bluuebunny/crossref_metadata_2025 huggingface dataset:
Advanced Electron Microscopy for Advanced Materials
Authors: Van Tendeloo Gustaaf , Bals Sara , Van Aert Sandra , Verbeeck Jo , Van Dyck Dirk
Published: August 2012

The idea of this Review is to introduce newly developed possibilities of advanced electron microscopy to the materials science community. Over the last decade, electron microscopy has evolved into a full analytical tool, able to provide atomic scale information on the position, nature, and even the valency atoms. This information is classically obtained in two dimensions (2D), but can now also be obtained in 3D. We show examples of applications in the field of nanoparticles and interfaces.
Compensation of pleural mesothelioma in France: Data from the French National Mesothelioma Surveillance Programme
Authors: Chamming's Soizick , Clin Bénédicte , Brochard Patrick , Astoul Philippe , Ducamp Stéphane , Galateau‐Salle Fançoise , Ilg Annabelle Gilg Soit , Goldberg Marcel , Gramond Céline , Imbernon Ellen , Rolland Patrick , Pairon Jean‐Claude
Published: August 2012

Background

The aim of this study was to determine the rates of compensation awarded to patients presenting with pleural mesothelioma and factors linked to such compensation in France.

Methods

The study population consisted of 2,407 patients presenting with pleural mesothelioma, recorded by the National Mesothelioma Surveillance Programme between January 1, 1999 and December 31, 2009. Analysis of claims for recognition as “occupational disease” (OD) and claims for compensation by the Compensation Fund for Asbestos Victims (FIVA) were analyzed.

Results

Approximately 30% of subjects presenting with pleural mesothelioma, affiliated to the General National Health Insurance fund, neither sought recognition as an OD nor claimed for FIVA compensation. Gender, age at diagnosis, type of health insurance, and socio‐professional category influence the likelihood of patients presenting with mesothelioma seeking compensation for this disease.

Conclusions

Results show an under‐compensation of pleural mesothelioma as OD and by the FIVA in France. Am. J. Ind. Med. 56:146–154, 2013. © 2011 Wiley Periodicals, Inc.
Blood cadmium, mercury, and lead and metabolic syndrome in South Korea: 2005–2010 Korean National Health and Nutrition Examination Survey
Authors: Lee Byung‐Kook , Kim Yangho
Published: August 2012

Introduction

We present data from the Korean National Health and Nutrition Examination Survey 2005–2010 regarding the association between levels of blood cadmium, mercury, and lead and metabolic syndrome (MS) in a representative sample of the adult South Korean population. MS is defined as a cluster of disorders including central obesity, glucose intolerance, hypertension, low high‐density lipoprotein cholesterol, and high triglycerides.

Methods

The analysis was restricted to participants ≥20 years of age who completed the health examination survey, including blood lead, cadmium, and mercury measurements. Odds ratios (ORs) for MS were calculated for log2‐transformed blood metal levels and tertiles thereof after covariate adjustment.

Results

No significant results were observed in females. In males, adjusted ORs indicated that a doubling of blood cadmium resulted in a 23.0% increase in the risk of MS. Male subjects in the highest tertile of blood cadmium were 36.7% more likely to have MS versus those in the lowest tertile. There were no significant ORs for having MS or its components in any of the models of blood lead and mercury levels after covariate adjustment.

Conclusion

The association between blood cadmium level and MS was significant regardless of the type of variable (continuous or categorical) among men with lower blood cadmium levels. Thus, blood cadmium levels were robust risk factors for MS in men. To our knowledge, this is the first report of an association between cadmium exposure and MS. Am. J. Ind. Med. 56:682–692, 2013. © 2012 Wiley Periodicals, Inc.
The conditions of cationic exchange with the use of recycling polystyrene derivative, the product of sulfonation by silica sulfuric acid
Authors: Sułkowski Wiesław W. , Nowak Krzysztof , Sułkowska Anna , Mikuła Barbara , Wierzba Piotr
Published: August 2012

Growing amount of waste plastics has become an environmental problem on a global scale. This study presents an investigation of the conditions of cleaning water from heavy metal ions using chemically recycled polystyrene. To get effective ion exchangers, the sulfonation of virgin polystyrene and expanded polystyrene wastes were obtained using silica sulfuric acid. As it turned out, the use of this solid sulfonating agent simplifies the separation of the polymeric product from the acid and the solvent in comparison to conventional sulfonation methods. The ion exchange behavior of copper and zinc cations in the yielded sulfonated derivatives of polystyrene was studied. Batch shaking adsorption experiments depending on contact time, pH, temperature, and dosage of adsorbate were carried out. The stability of resin to cyclical adsorption and regeneration (column experiment) was also investigated. We report that resins have a high adsorption efficiency with total ion exchange capacity (IEC) about 2.6 meq g−1, which drops with decreasing pH owing to competition between protons H+ and metal cations, whereas with the increasing resin doses the removal of cations rises for a constant initial metal concentration. The speed of cation exchange for yielded adsorbents was even better than for commercial resins. After 360 cyclical adsorption and regeneration in column, resin had working IEC of about 2.3 meq g−1. The study shows that cation exchange resin from polystyrene wastes can be used as an efficient adsorbent for the removal of heavy metal ions from water. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Mitochondrial Swelling and Incipient Outer Membrane Rupture in Preapoptotic and Apoptotic Cells
Authors: Sesso A. , Belizário J.E. , Marques M.M. , Higuchi M.L. , Schumacher R.I. , Colquhoun A. , Ito E. , Kawakami J.
Published: August 2012

