bluuebunny/crossref_metadata_2025 huggingface dataset:
Current Statin Usage for Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: Multicenter Survey in Korea
Authors: Kim Mi‐Jeong , Jeon Doo Soo , Gwon Hyeon‐Cheol , Kim Soo‐Joong , Chang Kiyuk , Kim Hyo‐Soo , Tahk Seung‐Jea ,   for Korean MUSTANG Investigators
Published: July 2012

Background:

Although high‐dose statin therapy has been reported to improve outcomes in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), patterns of statin usage for such patients have not been reported in real‐world clinical practice.

Hypothesis:

Some clinical factors would affect the pattern of statin usage in patients with ACS.

Methods:

In the multicenter prospective registry, 3362 patients with ACS who underwent PCI were analyzed. High‐dose statin treatment was defined as atorvastatin ≥40 mg or rosuvastatin ≥20 mg per day. The patterns of statin usage were investigated for 30 days after the index PCI.

Results:

High‐dose statins were administered prior to PCI to 13.7% and 19.6% of patients with unstable angina/non–ST‐elevated myocardial infarction (UA/NSTEMI) and ST‐elevated myocardial infarction (STEMI), respectively (P < 0.001). After PCI, 476 (14.2%) patients were maintained on high‐dose statins, and 550 (16.4%) patients received no statins. Independent factors associated with high‐dose statin usage after PCI were STEMI (odds ratio [OR]: 1.704, 95% confidence interval [CI]: 1.321–2.197, P < 0.001), high total cholesterol level (OR: 1.445, 95% CI: 1.136–1.837, P = 0.003), and current smoker (OR: 1.556, 95% CI: 1.206–2.008, P < 0.011). The absence of hypercholesterolemia was an independent factor determining the nonuse of statins (OR: 0.229, 95% CI: 0.148–0.353, P < 0.001).

Conclusions:

In real‐world clinical practice, high‐dose statin treatment is being underused despite extensive evidence for patients with ACS undergoing PCI, particularly in UA/NSTEMI. Efforts are needed to ensure that clinical practice complies with evidence‐based guidelines. Clin. Cardiol. 2012 doi: 10.1002/clc.22038

This work was supported financially by Pfizer Pharmaceuticals Korea Ltd., which had no role in the study design, data collection, analysis, manuscript writing, or decision to proceed with publication. The authors have no other funding, financial relationships, or conflicts of interest to disclose.
Peritoneal washing cytologic analysis of ovarian serous tumors of low malignant potential to detect peritoneal implants and predict clinical outcome
Authors: Sneige Nour , Thomison John B. , Malpica Anais , Gong Yun , Ensor Joe , Silva Elvio G.
Published: July 2012

BACKGROUND:

Patients with ovarian serous tumors of low malignant potential (OSLMP) who have peritoneal implants, especially invasive implants, are at an increased risk of developing tumor recurrence. To the best of the authors' knowledge, the ability of peritoneal washing (PW) cytology to detect the presence and type of peritoneal implants has not been adequately investigated, and its prognostic significance is unknown.

METHODS:

Records and PW specimens of 101 patients diagnosed with and treated for OSLMP between 1996 and 2010 at The University of Texas MD Anderson Cancer Center were retrospectively reviewed. Patients' staging biopsy findings were compared with the results of the authors' review of the PWs. Follow‐up data were also analyzed.

RESULTS:

Of the 96 patients for whom staging biopsy results were available, 26 (27%) had peritoneal implants (17 noninvasive and 9 invasive), 19 (20%) had endosalpingiosis, and 51 (53%) had negative findings. The PW specimens of 18 of the 26 patients (69%) with peritoneal implants were positive for serous neoplasm, and a correlation was found between cytologic and histologic findings (P < .0001). The sensitivity, specificity, positive predictive value, and negative predictive value were 69%, 84%, 62%, and 88%, respectively. Four of 101 patients had disease recurrence; 3 of these patients had invasive implants and 1 patient had noninvasive implants. None of the patients who had negative staging biopsy findings or endosalpingiosis but did have PW specimens that were positive for serous neoplasm developed disease recurrence.

CONCLUSIONS:

PW cytology detects the presence of peritoneal implants with moderate accuracy. However, long‐term studies are needed to determine whether positive PW cytologic findings are an independent predictor of tumor recurrence. Cancer (Cancer Cytopathol) 2012;. © 2012 American Cancer Society.
Serous epithelium, serious interpretations
Authors: Geisinger Kim R. , Parks Graham E.
Published: July 2012

The authors focus their expertise in the area of peritoneal washings on the detection of gynecologic neoplasms, specifically on the challenging area of ovarian serous tumors of low malignant potential. Particular attention is paid to the cytomorphologic differential diagnosis with endosalpingiosis; investigation of the prognostic significance of positive peritoneal washings is advanced.
Selective expression of α‐synuclein‐immunoreactivity in vesicular acetylcholine transporter‐immunoreactive axons in the guinea pig rectum and human colon
Authors: Sharrad Dale F. , de Vries Elsbeth , Brookes Simon J.H.
Published: July 2012

