bluuebunny/crossref_metadata_2025 huggingface dataset:
Advancing Small‐Molecule‐Based Chemical Biology with Next‐Generation Sequencing Technologies
Authors: Anandhakumar Chandran , Kizaki Seiichiro , Bando Toshikazu , Pandian Ganesh N. , Sugiyama Hiroshi
Published: November 2014

Next‐generation‐sequencing (NGS) technologies enable us to obtain extensive information by deciphering millions of individual DNA sequencing reactions simultaneously. The new DNA‐sequencing strategies exceed their precursors in output by many orders of magnitude, resulting in a quantitative increase in valuable sequence information that could be harnessed for qualitative analysis. Sequencing on this scale has facilitated significant advances in diverse disciplines, ranging from the discovery, design, and evaluation of many small molecules and relevant biological mechanisms to maturation of personalized therapies. NGS technologies that have recently become affordable allow us to gain in‐depth insight into small‐molecule‐triggered biological phenomena and empower researchers to develop advanced versions of small molecules. In this review we focus on the overlooked implications of NGS technologies in chemical biology, with a special emphasis on small‐molecule development and screening.
Reversible Assembly and Disassembly of Receptor‐Decorated Gold Nanoparticles Controlled by Ion Recognition
Authors: Aydogan Abdullah , Lee Gawon , Lee Chang‐Hee , Sessler Jonathan L.
Published: November 2014

The controlled assembly of randomly dispersed colloidal particles can provide access to materials with advanced optical and electronic properties while providing fundamental insights into self‐assembly processes in nature and nanotechnology. Typically, self‐assembled nanoparticles are prepared by exploiting electrostatic interactions, lithographic techniques, and covalently linked molecular scaffolds. This results in static morphologies that cannot be disassembled easily. On the other hand, having access to systems that can be assembled or disassembled in a controlled manner could allow for in‐depth understanding of the nanoparticles as well as rational control over the morphology and fundamental properties of the resulting constructs. If the changes in aggregation are induced by a specific external chemical stimulus, it could also permit the development of new chemosensors. Here we demonstrate the reversible assembly and disassembly of gold nanoparticles achieved by modulating the noncovalent interactions between surface‐bound calix[4]pyrroles and added bis‐imidazolium cations. We also demonstrate the use of these nanoparticles in the selective sensing of anions.
Unusual Chemoselective RhII‐Catalysed Transformations of α‐Diazocarbonyl Piperidine Cores
Authors: Bonetti Andrea , Beccalli Egle , Caselli Alessandro , Clerici Francesca , Pellegrino Sara , Gelmi Maria Luisa
Published: November 2014

The reactivity of various α‐diazocarbonyl piperidine scaffolds, characterised by an increased molecular complexity, was tested with various RhII catalysts. The structure of the starting reagent is of relevance to the synthetic results. An unexpected dimerisation took place, starting from the simple piperidine scaffold, to give the hexahydrotetrazine ring system. Products derived from a nitrogen ylide intermediate or aromatic substitution (1,3,4,5‐tetrahydro‐2,5‐methanobenzo[c]azepine and 1,2,3,3a‐tetrahydrocyclopenta[de]isoquinolin‐4(5 H)‐one rings, respectively) were obtained from tetrahydroisoquinoline derivatives. The chemoselectivity of the reaction could be controlled by the choice of starting reagent, RhII catalyst and the reaction conditions. Finally, it was found that the azepino heterocycle could coordinate to the catalyst to give new RhII complexes.
Evaluation of targets for color calibrating digital images from an optical bright‐field transmission microscope
Authors: Wei Hong , Brill Michael H. , Park Taeyoung
Published: November 2014

Color calibration of digital microscope images of stained biological slides may use a special slide (called a calibration slide) with known color samples that are usually filters. To evaluate quantitatively how well the calibration has been done by a particular system, another set of different known samples is needed, with transmittance spectra that are typical of stained biological material. A slide with such colors comprises what is called a reference slide. In this article, a method is described for selecting the colors for such a slide. A reference slide was created by this prescription and then used to evaluate two embodiments of a color management system for several microscope and illumination combinations. It was found that a set of 20 reference colors spans the gamut of colors produced by a particular kind of stain. Using the reference slide, Datacolor's ChromaCal™ system performance was quantitatively evaluated. The performance is robust to change of microscope and illumination and does not degrade much when a tungsten light is increased in intensity (hence in correlated color temperature) with only one initial calibration at a single color temperature followed by automatic white balancing of a traditional sort. © 2014 Wiley Periodicals, Inc. Col Res Appl, 40, 577–584, 2015
Control of Spatial Organization of Electrospun Fibers in a Carbon Felt for Enhanced Bioelectrode Performance
Authors: Both Engel Adriana , Cherifi Aziz , Bechelany Mikhael , Tingry Sophie , Cornu David
Published: November 2014

Electrospun carbon fiber electrodes showing high performance for bio‐electrochemical applications were developed. Easy to handle and manipulate aligned and unaligned carbon fibers with a mean diameter of (330±50) nm were synthesized through an electrospinning technique. Electrical resistivity measurements, which are a challenge that has not been much explored in the case of fibrous materials, were realized through two different techniques, and a study of contact resistances between electrical clips and the carbon fibers was performed. To target the creation of a bioelectrode, carbon fibers were characterized electrochemically by cyclic voltammetry. After being modified with the enzyme laccase, its response to oxygen electroreduction was studied. Aligned fibers present a cathodic current that is 30 % higher than that of randomly distributed fibers. Overall, the results show that aligned fibers are more appropriate for bio‐electrochemical applications when exploiting anisotropic spatial organization.
Highly Functionalized Biaryls via Suzuki–Miyaura Cross‐Coupling Catalyzed by Pd@MOF under Batch and Continuous Flow Regimes
Authors: Pascanu Vlad , Hansen Peter R. , Bermejo Gómez Antonio , Ayats Carles , Platero‐Prats Ana E. , Johansson Magnus J. , Pericàs Miquel À. , Martín‐Matute Belén
Published: November 2014