Outer mitochondrial membrane (OMM) rupture was first noted in isolated mitochondria in which the inner mitochondrial membrane (IMM) had lost its selective permeability. This phenomenon referred to as mitochondrial permeability transition (MPT) refers to a permeabilized inner membrane that originates a large swelling in the mitochondrial matrix, which distends the outer membrane until it ruptures. Here, we have expanded previous electron microscopic observations that in apoptotic cells, OMM rupture is not caused by a membrane stretching promoted by a markedly swollen matrix. It is shown that the widths of the ruptured regions of the OMM vary from 6 to 250 nm. Independent of the perforation size, herniation of the mitochondrial matrix appeared to have resulted in pushing the IMM through the perforation. A large, long focal herniation of the mitochondrial matrix, covered with the IMM, was associated with a rupture of the OMM that was as small as 6 nm. Contextually, the collapse of the selective permeability of the IMM may precede or follow the release of the mitochondrial proteins of the intermembrane space into the cytoplasm. When the MPT is a late event, exit of the intermembrane space proteins to the cytoplasm is unimpeded and occurs through channels that transverse the outer membrane, because so far, the inner membrane is impermeable. No channel within the outer membrane can expose to the cytoplasm a permeable inner membrane, because it would serve as a conduit for local herniation of the mitochondrial matrix. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.
Joint monitoring and prediction of accrual and event times in clinical trials
Authors: Zhang Xiaoxi , Long Qi
Published: August 2012

In many clinical trials, the primary endpoint is time to an event of interest, for example, time to cardiac attack or tumor progression, and the statistical power of these trials is primarily driven by the number of events observed during the trials. In such trials, the number of events observed is impacted not only by the number of subjects enrolled but also by other factors including the event rate and the follow‐up duration. Consequently, it is important for investigators to be able to monitor and predict accurately patient accrual and event times so as to predict the times of interim and final analyses and enable efficient allocation of research resources, which have long been recognized as important aspects of trial design and conduct. The existing methods for prediction of event times all assume that patient accrual follows a Poisson process with a constant Poisson rate over time; however, it is fairly common in real‐life clinical trials that the Poisson rate changes over time. In this paper, we propose a Bayesian joint modeling approach for monitoring and prediction of accrual and event times in clinical trials. We employ a nonhomogeneous Poisson process to model patient accrual and a parametric or nonparametric model for the event and loss to follow‐up processes. Compared to existing methods, our proposed methods are more flexible and robust in that we model accrual and event/loss‐to‐follow‐up times jointly and allow the underlying accrual rates to change over time. We evaluate the performance of the proposed methods through simulation studies and illustrate the methods using data from a real oncology trial.
2,2′:3′,2′′‐Terthiophene‐Based all‐Thiophene Dendrons and Dendrimers: Synthesis, Structural Characterization, and Properties
Authors: Ma Chang‐Qi , Mena‐Osteritz Elena , Wunderlin Markus , Schulz Gisela , Bäuerle Peter
Published: August 2012

The synthesis of generational dendritic oligothiophenes (DOTs) has been successfully achieved by a divergent/convergent approach that involves halogenation, boronation, and palladium‐catalyzed Suzuki coupling reactions. The key point in the presented synthetic approach is the use of trimethylsilyl (TMS) protecting groups, which allow for the core‐lithiation and subsequent boronation of the dendrons and for the peripheral ipso‐substitution with iodine monochloride or N‐bromosuccimide. In addition, the TMS protecting groups can be completely removed by using tetrabutylammonium fluoride, thus yielding only‐thiophene‐based dendrons and dendrimers. Due to their highly branched structure, all these synthesized DOTs are soluble in organic solvents. Chemical structures were confirmed by NMR spectroscopic, mass spectrometric, and elemental analysis. Concentration‐dependent 1H NMR spectroscopic investigations revealed that the higher generation compounds tend to aggregate in solution. Such an aggregation behavior was further confirmed by measuring with MALDI‐TOF MS. Both MALDI‐TOF MS and gel‐permeation chromatography (GPC) analyses confirmed the monodispersity of the DOTs. Furthermore, GPC results revealed that these DOT molecules adopt a condensed globular molecular shape. Their optical and electronic properties were also investigated. The results indicated that these DOTs comprise various conjugated α‐oligothiophenes with different chain lengths, which results in the higher generation compounds showing broad and featureless UV/Vis absorption spectra and ill‐defined redox waves.
Absolute Stereochemical Determination of Chiral Carboxylates Using an Achiral Molecular Tweezer
Authors: Yoon Hongsik , Lee Chi‐Hwa , Jang Woo‐Dong
Published: August 2012

A new type of molecular tweezer (1) has been synthesized for the direct determination of the absolute configuration of chiral carboxylates without analyte derivatization. Upon the addition of diamine and anionic guests, 1 exhibited shifts in its absorption spectrum with clear isosbestic points. The continuous variation method indicated that both the diamine and anionic guests form 1:1 host–guest complexes with 1 with very high binding affinity. When Boc‐L‐Ala (BLA) as a form of tetrabutylammonium salt was added to 1, a weak negative CD signal was observed. This weak CD signal was dramatically changed to a strong positive CD couplet upon addition of achiral 1,12‐diaminododecane. Such a positive CD couplet was observed for all of the tested L‐amino acid derivatives, while the D‐amino acid derivatives gave the opposite signals. As a result of these unique characteristics of 1, it can be utilized as a highly sensitive probe for the absolute stereochemical determination of chiral carboxylates.
On the Mechanism Behind the Instability of Isoreticular Metal–Organic Frameworks (IRMOFs) in Humid Environments
Authors: Bellarosa Luca , Castillo Juan Manuel , Vlugt Thijs , Calero Sofía , López Núria
Published: August 2012

