bluuebunny/crossref_metadata_2025 huggingface dataset:
Trimethylaluminium: Bindungsverhältnisse nach Ladungs‐ und Stromtopologie
Authors: Stammler Hans‐Georg , Blomeyer Sebastian , Berger Raphael J. F. , Mitzel Norbert W.
Published: September 2015

Die Ladungsdichteverteilung des dimeren Trimethylaluminiums wurde mittels Hochwinkelröntgenbeugung am Einkristall und quantenchemischen Methoden bestimmt und im Rahmen der “Quantum Theorie of Atoms in Molecules” analysiert. Die Daten können dahingehend interpretiert werden, dass Al2Me6vorherrschend ionisch gebunden ist und deutliche Anzeichen einer topologischen Asymmetrie aufgrund delokalisierter Mehrzentrenbindungen der verbrückenden Al‐C‐Bindungen zeigt. Diese Interpretation wird durch die Ergebnisse von Berechnungen magnetischer Ansprechströme gestützt. Die Befunde werfen ein neues Licht auf die für diese organometallische Grundchemikalie bisher widersprüchlich interpretierte Bindungssituation.
Synthesis of Chiral Pyrazoles: A 1,3‐Dipolar Cycloaddition/[1,5] Sigmatropic Rearrangement with Stereoretentive Migration of a Stereogenic Group
Authors: Pérez‐Aguilar M. Carmen , Valdés Carlos
Published: September 2015

The reactions between terminal alkynes and α‐chiral tosylhydrazones lead to the obtention of chiral pyrazoles with a stereogenic group directly attached at a nitrogen atom. The cascade reaction includes decomposition of the hydrazone into a diazocompound, 1,3‐dipolar cycloaddition of the diazo compound with the alkyne, and [1,5] sigmatropic rearrangement with migration of the stereogenic group. This strategy has been successfully applied to the synthesis of structurally diverse chiral pyrazoles through α‐chiral tosylhydrazones, obtained from α‐phenylpropionic acid, α‐amino acids, and 2‐methoxycyclohexanone. Notably, the stereoretention of the [1,5] sigmatropic rearrangements represent very rare examples of this stereospecific transformation.
Preparation and characterization of Ni2(mal)2(bpy) homochiral MOF membrane
Authors: Li Qianqian , Liu Gongping , Huang Kang , Duan Jingui , Jin Wanqin
Published: September 2015

As an important subclass of metal‐organic frameworks (MOFs), homochiral MOFs show special ability of asymmetric catalysis and enantioselective separation via the open chiral channels or cavities. A new homochiral MOF membrane [Ni2(mal)2(bpy)]•2H2O (Ni‐MB) was synthesized by a secondary growth technique, in which high energy ball milling was employed to prepare nanosized MOF seeds, and their synthesis condition were optimized. X‐ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), and thermal gravimetric analysis were used to measure physicochemical properties of the MOF crystals and membranes. In particular, the homochiral MOF membranes were characterized by nano‐indentation/scratch technique with high‐resolution mechanical property analysis. The SEM results indicated that the membrane was continuous and integrated without observable defects; the permeation measurements of single gas show that the permeate flux of nitrogen was independent on the transmembrane pressure, further confirming the absence of macroporous defects in the as‐prepared chiral MOF membranes. It is expected that the proposed chiral MOF membrane can be potentially applied to enantioselective separation in the future. © 2015 Curtin University of Technology and John Wiley & Sons, Ltd.
The 2014 War on Gaza: engineering trauma and mass torture to break Palestinian resilience
Authors: Shehadeh Said
Published: September 2015

This paper discusses the psychological sequelae of the recent Israeli war on Gaza, codenamed Operation Protective Edge, and its detrimental impact on the mental health of its Palestinian population. The author contends that deliberate measures by the Israeli military to induce feelings of helplessness, uncontrollability, horror, persistent life‐threatening fear, and sleep deprivation against an entire besieged population for 50‐days, constitutes mass torture. This policy of engineering mass trauma and torture through war to achieve political subjugation is framed as a paradigm shift in the Israeli colonial occupation of Palestine. Ramifications of this policy are discussed with regard to its potentially caustic effects on Palestinian resilience, and the serious mental health risks it poses, including complex traumatic reactions, identity distortions, severe psychopathology, and multigenerational transmission of trauma. Recommendations emphasize the need to fortify Palestinian resilience to protect individuals and communities from political violence and further mass trauma. Copyright © 2015 John Wiley & Sons, Ltd.
Breakable and Unbreakable Silences: Implicit Dehumanization and Anti‐Arab Prejudice in Israeli Soldiers’ Narratives Concerning Palestinian Women
Authors: Cohen Shuki J.
Published: September 2015

This paper illustrates an empirical paradigm for a minimally‐biased characterization of the internal representations of female enemy members by male soldiers in the context of a military occupation. Using a combination of psycholinguistic and psychoanalytic tools, the study examined the associative structure of the language that was used by Israeli ex‐soldiers in a large corpus of verbatim testimonies detailing their service in the Palestinian occupied territories. Since explicit dehumanization is rare in Israeli official discourse and in media‐ and political correctness‐savvy occupying forces worldwide, this study examined implicit dehumanization through the non‐conscious use of spontaneous linguistic choices. Using both computerized and quantitative linguistic analyses, this study tracked a particular pattern or word choice, presumed to capture implicit dehumanization based on a trans‐disciplinary definition of the construct. Furthermore, to mitigate the potential confound between fear of the enemy and its dehumanization, this study focused on anecdotes concerning Palestinian women, as they pose less realistic threat to Israeli soldiers. Consistent with this study's formulation of implicit dehumanization, Israeli soldiers tended to describe Palestinian women's mental state in situational and behavioral terms (e.g. scream, make a mess, piss her pants, had a heart attack, etc.). In contrast, empathic inference – whereby the narrator extends their emotional understanding of themselves and other humans to the person whose emotional state they attempt to describe or understand – was often reserved in the testimonials only to the narrator and his fellow comrades. This evidence for implicit dehumanization is then discussed as a borderline‐level defense mechanism within the larger context of both individual‐ and national‐level anti‐Arab prejudice in Israel. Copyright © 2015 John Wiley & Sons, Ltd.
Laparoscopic two-stage hepatectomy for bilobar colorectal liver metastases
Authors: Fuks D , Nomi T , Ogiso S , Gelli M , Velayutham V , Conrad C , Louvet C , Gayet B
Published: September 2015