A diverse set of more than 40 highly functionalized biaryls was synthesized successfully through the Suzuki–Miyaura cross‐coupling reaction catalyzed by Pd nanoparticles supported in a functionalized mesoporous MOF (8 wt % Pd@MIL‐101(Cr)‐NH2). This could be achieved under some of the mildest conditions reported to date and a strong control over the leaching of metallic species could be maintained, despite the presence of diverse functional groups and/or several heteroatoms. Some of the targeted molecules are important intermediates in the synthesis of pharmaceuticals and we clearly exemplify the versatility of this catalytic system, which affords better yields than currently existing commercial procedures. Most importantly, Pd@MIL‐101‐NH2 was packed in a micro‐flow reactor, which represents the first report of metallic nanoparticles supported on MOFs employed in flow chemistry for catalytic applications. A small library of 11 isolated compounds was created in a continuous experiment without replacing the catalyst, demonstrating the potential of the catalyst for large‐scale applications.
Growth and Properties of Amorphous Erbium‐doped Aluminum‐yttrium Oxide Films Deposited by Aerosol‐UV‐Assisted MOCVD
Authors: Salhi Rached , Jimenez Carmen , Deschanvres Jean‐Luc , Maâlej Ramzi , Fourati Mohieddine
Published: November 2014

Erbium‐doped yttrium‐aluminum oxide films (Er:Y2O3‐Al2O3) are deposited by aerosol‐assisted metal‐organic (AA‐MO)CVD. The effects of the humidity of the carrier gas and UV assistance on their structure and optical properties during the deposition are investigated as a function of the substrate temperature and the aluminum mole fraction (Al2O3 mol.‐%) in the liquid solution. The effect of substrate temperature is studied for a constant Al concentration of 33.33 mol.‐% of Al‐acac in the solution. The maximum deposition rates are reached under lower air humidity and with UV assistance in a surface temperature range between 350 and 460 °C. Nevertheless, as‐deposited Er:Al2O3‐Y2O3 films show a very low organic contamination when depositions take place under high air humidity and with UV assistance. The film composition is strongly dependent on air humidity, showing a very high aluminum content when working with a high humidity of the carrier gas, and yttrium‐rich when working with a low humidity of the carrier gas. The refractive index of Er:Al2O3‐Y2O3 films under these conditions is relatively high, reaching 1.76 when deposited at 460 °C.

The effect of composition is studied at a substrate temperature of 410 °C. The effect on film composition when varying the aluminum mole fraction in the liquid solution is studied. The most influential parameter is the high air humidity, which induces stronger variation on the layer composition for the same liquid composition.
Don't be afraid to mentor a millennial
Authors: Williams Kate
Published: November 2014

As a college administrator, you may have thought about mentoring one of your junior millennial employees but are hesitant due to negative generational stereotypes. As a millennial who is currently in a mentor‐mentee relationship with a baby boomer, I want to plead our case and explain the top five reasons we need your help.
Create a crisis communications plan to guide your institution, protect its reputation
Authors: Hope Joan
Published: November 2014

Read any major newspaper and you're likely to find out about another college or university facing a crisis. Whether it's charges of sexual harassment or assault, allegations of academic fraud in the athletics department, or an alcohol‐related campus death, you need to be ready to communicate effectively if a crisis occurs on your campus.
Work effectively with your chief financial officer for success in changing environment
Authors: Hope Joan
Published: November 2014

KAREN GOLDSTEIN, EXECUTIVE SEARCH CONSULTANT, WITT/KIEFFER
Combination of Diacerhein and Antiepileptic Drugs After Local Peripheral, and Oral Administration in the Rat Formalin Test
Authors: Zúñiga‐Romero Angel , Ponce‐Chávez Martha Karina , Gauthereau‐Torres Marcia Yvette , Ortega‐Varela Luis Fernando
Published: November 2014

Preclinical Research

The present study was designed to evaluate the possible antinociceptive interaction between diacerhein and some antiepileptic drugs (carbamazepine, topiramate and gabapentin) on formalin‐induced nociception. Diacerhein, each of the antiepileptics or a fixed dose‐ratio combination of these drugs was assessed after local peripheral and oral administration in rats. lsobolographic analyses were used to define the interaction between drugs. Diacerhein, antiepileptic drugs (carbamazepine, topiramate and gabapentin) or their combinations yielded a dose‐dependent antinociceptive effect when administered by both routes. Theoretical ED30 values for the combination estimated from the isobolograms were obtained as follows: diacerhein‐carbamazepine (85.99 ± 7.07 μg/paw; 56.53 ± 4.56 mg/kg po), diacerhein‐topiramate (197.97 ± 22.90 μg/paw; 13.06 ± 2.44 mg/kg po) and diacerhein‐gabapentin (96.87 ± 17.73 μg/paw; 17.90 ± 4.70 mg/kg p.o.) for the local peripheral and oral administration routes, respectively. These values were significantly higher than the experimentally obtained ED30 values: diacerhein‐carbamazepine (49.33 ± 3.37 μg/paw; 35.49 ± 7.91 mg/kg po), diacerhein‐topiramate (133.00 ± 39.10 μg/paw; 8.87 ± 1.46 mg/kg po) and diacerhein‐gabapentin (70.98 ± 14.73 μg/paw; 10.95 ± 3.23 mg/kg po). The combinations produced their antinociceptive effects without motor impairment in the rotarod test indicating synergistic interactions with a good side effect profile.
Engaging Local Private and Public Actors in Biodiversity Conservation: The role of Agri‐Environmental schemes and Ecological fiscal transfers
Authors: dos Santos Rui Ferreira , Antunes Paula , Ring Irene , Clemente Pedro
Published: November 2014