Increasing the resistance to humid environments is mandatory for the implementation of isoreticular metal–organic frameworks (IRMOFs) in industry. To date, the causes behind the sensitivity of [Zn4(μ4‐O)(μ‐bdc)3]8 (IRMOF‐1; bdc=1,4‐benzenedicarboxylate) to water remain still open. A multiscale scheme that combines Monte Carlo simulations, density functional theory and first‐principles Born–Oppenheimer molecular dynamics on IRMOF‐1 was employed to unravel the underlying atomistic mechanism responsible for lattice disruption. At very low water contents, H2O molecules are isolated in the lattice but provoke a dynamic opening of the terephthalic acid, and the lattice collapse occurs at about 6 % water weight at room temperature. The ability of Zn to form fivefold coordination spheres and the increasing basicity of water when forming clusters are responsible for the displacement of the organic linker. The present results pave the way for synthetic challenges with new target linkers that might provide more robust IRMOF structures.
A Highly anti‐Selective Asymmetric Henry Reaction Catalyzed by a Chiral Copper Complex: Applications to the Syntheses of (+)‐Spisulosine and a Pyrroloisoquinoline Derivative
Authors: Xu Kun , Lai Guoyin , Zha Zhenggen , Pan Susu , Chen Huanwen , Wang Zhiyong
Published: August 2012

A highly anti‐selective asymmetric Henry reaction has been developed, affording synthetically versatile β‐nitroalcohols in a predominately anti‐selective manner (mostly above 15:1) and excellent ee values (mostly above 95 %). Moreover, the anti‐selective Henry reaction was carried out in the presence of water for the first time with up to 99 % ee. The catalytic mechanism was proposed based on the detection of the intermediates by extractive electrospray ionization mass spectrometry (EESI‐MS). Furthermore, the anti adducts have been successfully transformed into the biochemically important (+)‐spisulosine and a pyrroloisoquinoline derivative.
Synthesis of High‐Quality Diesel with Furfural and 2‐Methylfuran from Hemicellulose
Authors: Li Guangyi , Li Ning , Wang Zhiqiang , Li Changzhi , Wang Aiqin , Wang Xiaodong , Cong Yu , Zhang Tao
Published: August 2012

Hydroxyalkylation–alkylation (HAA) coupled with hydrodeoxygenation is a promising route for the synthesis of renewable high‐quality diesel or jet fuel. In this work, a series of solid‐acid catalysts were firstly used for HAA between lignocellulose‐derived furan and carbonyl compounds. Among the investigated catalysts, Nafion‐212 resin demonstrated the highest activity and stability. Owing to the high activity of the reactants and the advantage in industrial integration, the HAA of 2‐methylfuran (2‐MF) and furfural can be considered as a prospective route in future applications. Catalyst loading, reaction temperature, and time had evident effects on the HAA of 2‐MF and furfural over Nafion‐212 resin. Finally, the HAA product of 2‐MF and furfural was hydrogenated over a Pd/C catalyst and hydrodeoxygenated over Pt‐loaded solid‐acid catalysts. Pt/zirconium phosphate (Pt/ZrP) was found to be the best catalyst for hydrodeoxygenation. Over the 4 % Pt/ZrP catalyst, a 94 % carbon yield of diesel and 75 % carbon yield of C15 hydrocarbons (with 6‐butylundecane as the major component) was achieved.
Efficient CO2 Capture by Porous, Nitrogen‐Doped Carbonaceous Adsorbents Derived from Task‐Specific Ionic Liquids
Authors: Zhu Xiang , Hillesheim Patrick C. , Mahurin Shannon M. , Wang Congmin , Tian Chengcheng , Brown Suree , Luo Huimin , Veith Gabriel M. , Han Kee Sung , Hagaman Edward W. , Liu Honglai , Dai Sheng
Published: August 2012

The search for a better carbon dioxide (CO2) capture material is attracting significant attention because of an increase in anthropogenic emissions. Porous materials are considered to be among the most promising candidates. A series of porous, nitrogen‐doped carbons for CO2 capture have been developed by using high‐yield carbonization reactions from task‐specific ionic liquid (TSIL) precursors. Owing to strong interactions between the CO2 molecules and nitrogen‐containing basic sites within the carbon framework, the porous nitrogen‐doped compound derived from the carbonization of a TSIL at 500 °C, CN500, exhibits an exceptional CO2 absorption capacity of 193 mg of CO2 per g sorbent (4.39 mmol g−1 at 0 °C and 1 bar), which demonstrates a significantly higher capacity than previously reported adsorbents. The application of TSILs as precursors for porous materials provides a new avenue for the development of improved materials for carbon capture.
A simple and novel method for RNA‐seq library preparation of single cell cDNA analysis by hyperactive Tn5 transposase
Authors: Brouilette Scott , Kuersten Scott , Mein Charles , Bozek Monika , Terry Anna , Dias Kerith‐Rae , Bhaw‐Rosun Leena , Shintani Yasunori , Coppen Steven , Ikebe Chiho , Sawhney Vinit , Campbell Niall , Kaneko Masahiro , Tano Nobuko , Ishida Hidekazu , Suzuki Ken , Yashiro Kenta
Published: August 2012

