bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional and Transcriptional Characterization of Histone Deacetylase Inhibitor-Mediated Cardiac Adverse Effects in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Authors: Kopljar Ivan , Gallacher David J. , De Bondt An , Cougnaud Laure , Vlaminckx Eddy , Van den Wyngaert Ilse , Lu Hua Rong
Published: April 2016

Histone deacetylase (HDAC) inhibitors possess therapeutic potential to reverse aberrant epigenetic changes associated with cancers, neurological diseases, and immune disorders. Unfortunately, clinical studies with some HDAC inhibitors displayed delayed cardiac adverse effects, such as atrial fibrillation and ventricular tachycardia. However, the underlying molecular mechanism(s) of HDAC inhibitor-mediated cardiotoxicity remains poorly understood and is difficult to detect in the early stages of preclinical drug development because of a delayed onset of effects. In the present study, we show for the first time in human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) that HDAC inhibitors (dacinostat, panobinostat, vorinostat, entinostat, and tubastatin-a) induce delayed dose-related cardiac dysfunction at therapeutic concentrations associated with cardiac adverse effects in humans. HDAC inhibitor-mediated delayed effects on the beating properties of hiPS-CMs developed after 12 hours by decreasing the beat rate, shortening the field potential duration, and inducing arrhythmic behavior under form of sustained contractions and fibrillation-like patterns. Transcriptional changes that are common between the cardiotoxic HDAC inhibitors but different from noncardiotoxic treatments identified cardiac-specific genes and pathways related to structural and functional changes in cardiomyocytes. Combining the functional data with epigenetic changes in hiPS-CMs allowed us to identify molecular targets that might explain HDAC inhibitor-mediated cardiac adverse effects in humans. Therefore, hiPS-CMs represent a valuable translational model to assess HDAC inhibitor-mediated cardiotoxicity and support identification of better HDAC inhibitors with an improved benefit-risk profile.

Significance

Histone deacetylase (HDAC) inhibitors are a promising class of drugs to treat certain cancers, autoimmune, and neurodegenerative diseases. However, treated patients can experience various cardiac adverse events such as hearth rhythm disorders. This study found that human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) can predict cardiac adverse events in patients caused by HDAC inhibitors. Furthermore, transcriptional changes at the level of gene expression supported the effects on the beating properties of hiPS-CMs and highlight targets that might cause these cardiac adverse effects. hiPS-CMs represent a valuable translational model to assess HDAC inhibitor-mediated cardiotoxicity and to support development of safer HDAC inhibitors.
Inclusion of Blend of L-lysine, DL-Methionine and Vitamins D3, E in Diets for Broiler; Effects on Growth Performance, Feed Intake and Conversion and Water Intake.
Authors: Rani Abro  , Abdul Ghaffar  , Shahid Hussain Abro  , Hakimzadi Wagan  , Ahmed Nawaz Tunio  , Jameel Ahmed Gandahi  , Pershotum Khatri  , Huma Rizwana  , Riaz Ahmed Leghari  , Bakhtawar Wagan  , Mohsan Ullah Goraya
Published: April 2016

The blend comprising of L-lysine, DL-methionine and vitamins D3, E in diets evaluated for growth performance, water intake, feed consumption and conversion ratio and live body weight in broiler was investigated. The study was performed on 360 day old broiler chickens and divided into four groups i.e. A (control), B,C and D (30 chickens in each group) randomly. The birds were fed blend in the diets; group B (40gm / 50 kg feed), group C (80 gm / 50 kg feed) and group D (120 gm / 50 kg feed). The growth parameters of broilers were significant (P
Fulfill Your Digital Preservation Goals with a Budget Studio
Authors: Zhou Yongli
Published: April 2016

In order to fulfill digital preservation goals, many institutions use high-end scanners for in-house scanning of historical print and oversize materials. However, high-end scanners’ prices do not fit in many small institutions’ budget. As digital single-lens reflex (DSLR) camera technologies advance and camera prices drop quickly, a budget photography studio can help to achieve institutions’ preservation goals.  This paper compares images delivered by a high-end overhead scanner and a consumer level DSLR camera, discusses pros and cons of using each method, demonstrates how to set up a cost efficient shooting studio, and presents a budget estimate for a studio.
Lessons Learned: A Primo Usability Study
Authors: Brett Kelsey Renee , Lierman Ashley , Turner Cherie
Published: April 2016