Biodiversity conservation policies have relied on regulatory approaches, such as the designation of protected areas, which have generally been insufficient to ensure long‐term conservation. This is partially explained by the mismatch between those who bear the costs of and those who benefit from conservation. While local actors, private and public, face management and opportunity costs due to conservation policies, the benefits reach beyond local borders. In this paper, we argue that a successful biodiversity conservation policy mix should include economic instruments directed at public and private local stakeholders. These instruments should be mutually reinforcing and target decision processes regarding land‐use zoning and land management practices. To illustrate our argument, we focus on European agri‐environmental measures (directed at private landowners) and ecological fiscal transfers (for local governments). We describe each of these instruments and derive main lessons from their implementation. Finally, we present proposals for linking them to reinforce their individual contributions to the overall goal of halting biodiversity loss, taking the Portuguese case as an example. Copyright © 2014 John Wiley & Sons, Ltd and ERP Environment
Clinical trials update from the European Society of Cardiology meeting 2014: PARADIGM‐HF, CONFIRM‐HF, SIGNIFY, atrial fibrillation, beta‐blockers and heart failure, and vagal stimulation in heart failure
Authors: Clark Andrew L. , Pellicori Pierpaolo
Published: November 2014

This article provides an overview of trials relevant to the pathophysiology, prevention, and treatment of heart failure, presented at the European Society of Cardiology meeting held in Barcelona in autumn 2014. Trials reported here include PARADIGM‐HF (LCZ696 versus enalapril in heart failure), CONFIRM‐HF (treatment of iron deficiency in heart failure), and SIGNIFY (ivabradine in patients with stable coronary artery disease). In addition, we discuss recent developments in the treatment of atrial fibrillation and the lack of benefit with the use of beta‐blockers in these patients. Finally, the article describes recent advances in the use of vagal stimulation in patients with heart failure. © 2014 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.
Sexual function in patients supported with left ventricular assist device and with heart transplant
Authors: Hasin Tal , Jaarsma Tiny , Murninkas Daniel , Setareh‐Shenas Saman , Yaari Victoria , Bar‐Yosef Simona , Medalion Benjamin , Gerber Yariv , Ben‐Gal Tuvia
Published: November 2014

Aims

Sexual dysfunction is common among patients with heart failure (HF) and considered an important hamper to quality of life. While implantation of left ventricular assist device (LVAD) may prolong and improve life in advanced HF, limited data are available on its impact on sexual function. The aim of this study is to evaluate sexual function in LVAD patients and compare this with patients after heart transplantation (HTx).

Methods and results

Sexual activity and satisfaction of stable patients with durable LVAD or after HTx were evaluated using a validated questionnaire and visual analogue scale from 0 to 10. Data were collected from 31 patients (mean age 59 ± 12 years, 87% male), 17 after HTx and 14 with LVAD. Pleasure or satisfaction with sex was significantly higher in HTx patients (P = 0.0005). In total, 29% LVAD patients and 71% HTx patients reported content with sexual activity. Recalled satisfaction with sex life pre‐operation was comparable between the groups. During support, satisfaction with sex life using visual analogue scale was 7.6 ± 3.1 for HTx versus 3.9 ± 4.0 for LVAD patients (P = 0.017). In total, 11 LVAD patients (79%) reported specific problems in sexual function including erectile dysfunction or vaginal dryness (8, 57%); problems with the LVAD, cable, or batteries (5, 36%); problems with orgasm (4,29%); and other problems such as fear of injury, feeling depressed, partner issues, self‐image, and pain (1, 7% each).

Conclusion

Sexual dysfunction occurs in patients with LVAD support and may be more prominent than after HTx. Problems limiting sexual function related to physiological, psychological, and equipment merit consideration during follow‐up.
Integration of biocatalyst and process engineering for sustainable and efficient n‐butanol production
Authors: Köhler Kirsten A. K. , Rühl Jana , Blank Lars M. , Schmid Andreas
Published: November 2014

Recent environmental economic developments generate a need for sustainable and cost‐effective (microbial) processes for the production of high‐volume, low‐priced bulk chemicals. As an example, n‐butanol has, as a second‐generation biofuel, beneficial characteristics compared to ethanol in liquid transportation fuel applications. The industrial revival of the classic n‐butanol (ABE) fermentation requires process and strain engineering solutions for overcoming the main process limitations: product toxicity and low space–time yield. Reaction intensification on the biocatalyst, fermentation, and bioprocess level can be based on economic and ecologic evaluations using quantifiable constraints. This review describes the means of process intensification for biotechnological processes. A quantitative approach is then used for the comparison of the massive literature on n‐butanol fermentation. A comprehensive literature study—including key fermentation performance parameters—is presented and the results are visualized using the window of operation methodology. The comparison allowed the identification of the key constraints, high cell densities, high strain stability, high specific production rate, cheap in situ product removal, high n‐butanol tolerance, to operate in situ product removal efficiently, and cheap carbon source. It can thus be used as a guideline for the bioengineer during the combined biocatalyst, fermentation, and bioprocess development and intensification.
Be ready to evaluate applications with Cambridge credentials
Authors: Hope Joan
Published: November 2014