Background: Deep sequencing of single cell‐derived cDNAs offers novel insights into oncogenesis and embryogenesis. However, traditional library preparation for RNA‐seq analysis requires multiple steps with consequent sample loss and stochastic variation at each step significantly affecting output. Thus, a simpler and better protocol is desirable. The recently developed hyperactive Tn5‐mediated library preparation, which brings high quality libraries, is likely one of the solutions. Results and Conclusions: Here, we tested the applicability of hyperactive Tn5‐mediated library preparation to deep sequencing of single cell cDNA, optimized the protocol, and compared it with the conventional method based on sonication. This new technique does not require any expensive or special equipment, which secures wider availability. A library was constructed from only 100 ng of cDNA, which enables the saving of precious specimens. Only a few steps of robust enzymatic reaction resulted in saved time, enabling more specimens to be prepared at once, and with a more reproducible size distribution among the different specimens. The obtained RNA‐seq results were comparable to the conventional method. Thus, this Tn5‐mediated preparation is applicable for anyone who aims to carry out deep sequencing for single cell cDNAs. Developmental Dynamics 241:1584–1590, 2012. © 2012 Wiley Periodicals Inc.
Analysis of Amyloid Beta Aggregation Kinetics Using Sym‐Triazine β‐Sheet Inhibitors
Authors: Veloso Anthony J. , Hung Vinci W. S. , Cheng Xin R. , Kerman Kagan
Published: August 2012

AD (Alzheimer’s disease) is a progressive neurodegenerative disorder characterized by the cerebral accumulation of fibrillar amyloid‐beta (Aβ) aggregates. Here we present the electrochemistry of two novel sym‐triazine derivatives (TAE‐1, TAE‐2) as modulators of Aβ1–42 aggregation in vitro. Incubation studies conducted at physiological conditions demonstrated strong inhibition of β‐sheet fibril formation. Uniquely, square‐wave voltammetry indicated progressive changes in the surface‐availability of amyloid‐intercalated triazines for oxidation, mediated by competing peptide self‐assembly. Time‐resolved voltammetric analysis showed increasing anodic peak currents (≥3‐fold) and progressive shifts in redox potentials, measured over 24 h. The more potent aggregation modulator (TAE‐2) showed prolonged association during the pre‐nucleation states of Aβ.
Fate and effects of acetyl cedrene in sediments inhabited by different densities of the deposit feeder, Capitella teleta
Authors: Dai Lina , Selck Henriette , Salvito Daniel , Forbes Valery E.
Published: August 2012

Fragrance materials, such as acetyl cedrene (AC), are of environmental concern because they are continuously released to aquatic systems down the drain. In the present study, Capitella teleta (formerly Capitella capitata species I) was exposed to AC-amended sediment at two population densities corresponding to 44,000 and 88,000 worms/m2. The fate of AC in systems with worms was compared to that in identical systems without worms. We examined the toxicity of AC on worm survival, growth, and feeding rate, and quantified the fate of AC in exposure systems by mass balance. Worm survival was close to 100% in all treatments. Acetyl cedrene had some positive effects on worm growth, but not feeding, whereas density had negative effects on both growth and feeding rates. After 14 d, the sediment concentration of AC was reduced by 88 to 99% in the presence of worms, whereas sediment AC concentration was reduced by 13 to 31% or less in the absence of worms. Acetyl cedrene was detected in fecal pellets, at low concentrations compared to the initial concentration in the sediment, but not in worm tissue, suggesting that ingested AC is bioavailable to Capitella teleta and that worms can biotransform sediment-associated AC effectively. Environ. Toxicol. Chem. 2012; 31: 2639–2646. © 2012 SETAC
Airway management after maxillectomy with free flap reconstruction
Authors: Brickman Daniel S. , Reh Douglas D. , Schneider Daniel S. , Bush Ben , Rosenthal Eben L. , Wax Mark K.
Published: August 2012

Background

Maxillectomy defects require complex 3‐dimensional reconstructions often best suited to microvascular free tissue transfer. Postoperative airway management during this procedure has little discussion in the literature and is often dictated by surgical dogma. The purpose of this article was to review our experience in order to evaluate the effect of airway management on perioperative outcomes in patients undergoing maxillectomy with free flap reconstruction.

Methods

A retrospective chart review was performed on patients receiving maxillectomy with microvascular reconstruction at 2 institutions between 1999 and 2011. Patient's airways were managed with or without elective tracheotomy at the surgical team's discretion and different perioperative outcomes were measured. The primary outcome was incidence of airway complication including pneumonia and need for further airway intervention. Secondary outcome was measured as factors leading to perioperative performance of the tracheotomy.

Results

Seventy‐nine of 143 patients received elective tracheotomy perioperatively. The incidence of airway complication was equivalent between groups (10.1% vs 9.4%; p = .89). Patients with cardiopulmonary comorbidities were more likely to receive perioperative tracheotomy (74.1% vs 50.9%; p = .03) without a difference in airway complications. Other patient cofactors did not have an impact on perioperative tracheotomy or airway complication rate.