Parkinson's disease is a neurodegenerative disorder characterized by motor and nonmotor impairments, including constipation. The hallmark pathological features of Parkinson's disease are Lewy bodies and neurites, of which aggregated α‐synuclein is a major constituent. Frequently, Lewy pathology is identified in the distal gut of constipated Parkinson's disease patients. The neurons that innervate the distal gut that express α‐synuclein have not been identified. We used multiple‐labeling immunohistochemistry and anterograde tracing to quantify which neurons projecting to the guinea pig rectum and human colon expressed α‐synuclein in their axons. α‐Synuclein‐immunoreactivity was present in 24 ± 0.7% of somatostatin (SOM)‐immunoreactive (IR) varicosities; 20 ± 4.3% of substance P (SP)‐IR varicosities and 9 ± 1.3% vasoactive intestinal polypeptide (VIP)‐IR varicosities in guinea pig rectal myenteric ganglia. However, α‐synuclein‐immunoreactivity was localized in significantly more vesicular acetylcholine transporter (VAChT)‐IR varicosities (88 ± 3%,P< 0.001). Of SOM‐IR, SP‐IR, and VIP‐IR varicosities that lacked VAChT‐immunoreactivity, only 1 ± 0.3%, 0 ± 0.3%, and 0% contained α‐synuclein‐immunoreactivity, respectively. 71 ± 0.8% of VAChT‐IR varicosities in myenteric ganglia of human colon were α‐synuclein‐IR. In guinea pig rectal myenteric ganglia, α‐synuclein‐ and VAChT‐immunoreactivity coexisted in 15 ± 1.4% of biotinamide‐labeled extrinsic varicosities; only 1 ± 0.3% of biotinamide‐labeled extrinsic varicosities contained α‐synuclein‐immunoreactivity without VAChT‐immunoreactivity. α‐Synuclein expression in axons to the distal gut correlates closely with expression of the cholinergic marker, VAChT. This is the first report of cell‐selective α‐synuclein expression in the nervous system. Our results suggest cholinergic neurons in the gut may be vulnerable in Parkinson's disease. J. Comp. Neurol. 521:657–676, 2013. © 2012 Wiley Periodicals, Inc.
Semantic link‐based constructing of multi‐dimensional service resource space for collaboration
Authors: Zhao Anping , Ma Yan
Published: July 2012

Automatic service collaboration calls for the development of semantically structured service resource space to maximize the utility of Web services. Semantic links contain rich semantic information that may indicate important relationships among services. We provided an effective method for constructing multi‐dimensional service resource space based on semantic links for service collaboration, in which similar and related semantic relationship between services are considered. We first clustered services with similar and related relations on the basis of a hierarchical structure respectively and then took advantage of the resource space model to construct multi‐dimensional service resource space. Finally, experimental results show the effectiveness of the method. Concurrency and Computation: Practice and Experience, 2012.© 2012 Wiley Periodicals, Inc.
Spectral Diffusion of Single Dibenzoterrylene Molecules in 2,3‐Dimethylanthracene
Authors: Tian Yuxi , Navarro Pedro , Kozankiewicz Boleslaw , Orrit Michel
Published: July 2012

We study single dibenzoterrylene molecules embedded in the dipolar disordered crystal 2,3‐dimethylanthracene at 1.25 K. Broad linewidths (about 1 GHz, ∼30 times broader than in the anthracene crystal), high saturation excitation intensities (∼1000 times larger than in anthracene), as well as strong spectral diffusions are observed. Additionally, spectral jumping is studied by varying the excitation intensity and the temperature. We propose that the spectral diffusion and dynamic disorder in this system arise from the combination of a static disorder with slight reorientations of the methyl groups of the host molecules.
Structured youth dialogue to empower peacebuilding and leadership
Authors: Ungerleider John
Published: July 2012

Through structured dialogue during Youth Peacebuilding and Leadership Programs, high school and college students from Cyprus, Iraq, Serbia, Armenian, Azerbaijan, Denmark, the U.K., and the United States developed expressive, relational, intercultural, and analytical skills, plus a sense of personal transformation. Well‐facilitated peer dialogue promotes self‐awareness, compassion, diverse perspectives on current issues, and capacities for social action. Facilitators structure process and content for sessions, creating a mood of safety and openness, focusing topics for appropriate risk and relevance, reconciliation, and empowerment. Participants practice communication skills essential for shared leadership: listening and speaking effectively, recognizing cross‐cultural difference, analyzing issues cooperatively, and making decisions collaboratively.
Transfer up or down? Dialogue groups between Turkish and Armenian communities in the United States
Authors: Ohanyan Anna
Published: July 2012

Drawing from four case studies of dialogue groups between Turkish American and Armenian American communities organized over the past decade, this article examines the political value of grassroots diplomacy. In particular, it questions the emphasis on the transfer‐up paradigm prevalent in the literature of conflict resolution, which is premised on the ultimate importance of governmental structures in brokering a resolution. Instead, the article focuses on the role that grassroots communities can play in civil society development between two communities as an alternate pathway toward conflict resolution and reconciliation. The article also takes up the dilemma that dialogue groups face: to promote a resolution to a conflict versus advancing social justice and human rights. The article concludes with a set of theoretical and policy recommendations.
Transesterification of Diethyl Oxalate with Phenol over Sol–Gel MoO3/TiO2 Catalysts
Authors: Kotbagi Trupti , Nguyen Duy Luan , Lancelot Christine , Lamonier Carole , Thavornprasert Kaew‐Arpha , Wenli Zhu , Capron Mickaël , Jalowiecki‐Duhamel Louise , Umbarkar Shubhangi , Dongare Mohan , Dumeignil Franck
Published: July 2012

The transesterification of diethyl oxalate (DEO) with phenol to form diphenyl oxalate (DPO) has been carried out in the liquid phase over very efficient MoO3/TiO2 solid‐acid sol–gel catalysts. A selectivity of 100 % with a remarkable maximum yield of 88 % were obtained, which opens the route to downstream phosgene‐free processes for the synthesis of polycarbonates. Interpretation of the results of various acidity measurements (NH3 and pyridine desorption, methanol oxidation as a probe reaction) allowed us to identify the catalytic sites as Lewis acid sites.
Effects of retinoic acid and Gbx1 on feather‐bud formation and epidermal transdifferentiation in chick embryonic cultured dorsal skin
Authors: Obinata Akiko , Akimoto Yoshihiro
Published: July 2012