Your institution has no doubt received enough high school transcripts that show Advanced Placement and International Baccalaureate courses to know just what those represent. And if you haven't already, you're likely to start getting applications from students who have taken Cambridge International courses and examinations.
Separation of transition metals and chelated complexes in wastewaters
Authors: Cheung Philip C.W. , Williams Daryl R.
Published: November 2014

This review responds to the ongoing needs of wastewater engineers tasked with treating aqueous solutions containing chelated complexes of metal ions, of which nickel citrate in electrodeless plating and copper–EDTA in electronic chip board manufacturing are two key examples. Because of the presence of these sequestering agents, metallic ions cannot be readily precipitated by alkalinity, making a compelling case for the discovery of alternative methods of treatment. This review is a critical appraisal of the varying degrees of success in separation process strategies deployed for the recovery of metallic ions under such challenging chemical conditions. Guidance is provided on making progress toward satisfactory industrial solutions to surmount these difficulties. © 2014 American Institute of Chemical Engineers Environ Prog, 34: 761–783, 2015
Metal Mixture Modeling Evaluation project: 2. Comparison of four modeling approaches
Authors: Farley Kevin J. , Meyer Joseph S. , Balistrieri Laurie S. , De Schamphelaere Karel A. C. , Iwasaki Yuichi , Janssen Colin R. , Kamo Masashi , Lofts Stephen , Mebane Christopher A. , Naito Wataru , Ryan Adam C. , Santore Robert C. , Tipping Edward
Published: November 2014

As part of the Metal Mixture Modeling Evaluation (MMME) project, models were developed by the National Institute of Advanced Industrial Science and Technology (Japan), the US Geological Survey (USA), HDR|HydroQual (USA), and the Centre for Ecology and Hydrology (United Kingdom) to address the effects of metal mixtures on biological responses of aquatic organisms. A comparison of the 4 models, as they were presented at the MMME workshop in Brussels, Belgium (May 2012), is provided in the present study. Overall, the models were found to be similar in structure (free ion activities computed by the Windermere humic aqueous model [WHAM]; specific or nonspecific binding of metals/cations in or on the organism; specification of metal potency factors or toxicity response functions to relate metal accumulation to biological response). Major differences in modeling approaches are attributed to various modeling assumptions (e.g., single vs multiple types of binding sites on the organism) and specific calibration strategies that affected the selection of model parameters. The models provided a reasonable description of additive (or nearly additive) toxicity for a number of individual toxicity test results. Less-than-additive toxicity was more difficult to describe with the available models. Because of limitations in the available datasets and the strong interrelationships among the model parameters (binding constants, potency factors, toxicity response parameters), further evaluation of specific model assumptions and calibration strategies is needed. Environ Toxicol Chem 2015;34:741–753. © 2014 SETAC
Cervical cancer screening in sub‐Saharan Africa: A randomized trial of VIA versus cytology for triage of HPV‐positive women
Authors: Bigoni Jérôme , Gundar Mélissa , Tebeu Pierre‐Marie , Bongoe Adamo , Schäfer Sonja , Fokom‐Domgue Joël , Catarino Rosa , Tincho Evelyne Foguem , Bougel Stéphanie , Vassilakos Pierre , Petignat Patrick
Published: November 2014

Developing countries are interested in using human papillomavirus (HPV) testing as a primary screening test for cervical cancer prevention programs. The low specificity of the HPV assay requires triage testing of HPV‐positive women. The aim of the study is to compare visual inspection with acetic acid (VIA) and cytology as triage testing methods in HPV‐positive women to detect cervical intraepithelial neoplasia or Grade 2 or higher (CIN2+). The study was conducted in two Cameroonian towns (Yaoundé and Edea) and included 846 eligible women aged 25 to 65 years. All participants performed self‐HPV testing. HPV‐positive women (n = 259) were randomly assigned to be tested either by VIA (VIA group) or cytology (cytology group). HPV‐positive women had both cervical biopsy and endocervical curettage to detect biopsy‐confirmed CIN2+. All statistical tests were two‐sided. The prevalence of HPV was 38.5%, and the mean age of HPV‐positive women was 41.5 ± 10.1 years. One hundred ninety‐eight women (97 in the VIA group and 99 in the cytology) were randomly assigned to one of the two testing arms. The sensitivity of VIA was 25.0% (95% CI, 7.1–59.1%), and the sensitivity of cytology was 90.0% (59.6–98.2%). The specificity was 74.2% (95% CI, 64.2–82.1%) for VIA and 85.2% (76.3–91.2%) for cytology. ROC area for cytology was 0.910 against the 0.496 area for VIA. In this trial, VIA was inferior to cytology as a triage test among HPV‐positive women. Further investigations are needed to determine the optimal triage method for HPV‐positive women.
Nonsteroidal anti‐inflammatory drugs and the risk of nonmelanoma skin cancer
Authors: Reinau Daphne , Surber Christian , Jick Susan S. , Meier Christoph R.
Published: November 2014

