastropoda) studied previously. The basis of the jaw is a cuticular plate formed by the activity of the strongly developed microvillar apparatus of the gnathoepithelium. However, the mechanism of renewal of the jaw anterior part in P. noachina is much more complex as its scraping edge consists not just of a thick cuticular matrix rather than of a system of denticles being the projecting endings of rodlets. J. Morphol. 275:775–787, 2014. © 2014 Wiley Periodicals, Inc.
Femtosecond laser‐induced cell‐cell surgical attachment
Authors: Katchinskiy Nir , Godbout Roseline , Goez Helly R. , Elezzabi Abdulhakem Y. 
Published: February 2014

Background and ObjectiveLaser‐induced cell‐cell surgical attachment using femtosecond laser pulses is reported.Study Design/Materials and MethodsWe have demonstrated the ability to attach single cells using sub‐10 femtosecond laser pulses, with 800 nm central wavelength delivered from a Ti:Sapphire laser. To check that the cells did not go through a cell‐fusion process, a fluorescent dye Calcein AM was used to verify that the fluorescent dye did not migrate from a dyed cell to a non‐dyed cell. The mechanical integrity of the attached joint was assessed using an optical tweezer.ResultsAttachment of cells was performed without the induction of cell‐cell fusion, with attachment efficiency of 95%, and while preserving the cells' viability. Cell‐cell attachment was achieved by delivery of one to two trains of femtosecond laser pulses lasting 15 ms each.ConclusionsLaser‐induced ionization process led to an ultrafast reversible destabilization of the phospholipid layer of the cellular membrane. The inner cell membrane remained intact during the attachment procedure, and isolation of the cells' cytoplasm from the surrounding medium was obtained. A strong physical attachment between the cells was obtained due to the bonding of the membranes' ionized phospholipid molecules and the formation of a joint cellular membrane at the connection point. The cellular attachment technique, femtosecond laser‐induced cell‐cell surgical attachment, can potentially provide a platform for the creation of engineered tissue and cell cultures. Lasers Surg. Med. 46:335–341, 2014. © 2014 Wiley Periodicals, Inc.
Dexamethasone‐Loaded Reconstitutable Charged Polymeric (PLGA)n‐b‐bPEI Micelles for Enhanced Nuclear Delivery of Gene Therapeutics
Authors: Mishra Deepa , Kang Han Chang , Cho Hana , Bae You Han 
Published: February 2014

AbstractThis study investigates the potential of dexamethasone (Dex) to enhance the nuclear accumulation and subsequent gene expression of plasmid DNA (pDNA) delivered using a charged polymeric micelle‐based gene delivery system. (PLGA)n‐b‐bPEI25kDa block copolymers are synthesized and used to prepare Dex‐loaded cationic micelles (DexCM). After preparing DexCM/pDNA complexes, bPEI1.8kDa is coated on the complexes using a Layer‐by‐Layer (LbL) technique to construct DexCM/pDNA/bPEI1.8kDa complexes (i.e., LbL‐DexCM polyplexes) that are 100–180 nm in diameter and have a zeta potential of 30–40 mV. In MCF7 cells, LbL‐DexCM polyplexes cause 3–13‐fold higher transfection efficiencies compared to LbL‐CM polyplexes and show negligible cytotoxicity. LbL‐DexCM3 polyplexes induce much higher nuclear delivery of pDNA compared to LbL‐CM3 polyplexes. These results suggest that Dex‐loaded polyplexes could be used in gene and drug delivery applications to increase nuclear accumulation of therapeutic payloads, further leading to a decrease in the dose of the drug and gene necessary to achieve equivalent therapeutic effects.
Enzymatically Cross‐Linked Gelatin/Chitosan Hydrogels: Tuning Gel Properties and Cellular Response
Authors: da Silva Marcelo A. , Bode Franziska , Drake Alex F. , Goldoni Silvia , Stevens Molly M. , Dreiss Cécile A. 
Published: February 2014