Background

Despite the gradual diffusion of laparoscopic liver resection, the feasibility and results of laparoscopic two-stage hepatectomy (TSH) for bilobar colorectal liver metastases (CRLM) have not been described frequently. This study aimed to evaluate the feasibility, safety and oncological outcomes of laparoscopic TSH for bilobar CRLM.

Methods

All patients eligible for laparoscopic TSH among those treated for bilobar CRLM from 2000 to 2013 were included. Demographics, tumour characteristics, surgical procedures, and short- and long-term outcomes were analysed.

Results

Laparoscopic TSH was planned in 34 patients with bilobar CRLM, representing 17·2 per cent of all 198 patients treated for bilobar CRLM. Thirty patients received preoperative chemotherapy, and 20 had portal vein occlusion to increase the volume of the remnant liver. Laparoscopic resection of the primary colorectal tumour was integrated within the first-stage hepatectomy in 11 patients. After a median interval of 3·1 months, 26 patients subsequently had a successful laparoscopic second-stage hepatectomy, including 18 laparoscopic right or extended right hepatectomies. The mortality rate for both stages was 3 per cent (1 of 34), and the overall morbidity rate for the first and second stages was 50 per cent (17 of 34) and 54 per cent (14 of 26) respectively. Mean length of hospital stay was 6·1 and 9·0 days respectively. With a median follow-up of 37·8 (range 6–129) months, 3- and 5-year overall survival rates in patients who completed TSH were 78 and 41 per cent respectively. The 3- and 5-year disease-free survival rates were 26 and 13 per cent respectively.

Conclusion

Laparoscopic TSH for bilobar CRLM is safe and does not jeopardize long-term outcomes in selected patients.
Variations in chemical fingerprints and major flavonoid contents from the leaves of thirty‐one accessions of Hibiscus sabdariffa L.
Authors: Wang Jin , Cao Xianshuang , Ferchaud Vanessa , Qi Yadong , Jiang Hao , Tang Feng , Yue Yongde , Chin Kit L.
Published: September 2015

The leaves of Hibiscus sabdariffa L. have been used as traditional folk medicines for treating high blood pressure and fever. There are many accessions of H. sabdariffa L. throughout the world. To assess the chemical variations of 31 different accessions of H. sabdariffa L., fingerprinting analysis and quantitation of major flavonoids were performed by high‐performance liquid chromatography (HPLC). The HPLC method was validated for linearity, sensitivity, precision, repeatability and accuracy. A quadrupole‐time‐of‐flight mass spectrometry (Q‐TOF‐MS) was applied for the characterization of major compounds. A total of 9 compounds were identified, including 6 flavonoids and 3 phenolic acids. In the fingerprint analysis, similarity analysis (SA) and principal component analysis (PCA) were used to differentiate the 31 accessions of H. sabdariffa L. Based on the results of PCA and SA, the samples No. 15 and 19 appeared much different from the main group. The total content of five flavonoids varied greatly among different accessions, ranging from 3.35 to 23.30 mg/g. Rutin was found to be the dominant compound and the content of rutin could contribute to chemical variations among different accessions. This study was helpful to understand the chemical variations between different accessions of H. sabdariffa L., which could be used for quality control. © 2015 The Authors Biomedical Chromatography Published by John Wiley & Sons Ltd.
A primer for the treatment of tic disorders in youth
Authors: Selles Robert R. , Freeman Jennifer B.
Published: September 2015

Tic disorders commonly occur among youth and are characterized by the presence of sudden and repetitive body movements and/or vocalizations. Tics range in location (e.g., face, legs) and complexity (e.g., eye blinks, humming, multistep movements, phrases). Typically, tics onset early in childhood (i.e., ages 5–8), peak in severity and prevalence in preadolescence (i.e., ages 10–12), and begin to decline during adolescence. Only a small percentage of youth (around 20%) continue to have moderate or severe tics in adulthood.
When you get the diagnosis: ADHD primer for parents
Authors: Knopf Alison
Published: September 2015

When their children are diagnosed with a disease that has no cure, parents are concerned, even terrified. But there's no reason for panic. While their worries are understandable, there are many treatment options, and parents — by being the main advocate for their child — can make sure that all possible resources are used to the child's best advantage.
A New Statistical Parameter for Identifying the Main Transition Velocities in Bubble Columns*
Authors: Nedeltchev Stoyan , Rabha Swapna , Hampel Uwe , Schubert Markus
Published: September 2015

The identification of the main flow regime boundaries in bubble columns is essential since the degrees of mixing and mass and heat transfer vary with the flow regime. In this work, a new statistical parameter was extracted from the time series of the cross‐sectional averaged gas holdup. The measurements were performed in bubble columns by means of conductivity wire‐mesh sensors at very high sampling frequency. The columns were operated with an air/deionized water system under ambient conditions. As a flow regime indicator, a new dimensionless statistical parameter called “relative maximum number of visits in a region” was introduced. This new parameter is a function of the difference between the maximum numbers of visits in a region, calculated from two different division schemes of the signal range.
Spin algebra andNMRtheory using numerical software
Authors: Grivet Jean‐Philippe
Published: September 2015