Nonsteroidal anti‐inflammatory drugs (NSAIDs) have been assigned a promising role in the chemoprevention of various malignancies. However, epidemiological data on the association between NSAID use and nonmelanoma skin cancer (NMSC) are limited. To explore whether patients regularly exposed to systemic NSAIDs are at a reduced risk of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC), we conducted a population‐based case‐control analysis using the Clinical Practice Research Datalink, a United Kingdom primary care database. We identified 65,398 patients with incident BCC and 7,864 patients with incident SCC diagnosed between 1995 and 2013 and matched 1 and 4 NMSC‐free controls to each BCC and SCC case, respectively, on age, sex, general practice, calendar time and years of history in the database. We compared prior NSAID exposure between cases and controls using multivariate conditional logistic regression analyses controlling for several potential confounders. Overall, we found no association between NSAID use and BCC, but when looking exclusively at users of single NSAID substances there was a suggestion of a reduced BCC risk in regular users of aspirin and ibuprofen (adjusted odds ratio [adj. OR]: 0.92, 95% confidence interval [CI]: 0.85–0.99 and adj. OR: 0.61, 95% CI: 0.48–0.78, respectively). The risk of SCC was slightly decreased in regular users of any NSAIDs (adj. OR: 0.89, 95% CI: 0.82–0.97), with the strongest risk reduction observed in current users of coxibs (adj. OR: 0.77, 95% CI: 0.62–0.95). These findings provide evidence that patients predisposed to NMSC might benefit from chemoprevention with NSAIDs.
Examination of the prevalence of stimulus overselectivity in children with ASD
Authors: Rieth Sarah R. , Stahmer Aubyn C. , Suhrheinrich Jessica , Schreibman Laura
Published: November 2014

Many individuals with autism spectrum disorders (ASD) display stimulus overselectivity, wherein a subset of relevant components in a compound stimulus controls responding, which impairs discrimination learning. The original experimental research on stimulus overselectivity in ASD was conducted several decades ago; however, interventions for children with ASD now typically include programming to target conditional discriminations in ways that might minimize the prevalence of stimulus overselectivity. The present study assessed 42 children who had been diagnosed or educationally identified with ASD using a discrimination learning assessment. Of these 42 children, 19% displayed overselective responding, which is a lower percentage than that seen in early research. Possible explanations for this decreased percentage, implications for intervention, and future directions for research are discussed.
Electrospun poly(ε‐caprolactone)‐based skin substitutes: In vivo evaluation of wound healing and the mechanism of cell proliferation
Authors: Augustine Robin , Dominic Edwin Anto , Reju Indu , Kaimal Balarama , Kalarikkal Nandakumar , Thomas Sabu
Published: November 2014

In the present study, we have fabricated electrospun poly(ε‐caprolactone)‐based membranes, characterized and studied the in vivo cell migration and proliferation and wound healing activity. Moreover, we did not seed any cells prior to the animal implantation and we could observe excellent fibroblast attachment and cell proliferation. Further full thickness excision wound on guinea pig completely healed within 35 days. We could reach in an assumption that the enhanced cell proliferation and wound healing might be due to the surface degradation of the polymer under physiological conditions and the formation of functional groups like hydroxyl and carboxyl groups that promoted cell proliferation in a cell adhesion protein mediated mechanism. This study is a novel tissue engineering concept for the reconstruction of a damaged tissue without the in vitro cell seeding and proliferation prior to the in vivo implantation. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 1445–1454, 2015.
Femoral Volumetric Bone Density, Geometry, and Strength in Relation to 25-Hydroxy Vitamin D in Older Men
Authors: Martin Elizabeth N , Haney Elizabeth M , Shannon Jackie , Cauley Jane A , Ensrud Kristine E , Keaveny Tony M , Zmuda Joseph M , Orwoll Eric S , Harrison Stephanie Litwack , Marshall Lynn M
Published: November 2014

Low serum 25-hydroxy vitamin D (25(OH)D) concentrations are associated with increased hip fracture risk and decreased femoral areal bone mineral density (BMD) among elderly men. Structural dimensions of the proximal femur and volumetric BMD in cortical and trabecular compartments are also associated with hip fracture risk. However, associations of volumetric BMD or structural dimensions with serum 25(OH)D concentrations among older men remain unclear. In a random sample of 1608 men aged ≥65 years from the Osteoporotic Fractures in Men Study (MrOS), baseline serum 25(OH)D concentrations were measured by liquid chromatography/mass spectrometry assays. Femoral neck geometry and volumetric BMD derived from quantitative computed tomography included integral, cortical, and trabecular volumetric BMD; cross-sectional area; integral and cortical volume; and cortical volume as a percent of integral volume. We studied 888 men with vitamin D, parathyroid hormone (PTH), femoral neck geometry, and BMD measures. Whole-bone femoral strength and load-strength ratio from finite element (FE) analysis were also available for 356 men from this sample. Multivariable linear regression was used to estimate least square means of each femoral measure within quartiles of 25(OH)D adjusted for age, race, body mass index, height, latitude, and season of blood draw. Tests of linear trend in the means were performed across increasing quartile of serum 25(OH)D levels. Mean cortical volume (p trend = 0.006) and cortical volume as a percent of integral volume (p trend < 0.001) increased across increasing quartile of 25(OH)D level. However, overall femoral neck size (area and integral volume) did not vary by 25(OH)D level. Femoral neck volumetric BMD measures increased in a graded manner with higher 25(OH)D levels (p trend < 0.001). Femoral strength, but not load-strength ratio, increased with increasing 25(OH)D. Adjustment for PTH did not materially change these associations. We conclude that in older men, higher levels of endogenous 25(OH)D may increase whole-bone strength by increasing femoral volumetric BMD and cortical volume. © 2014 American Society for Bone and Mineral Research.
Partial Geometric Difference Families
Authors: Nowak Kathleen , Olmez Oktay , Song Sung Y.
Published: November 2014