Background: Retinoic acid, an active metabolite of retinol, is known to regulate cell proliferation, differentiation, and morphogenesis during normal development of many tissues. Using chick embryonic tarsometatarsal skin, we showed previously that the expression of Gbx1, a divergent homeobox gene, is increased in the epidermis through interaction with retinol‐pretreated dermal fibroblasts followed by epidermal transdifferentiation to mucous epithelium. This present study was performed to elucidate the effects of retinoic acid and Gbx1 on feather‐bud formation and epidermal transdifferentiation. Results: We showed that Gbx1 was expressed in the chick embryonic dorsal epidermis as early as at placode stage (Hamburger and Hamilton stage 31) and increased in amount during feather‐bud formation. Treatment with 1 μM retinoic acid for 24 hr inhibited feather‐bud formation and induced the transdifferentiation of the epidermis to a mucosal epithelium with a concomitant increase in Gbx1 mRNA expression in the epithelium. Furthermore, transient transfection of the epidermis with Gbx1 cDNA by electroporation induced elongation of the feather bud, but did not result in transdifferentiation. Conclusions: These results indicate that Gbx1 was involved in the feather‐bud formation and was one of target genes of retinoic acid and that other signals in addition to Gbx1 were required for epidermal mucous transdifferentiation. Developmental Dynamics 241:1405–1412, 2012. © 2012 Wiley Periodicals, Inc.
Microarray‐based identification of Pitx3 targets during Xenopus embryogenesis
Authors: Hooker Lara , Smoczer Cristine , KhosrowShahian Farhad , Wolanski Marian , Crawford Michael J.
Published: July 2012

Background: Unexpected phenotypes resulting from morpholino‐mediated translational knockdown of Pitx3 in Xenopus laevis required further investigation regarding the genetic networks in which the gene might play a role. Microarray analysis was, therefore, used to assess global transcriptional changes downstream of Pitx3. Results: From the large data set generated, selected candidate genes were confirmed by reverse transcriptase‐polymerase chain reaction (RT‐PCR) and in situ hybridization. Conclusions: We have identified four genes as likely direct targets of Pitx3 action: Pax6, β Crystallin‐b1 (Crybb1), Hes7.1, and Hes4. Four others show equivocal promise worthy of consideration: Vent2, and Ripply2 (aka Ledgerline or Stripy), eFGF and RXRα. We also describe the expression pattern of additional and novel genes that are Pitx3‐sensitive but that are unlikely to be direct targets. Developmental Dynamics 241:1487–1505, 2012. © 2012 Wiley Periodicals, Inc.
A pilot evaluation of appetite‐awareness training in the treatment of childhood overweight and obesity: A preliminary investigation
Authors: Bloom Taryn , Sharpe Louise , Mullan Barbara , Zucker Nancy
Published: July 2012

Objective:

The aim of this study was to conduct a preliminary evaluation of Children's Appetite Awareness Training (CAAT), a treatment for childhood obesity which encourages overweight children to eat in response to internal appetite cues.

Method

Overweight children (ages 6–12 years old) were randomized to either the CAAT treatment group (N = 23), to receive 1‐h treatment sessions over 6 weeks, or a wait‐list group (N = 24). Weight and height of children and parents in both groups were assessed at pre‐ and post‐treatment (or equivalent time for wait‐list control) and at a 6‐month follow‐up for those in the CAATgroup.

Results:

The intervention had a significant, short‐term effect on the BMI of children who participated. Although at 6‐month follow‐up, children's BMI has not increased significantly, the difference between pretreatment and follow‐up BMI was no longer significant.

Discussion:

These results are encouraging for the use of CAAT with overweight children. Long‐term effectiveness could be enhanced through increasing the duration of the program, adding booster sessions and increased involvement of parents. © 2012 by Wiley Periodicals, Inc. (Int J Eat Disord 2013)
Absence of seasonal pattern of birth in patients with anorexia nervosa
Authors: Vellisca María Y. , Latorre José I. , Santed Miguel A. , Reales José M.
Published: July 2012

Objective:

An excess of spring births has been suggested in patients with anorexia nervosa (AN), especially in the restricting subtype, but most of the research has been carried out inside the United Kingdom. The aim of this study was to assess whether there is a seasonal pattern of birth in a representative sample of patients with AN in a different latitude in the northern hemisphere.

Method:

We examined the month of birth in a sample of 210 female patients with a DSM‐IV diagnosis of AN at first presentation to a specialized eating disorders service in Spain.

Results:

We found no evidence of significant variation in month or season of birth in AN when compared to general population.

Discussion:

There is not enough evidence of a season of birth bias under the latitude of the United Kingdom in the risk of developing AN. © 2012 by Wiley Periodicals, Inc. (Int J Eat Disord 2013)
The disappearing northern leopard frog (Lithobates pipiens): conservation genetics and implications for remnant populations in westernNevada
Authors: Rogers Serena D. , Peacock Mary M.
Published: July 2012