A simple method to execute spin algebra computations is presented. It uses the high‐level numerical program Scilab and its large and convenient set of linear algebra routines. The techniques thus developed are applied to various nuclear magnetic resonance (NMR)‐related simulations. Static spectra of AB and ABC spin systems are computed. Free precession of single or multispin systems are simulated using the density matrix formalism. Magnetization transfer under simple pulse sequences is examined. Matrices representing product operators are displayed and coherence orders are explained. COSY correlation maps for two and three spins are obtained without approximation. The simulation of a DQF‐COSY spectrum, with its eight‐step phase program, is explained. Two simple pulsed field gradient experiments are described. Computation times are under 100 s on a 1.66‐GHz laptop computer. The approach is elementary, requiring only a basic knowledge of spin quantum mechanics. © 2015 Wiley Periodicals, Inc. Concepts Magn Reson Part A 44A: 114–132, 2015.
Anchoring of Gold Nanoparticles on Graphene Oxide and Noncovalent Interactions with Porphyrinoids
Authors: Andrade Suzana M. , Bueno‐Alejo Carlos J. , Serra Vanda V. , Rodrigues João M. M. , Neves Maria G. P. M. S. , Viana Ana S. , Costa Sílvia M. B.
Published: September 2015

The interaction of tetrasulfonated aluminium phthalocyanine (AlPcS4) and meso‐tetraarylporphyrin monosubstituted with poly‐l‐lysine (MM‐PLL), with graphene oxide (GO) is studied in aqueous solution using spectroscopic and microscopic techniques. The study is also performed in the presence of gold nanoparticles (AuNP) grown on the surface of GO using a sonochemical method. The strong quenching of the porphyrin luminescence demonstrates the important interactions between the excited state of the molecule with GO which are absent in the case of the phthalocyanine. However, in the presence of AuNP@GO hybrid a concomitant increase of the phthalocyanine fluorescence intensity takes place together with a decrease of the fluorescence lifetimes involving a surface plasmon coupling effect. The latter is overcome in case of MM‐PLL due to stronger interactions with GO, and is corroborated for deposited samples using fluorescence lifetime imaging microscopy (FLIM). These new nanostructures are thus expected to have selective sensing abilities.
Absorption, Distribution, and Excretion of the Investigational Agent Orteronel (TAK‐700) in Healthy Male Subjects: A Phase 1, Open‐Label, Single‐Dose Study
Authors: Suri Ajit , Pusalkar Sandeepraj , Li Yuexian , Prakash Shimoga
Published: September 2015

This study evaluated the absorption, distribution, and excretion of orteronel, an investigational, nonsteroidal, reversible, selective 17,20‐lyase inhibitor. Six healthy male subjects received a single 400‐mg dose of radiolabeled [14C]‐orteronel (18.5 kBq). The pharmacokinetics of [14C]‐radioactivity, orteronel, and the primary metabolite M‐I were characterized by ultra‐performance liquid chromatography–tandem mass spectrometry, and mass balance recovery of [14C]‐radioactivity was determined by liquid scintillation counting and accelerator mass spectrometry. Median time to maximum observed concentration of [14C]‐radioactivity was 2.5 hours (plasma/whole blood) and of orteronel was 1 hour (plasma). Mean terminal half‐life for [14C]‐radioactivity in plasma and whole blood was 9.46 and 7.39 hours, respectively. For [14C]‐radioactivity, the geometric mean whole blood–to–plasma ratios for maximum observed plasma/whole‐blood concentration, area under the plasma concentration–time curve from time 0 to last quantifiable concentration (AUC0–last), and AUC0–inf (AUC from time 0 to infinity) were 1.04, 0.92, and 0.93, respectively. Dose recovery accounted for 95.9% of the administered orteronel dose; the majority of excretion occurred by 96 hours postdose. The principal excretion route was via urine (mean, 77.5%; including 49.7% unchanged drug and 16.3% M‐I) compared with 18.4% via feces. Three mild adverse events were reported; none were considered serious or related to orteronel.
The Effect of the Scattering Layer in Dye‐Sensitized Solar Cells Employing a Cobalt‐Based Aqueous Gel Electrolyte
Authors: Xiang Wanchun , Chen Dehong , Caruso Rachel A. , Cheng Yi‐Bing , Bach Udo , Spiccia Leone
Published: September 2015

We developed an aqueous gel electrolyte based on the [Co(bpy)3]2+/3+ (bpy=2,2′‐bipyridine) redox mediator for use in n‐type dye‐sensitized solar cells. Application of this electrolyte in combination with titania nanoparticle‐based photoanodes and mesoporous titania bead scattering layers resulted in devices with efficiencies of 4.1 % under simulated AM 1.5 sunlight, compared with 3.5 % for devices using scattering layers made from a commercial paste. This difference was largely a result of a 25 % improvement in the short‐circuit current density and was ascribed to lower diffusion resistance for the gel electrolyte within mesoporous TiO2 beads, as confirmed by electrochemical impedance spectroscopy. Transient photocurrent measurements identified mass‐diffusion problems for DSCs employing the commercial TiO2 paste. Moreover, under continuous 1 sun illumination, the devices based on an aqueous gel electrolyte displayed higher stability relative to those assembled with the corresponding liquid electrolyte.
A Methyl‐Substituted Thiophene–Tetra­thiafulvalene Donor and Its Salts
Authors: Silva Rafaela A. L. , Santos Isabel C. , Lopes Elsa B. , Rabaça Sandra , Galindo Sergi , Mas‐Torrent Marta , Rovira Concepció , Almeida Manuel , Belo Dulce
Published: September 2015