We introduce the notion of a partial geometric difference family as a variation on the classical difference family and a generalization of partial geometric difference sets. We study the relationship between partial geometric difference families and both partial geometric designs and difference families, and show that partial geometric difference families give rise to partial geometric designs. We construct several infinite families of partial geometric difference families using Galois rings and the cyclotomy of Galois fields. From these partial geometric difference families, we generate a list of infinite families of partial geometric designs and directed strongly regular graphs.
Inhibitory effect of single and repeated doses of nilotinib on the pharmacokinetics of CYP3A substrate midazolam
Authors: Zhang Hefei , Sheng Jennifer , Ko Jin H. , Zheng Cheng , Zhou Wei , Priess Petra , Lin Wen , Novick Steven
Published: November 2014

Effects of single and repeated doses of nilotinib on the pharmacokinetics of midazolam, a cytochrome P450 3A (CYP3A) substrate, were assessed in 2 separate studies. In the single‐dose nilotinib study, 18 healthy subjects were randomized to 6 treatment sequences to receive single dose of nilotinib 600 mg, midazolam 4 mg, and coadministration of both in a crossover manner. In the repeated‐dose nilotinib study, 19 chronic myeloid leukemia patients took a single dose of midazolam 2 mg on days 1 and 13, and nilotinib 400 mg twice daily from days 2–13. In the single‐dose study, the geometric mean ratio of the area under the plasma concentration time curve extrapolated to infinity (AUCinf) of midazolam plus nilotinib vs. midazolam was 1.3 (90%CI, 1.2–1.5) and the maximum observed serum concentration (Cmax) was 1.2 (90%CI, 1.0–1.4). In the repeated‐dose study, the values for AUCinf and Cmax were 2.6 (90%CI, 2.1–3.3) and 2.0 (90%CI, 1.7–2.4), respectively. These results indicate that single‐dose and repeated‐dose administration of nilotinib results in weak and moderate inhibition of CYP3A, respectively. Therefore, appropriate monitoring and dose adjustment may be needed for drugs that are mainly metabolized by CYP3A, and have narrow therapeutic index, when coadministered with nilotinib.
Dual mobility bearings withstand loading from steeper cup‐inclinations without substantial wear
Authors: Loving LaQuawn , Herrera Lizeth , Banerjee Samik , Heffernan Christopher , Nevelos Jim , Markel David C. , Mont Michael A.
Published: November 2014

Steep cup abduction angles with adverse joint loading may increase traditional polyethylene bearing wear in total hip arthroplasties. However, there have been few reports evaluating the effect of cup inclination on the wear of dual‐mobility devices. In a hip joint simulation, we compared the short‐term wear of two‐sizes of modular highly cross‐linked dual‐mobility bearings (28 mm femoral head diameter/42 mm polyethylene insert outer diameter/54 mm acetabular shell diameter; 22.2 mm femoral head diameter/36 mm polyethylene insert outer diameter/48 mm acetabular shell diameter) at 50 and 65° of cup inclination with modular 28 mm femoral head on 54 mm cup diameter metal‐on‐highly cross‐linked polyethylene bearings. Increasing inclination from 50–65° had no changes in volumetric wear of 28/42/54 mm (mean, 1.7 vs. 1.2 mm3/million cycles, respectively; p = 0.50) and 22.2/36/48 mm (mean, 1.7 vs. 1.2 mm3/million cycles, respectively; p = 0.48) dual mobility bearings. At 65°, 22.2/36/48 mm dual‐mobility bearings had lower volumetric loss (mean, 2.2 vs. 6.3 mm3; p = 0.03) and wear rates (mean, 1.2 vs. 2.7 mm3/million cycles; p = 0.02) compared to metal‐on‐highly cross‐linked polyethylene bearings. Modern‐generation dual‐mobility designs with highly cross‐linked polyethylenes may potentially withstand edge‐loading from steeper cup‐inclinations without substantial decreases in wear. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:???–???, 2015.
Soft tissue tumors of the trunk: Management of local disease in the breast and chest and abdominal walls
Authors: Wilder Fatima , D'Angelo Sandra , Crago Aimee M.
Published: November 2014

Soft tissue sarcomas of the trunk are rare lesions, generally managed using an algorithm similar to that employed for extremity sarcomas. This review summarizes the standard treatment of truncal sarcomas and considers how these recommendations differ for each of the various common histologic subtypes observed on the trunk: desmoid, dermatofibrosarcoma protuberans (DFSP), and angiosarcoma. J. Surg. Oncol. 2015 111:546–552. © 2014 Wiley Periodicals, Inc.
Evaluation of prophylaxis treatment of Candida in alaryngeal patients with tracheoesophageal voice prostheses
Authors: Messing Barbara P. , Kim Melissa , Hirata Richard , Thompson Carol B. , Gebhart Samantha , Sugar Elizabeth A. , Saunders John M. , Sciubba James , Califano Joseph A.
Published: November 2014

Objectives/Hypothesis

The objective of this study was to evaluate the effectiveness of nystatin and Biotène® mouthwash Oral Rinse for controlling Candida in total laryngectomy (TL) patients with a tracheosophageal voice prosthesis (TEP) because Biotène® mouthwash Oral Rinse is a less costly alternative to nystatin and requires less adherence time.