Global amphibian declines suggest a major shift in the amount and quality of habitat for these sensitive taxa. Many species that were once widespread are now experiencing declines either in part of or across their historic range. The northern leopard frog (Rana[Lithobates]pipiens] has undergone significant declines particularly in the westernUnitedStates andCanada. Leopard frog population losses inNevada are largely due to habitat fragmentation and the introduction of nonnative fish, amphibian, and plant species. Only two populations remain in theTruckee andCarsonRiver watersheds of westernNevada which represents the western boundary of this species range. We used sequence data for an 812 base pair fragment of the mitochondrialNADHdehydrogenase 1 (ND1) gene to support a native origin for westernNevada populations. All frogs had a single haplotype (W07) from the distinct westernNorthAmericaND1 haplotype clade. Data from seven polymorphic microsatellite loci show thatTruckee andCarsonRiver populations are highly differentiated from each other and from leopard frogs collected from easternNevada sites. Lack of gene flow among and distinct color morphs among the westernNevada populations likely predates the current geographical isolation. Comparisons with other peripheralL. pipienspopulations show westernNevada populations have similar levels of gene diversity despite their contemporary isolation (HE0.411, 0.482). Restoration of leopard frog populations in these watersheds will be challenging given well‐entrenched nonnative bullfrog populations and major changes to the riparian zone over the past century. Declines of once common amphibian species has become a major conservation concern. Contemporary isolation of populations on a species range periphery such as the leopard frog populations in theTruckee andCarson rivers further exacerbate extirpation risk as these populations are likely to have fewer genetic resources to adaptively respond to rapidly changing biotic and abiotic environments.
From Coordination Polymers to Doped Rare‐Earth Oxides
Authors: Demars Thomas , Boltoeva Maria , Vigier Nicolas , Maynadié Jérôme , Ravaux Johann , Genre Caroline , Meyer Daniel
Published: July 2012

A series of bimetallic coordination polymers were synthesised from lanthanide salts (chlorides or nitrates of Ce, Nd, Gd) and 2,5‐dihydroxy‐1,4‐benzoquinone (DHBQ) under aqueous and anhydrous conditions, to be used as preceramics for mixed oxide synthesis. Syntheses in water or tetrahydrofuran (THF) gave rise to two different types of metal–organic frameworks. A new polymeric species, [Gd(DHBQ)Cl(THF)2]n, was characterised by single‐crystal X‐ray diffraction {[Gd(DHBQ)Cl(THF)2]n, a = 8.643(2) Å, b = 9.917(5) Å, c = 10.422(3) Å, α = 104.611(3)°, β = 109.623(3)°, γ = 96.097(3)°, V = 796.1(5) Å3, triclinic, P$\bar {1}$, Z = 2}. Characterisation by IR and Raman spectroscopy, powder X‐ray diffraction and scanning electron microscopy showed that the mixed‐metal polymers are solid solutions and highlighted the fact that their shape and morphology are strongly influenced by the presence of water in the reaction mixture. Micrometric, well‐defined cylindrical objects were obtained from the aqueous synthesis, while the reaction in anhydrous THF led to nanometric spheres. Calcination at 850 °C of the coordination polymer preceramics easily yielded mixed NdxGd(1–x) and NdxCe(1–x) oxides as solid solutions, in which x varies between 0 and 1. The morphology of the preceramic powders is retained upon calcination. This allows easy control of some of the oxide properties from the coordination compound synthesis step. Indeed, BET measurements pointed out that the choice of anhydrous reaction conditions for the preceramic synthesis leads to enhancement of the specific surface areas of the oxides by one order of magnitude.
Luminescent AuI–CuI Triphosphane Clusters That Contain Extended Linear Arylacetylenes
Authors: Shakirova Julia R. , Grachova Elena V. , Melekhova Anna A. , Krupenya Dmitrii V. , Gurzhiy Vladislav V. , Karttunen Antti J. , Koshevoy Igor O. , Melnikov Alexei S. , Tunik Sergey P.
Published: July 2012

Reactions of the [(tppm)Au3Cl3] [tppm = tris(diphenylphosphanyl)methane] precursor and CuI ions with a stoichiometric amount of the corresponding linear mono‐ [HC2(C6H4)nC6H5; n = 1, 2] and diacetylenes [HC2(C6H4)nC2H; n = 1–3] that contain extended polyaryl moieties afford a series of luminescent heterometallic complexes with a common structural motif based on the {(AuC2)3Cu} cluster core. The complexes obtained were characterized by using X‐ray crystallography and NMR spectroscopy. All compounds studied display dual singlet and triplet luminescence, the former component of which can be completely suppressed in concentrated solution by a self‐absorption phenomenon. The results of the photophysical measurements together with the quantum chemical calculations (PBE0‐DFT level of theory) indicate that singlet emission originates mainly from copper‐perturbed intraligand transitions, whereas the phosphorescence can be assigned to the {(AuC2)3Cu} core‐centered transitions. Due to the low contribution of the gold atoms to the orbitals responsible for the singlet and triplet emission, the emissive excited states are very weakly coupled, thereby resulting in a negligible energy transfer between these excited states.
Heterogeneous Bifunctional Metal/Acid Catalysts for Selective Chemical Processes
Authors: Barbaro Pierluigi , Liguori Francesca , Linares Noemi , Marrodan Carmen Moreno
Published: July 2012

Heterogeneous catalysts enabling multiple reaction sequences in one pot have a great potential for large‐scale production processes in terms of productivity, cost‐effectiveness, and low environmental impact. This paper reviews the most representative examples and the recent achievements in the field of solid bifunctional metal/acid‐site catalysts and their application to the production of fine chemicals through selective, cooperative, or sequential processes in single reactor units. The literature that appeared from January 2009 to January 2012 is covered.
A validated microfluidics‐based LC‐chip‐MS/MS method for the quantitation of fluoxetine and norfluoxetine in rat serum
Authors: Houbart Virginie , Servais Anne‐Catherine , Charlier Thierry D. , Pawluski Jodi L. , Abts Frederic , Fillet Marianne
Published: July 2012