α‐Methyldithiophene–tetrathiafulvalene (α‐mDT‐TTF), the first alkyl‐substituted thiophene–tetrathiafulvalene electronic donor, and some of its charge‐transfer salts were explored. The crystal structure of α‐mDT‐TTF is composed of molecular stacks aligned parallel to each other. Its cyclic voltammetry shows higher electron‐donor ability than the unsubstituted analogue. This material was employed as a semiconductor in an organic field‐effect transistor and showed a mobility of 4 × 10–4 cm2 V–1 s–1. Two charge‐transfer salts of this donor with [M(mnt)2]– anions (mnt = maleonitriledithiolate), M = Co and Au, were obtained by electrocrystallization; they present unusual stoichiometries: (α‐mDT‐TTF)[Co(mnt)2] and (α‐mDT‐TTF)3[Au(mnt)2]2. In the cobalt compound, the donor molecules are fully oxidized and the Co complex is dimerized; it presents semiconducting behavior (7 × 10–3 S cm–1). The gold compound is composed of alternating stacks of donor trimers and pairs of anions.
Investigation into the Chemistry of Highly Substituted [(Aminocyclopropyl)methyl]alk­oxyamines (3‐Azabicyclo[3.1.0]hexanes)
Authors: Hauck Stefan , Kuepfert Michael , Schoening Kai‐Uwe
Published: September 2015

Enamines prepared from N‐alkoxy‐4‐oxo‐2,2′,6,6′‐tetramethylpiperidines were selectively chlorinated in the allyl position and subsequently transformed into bicyclic [(aminocyclopropyl)methyl]alkoxyamines by reaction with various nucleophiles. The products were formed, supposedly via iminium intermediates, in reasonable to high yields, possessing varying degrees of hydrolytic stability. Structural elucidation by NMR spectroscopy strongly suggested an endo position of the amine substituent. The obtained, highly functionalized alkoxyamines could be of interest as polymer additives or biologically active intermediates.
The effects of catastrophizing on central motor activity
Authors: Henderson L.A. , Akhter R. , Youssef A.M. , Reeves J.M. , Peck C.C. , Murray G.M. , Svensson P.
Published: September 2015

Background

Pain catastrophizing significantly affects an individual's experience of pain. High pain catastrophizing is associated with increased fear avoidance behaviours, pain intensity and disability. The aim of this investigation was to determine the effect of pain catastrophizing on ongoing brain activity and movement‐evoked brain activity during acute orofacial muscle pain.

Methods

Thirty‐four healthy, pain‐free subjects were recruited. In 17 subjects, the effect of catastrophizing on regional brain activity was determined. In 19 subjects, functional magnetic resonance imaging was used to determine the effects of pain catastrophizing on brain activation patterns during jaw movements in the presence of ongoing pain.

Results

We found that in the presence of pain, catastrophizing was significantly correlated with activity in multi‐sensory integrative brain regions, including the dorsolateral and medial prefrontal cortices. Importantly, this relationship did not exist when subjects were not experiencing pain. In addition, during repetitive open–close jaw movements in the presence of pain, activity in the primary motor cortex, cerebellar cortex and the trigeminal motor nucleus was positively correlated with pain catastrophizing scores. In contrast, in the dorsolateral prefrontal cortex, as pain catastrophizing scores increased, the magnitude of signal intensity change during jaw movements decreased. Again, no such relationships occurred when the individual was not in pain.

Conclusions

These data show that during pain, catastrophic thinking has a significant impact on activity in motor and sensory integrative regions. Reducing negative coping strategies may be an effective means in reducing fear avoidance behaviours and the intensity of ongoing pain.
Potent mutagenicity in the Ames test of 2‐cyano‐4‐nitroaniline and 2,6‐dicyano‐4‐nitroaniline, components of disperse dyes
Authors: Josephy P. David , Zahid Muhammad , Dhanoa Joban , de Souza Giovanna Brondino Duarte , Groom Hilary , Lambie Meghan
Published: September 2015

Genotoxicity data on commercial azo dyes and their components remain sparse, despite their widespread use. We have tested the mutagenicity of 2‐cyano‐4‐nitroaniline (CNNA) and 2,6‐dicyano‐4‐nitroaniline (CNCNNA), components of azo dyes such as Disperse Blue 165 and Disperse Red 73, in Ames test strains. Both compounds are extraordinarily potent frameshift mutagens, with much greater activity than structurally similar dihalonitroanilines and halodinitroanilines. Analysis of the responses of strains over‐expressing or deficient in bioactivation enzymes shows that bacterial nitroreductase and acetyl CoA: arylamine N‐acetyltransferase are important mediators of the mutagenicity of CNNA and CNCNNA. Environ. Mol. Mutagen. 57:10–16, 2016. © 2015 Wiley Periodicals, Inc.
Proteolipid protein modulates preservation of peripheral axons and premature death when myelin protein zero is lacking
Authors: Patzig Julia , Kusch Kathrin , Fledrich Robert , Eichel Maria A. , Lüders Katja A. , Möbius Wiebke , Sereda Michael W. , Nave Klaus‐Armin , Martini Rudolf , Werner Hauke B.
Published: September 2015