AbstractThis work investigates the effect of combining physical and chemical gelation processes in a biopolymer blend: chitosan and tilapia fish gelatin. Chemical (C) gels are obtained by cross‐linking with the microbial enzyme transglutaminase at 37 °C. Hybrid physical‐co‐chemical (PC) gels are cross‐linked at 21 °C, below gelatin gelation temperature. These protocols provide two microenvironments for the gelation process: in C gels, both gelatin and chitosan are present as single strands; in PC gels, cross‐linking proceeds within a transient physical gel of gelatin, filled by chitosan strands. The chitosan/gelatin chemical networks generated in PC gels show a consistently higher shear modulus than pure C gels; they are also less turbid than their C gels counterparts, suggesting a more homogeneous network. Finally, chitosan enhances the gels' shear modulus in all gels. Proliferation assays show that MC3T3 cells proliferate in these mixed, hybrid gels and better so on PC gels than in C mixed gels.
Light‐Induced Catalyst and Solvent‐Free High Pressure Synthesis of High Density Polyethylene at Ambient Temperature
Authors: Ceppatelli Matteo , Bini Roberto 
Published: February 2014

The combined effect of high pressure and electronic photo‐excitation has been proven to be very efficient in activating extremely selective polymerisations of small unsaturated hydrocarbons in diamond anvil cells (DAC). Here we report an ambient temperature, large volume synthesis of high density polyethylene based only on high pressure (0.4–0.5 GPa) and photo‐excitation (~350 nm), without any solvent, catalyst or radical initiator. The reaction conditions are accessible to the current industrial technology and the laboratory scale pilot reactor can be scaled up to much larger dimensions for practical applications. FTIR and Raman spectroscopy, and X‐ray diffraction, indicate that the synthesised material is of comparable quality with respect to the outstanding crystalline material obtained in the DAC. The polydispersity index is comparable to that of IV generation Ziegler‐Natta catalysts. Moreover the crystalline quality of the synthesised material can be further enhanced by a thermal annealing at 373 K and ambient pressure.
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On the spatial distribution of rainfall nowcasting errors due to orographic forcing
Authors: Foresti Loris , Seed Alan 
Published: February 2014

ABSTRACTThe goal of this research is to study the effect of orography on the spatial distribution of rainfall nowcasting errors. Twenty months of forecasts of hourly rainfall accumulations from the short‐term ensemble prediction system (STEPS) for the weather radar composite over eastern Victoria, Australia, were verified against radar observations. The verification was stratified according to six different flow regimes derived by applying a k‐means clustering algorithm on the archive of motion fields. STEPS biases were found to have a strong flow‐regime dependence, which appears as an underestimation of rainfall on the windward side of terrain features followed by an overestimation on the leeward side. In the regions characterized by strong orographic forcing, the relative contribution of the bias to the root mean square error (RMSE) of the nowcast is locally important. The results also highlighted areas where the errors in the radar rainfall estimates contributed a significant fraction of the observed forecast error. These promising results open ways to integrate flow‐dependent and spatially inhomogeneous growth and decay mechanisms in the stochastic simulation of radar rainfall fields performed by STEPS.
Health‐related quality‐of‐life and treatment targets in myasthenia gravis
Authors: Utsugisawa Kimiaki , Suzuki Shigeaki , Nagane Yuriko , Masuda Masayuki , Murai Hiroyuki , Imai Tomihiro , Tsuda Emiko , Konno Shingo , Nakane Shunya , Suzuki Yasushi , Fujihara Kazuo , Suzuki Norihiro 
Published: February 2014

ABSTRACTIntroduction: The aim of this study was to determine factors affecting health‐related quality of life (HRQOL) and to propose appropriate treatment targets for patients with myasthenia gravis (MG). Methods: We evaluated 640 consecutive patients with MG seen at 11 neurological centers. Two‐year follow‐up data were obtained for 282 patients. Correlations between detailed clinical factors and the Japanese version of the 15‐item MG‐specific QOL scale score were analyzed. Results: In a cross‐sectional analysis of 640 MG patients, multivariate regression revealed that disease severity, as evaluated by the MG Composite (P < 0.0001), total dose of oral prednisolone during the last year (P = 0.002), and Cushingoid appearance index (P = 0.0004), showed significant negative effects on HRQOL, but the quantitative MG score and current prednisolone dose did not. Conclusions: Achieving minimal manifestations (MM) status or better with prednisolone ≤5 mg/day was found to exert a major positive impact on HRQOL in both the cross‐sectional and 2‐year follow‐up patient samples and can be recommended as a treatment target. Muscle Nerve 50: 493–500, 2014
Operations sequencing for a multi‐stage production inventory system
Authors: Shi Jim (Junmin) , Yue Xiaohang , Zhao Yao 
Published: February 2014