Conclusions

Elective tracheotomy may safely be avoided in a subset of patients undergoing maxillectomy with microvascular reconstruction. Elective tracheotomy should be considered in patients with cardiopulmonary risk factors. Head Neck, 2013
Aggressive fibromatosis in the head and neck region: Benign tumor with often mutilating effects
Authors: Hendriks Mathijs P. , Driessen Chantal M. L. , van Laarhoven Hanneke W. M. , Janssens Geert O. R. J. , Verbist Berit M. , van der Graaf Winette T. A. , Slootweg Piet J. , Merkx Matthias A. W. , van Herpen Carla M. L.
Published: August 2012

Background

Aggressive fibromatosis (AF) or desmoid tumor of the head and neck region is a rare, usually unresectable, benign soft tissue tumor with locally aggressive behavior.

Methods and Results

A 31‐year‐old woman presented with a progressive trismus, a swelling in the retromandibular area, as well as loss of sensibility of the maxillary and mandibular branch of the trigeminal nerve. MRI of the head and neck revealed an infiltrative mass involving the masticator, parapharyngeal, and prevertebral and paravertebral space on the left with intracranial extension through the orbital fissure. After the fifth biopsy, 15 months after presentation, the diagnosis of AF was made. The tumor was unresectable, so intensity‐modulated radiotherapy was given with curative intent using a total dose of 60 Gy in 30 fractions of 2 Gy. After 16 months, she showed progressive disease, for which tamoxifen 40 mg twice daily was started with a good response for 2 years. After that, she started with sorafinib, on which she has stable disease now.

Conclusion

The often long delay in proper diagnosis and the treatment challenges of a desmoid tumor are illustrated in this case. Furthermore, this article reviews the literature concerning AF, especially of the head and neck region. Head Neck, 2013
Angiogenesis and lymphangiogenesis in early‐stage laryngeal carcinoma: Prognostic implications
Authors: Bolzoni Villaret Andrea , Barbieri Diego , Peretti Giorgio , Schreiber Alberto , Fisogni Simona , Lonardi Silvia , Facchetti Fabio , Nicolai Piero
Published: August 2012

Background

Many studies have recently emphasized the role of tumor angiogenesis and lymphangiogenesis in regional and distant spread of disease. Although early laryngeal cancer has a favorable oncologic outcome after conservative surgery or radiation therapy, we observed few cases with poor prognosis in terms of locoregional relapse, organ preservation, and survival. The aim of our study was to evaluate the immunohistochemical expression of CD31 and podoplanin to define angiogenic and lymphangiogenic patterns and their possible prognostic implications in previously untreated T1–T2 glottic squamous cell carcinoma.

Methods

Four hundred twenty‐eight patients with previously untreated early‐stage laryngeal cancer underwent a laser surgical resection in the period between January 1994 and December 2007. Twenty‐seven cases with poor outcome were identified and compared with a selected sample of 28 patients. All specimens were negative for the presence of high‐risk human papillomavirus genotypes. Patients were followed up until death or for at least 24 months after treatment. Three‐micrometer sections were obtained from formalin‐fixed and paraffin‐embedded tumoral tissues, and an immunohistochemical evaluation was performed. Monoclonal antibodies against CD31 and podoplanin were used for the detection of blood and lymphatic vessels, respectively. A morphometric measurement was used for the analysis of angiogenesis whereas lymphangiogenesis was studied with a semiquantitative technique. The data were analyzed by use of chi‐square and Mann‐Whitney tests as appropriate.

Results

An increased tumor angiogenesis correlated with local relapse (p = .01), locoregional relapse (p = .01), and death of disease (p = .03). The presence of lymphatic vessels in peritumoral fields had an impact on local (p = .004) and locoregional recurrence (p = .01).

Conclusions

Evaluation of angiogenesis and lymphangiogenesis in early‐stage laryngeal cancer could be useful to identify patients at higher risk of recurrence and consequently to modulate treatment planning and follow‐up strategy. © 2012 Wiley Periodicals, Inc. Head Neck, 2013
Paclitaxel‐based chemotherapy for aggressive kaposiform hemangioendothelioma of the temporomastoid region: Case report and review of the literature
Authors: Funato Michinori , Fukao Toshiyuki , Sasai Hideo , Hori Tomohiro , Terazawa Daisuke , Kanda Kaori , Ozeki Michio , Mizuta Keisuke , Hirose Yoshinobu , Kaneko Hideo , Kondo Naomi
Published: August 2012

Background

Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor of infancy and childhood. This tumor results in poor prognosis, and therefore, development of a more effective treatment is needed.

Methods and Results

We describe an 11‐year‐old boy presenting with left facial palsy caused by aggressive KHE of the left temporomastoid region. He was treated with paclitaxel‐based chemotherapy, because of the difficulty with complete surgical resection for anatomic factor, multiple lung metastases on diagnosis, and no response to conventional treatments. This treatment reduced the volume of primary tumor and lung metastatic lesions, but the efficacy was transitory.

Conclusions

Paclitaxel‐based chemotherapy for aggressive KHE may be effective, therefore the multimodality therapy including paclitaxel of aggressive KHE, particularly in the head and neck, needs to be investigated in further studies. © 2012 Wiley Periodicals, Inc. Head Neck, 2013
Aggressive multimodality management of locally advanced retromolar trigone tumors
Authors: Suryanarayana Deo S. V. , Shukla Nootan K. , Kallianpur Ashwin A. , Mohanti Bidhu K. , Thulkar Sanjay P.
Published: August 2012

Background

Retromolar trigone tumors are rare and aggressive malignancies. There is lack of quality evidence pertaining to their management due to the heterogeneity in treatment policies adopted. We retrospectively reviewed the patients of locally advanced retromolar trigone tumors treated with a standard and uniform multimodality management.