Protein zero (P0) is the major structural component of peripheral myelin. Lack of this adhesion protein from Schwann cells causes a severe dysmyelinating neuropathy with secondary axonal degeneration in humans with the neuropathy Dejerine‐Sottas syndrome (DSS) and in the corresponding mouse model (P0null‐mice). In the mammalian CNS, the tetraspan‐membrane protein PLP is the major structural myelin constituent and required for the long‐term preservation of myelinated axons, which fails in hereditary spastic paraplegia (SPG type‐2) and the relevant mouse model (Plpnull‐mice). The Plp‐gene is also expressed in Schwann cells but PLP is of very low abundance in normal peripheral myelin; its function has thus remained enigmatic. Here we show that the abundance of PLP but not of other tetraspan myelin proteins is strongly increased in compact peripheral myelin of P0null‐mice. To determine the functional relevance of PLP expression in the absence of P0, we generated P0null*Plpnull‐double‐mutant mice. Compared with either single‐mutant, P0null*Plpnull‐mice display impaired nerve conduction, reduced motor functions, and premature death. At the morphological level, axonal segments were frequently non‐myelinated but in a one‐to‐one relationship with a hypertrophic Schwann cell. Importantly, axonal numbers were reduced in the vital phrenic nerve of P0null*Plpnull‐mice. In the absence of P0, thus, PLP also contributes to myelination by Schwann cells and to the preservation of peripheral axons. These data provide a link between the Schwann cell‐dependent support of peripheral axons and the oligodendrocyte‐dependent support of central axons. GLIA 2016;64:155–174
Need for uniqueness as a mediator of the relationship between face consciousness and status consumption in China
Authors: Sun Gong , Chen Jun , Li Jie
Published: September 2015

Strong economic development in China has led to a surge in status consumption as a means of gaining face. In Eastern culture, people interpret uniqueness as status distinction rather than separateness or deviance. This type of uniqueness can be used to meet others' expectations and gain social approval. Thus its relationship with face consciousness and status consumption is to be expected. This study investigates 2 hypotheses: (a) Face consciousness has a positive effect on status consumption and (b) Consumer need for uniqueness mediates the relationship between face consciousness and status consumption. Two‐hundred and forty‐six working respondents in eastern China completed a survey. Regression analysis of the results supported both hypotheses.
High Serum SHBG Predicts Incident Vertebral Fractures in Elderly Men
Authors: Vandenput Liesbeth , Mellström Dan , Kindmark Andreas , Johansson Helena , Lorentzon Mattias , Leung Jason , Redlund-Johnell Inga , Rosengren Björn E , Karlsson Magnus K , Wang Yi-Xiang , Kwok Timothy , Ohlsson Claes
Published: September 2015

Previous prospective cohort studies have shown that serum levels of sex steroids and sex hormone-binding globulin (SHBG) associate with nonvertebral fracture risk in men. The predictive value of sex hormones and SHBG for vertebral fracture risk specifically is, however, less studied. Elderly men (aged ≥65 years) from Sweden and Hong Kong participating in the Osteoporotic Fractures in Men (MrOS) study had baseline estradiol and testosterone analyzed by gas chromatography–mass spectrometry (GC-MS) and SHBG by immunoradiometric assay (IRMA). Incident clinical vertebral fractures (n = 242 cases) were evaluated in 4324 men during an average follow-up of 9.1 years. In a subsample of these men (n = 2256), spine X-rays were obtained at baseline and after an average follow-up of 4.3 years to identify incident radiographic vertebral fractures (n = 157 cases). The likelihood of incident clinical and radiographic vertebral fractures was estimated by Cox proportional hazards models and logistic regression models, respectively. Neither serum estradiol (hazard ratio [HR] per SD increase = 0.93, 95% confidence interval [CI] 0.80–1.08) nor testosterone (1.05, 0.91–1.21) predicted incident clinical vertebral fractures in age-adjusted models in the combined data set. High serum SHBG, however, associated with increased clinical vertebral fracture risk (1.24, 1.12–1.37). This association remained significant after further adjustment for FRAX with or without bone mineral density (BMD). SHBG also associated with increased incident radiographic vertebral fracture risk (combined data set; odds ratio [OR] per SD increase = 1.23, 95% CI 1.05–1.44). This association remained significant after adjustment for FRAX with or without BMD. In conclusion, high SHBG predicts incident clinical and radiographic vertebral fractures in elderly men and adds moderate information beyond FRAX with BMD for vertebral fracture risk prediction. © 2015 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
The Transcriptional Modulator Interferon-Related Developmental Regulator 1 in Osteoblasts Suppresses Bone Formation and Promotes Bone Resorption
Authors: Iezaki Takashi , Onishi Yuki , Ozaki Kakeru , Fukasawa Kazuya , Takahata Yoshifumi , Nakamura Yukari , Fujikawa Koichi , Takarada Takeshi , Yoneda Yukio , Yamashita Yui , Shioi Go , Hinoi Eiichi
Published: September 2015