Study Design

Randomized, unblinded, crossover trial.

Methods

Twenty‐one TL patients were randomized to receive nystatin followed by Biotène® mouthwash Oral Rinse, or the reverse order, after a basic oral‐care phase (i.e., brushing teeth, cleaning dentures). A Provox® 2, 22.5 French TEP, which is an indwelling silicone voice prosthesis, was placed at the beginning of each phase. Patients were provided with oral care instructions at randomization and medication‐specific instructions with each treatment's initiation. TEPs were processed and evaluated for Candida growth as colony‐forming units (CFUs). Wilcoxon signed‐rank tests were used for comparisons between treatments.

Results

Fifteen patients were available for comparisons of Candida counts (6 received nystatin; 9 received Biotène® mouthwash first). Overall, the median log10 (CFUs) remained high regardless of treatment (no medication: 8.9; nystatin: 8.7; Biotène® mouthwash: 8.4). However, the median counts for both nystatin and Biotène® mouthwash Oral Rinse were lower than those for no medication (difference [Δ]:−0.9 and −0.3, respectively), although only nystatin was significantly lower (P = 0.02). There was no significant difference between the two treatments (P = 0.22). Overall, median medication‐adherence was high (97%), and Biotène® mouthwash adherence was significantly higher than that of nystatin (Δ: 7.6%; P = 0.03).

Conclusion

Nystatin and Biotène® mouthwash Oral Rinse had similar CFU levels, with nystatin showing a significant improvement over usual oral care. Biotène® mouthwash is a less costly alternative to nystatin, with a less complex treatment protocol that might make it preferable to patients and clinicians.

Level of Evidence

1b Laryngoscope, 125:1118–1123, 2015
Systematic review of outcomes following observational and operative endoscopic middle ear surgery
Authors: Kozin Elliott D. , Gulati Shawn , Kaplan Alyson B. , Lehmann Ashton E. , Remenschneider Aaron K. , Landegger Lukas D. , Cohen Michael S. , Lee Daniel J.
Published: November 2014

Objectives

Middle ear surgery increasingly employs endoscopes as an adjunct to or replacement for the operative microscope. We provide a systematic review of endoscope applications in middle ear surgery with an emphasis on outcomes, including the need for conversion to microscope, audiometric findings, length of follow‐up, as well as disease‐specific outcomes.

Data Sources

PubMed, Embase, and Cochrane CENTRAL database.

Methods

A literature review was performed using the Preferred Reporting Items for Systematic Reviews and Meta‐Analysis recommendations. Articles were categorized based on study design, indication, and use of an endoscope either as an adjunct to or as a replacement for a microscope. Qualitative and descriptive analyses of studies and outcomes data were performed.

Results

One‐hundred three articles met inclusion and exclusion criteria. Of the identified articles, 38 provided outcomes data. The majority of these studies were moderate quality, retrospective, case‐series reports. The indications for use of the endoscope were broad, with the most common being resection of cholesteatoma. In cholesteatoma surgery, endoscope approaches routinely identified residual cholesteatoma in primary and second‐look cases. Other outcomes, including robust audiometric data, operating room times, wound healing, and quality of life surveys were not well described.

Conclusions

Endoscopes have consistently been used as an adjunct to the microscope to improve visualization of the tympanic cavity. Recent reports utilize the endoscope exclusively during surgical dissection; however, data comparing patient outcomes following the use of an endoscope to a microscope are lacking. Areas in need of additional research are highlighted.

Level of Evidence

NA Laryngoscope, 125:1205–1214, 2015
Decreased expression and aberrant methylation of RASSF5A correlates with malignant progression of gastric cardia adenocarcinoma
Authors: Han Lijie , Dong Zhiming , Wang Cong , Guo Yanli , Shen Supeng , Kuang Gang , Guo Wei
Published: November 2014

Due to alternative splicing and differential promoter usage, RASSF5 exists in at least three isoforms, RASSF5A, RASSF5B, and RASSF5C. Expression and epigenetic inactivation of different transcripts of RASSF5 in gastric cardia adenocarcinoma (GCA) progression have not been evaluated. Quantitative real‐time RT‐PCR and immunohistochemistry (IHC) methods were used respectively to detect the role of RASSF5A, RASSF5B, and RASSF5C in 132 GCA cases and BS‐MSP method was used to clarify the critical CpG sites of RASSF5A. Expression of RASSF5A and RASSF5C transcripts were easily detectable in all normal gastric cardia epithelial tissues; however, expression of RASSF5B was rare detected in normal gastric cardia epithelial tissues and tumor tissues. Both RASSF5A and RASSF5C expression were frequently downregulated in GCA tumor tissues and RASSF5A was more commonly down‐regulated compared to RASSF5C. Abnormal reduction of RASSF5A was more commonly observed in advanced stage and poor differentiated tumors. The methylation frequency of CpG island 1 region of RASSF5A in GCA tumor tissues was significantly higher than that in corresponding normal tissues and was inversely correlated with RASSF5A expression. Aberrant promoter methylation of RASSF5C was not found in GCA. RASSF5A methylation and protein expression were independently associated with GCA patients' survival. These results indicate that down‐regulation of RASSF5A and RASSF5C expression is a tumor‐specific phenomenon and RASSF5A may be a more common target for inactivation in GCA. Inactivation of RASSF5A through CpG island 1 methylation may play an important role in GCA carcinogenesis and may serve as a prognostic biomarker for GCA. © 2014 Wiley Periodicals, Inc.
Freestyle perforator‐based propeller flap of medial arm for medial elbow reconstruction
Authors: Zang Mengqing , Yu Shengji , Xu Libin , Zhao Zhenguo , Ding Qiang , Guo Lingling , Liu Yuanbo
Published: November 2014