Methods

A retrospective review of patients with locally advanced retromolar trigone tumors was performed and an analysis of clinicopathologic profile, treatment details, and survival outcomes was carried out.

Results

Forty‐two patients of locally advanced retromolar trigone tumors underwent the standard multimodality treatment. The majority of them presented with stage IVa disease. Margin negative resection could be achieved in 93% of patients. Histopathologically proven bone and node involvement was seen in 20 patients (47.6%) and 21 patients (50%), respectively. The 3‐year disease‐free and overall survival rates were 64% and 71%, respectively.

Conclusions

Treatment of patients with locally advanced retromolar trigone tumors is challenging. However, good oncologic outcomes can be achieved by advocating an aggressive surgical approach with postoperative radiation therapy. © 2012 Wiley Periodicals, Inc. Head Neck, 2013
Global sensitivity analyses for a complex hydrological model applied in an Alpine watershed
Authors: Dobler C. , Pappenberger F.
Published: August 2012

The increasing complexity of hydrological models results in a large number of parameters to be estimated. In order to better understand how these complex models work, efficient screening methods are required in order to identify the most important parameters. This is of particular importance for models that are used within an operational real‐time forecasting chain such as HQsim. The objectives of this investigation are to (i) identify the most sensitive parameters of the complex HQsim model applied in the Alpine Lech catchment and (ii) compare model parameter sensitivity rankings attained from three global sensitivity analysis techniques. The techniques presented are the (i) regional sensitivity analysis, (ii) Morris analysis and (iii) state‐dependent parameter modelling. The results indicate that parameters affecting snow melt as well as processes in the unsaturated soil zone reveal high significance in the analysed catchment. The snow melt parameters show clear temporal patterns in the sensitivity whereas most of the parameters affecting processes in the unsaturated soil zone do not vary in importance across the year. Overall, the maximum degree day factor (meltfunc_max) has been identified to play a key role within the HQsim model. Although the parameter sensitivity rankings are equivalent between methods for a number of parameters, for several key parameters differing results were obtained. An uncertainty analysis demonstrates that a parameter ranking attained from only one method is subjected to large uncertainty. Copyright © 2012 John Wiley & Sons, Ltd.
Contribution of Na+,HCO3−‐cotransport to cellular pH control in human breast cancer: A role for the breast cancer susceptibility locus NBCn1 (SLC4A7)
Authors: Boedtkjer Ebbe , Moreira José M.A. , Mele Marco , Vahl Pernille , Wielenga Vera T. , Christiansen Peer M. , Jensen Vibeke E.D. , Pedersen Stine F. , Aalkjaer Christian
Published: August 2012

Genome‐wide association studies recently linked the locus for Na+,HCO3−‐cotransporter NBCn1 (SLC4A7) to breast cancer susceptibility, yet functional insights have been lacking. To determine whether NBCn1, by transporting HCO3− into cells, may dispose of acid produced during high metabolic activity, we studied the expression of NBCn1 and the functional impact of Na+,HCO3−‐cotransport in human breast cancer. We found that the plasmalemmal density of NBCn1 was 20–30% higher in primary breast carcinomas and metastases compared to matched normal breast tissue. The increase in NBCn1 density was similar in magnitude to that observed for Na+/H+‐exchanger NHE1 (SLC9A1), a transporter previously implicated in cell migration, proliferation and malignancy. In primary breast carcinomas, the apparent molecular weight for NBCn1 was increased compared to normal tissue. Using pH‐sensitive fluorophores, we showed that Na+,HCO3−‐cotransport is the predominant mechanism of acid extrusion and is inhibited 34 ± 9% by 200 μM 4,4′‐diisothiocyanatostilbene‐2,2′‐disulfonic acid in human primary breast carcinomas. At intracellular pH (pHi) levels >6.6, CO2/HCO3−‐dependent mechanisms accounted for >90% of total net acid extrusion. Na+/H+‐exchange activity was prominent only at lower pHi‐values. Furthermore, steady‐state pHi was 0.35 ± 0.06 units lower in the absence than in the presence of CO2/HCO3−. In conclusion, expression of NBCn1 is upregulated in human primary breast carcinomas and metastases compared to normal breast tissue. Na+,HCO3−‐cotransport is a major determinant of pHi in breast cancer and the modest DIDS‐sensitivity is consistent with NBCn1 being predominantly responsible. Hence, our results suggest a major pathophysiological role for NBCn1 that may be clinically relevant.
Tumor‐initiating properties of breast cancer and melanoma cells in vivo are not invariably reflected by spheroid formation in vitro, but can be increased by long‐term culturing as adherent monolayers
Authors: Kuch Vanessa , Schreiber Caroline , Thiele Wilko , Umansky Viktor , Sleeman Jonathan P.
Published: August 2012