Bone homeostasis is maintained by the synergistic actions of bone-resorbing osteoclasts and bone-forming osteoblasts. Although interferon-related developmental regulator 1 (Ifrd1) has been identified as a transcriptional coactivator/repressor in various cells, little attention has been paid to its role in osteoblastogenesis and bone homeostasis thus far. Here, we show that Ifrd1 is a critical mediator of both the cell-autonomous regulation of osteoblastogenesis and osteoblast-dependent regulation of osteoclastogenesis. Osteoblast-specific deletion of murine Ifrd1 increased bone formation and decreased bone resorption, causing high bone mass. Ifrd1 deficiency enhanced osteoblast differentiation and maturation along with increased expression of Runx2 and osterix (Osx). Mechanistically, Ifrd1 deficiency increased the acetylation status of p65, a component of NF-κB, at residues K122 and K123 via the attenuation of the interaction between p65 and histone deacetylase (HDAC). This led to the nuclear export of p65 and a decrease in NF-κB-dependent Smad7 expression and the subsequent enhancement of Smad1/Smad5/Smad8-dependent transcription. Moreover, a high bone mass phenotype in the osteoblast-specific deletion of Ifrd1 was markedly rescued by the introduction of one Osx-floxed allele but not of Runx2-floxed allele. Coculture experiments revealed that Ifrd1-deficient osteoblasts have a higher osteoprotegerin (OPG) expression and a lower ability to support osteoclastogenesis. Ifrd1 deficiency attenuated the interaction between β-catenin and HDAC, subsequently increasing the acetylation of β-catenin at K49, leading to its nuclear accumulation and the activation of the β-catenin-dependent transcription of OPG. Collectively, the expression of Ifrd1 in osteoblasts repressed osteoblastogenesis and activated osteoclastogenesis through modulating the NF-κB/Smad/Osx and β-catenin/OPG pathways, respectively. These findings suggest that Ifrd1 has a pivotal role in bone homeostasis through its expression in osteoblasts in vivo and represents a therapeutic target for bone diseases. © 2015 American Society for Bone and Mineral Research.
Milk Fat Globule-Epidermal Growth Factor 8 (MFG-E8) Is a Novel Anti-inflammatory Factor in Rheumatoid Arthritis in Mice and Humans
Authors: Albus Elise , Sinningen Kathrin , Winzer Maria , Thiele Sylvia , Baschant Ulrike , Hannemann Anke , Fantana Julia , Tausche Anne-Kathrin , Wallaschofski Henri , Nauck Matthias , Völzke Henry , Grossklaus Sylvia , Chavakis Triantafyllos , Udey Mark C , Hofbauer Lorenz C , Rauner Martina
Published: September 2015

Milk fat globule-epidermal growth factor 8 (MFG-E8) is an anti-inflammatory glycoprotein that mediates the clearance of apoptotic cells and is implicated in the pathogenesis of autoimmune and inflammatory diseases. Because MFG-E8 also controls bone metabolism, we investigated its role in rheumatoid arthritis (RA), focusing on inflammation and joint destruction. The regulation of MFG-E8 by inflammation was assessed in vitro using osteoblasts, in arthritic mice and in patients with RA. K/BxN serum transfer arthritis (STA) was applied to MFG-E8 knock-out mice to assess its role in the pathogenesis of arthritis. Stimulation of osteoblasts with lipopolysaccharide (LPS) and tumor necrosis factor (TNF)-α downregulated the expression of MFG-E8 by 30% to 35%. MFG-E8-deficient osteoblasts responded to LPS with a stronger production of pro-inflammatory cytokines. In vivo, MFG-E8 mRNA levels were 52% lower in the paws of collagen-induced arthritic (CIA) mice and 24% to 42% lower in the serum of arthritic mice using two different arthritis models (CIA and STA). Similarly, patients with RA (n = 93) had lower serum concentrations of MFG-E8 (–17%) compared with healthy controls (n = 140). In a subgroup of patients who had a moderate to high disease activity (n = 21), serum concentrations of MFG-E8 rose after complete or partial remission had been achieved (+67%). Finally, MFG-E8-deficient mice subjected to STA exhibited a stronger disease burden, an increased number of neutrophils in the joints, and a more extensive local and systemic bone loss. This was accompanied by an increased activation of osteoclasts and a suppression of osteoblast function in MFG-E8-deficient mice. Thus, MFG-E8 is a protective factor in the pathogenesis of RA and subsequent bone loss. Whether MFG-E8 qualifies as a novel biomarker or therapeutic target for the treatment of RA is worth addressing in further studies. © 2015 American Society for Bone and Mineral Research.
Synthesis and Antioxidant Activity of New Pyrazolo[1,5‐a]Pyrimidine Derivatives Incorporating a Thiazol‐2‐yldiazenyl Moiety
Authors: El‐Mekabaty Ahmed , Habib Osman M. O. , Moawad Evelin B. , Hasel Ali M.
Published: September 2015

4‐(Thiazol‐2‐yldiazenyl)‐1H‐pyrazole‐3,5‐diamine (2) was prepared by the reaction of 2‐thiazolylazomalononitrile (1) with hydrazine hydrate in boiling ethanol and used as key intermediate for the synthesis of polyfunctionally substituted pyrazolo[1,5‐a]pyrimidines via its reactions with reagents having 1,3‐dielectrophilic centers. Structures of the newly synthesized compounds were established by elemental analysis and spectral data. Representative compounds of the synthesized products were tested and evaluated as antioxidant agents. The results revealed that compounds (3), (4), (5), and (9) displayed promising antioxidant activity compared to the activity of ascorbic acid.
Synthesis of Various Schiff Bases Containing Isoxazole Ring and Their Applications with Thioglycollic Acid and Diverse Phosphorus Reagents
Authors: Shady Abeer A. , Abu Bakr Sherifa M. , Khidre Maha D.
Published: September 2015

A series of Schiff bases bearing isoxazole and pyrazole rings were synthesized. Application of thioglycollic acid on two selective synthesized Schiff bases afforded the corresponding thiazolidin‐4‐one derivatives. On the other hand, following the multicomponents one‐pot Kabachnik– Fields reaction, the Schiff base generated in situ from 4‐chlorobenzaldehyde and 5‐methyl isoxazol‐3‐amine was trapped by phosphorus reagents to produce the corresponding amino phosphonates in moderate yields. However, the latter products could also be obtained in better yields (≥78%) by directly applying the dialkylphosphites to a selective synthesized Schiff base. Similarly, a series of α‐aminophosphonates could be obtained from 5‐chloro‐3‐methyl‐1H‐pyrazol‐4‐carbaldehyde, 5‐methylisoxazol‐3‐amine, and phosphorus reagents. Moreover, applying hexaalkyl triamido phosphites to the N‐(4‐chlorobenzylidene)‐5‐methylisoxazol‐3‐amine in ethanol afforded methylphosphonic diamide derivatives, whereas N‐((5‐chloro‐3‐methyl‐1H‐pyrazol‐4‐yl)methylene)‐5‐methylisoxazol‐3‐amine underwent dechlorination through reaction with hexaalkyl triamido phosphites to give the respective amine derivatives.
Synthesis of two potent glucocorticoid receptor agonists labeled with carbon‐14 and stable isotopes
Authors: Latli Bachir , Reeves Jonathan T. , Tan Zhulin , Hrapchak Matt , Song Jinhua J. , Busacca Carl B. , Senanayake Chris H.
Published: September 2015