An increasing number of quantitative bioanalyses need to be performed on samples available in limited volumes, such as pharmacokinetic studies on small animals. In this context, microfluidic systems as the LC‐chip device coupled to a mass spectrometer combine small sample volume requirements and high sensitivity. In this study, we present the development of a microfluidics‐based method for fluoxetine (FLX) and norfluoxetine (NFL) quantitation dedicated to pharmacokinetic investigations in the rat serum. Using the methodology of experimental design, LC parameters were optimised in terms of peak resolution, analysis time, and sensitivity. An SPE method was then developed for serum samples on miniaturised 96‐well plates containing a mixed‐mode strong cation exchanger that provided very clean extracts with good analyte recovery (≥66.0%). The total SPE‐LC‐MS/MS process required only 20 μL per sample and the method provided a good sensitivity in a total run time of 12 min. Finally, the developed method for FLX and NFL quantitation in rat serum was fully validated. After having selected the most appropriate regression model on the basis of the accuracy profiles, method selectivity, trueness, precision, accuracy and linearity were demonstrated.
Disclosure of a fundamental clue for the elucidation of the myricetin mechanism of action as amyloid aggregation inhibitor by mass spectrometry
Authors: Fiori Jessica , Naldi Marina , Bartolini Manuela , Andrisano Vincenza
Published: July 2012

Progression of Alzheimer's disease involves aggregation of amyloid‐beta (Aβ) peptides, a complex process that involves the formation of several soluble intermediates and ends up with the deposition of ordered fibrillar architectures. The determination of the Aβ42 self‐assembly species targeted by an inhibitor is a key step in the identification of new inhibitors endowed with a suitable profile. In this context, the subtle characterization of myricetin (Myr) mode of action at a molecular level was performed by using different MS techniques, which allowed the monitoring of the modifications induced by Myr on the first occurring Aβ42 self‐assembly species. Results showed a persistent level of monomer and decreased formation of ordered Aβ42 aggregates in the presence of Myr, further, nano‐LC‐nano‐ESI‐QTOF, MALDI‐TOF, and ESI‐IT highlighted the formation of a new oxidized Aβ42 species, which is less prone to aggregation, in the presence of Myr. Coupling tryptic digestion and nano‐LC‐nano‐ESI‐QTOF also allowed the identification of Met35 as the specific site of oxidation along the Aβ aminoacid chain. Therefore, the detailed investigation by different MS techniques allowed better understanding of the molecular modification at the basis of the antiaggregating properties of Myr and highlighted its oxidizing action on the residue Met35 in Aβ monomers.
Elution behavior of short dsDNA strands in silicon micropillar array columns in ion pair reversed‐phase chromatography mode
Authors: Zhang Lei , Majeed Bivragh , Lynen Frederic , Van Hoof Chris , De Malsche Wim
Published: July 2012

In the present paper, dsDNA separation has been studied in a silicon micropillar array column using ion‐pair RP‐HPLC (IP‐RP‐HPLC). The deep‐etched (32.0 μm) silicon micropillar array was fabricated by advanced deep UV lithography and by a dedicated Bosch etch process and then sealed by anodic bonding to a Pyrex glass. The pillar surface was subsequently conditioned hydrophobic. Working in isocratic mode under nonretained conditions, van Deemter curves of dsDNA and coumarin were established to assess the performance of the micropillar array column, resulting in plate heights of only a few micrometers. Working in gradient mode, separations of dsDNA fragments were evaluated. The relevant gradient operation parameters were studied to understand their influence on dsDNA separations. The correlation between DNA length and retention was measured and theoretically described in a length range of 50–500 bp, promising for the determination of DNA of an unknown length. Finally, a separation example demonstrated the excellent separation power of on‐chip IP‐RP chromatography by achieving a large operation range of DNA length (10–300 bp) with a 5‐bp difference among 11 dsDNA fragments.
Integrated electrokinetic sample fractionation and solid‐phase extraction in microfluidic devices
Authors: Wang Zhen , Jemere Abebaw B. , Jed Harrison D.
Published: July 2012

A microfluidic device that performs “in space” sample fractionation, collection, and preconcentration for proteomics is described. Effluents from a 2.75 mm long fractionation channel, focused via sheath flow, were sequentially delivered into an array of 36‐collection channels containing monolithic polymer beds for SPE. Optimum conditions for the device design, and simultaneous photolytic fabrication of 36 monolithic columns in the 36 channels, as well as for their proper performance in electrokinetic sample fractionation and collection are described. A hydrophobic butyl methacrylate‐based monolithic porous polymer was copolymerized with an ionizable monomer, acryloamido‐methyl‐propane sulfonate, to form a polymer monolith for SPE that also sustains cathodic electroosmotic flow. The SPE bed was made deep enough to greatly reduce the linear flow rate within the bed, in order to compensate for the lower electroosmotic mobility of the cationically charged SPE bed relative to the glass walled device. Under these conditions, electrokinetic fractionation of a protein sample resulted in tightly focused sample zones delivered into each of the 36‐channel polymer beds with no observed crosscontamination. Monolithic columns showed reproducible performance with preconcentration factor of 30 for 2 min loading time. The ability to fractionate, collect, and preconcentrate samples on a microfluidic platform will be especially useful for automated or continuous operation of these devices in proteomics research.
Homotypic cell cannibalism, a cell‐death process regulated by the nuclear protein 1, opposes to metastasis in pancreatic cancer
Authors: Cano Carla E. , Sandí María José , Hamidi Tewfik , Calvo Ezequiel L. , Turrini Olivier , Bartholin Laurent , Loncle Céline , Secq Véronique , Garcia Stéphane , Lomberk Gwen , Kroemer Guido , Urrutia Raul , Iovanna Juan L.
Published: July 2012