Cancer stem cells (CSCs) have been studied intensively in recent years due to their potential importance for understanding neoplastic disease and the design of antitumor therapies. A number of properties attributed to CSCs have been used to define the CSC population, the most important of which is the ability to initiate reproducibly the growth of tumors in vivo. Other assays such as spheroid formation, expression of particular markers and label retention are also used for defining CSCs, although the degree to which these assays invariably reflect the ability to form tumors in vivo remains to be carefully evaluated. Given the importance of correctly defining and isolating CSCs if valid conclusions about their characteristics are to be made, we used syngeneic animal models to compare these different assays. In standard spheroid assays, cell aggregation rather than spheroid growth from single cell suspensions ensued, but aggregation was circumvented by the inclusion of methylcellulose in the medium. Label‐retaining subpopulations did not reliably exhibit an enhanced ability to form spheroids and were enriched for senescent cells. Spheroid‐forming ability was found to correspond to expression of established CSC markers, although not invariably. Furthermore, spheroid‐forming ability was not always reflected in tumor‐initiating properties in vivo. Long‐term culture of primary mammary tumor cells as adherent monolayers increased their tumor‐initiating ability in vivo. This increase was attenuated when the cells were subsequently cultivated as spheroids. Together these data indicate that assays that are widely used to define CSC subpopulations do not invariably reflect tumor‐initiating properties in vivo.
High‐risk HPV testing on self‐sampled versus clinician‐collected specimens: A review on the clinical accuracy and impact on population attendance in cervical cancer screening
Authors: Snijders Peter J.F. , Verhoef Viola M.J. , Arbyn Marc , Ogilvie Gina , Minozzi Silvia , Banzi Rita , van Kemenade Folkert J. , Heideman Daniëlle A.M. , Meijer Chris J.L.M.
Published: August 2012

This review elaborates on the accuracy and feasibility of human papillomavirus (HPV) self‐sampling, i.e., offering self‐sampling of (cervico‐)vaginal cell material by women themselves in nonclinical settings for high‐risk HPV (hrHPV) detection in the laboratory, for cervical screening. To that end a bibliographic database search (PubMed) was performed to identify studies (published between January 1992 and January 2012) that compared clinical accuracy of HPV testing on self‐sampled material with that of cytology or HPV testing on clinician‐taken samples, and studies comparing response to offering HPV self‐sampling with a recall invitation. Overall, hrHPV testing on self‐samples appeared to be at least as, if not more, sensitive for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) as cytology on clinician‐obtained cervical samples, though often less specific. In most studies, hrHPV testing on self‐ and clinician‐sampled specimens is similarly accurate with respect to CIN2+ detection. Variations in clinical performance likely reflect the use of different combinations of collection devices and HPV tests. Because it is known that underscreened women are at increased risk of cervical cancer, targeting non‐attendees of the screening program could improve the effectiveness of cervical screening. In developed countries offering self‐sampling has shown to be superior to a recall invitation for cytology in re‐attracting original non‐attendees into the screening program. Additionally, self‐testing has shown to facilitate access to cervical screening for women in low resource areas. This updated review of the literature suggests that HPV self‐sampling could be an additional strategy that can improve screening performance compared to current cytology‐based call‐recall programs.
Synthesis and Development of Lipoprotein‐Based Nanocarriers for Light‐Activated Theranostics
Authors: Jin Honglin , Chen Juan , Lovell Jonathan F. , Zhang Zhihong , Zheng Gang
Published: August 2012

The design and synthesis of new light‐activated contrast agents for theranostics (therapy/diagnosis) has the potential to facilitate multifunctional and improved personalized medicine. The use of light as a remote activation strategy provides spatial and temporal control of drug effect and nanotechnology can play a key role in this process. Lipoproteins (LDL and HDL), which transport water‐insoluble cholesteryl esters and triacylglycerols in nature, have evolved to efficiently ferry exogenous hydrophobic compounds in vivo. They are naturally biocompatible, maneuverable due to their small size (<30 nm), and can be loaded through various methods, and are therefore ideal vehicles to load and transport hydrophobic theranostic agents. This review examines the history and ongoing research activities regarding the design and synthesis of lipoprotein‐based formulations, and their applications or potential applications as light‐activated theranostic agents, with a main focus on photodynamic therapy. This field, while still in its infancy, will benefit from improved design and modulation of enhanced lipoprotein‐based nanocarriers, with the ultimate goal of simultaneous imaging and photoactivation of therapeutic agents in a clinical setting.
The Vitamin D Analog Calcipotriol Combined with Aminolevulinate‐Mediated Photodynamic Therapy for Human Psoriasis: A Proof‐of‐Principle Study
Authors: Maytin Edward V. , Honari Golara , Khachemoune Amor , Taylor Charles R. , Ortel Bernhard , Pogue Brian W. , Sznycer‐Taub Nathaniel , Hasan Tayyaba
Published: August 2012

We previously showed that select agents (methotrexate or vitamin D), when administered as a preconditioning regimen, are capable of promoting cellular differentiation of epithelial cancer cells while simultaneously enhancing the efficacy of 5‐aminolevulinic acid (ALA)‐mediated photodynamic therapy (PDT). In solid tumors, pretreatment with vitamin D simultaneously promotes cellular differentiation and leads to selective accumulation of target porphyrins (mainly protoporphyrin IX, PpIX) within diseased tissue. However, questions of whether or not the effects upon cellular differentiation are inexorably linked to PpIX accumulation, and whether these effects might occur in hyperproliferative noncancerous tissues, have remained unanswered. In this paper, we reasoned that psoriasis, a human skin disease in which abnormal cellular proliferation and differentiation play a major role, could serve as a useful model to test the effects of prodifferentiating agents upon PpIX levels in a nonneoplastic setting. In particular, vitamin D, a treatment for psoriasis that restores (i.e., increases) differentiation, might increase PpIX levels in psoriatic lesions and facilitate their responsiveness to ALA‐PDT. This concept was tested in a pilot study of seven patients with bilaterally matched psoriatic plaques. A regimen in which calcipotriol 0.005 % ointment was applied for six days prior to ALA‐PDT using blue light led to preferential increases in PpIX (ca. 50 %), and reductions in thickness, redness, scaling, and itching in the pretreated plaques. The results suggest that a larger clinical trial is warranted to confirm a role for combination treatments with vitamin D and ALA‐PDT for psoriasis.
Assessment of myelination in hypomyelinating disorders by quantitative MRI
Authors: Dreha‐Kulaczewski Steffi F. , Brockmann Knut , Henneke Marco , Dechent Peter , Wilken Bernd , Gärtner Jutta , Helms G.
Published: August 2012

Purpose:

To apply myelin‐sensitive quantitative magnetic resonance imaging (MRI) techniques in defined hypomyelinating conditions and to identify spatial patterns of myelination as criteria for characterization of undefined disorders.