Two potent glucocorticoid receptor agonists were prepared labeled with carbon‐14 and with stable isotopes to perform drug metabolism, pharmacokinetics, and bioanalytical studies. Carbon‐14 labeled (1) was obtained from an enantiopure alkyne (5) via a Sonogashira coupling to a previously reported 5‐amino‐4‐iodo‐[2‐14C]pyrimidine [14C]‐(6), followed by a base‐mediated cyclization (1) in 72% overall radiochemical yield. Carbon‐14 labeled (2) was prepared in five steps employing a key benzoic acid intermediate [14C]‐(13), which was synthesized in one pot from enolization of trifluoromethylketone (12), followed by bromine–magnesium exchange and then electrophile trapping reaction with [14C]‐carbon dioxide. A chiral auxiliary (S)‐1‐(4‐methoxyphenyl)ethylamine was then coupled to this acid to give [14C]‐(15). Propargylation and separation of diastereoisomers by crystallizations gave the desired diastereomer [14C]‐(17) in 34% yield. Sonogashira coupling to iodopyridine (10) followed by cyclization to the azaindole [14C]‐(18) and finally removal of the chiral auxiliary gave [14C]‐(2) in 7% overall yield. For stable isotope syntheses, [13C6]‐(1) was obtained in three steps using [13C4]‐(6) and trimethylsilylacetylene‐[13C2] in 26% yield, while [2H5]‐(2) was obtained by first preparing the iodopyridine [2H5]‐(10) in five steps. Then, Sonogashira coupling to chiral alkyne (24) and cyclization gave [2H5]‐(2) in 42% overall yield.
The minimal important difference of the epistaxis severity score in hereditary hemorrhagic telangiectasia
Authors: Yin Linda X. , Reh Douglas D. , Hoag Jeffrey B. , Mitchell Sally E. , Mathai Stephen C. , Robinson Gina M. , Merlo Christian A.
Published: September 2015

Objectives/Hypothesis

Hereditary hemorrhagic telangiectasia (HHT) is a disease of abnormal angiogenesis, causing epistaxis in over 96% of patients. The Epistaxis Severity Score (ESS) was developed as a standardized measurement of nasal symptoms among HHT patients. The minimal important difference (MID) of a disease index estimates the smallest change that a patient and clinician would identify as important. This study aims to establish the MID of the ESS in a diverse population of HHT patients.

Study Design

Retrospective cross‐sectional study in patients with a diagnosis of HHT using Curacao criteria or genetic testing.

Methods

The ESS questionnaire and Medical Outcomes Study 36‐Item Short Form (SF‐36) were administered to participants recruited through the HHT Foundation Web site. Demographics and relevant medical histories were collected from all participants. An anchor‐based method using a change of 5 in the Physical Component Summary (PCS) of the SF‐36 and a distributional method were used to estimate the MID.

Results

A total of 604 subjects were recruited between April and August 2008. All participants reported epistaxis. An increasing ESS in the study cohort showed a significant negative correlation to the PCS (r = −0.43, P < 0.001). The MID was determined to be 0.41 via the anchor‐based approach and 1.01 via the distribution‐based approach, giving a mean MID of 0.71.

Conclusion

Using both the anchor‐based and distribution‐based approaches, the estimated MID for the ESS in HHT is 0.71. Further implications include key metrics to help guide treatment responses in clinical care and essential information to calculate power and sample size for future clinical trials.

Level of Evidence

4. Laryngoscope, 126:1029–1032, 2016
Decade review of mandible fractures and arch bar impact on outcomes of nonsubcondylar fractures
Authors: Kopp Robert W. , Crozier Daniel L. , Goyal Parul , Kellman Robert M. , Suryadevara Amar C.
Published: September 2015

Objectives/Hypothesis

Review trends in mandible fracture management and outcomes in patients treated with and without intraoperative arch bar use.

Study Design

Retrospective chart review.

Methods

All patients with mandible fractures between October 1, 2001, and October 1, 2011, were reviewed. Excluded were those with concomitant midfacial fractures or inadequate follow‐up.

Results

Overall, 734 patients sustained 1,312 mandible fractures. Assault was the most common etiology. The parasymphyseal, subcondylar, and angle regions were most likely fractured. In total, 85% of patients underwent open‐reduction internal‐fixation (ORIF). This overall number had no significant annual deviation. However, use of arch bars to achieve intraoperative maxillomandibular fixation (MMF) with ORIF decreased annually, whereas the use of manual reduction with ORIF increased annually. These trends held statistical significance. Outcomes were reviewed in patients with one or two nonsubcondylar fractures by assessing complications of malocclusion, infection, and malunion. In 228 patients meeting criteria, the incidence of complications was 12.9% in those treated using intraoperative arch bars with ORIF and 12.5% in those using manual reduction with ORIF. When assessing individual complications, there was no statistically significant difference.