Pancreatic adenocarcinoma (PDAC) is an extremely deadly disease for which all treatments available have failed to improve life expectancy significantly. This may be explained by the high metastatic potential of PDAC cells, which results from their dedifferentiation towards a mesenchymal phenotype. Some PDAC present cell‐in‐cell structures whose origin and significance are currently unknown. We show here that cell‐in‐cells form after homotypic cell cannibalism (HoCC). We found PDAC patients whose tumours display HoCC develop less metastasis than those without. In vitro, HoCC was promoted by inactivation of the nuclear protein 1 (Nupr1), and was enhanced by treatment with transforming growth factor β. HoCC ends with death of PDAC cells, consistent with a metastasis suppressor role for this phenomenon. Hence, our data indicates a protective role for HoCC in PDAC and identifies Nupr1 as a molecular regulator of this process.
Genetic and environmental factors in late onset dementia: possible role for early parental death
Authors: Whalley Lawrence J. , Staff Roger T. , Murray Alison D. , Deary Ian J. , Starr John M.
Published: July 2012

Objective

We aimed to investigate three reports of a possible role of early parental death in late onset dementia. We tested a multivariate model of risk factors for late onset dementia that included established (female sex, a family history of dementia, APOE ε4) and putative influences (vascular risk factors, years of full‐time education, parental ages at death, and childhood IQ) on dementia risk.

Methods

We examined contributions of early life and late life risk factors for dementia by using childhood social and family data and blood samples obtained at interview at age about 78 years. In 1997–1999, we recruited 281 subjects without dementia from a 1932 Scottish IQ survey of children born in 1921 and followed them up to 2010 (at age 88). Binary logistic regression and Bayesian structural equation modelling were used to model dementia risk.

Results

Risk of dementia was associated with increasing age from 77 to 88 years, female sex, death of either parent before age 11 and APOE ε4 genotype. Family history of dementia, childhood IQ, years of education and vascular risk factors did not contribute to the model.

Conclusions

Our multivariate models of the possible causes of late onset dementia confirm previous associations of dementia with female sex and APOE ε4 genotype and supports earlier reports of a role for early parental death. Copyright © 2012 John Wiley & Sons, Ltd.
C-terminal truncated hepatitis B virus x protein is associated with metastasis and enhances invasiveness by c-jun/matrix metalloproteinase protein 10 activation in hepatocellular carcinoma
Authors: Sze Karen M.F. , Chu Glanice K.Y. , Lee Joyce M.F. , Ng Irene O.L.
Published: July 2012

Random integration of hepatitis B virus (HBV) DNA into the host genome is frequent in human hepatocellular carcinoma (HCC) and this leads to truncation of the HBV DNA, particularly at the C-terminal end of the HBV X protein (HBx). In this study, we investigated the frequency of this natural C-terminal truncation of HBx in human HCCs and its functional significance. In 50 HBV-positive patients with HCC, full-length HBx was detected in all nontumorous livers. However, full-length HBx was found in only 27 (54%) of the HCC tumors, whereas natural carboxylic acid (COOH)-truncated HBx was found in the remaining 23 (46%) tumors. Upon clinicopathological analysis, the presence of natural COOH-truncated HBx significantly correlated with the presence of venous invasion, a hallmark of metastasis (P = 0.005). Inducible stable expression of the COOH-truncated HBx protein (with 24 amino acids truncated at the C-terminal end) enhanced the cell-invasive ability of HepG2 cells, as compared to full-length HBx, using the Matrigel cell-invasion assay. It also resulted in increased C-Jun transcriptional activity and enhanced transcription of matrix metalloproteinase 10 (MMP10), whereas activation of the MMP10 promoter by COOH-truncated HBx was abolished when the activator protein 1–binding sites on the MMP10 promoter were mutated. Furthermore, silencing of MMP10 by short interfering RNA in HBxΔC1-expressing HepG2 cells resulted in significant reduction of cell invasiveness. Conclusions: Our data suggest that COOH truncation of HBx, particularly with 24 amino acids truncated at the C-terminal end, plays a role in enhancing cell invasiveness and metastasis in HCC by activating MMP10 through C-Jun. (Hepatology 2013)
Scavenger receptor a restrains T-cell activation and protects against concanavalin A-induced hepatic injury
Authors: Zuo Daming , Yu Xiaofei , Guo Chunqing , Wang Hongxia , Qian Jie , Yi Huanfa , Lu Xiao , Lv Zhi-Ping , Subjeck John R. , Zhou Huiping , Sanyal Arun J. , Chen Zhengliang , Wang Xiang-Yang
Published: July 2012

Negative feedback immune mechanisms are essential for maintenance of hepatic homeostasis and prevention of immune-mediated liver injury. We show here that scavenger receptor A (SRA/CD204), a pattern recognition molecule, is highly up-regulated in the livers of patients with autoimmune or viral hepatitis, and of mice during concanavalin A (Con A)-induced hepatitis (CIH). Strikingly, genetic SRA ablation strongly sensitizes mice to Con A-induced liver injury. SRA loss, increased mortality and liver pathology correlate with excessive production of IFN-γ and heightened activation of T cells. Increased liver expression of SRA primarily occurs in mobilized hepatic myeloid cells during CIH, including CD11b+Gr-1+ cells. Mechanistic studies establish that SRA on these cells functions as a negative regulator limiting T-cell activity and cytokine production. SRA-mediated protection from CIH is further validated by adoptive transfer of SRA+ hepatic mononuclear cells or administration of a lentivirus-expressing SRA, which effectively ameliorates Con A-induced hepatic injury. Also, CIH and clinical hepatitis are associated with increased levels of soluble SRA. This soluble SRA displays a direct T-cell inhibitory effect and is capable of mitigating Con A-induced liver pathology. Conclusion: Our findings demonstrate an unexpected role of SRA in attenuation of Con A-induced, T-cell-mediated hepatic injury. We propose that SRA serves as an important negative feedback mechanism in liver immune homeostasis, and may be exploited for therapeutic treatment of inflammatory liver diseases. (Hepatology 2013)
Retracted: The Relationship between Personality Traits and Sales Force Automation Usage: A Review of Methodology
Authors: Chen Cheng‐Wu , Yang Han‐Chung , Chen Chia‐Hung , Tseng Chun‐Pin , Lee King‐Ling
Published: July 2012