Materials and Methods:

Seven patients were included, based on the diagnosis of mitochondrial cytopathy, Pelizaeus‐Merzbacher disease, GJA12/GJC2‐related Pelizaeus‐Merzbacher‐like disease, hypomyelination with atrophy of the basal ganglia and cerebellum, and leukoencephalopathy with ataxia, delayed dentition, and hypomyelination. The control group comprised 23 children and adolescents (age range 2.6–22.4 years). The 3T MRI protocol consisted of high‐resolution T1‐ and T2‐weighted 3D MRI, diffusion tensor (DTI), and magnetization transfer (MT) imaging. Parameter maps of mean diffusivity, fractional anisotropy, and MT saturation were displayed as pseudocolor overlays and assessed by region‐of‐interest and histogram analysis.

Results:

Structural MRI revealed widespread signal alterations in white matter, but were hampered by signal heterogeneity. Quantitative DTI and MT reflected the degree of hypomyelination and discriminative patterns of myelination emerged on MT saturation maps.

Conclusion:

The quantitative parameters in the defined hypomyelination conditions provide additional criteria to further classify undefined white matter disorders. J. Magn. Reson. Imaging 2012; 36:1329–1338. © 2012 Wiley Periodicals, Inc.
T2′‐ and PASL‐based perfusion mapping at 3 Tesla: influence of oxygen‐ventilation on cerebral autoregulation
Authors: Wagner Marlies , Magerkurth Jörg , Volz Steffen , Jurcoane Alina , Singer Oliver C. , Neumann‐Haefelin Tobias , Zanella Friedhelm E. , Deichmann Ralf , Hattingen Elke
Published: August 2012

Purpose:

To use T2′‐mapping together with Pulsed Arterial Spin Labeling (PASL) providing quantitative information of deoxygenation level and cerebral blood flow (CBF) in the cerebral gray matter to obtain simultaneous information about the cerebral oxygen metabolism and the resulting cerebral vasoreactivity under normoxic and hyperoxic conditions.

Materials and Methods:

Twelve young, healthy volunteers underwent MRI under normoxic and hyperoxic conditions performing PASL and high‐resolution, motion‐corrected T2* and T2‐mapping to calculate T2′values. Regions of interest (ROI) were placed in the frontoparietal cortex and thalamus by manual and automatic segmentation. For each ROI, mean normoxic T2′‐ and CBF values were extracted and compared with the same parameters assessed under hyperoxic ventilation.

Results:

A hyperoxic‐induced decrease of the CBF could be shown in the frontoparietal cortex (P = 0.009). The T2 values of frontoparietal cortex decreased under hyperoxic inhalation compared with normoxia (P = 0.01), whereas T2′ remained unchanged.

Conclusion:

Motion‐corrected high‐resolution T2′‐maps can be used together with PASL to evaluate the DeoxyHb content in relation to CBF in the cerebral gray matter. We could show that cortical CBF decreases under hyperoxic inhalation in healthy young subjects, whereas the T2′ values remained constant. These data suggest that hyperoxic‐induced vasoconstriction may protect the brain against hyperoxemia. J. Magn. Reson. Imaging 2012; 36:1347–1352. © 2012 Wiley Periodicals, Inc.
Prognosis and predictors of ACL reconstructions using the MOON cohort: A model for comparative effectiveness studies
Authors: Spindler Kurt P. , Parker Richard D. , Andrish Jack T. , Kaeding Christopher C. , Wright Rick W. , Marx Robert G. , McCarty Eric C. , Amendola Annunziato , Dunn Warren R. , Huston Laura J. , Harrell Frank E. ,   MOON Group
Published: August 2012

Injury to the anterior cruciate ligament (ACL) threatens an active lifestyle and exposes the patient to risk of early osteoarthritis (OA). ACL reconstruction is typically chosen by individuals to allow a return to their previous work and sports activities. Primary ACL reconstruction (ACLR) has in general been effective at restoring functional stability, but patients' modifiable predictors of both short‐ and long‐term validated outcomes and OA are largely unknown. The Multicenter Orthopaedic Outcomes Network (MOON) consortium was established in 2002 to enroll and longitudinally follow a population cohort of ACL reconstructed patients. The objective was to establish patient‐specific predictive models of clinically important outcomes. Over the past 10 years, the overarching aims of this NIAMS‐funded prospective multicenter cohort of ACL reconstructions has been threefold: (1) to identify both short‐ and long‐term prognosis and predictors of sports function, activity level, and general health through validated patient‐reported outcomes, (2) to identify the symptoms and signs of OA, and (3) to quantify the incidence of ACL reconstruction graft and/or contralateral ACL failures and additional surgical procedures. This manuscript summarizes the Kappa Delta Ann Doner Vaughan Award paper and presentation at the 2012 ORS/AAOS Annual Meeting. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:2–9, 2012