Conclusion

Our data suggest a shifting trend in mandible fracture management. Our techniques for achieving fracture reduction ideal for ORIF favors manual reduction over the use of arch bars in select cases. We found no statistical increase in the incidence of complications when using manual reduction with ORIF in patients with one and two nonsubcondylar fractures. In appropriately selected cases, manual stabilization of fractured segments is an alternative to using arch bars to achieve intraoperative MMF.

Level of Evidence

4. Laryngoscope, 126:596–601, 2016
Glass ionomer application for vocal fold augmentation: Histopathological analysis on rabbit vocal fold
Authors: Demirci Sule , Tuzuner Arzu , Callıoglu Elif Ersoy , Yumusak Nihat , Arslan Necmi , Baltacı Bülent
Published: September 2015

Objectives/Hypothesis

The aim of this study was to investigate the use of glass ionomer cement (GIC) as an injection material for vocal fold augmentation and to evaluate the biocompatibility of the material.

Study Design

Ten adult New Zealand rabbits were used.

Methods

Under general anesthesia, 0.1‐cc GIC was injected to one vocal fold and the augmentation of vocal fold was observed. No injection was applied to the opposite side, which was accepted as the control group. The animals were sacrificed after 3 months and the laryngeal specimens were histopathologically evaluated.

Results

The injected and the noninjected control vocal folds were analyzed. The GIC particles were observed in histological sections on the injected side, and no foreign body giant cells, granulomatous inflammation, necrosis, or marked chronic inflammation were detected around the glass ionomer particles. Mild inflammatory reactions were noticed in only two specimens. The noninjected sides of vocal folds were completely normal.

Conclusion

The findings of this study suggest that GIC is biocompatible and may be further investigated as an alternative injection material for augmentation of the vocal fold. Further studies are required to examine the viscoelastic properties of GIC and the long‐term effects in experimental studies.

Level of Evidence

NA. Laryngoscope, 126:E171–E174, 2016
Soil Enzymatic Activity in Eucalyptus Grandis Plantations of Different Ages
Authors: Lino Ingrid Alexssandra Neris , dos Santos Vilma Maria , Escobar Indra Elena Costa , da Silva Danielle Karla Alves , de Araújo Ademir Sérgio Ferreira , Maia Leonor Costa
Published: September 2015

Eucalyptus plantations have become increasingly common in Latin America. However, because Eucalyptus is an exotic species, its presence has raised concerns about changes in the environment, especially to soil properties. The objective of this study was to investigate possible changes in selected soil enzyme activity after several years of Eucalyptus cultivation. Soil samples were collected from four locations: a native forest (Atlantic Forest) used as a reference for the original soil conditions and three E. grandis plantations aged 2, 3 and 5 years, established in 2008, 2007 and 2005, respectively. The native vegetation had been removed and the soil graded and ploughed to establish these plantations. We evaluated soil enzymatic activities (β‐glucosidase, acid phosphatase, dehydrogenase, urease and arylsulfatase) at each location. The activity of β‐glucosidase, phosphatase, dehydrogenase and urease was improved after 5 years, whereas arylsulphatase was impacted negatively. The multivariate analysis showed that the majority of enzyme activities reached the values observed in native forest after the third year of reforestation. The activity of β‐glucosidase was crucial in differentiating the area with 2 years of reforestation from the native forest. The removal of native vegetation in order to establish commercial plantations raises concerns about the real impacts of this practice on the soil. In the present study, plantations of Eucalyptus improved most of the selected enzyme activities after the third year of reforestation. Copyright © 2015 John Wiley & Sons, Ltd.
A stronger version of the Kleiman‐Chevalley projectivity criterion
Authors: Farnik Michał
Published: September 2015

We strengthen the classical Kleiman‐Chevalley projectivity criterion by showing that it is enough to assume that instead of .
TGFβ induces epithelial‐mesenchymal transition of thyroid cancer cells by both the BRAF/MEK/ERK and Src/FAK pathways
Authors: Baquero Pablo , Jiménez‐Mora Eva , Santos Adrián , Lasa Marina , Chiloeches Antonio
Published: September 2015

The epithelial‐mesenchymal transition (EMT) is a crucial process in tumour progression, by which epithelial cells acquire a mesenchymal phenotype, increasing its motility and the ability to invade distant sites. Here, we describe the molecular mechanisms by which V600EBRAF, TGFβ and the Src/FAK complex cooperatively regulate EMT induction and cell motility of anaplastic thyroid cancer cells. Analysis of EMT marker levels reveals a positive correlation between TGFβ and Snail expression, with a concomitant downregulation of E‐cadherin, accompanied by an increase of cell migration and invasion. Furthermore, we show that V600EBRAF depletion by siRNA or inhibition of its activity by treatment with its inhibitor PLX4720 reverses the TGFβ‐mediated effects on Snail, E‐cadherin, migration and invasion. Moreover, V600EBRAF induces TGFβ secretion through a MEK/ERK‐dependent mechanism. In addition, TGFβ activates the Src/FAK complex, which in turn regulates the expression of Snail and E‐cadherin as well as cell migration. The inhibition of Src with the inhibitor SU6656 or abrogation of FAK expression with a specific siRNA reverses the TGFβ‐induced effects. Interestingly, we demonstrate that activation of the Src/FAK complex by TGFβ is independent of V600EBRAF signalling, since inhibition of this oncogene does not affect its phosphorylation. Our data strongly suggest that TGFβ induces EMT and aggressiveness of thyroid cancer cells by parallel mechanisms involving both the V600EBRAF/MEK/ERK and Src/FAK pathways independently. Thus, we describe novel functions for Src/FAK in mediating the EMT program and aggressiveness regulated by TGFβ, establishing the inhibition of these proteins as a possible effective approach in preventing tumour progression of V600EBRAF‐expressing thyroid tumours. © 2015 Wiley Periodicals, Inc.