AbstractThis article studies operations sequencing for a multi‐stage production inventory system with lead times under predictable (deterministic) yield losses and random demand. We consider various cases with either full or partial release of work‐in‐process inventories, for either pre‐operation or post‐operation cost structures, and under either the total discounted or average cost criteria. We derive necessary and sufficient criteria for the optimal sequence of operations in all cases. While the criteria differ in their specific forms, they all lead to the same principal: those operations with (1) lower yields, (2) lower processing costs, (3) longer lead times, and (4) lower inventory holding costs should be placed higher upstream in the system.Copyright © 2014 Wiley Periodicals, Inc. Naval Research Logistics 61: 144–154, 2014
Spexin is a novel human peptide that reduces adipocyte uptake of long chain fatty acids and causes weight loss in rodents with diet‐induced obesity
Authors: Walewski José L. , Ge Fengxia , Lobdell Harrison , Levin Nancy , Schwartz Gary J. , Vasselli Joseph R. , Pomp Afons , Dakin Gregory , Berk Paul D. 
Published: February 2014

ObjectiveMicroarray studies identified Ch12:orf39 (Spexin) as the most down‐regulated gene in obese human fat. Therefore, we examined its role in obesity pathogenesis.MethodsSpexin effects on food intake, meal patterns, body weight, respiratory exchange ratio (RER), and locomotor activity were monitored electronically in C57BL/6J mice or Wistar rats with diet‐induced obesity (DIO). Its effects on adipocyte [3H]‐oleate uptake were determined.ResultsIn humans, Spexin gene expression was down‐regulated 14.9‐fold in obese omental and subcutaneous fat. Circulating Spexin changed in parallel, correlating (r = −0.797) with Leptin. In rats, Spexin (35 µg/kg/day SC) reduced caloric intake ∼32% with corresponding weight loss. Meal patterns were unaffected. In mice, Spexin (25 µg/kg/day IP) significantly reduced the RER at night, and increased locomotion. Spexin incubation in vitro significantly inhibited facilitated fatty acid (FA) uptake into DIO mouse adipocytes. Conditioned taste aversion testing (70 µg/kg/day IP) demonstrated no aversive Spexin effects.ConclusionsSpexin gene expression is markedly down‐regulated in obese human fat. The peptide produces weight loss in DIO rodents. Its effects on appetite and energy regulation are presumably central; those on adipocyte FA uptake appear direct and peripheral. Spexin is a novel hormone involved in weight regulation, with potential for obesity therapy.
Targeted learning in real‐world comparative effectiveness research with time‐varying interventions
Authors: Neugebauer Romain , Schmittdiel Julie A. , van der Laan Mark J. 
Published: February 2014

AbstractIn comparative effectiveness research (CER), often the aim is to contrast survival outcomes between exposure groups defined by time‐varying interventions. With observational data, standard regression analyses (e.g., Cox modeling) cannot account for time‐dependent confounders on causal pathways between exposures and outcome nor for time‐dependent selection bias that may arise from informative right censoring. Inverse probability weighting (IPW) estimation to fit marginal structural models (MSMs) has commonly been applied to properly adjust for these expected sources of bias in real‐world observational studies. We describe the application and performance of an alternate estimation approach in such a study. The approach is based on the recently proposed targeted learning methodology and consists in targeted minimum loss‐based estimation (TMLE) with super learning (SL) within a nonparametric MSM. The evaluation is based on the analysis of electronic health record data with both IPW estimation and TMLE to contrast cumulative risks under four more or less aggressive strategies for treatment intensification in adults with type 2 diabetes already on 2+ oral agents or basal insulin. Results from randomized experiments provide a surrogate gold standard to validate confounding and selection bias adjustment. Bootstrapping is used to validate analytic estimation of standard errors. This application does the following: (1) establishes the feasibility of TMLE in real‐world CER based on large healthcare databases; (2) provides evidence of proper confounding and selection bias adjustment with TMLE and SL; and (3) motivates their application for improving estimation efficiency. Claims are reinforced with a simulation study that also illustrates the double‐robustness property of TMLE. Copyright © 2014 John Wiley & Sons, Ltd.