In recent decades, pharmaceutical companies have been facing increasing difficulties in sustaining sales growth due to tight market competition (off‐patents, pricing erosion, and generics substitution). Pharmaceutical companies are desperately seeking ways to sustain and optimize their sales coverage and sales volume in the middle and long term. In such unpromising circumstances, one of the few options that comes to mind is customer relationship management (CRM). This study specifically looks at the “utilization‐individual impact” link. In particular, this study aims to identify the personality type of sales representative most closely linked with individual usage of sales forces automation systems in the pharmaceutical industry in Taiwan. © 2012 Wiley Periodicals, Inc.
Overexpression of HnRNP A1 promotes tumor invasion through regulating CD44v6 and indicates poor prognosis for hepatocellular carcinoma
Authors: Zhou Zheng‐Jun , Dai Zhi , Zhou Shao‐Lai , Fu Xiu‐Tao , Zhao Yi‐Ming , Shi Ying‐Hong , Zhou Jian , Fan Jia
Published: July 2012

Heterogeneous ribonucleoprotein (hnRNP) A1 is a member of the A/B subfamily of ubiquitously expressed hnRNPs, which have a wide variety of functions in gene expression and signal transduction. To investigate the biological function and clinical significance of hnRNP A1 in hepatocellular carcinoma (HCC), we measured hnRNP A1 expression in four HCC cell lines and two independent cohorts of HCC patients. We found that hnRNP A1 was overexpressed in the highly metastatic HCC cell lines and in tumor tissues of patients with recurrent HCC. Knockdown of hnRNP A1 in highly metastatic HCC cells caused a significant decrease in cell invasion, while upregulation of hnRNP A1 in poorly metastatic HCC cells led to a significant increase in their invasive capacity. We found that this effect may occur through the regulation of CD44v6 expression by hnRNP A1 in HCC cells. Both quantitative reverse transcription‐polymerase chain reaction (qRT‐RCR) and immunohistochemistry revealed that hnRNP A1 was upregulated in HCC tissues and coincided with overexpression of CD44v6. HCC patients with high hnRNP A1 tended to have higher levels of CD44v6, shorter overall survival (OS) and higher rates of tumor recurrence. Multivariate analyses revealed that hnRNP A1 alone or in combination with CD44v6 were independent prognostic indicators for OS and time to recurrence and have potential as therapeutic targets. In conclusion, overexpression of hnRNP A1 promotes HCC invasion by regulating the level of CD44v6 and indicates a poor prognosis for HCC patients after curative resection.
Biodegradable composites with aligned hydroxyapatite nanoneedles
Authors: Sun Shih‐Po , Wei Mei , Olson James R. , Shaw Montgomery T.
Published: July 2012

We prepared an anisotropic bone graft composite to mimic the hierarchical structure of the natural bone in which aligned hydroxyapatite (HA) nanocrystals deposit along collagen fibers. To approach the modulus and strength of the bone, we incorporated synthesized HA nanoneedles and melt drawn poly(L‐lactic acid) fibers in our composite as reinforcing components. Their preferred orientation was induced via a modified pultrusion process. The HA orientation distribution was examined using wide angle X‐ray diffraction. Micromechanical Halpin–Tsai model predictions considering the amount, shape, and orientation distribution of HA were compared, favorably, with the experimental observations. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
Understanding bioactivity and polarizability of hydroxyapatite doped with tungsten
Authors: Dhal Jharana , Fielding Gary , Bose Susmita , Bandyopadhyay Amit
Published: July 2012

This study investigates the use of hydroxyapatite (HAp) doped with hexavalent tungsten to improve its interaction with bone cells and to influence the polarizing capacity of HAp. Increases in dopant concentration increased the β‐TCP phases and decreased the HAp phases in sintered samples. Results of thermally stimulated depolarization current measurements suggested that doped HAp had stored fewer charge compared with pure HAp. However, the decrease in stored charge was related to fraction of HAp or β‐TCP phases present in sintered samples. Activation energy of dipole relaxation and stored charge was used to examine the mechanism of polarization. The charge stored in doped samples due to polarization was attributed to the migration of H+ ions in HAp phases and O2− or Ca2+ ions in β‐TCP phases. Hindrance of ion migration due to the presence of different phases appeared to lower charge storage ability in doped samples. In vitro study revealed an increase in bioactivity of doped HAp when compared with pure HAp. Polarization further improved the bioactivity of doped HAp. Results of our study provide evidence for the use of higher valent cations to improve biological performance of HAp ceramics. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
Behavior of poly(glycerol sebacate) plugs in chronic tympanic membrane perforations
Authors: Sundback C. A. , McFadden J. , Hart A. , Kulig K. M. , Wieland A. M. , Pereira M. J. N. , Pomerantseva I. , Hartnick C. J. , Masiakos P. T.
Published: July 2012