Elbow reconstruction is challenging for reconstructive surgeons. The purpose of this report is to present the results of the use of freestyle perforator‐based propeller flap designed from the medial arm region for elbow reconstruction. The defects following soft tissue sarcoma resection at the medial and posterior elbow were repaired in two patients. The dimensions of the defects were 11 × 7 cm2 and 10 × 7 cm2. Two perforators were identified in each case using Doppler ultrasound probe in the medial arm, adjacent to the defect. The perforator with visible pulsation was chosen as the pedicle vessel, which was 12‐cm and 7‐cm proximal to the medial epicondyle. An elliptical flap, extending almost the full length of arm, was raised and rotated 180° to repair medial elbow defects. The sizes of the flaps were 17 × 8 cm2 and 11 × 7 cm2. The donor sites were closed directly. Both flaps survived; temporary venous congestion occurred in one case. There were no other postoperative complications. These cases illustrated that the medial arm flap might be used for reconstruction of medial elbow defects with this freestyle perforator‐based propeller flap design. © 2014 Wiley Periodicals, Inc. Microsurgery 35:411–414, 2015.
Benchmarking a Wide Range of Chemical Descriptors for Drug‐Target Interaction Prediction Using a Chemogenomic Approach
Authors: Sawada Ryusuke , Kotera Masaaki , Yamanishi Yoshihiro
Published: November 2014

The identification of drug‐target interactions, or interactions between drug candidate compounds and target candidate proteins, is a crucial process in genomic drug discovery. In silico chemogenomic methods are recently recognized as a promising approach for genome‐wide scale prediction of drug‐target interactions, but the prediction performance depends heavily on the descriptors and similarity measures of drugs and proteins. In this paper, we investigated the performance of various descriptors and similarity measures of drugs and proteins for the drug‐target interaction prediction using a chemogenomic approach. We compared the prediction accuracy of 18 chemical descriptors of drugs (e.g., ECFP, FCFP,E‐state, CDK, KlekotaRoth, MACCS, PubChem, Dragon, KCF‐S, and graph kernels) and 4 descriptors of proteins (e.g., amino acid composition, domain profile, local sequence similarity, and string kernel) on about one hundred thousand drug‐target interactions. We examined the combinatorial effects of drug descriptors and protein descriptors using the same benchmark data under several experimental conditions. Large‐scale experiments showed that our proposed KCF‐S descriptor worked the best in terms of prediction accuracy. The comparative results are expected to be useful for selecting chemical descriptors in various pharmaceutical applications.
Clustering of 3D‐Structure Similarity Based Network of Secondary Metabolites Reveals Their Relationships with Biological Activities
Authors: Ohtana Yuki , Abdullah Azian Azamimi , Altaf‐Ul‐Amin Md. , Huang Ming , Ono Naoaki , Sato Tetsuo , Sugiura Tadao , Horai Hisayuki , Nakamura Yukiko , Morita (Hirai) Aki , Lange Klaus W. , Kibinge Nelson K. , Katsuragi Tetsuo , Shirai Tsuyoshi , Kanaya Shigehiko
Published: November 2014

Developing database systems connecting diverse species based on omics is the most important theme in big data biology. To attain this purpose, we have developed KNApSAcK Family Databases, which are utilized in a number of researches in metabolomics. In the present study, we have developed a network‐based approach to analyze relationships between 3D structure and biological activity of metabolites consisting of four steps as follows: construction of a network of metabolites based on structural similarity (Step 1), classification of metabolites into structure groups (Step 2), assessment of statistically significant relations between structure groups and biological activities (Step 3), and 2‐dimensional clustering of the constructed data matrix based on statistically significant relations between structure groups and biological activities (Step 4). Applying this method to a data set consisting of 2072 secondary metabolites and 140 biological activities reported in KNApSAcK Metabolite Activity DB, we obtained 983 statistically significant structure group‐biological activity pairs. As a whole, we systematically analyzed the relationship between 3D‐chemical structures of metabolites and biological activities.
Can metabolically healthy obesity be explained by diet, genetics, and inflammation?
Authors: Navarro Estanislau , Funtikova Anna N. , Fíto Montserrat , Schröder Helmut
Published: November 2014

A substantial proportion of obese individuals do not present cardiometabolic complications such as diabetes, hypertension, or dyslipidemia. Some, but not all, prospective studies observe similar risk of cardiovascular events and all‐cause mortality among individuals with this so‐called “metabolically healthy obese” (MHO) phenotype, compared to the metabolically healthy normal weight or metabolically healthy non‐obese phenotypes. Compared to the metabolically unhealthy obese (MUO) phenotype, MHO is often characterized by a more favorable inflammatory profile, less visceral fat, less infiltration of macrophages into adipose tissue, and smaller adipocyte cell size. Tipping the inflammation balance in adipose tissue might be particularly important for metabolic health in the obese. While the potential role of genetic predisposition or lifestyle factors such as diet in the MHO phenotype is yet to be clarified, it is well known that diet affects inflammation profile and contributes to the functionality of adipose tissue. This review will discuss genetic predisposition and the molecular mechanisms underlying the potential effect of food on the development of the metabolic phenotype characteristic of obesity.