The tympanic membrane (TM), separating the external and middle ear, consists of fibrous connective tissue sandwiched between epithelial layers. To treat chronic ear infections, tympanostomy drainage tubes are placed in surgically created holes in TMs which can become chronic perforations upon extrusion. Perforations are repaired using a variety of techniques, but are limited by morbidity, unsatisfactory closure rates, or minimal regeneration of the connective tissue. A more effective, minimally‐invasive therapy is necessary to enhance the perforation closure rate. Current research utilizing decellularized or alignate materials moderately enhance closure but the native TM architecture is not restored. Poly(glycerol sebacate) (PGS) is a biocompatible elastomer which supports cell migration and enzymatically degrades in contact with vascularized tissue. PGS spool‐shaped plugs were manufactured using a novel process. Using minimally invasive procedures, these elastomeric plugs were inserted into chronic chinchilla TM perforations. As previously reported, effective perforation closure occurred as both flange surfaces were covered by confluent cell layers; >90% of perforations were closed at 6‐week postimplantation. This unique in vivo environment has little vascularized tissue. Consequently, PGS degradation was minimal over 16‐week implantation, hindering regeneration of the TM fibrous connective tissue. PGS degradation must be enhanced to promote complete TM regeneration. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
Dual functionalization of titanium with vascular endothelial growth factor and β‐defensin analog for potential application in keratoprosthesis
Authors: Tan Xiao Wei , Lakshminarayanan R. , Liu Shou Ping , Goh Eunice , Tan Donald , Beuerman Roger W. , Mehta Jodhbir S.
Published: July 2012

Functionalization of material surfaces can improve their biointegration and bactericidal effect. To expand the biomedical applications of titanium in artificial cornea implantation surgery, titanium alloy substrates were coated with polydopamine and dual bound with recombinant vascular endothelial growth factor (VEGF) and anti‐microbial peptide (AMP), SESB2V. Successful chemical binding was assessed with attenuated total reflectance‐Fourier transform infrared spectroscopy and X‐ray photoelectron spectroscopy. Coating thickness was assessed by atomic force microscopy. Cellular studies revealed that the functionalized substrates displayed the abilities to enhance primary human corneal fibroblast adhesion, proliferation, and viability. Angiogenesis assay with human mesenchymal stem cells was used to verify the biological functions of immobilized VEGF while bactericidal assay was evaluated for the anti‐microbial activities of immobilized SESB2V peptide. We found that the titanium surface that was sequentially functionalized with VEGF and SESB2V had enhanced fibroblast proliferation and anti‐microbial properties. The incorporation of such peptides into an artificial cornea implant is important for implant‐tissue integration and wound healing. This may improve implant integration and reduce the risk of device infection following artificial cornea implantation. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
Design of Angiotensin‐converting Enzyme 2 (ACE2) Inhibitors by Virtual Lead Optimization and Screening
Authors: Torres Juan E. , Baldiris Rosa , Vivas‐Reyes Ricardo
Published: July 2012

A group of presumed drug‐like molecules that possess high in silico affinity for angiotensin‐converting enzyme 2 were computationally designed. This enzyme is a promising new target in both cardiorenal disease and some coronavirus infections. A set of substrate analogous molecules were optimized by means of the LeapFrog module of the SYBYL package. Later, Molinspiration and Molsoft were used for screening out the compounds with low oral bioavailability. Similarly, OSIRIS was used for screening out the compounds having serious side effects. At the end of several stages of screening, seven candidates to anti‐viral drugs fulfiling all the evaluated criteria were obtained. They are amenable for future studies in vitro and in vivo. These designed ligands were finally evaluated by Quantitative Structure Activity Relationship studies. 21 molecules were used to carry out the qsar models. Fom these four molecules were taken as external sets yielding models with q2 = 0.652 and r2 = 0.962 values.
Nanoporous Carbon as Anode Material of High Rate Capability for Lithium Ion Batteries
Authors: Liu Li‐Li , Tian Shu , Zhu Yu‐Song , Tang Wei , Li Lin‐Lin , Wu Yu‐Ping
Published: July 2012

A nanoporous carbon was prepared by calcining a mixture of nano‐CaCO3 and phenolic resin followed by an etching process to remove the remained impurities. It was characterized by X‐ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and charge–discharge measurement. With a pore‐distribution concentrated around 50 nm, the product presents a BET surface area of 543 m2/g. When used as an anode material for lithium ion battery, the nanoporous carbon exhibits good rate capability and cycling performance.
An Electrochemical Approach for Estimation of Intrinsic Active Area and Activation of Pt/C Nano‐catalysts
Authors: Pan Chun‐Jern , Su Wei‐Nien , Kumar Sakkarapalayam Murugesan Senthil , Al Andra Cun Cun , Yang Shaw‐Jing , Chen Hung‐Yi , Hwang Bing Joe
Published: July 2012

A methodology has been developed for the estimation of intrinsic active area of Pt/C nano‐catalysts which is crucial for the evaluation of catalyst's utilization in a membrane‐electrode‐assembly (MEA). The evaluation was carried out by employing the H‐UPD and CO stripping methods for both a thin porous Pt/C‐Nafion film coated on a glassy carbon disk and a carbon paper electrode. The results demonstrate that the measured values of intrinsic active area (i.e., the extents of utilization) of Pt/C in Nafion ionomer films are identical at both glassy carbon (GC) and carbon paper surfaces from 2 to 330 μg‐Pt/cm2 loading. However, the measured active area is strongly dependent on the electrode support for the loadings greater than 330 μg‐Pt /cm2 where the carbon paper electrodes show much higher active areas. Three different pre‐activation methods have been adopted to activate all the Pt sites in the catalyst layer namely potential cycling and constant potential treatment at an applied potential of 0 or 1.2 V (RHE). These results demonstrate the necessity of such a simple and convenient pre‐operation activation treatment for Pt/C catalysts in MEA to assess their intrinsic active area towards the electrochemical reactions.