The University of Houston Libraries implemented Primo as the primary search option on the library website in May 2014. In May 2015, the Libraries released a redesigned interface to improve user experience with the tool. The Libraries took a user-centered approach to redesigning the Primo interface by conducting a "think-aloud" usability test in order to gather user feedback and identify needed improvements. This article describes the methodology and findings from the usability study, the changes that were made to the Primo interface as a result, and implications for discovery system vendor relations and library instruction.
O Barroco, a arquitetura e a cidade nos séculos XVII e XVIII
Authors: Espinha Baeta Rodrigo
Published: April 2016

Este livro revela uma apreensão do “espírito” arrebatador que invadiu o mundo ocidental durante quase duzentos anos, contribuindo para as discussões sobre a arquitetura e o espaço urbano desse momento tão importante da História da Arte. O resultado final do estudo ambiciona alcançar um juízo próprio sobre o arcabouço conceitual exposto na poética barroca, uma ação crítica só possível através do reconhecimento e da apreciação pessoal de muitas das mais importantes manifestações barrocas na arquitetura e no espaço urbano do Seicento e do Settecento.
iPad Versus Handwriting: Pilot Study Exploring the Writing Abilities of Students with Learning Disabilities
Authors: Corkett Julie K. , Benevides Tina
Published: April 2016

Written expression is an essential skill to actively function in today's society. For many learners, especially those with a learning disability (LD), writing can be a source of frustration. Technology in its various forms, holds promise to assist students in this area. The current study examines the role that tablet technology, specifically, iPads, has on the writing skills of students who have an LD. Using a visual analysis approach and paired-sample t-tests, the current study examines how the writing of nine (female = 1, age = 12.5; male = 8; mean age = 11.5) grade six Caucasian students from Northern Ontario with an LD differs when they write by hand versus writing with an iPad. Specifically, the study examines whether there is a difference in (a) writing productivity; (b) spelling accuracy; (c) lexical diversity; (d) syntactical complexity; and, (e) ideas expressed. Results revealed that digital writing using an iPad was effective in significantly improving spelling accuracy, number of T-units and number of ideas expressed. There was also an insignificant improvement in the areas of writing productivity, number of sentences written, and grammatical errors. The results of the current study suggest that the use of iPads has a positive influence on' writing. Therefore, the use of iPads may have long-term effects that cannot be measured sufficiently in a short-term study.
Inclusive Classes in Physical Education: Teachers' Difficulties
Authors: Toloi Gabriela Gallucci , Manzini Eduardo José , Spoldaro Diego Machado , Ventura Zacarias Lucas
Published: April 2016

The successful inclusion of students with special needs in physical education classes requires much planning and preparation. Lack of preparation of physical education teachers working in inclusive settings in Brazil has demonstrated the need for specialized training in strategies for implementing inclusion. The goal of this study was to identify, through self-reporting, common difficulties physical education teachers experienced while teaching children with special needs in inclusive environments. Two focus groups of physical education teachers who taught children with special needs were interviewed to provide data. Focus groups met twice for an average of two hours each meeting. An interview guide was employed to encourage discussion and idea sharing. Verbal interactions were transcribed and subjected to content analysis. Data analysis identified seven subthemes related to difficulties commonly experienced by the teachers working in inclusive environments: 1) access to diagnoses; 2) physical education syllabus; 3) inclusion and physical education; 4) architectural and administrative barriers; 5) family collaboration; 6) relationships with other professionals; 7) teacher training. Identifying these subthemes of commonly shared difficulties relating to successful inclusion may help guide the development of a training program for including students with special needs in physical education classes.
ChemInform Abstract: Bi3n+1Ti7Fe3n‐3O9n+11 Homologous Series: Slicing Perovskite Structure with Planar Interfaces Containing Anatase‐Like Chains.
Authors: Batuk Dmitry , Tsirlin Alexander A. , Filimonov Dmitry S. , Zakharov Konstantin V. , Volkova Olga S. , Vasiliev Alexander , Hadermann Joke , Abakumov Artem M.
Published: April 2016

Title compounds with n = 3—6 are prepared by solid state reaction of Bi2O3, TiO2, and Fe2O3 (1000 °C, 60—100 h).
ChemInform Abstract: (Cs6Cl)6Cs3 [Ga53Se96]: A Unique Long Period‐Stacking Structure of Layers Made from Ga2Se6 Dimers via cis or trans Intralayer Linking.
Authors: Lin Hua , Chen Hong , Lin Zi‐Xiong , Zhao Hua‐Jun , Liu Peng‐Fei , Yu Ju‐Song , Chen Ling
Published: April 2016

The new title compound is synthesized by reaction of Ga and Se in a CsCl flux in the presence of Mn (CsCl:Mn:Ga:Se = 6:4:5:12,1273 K, 4 d; 60% yield).
ChemInform Abstract: Biimidazoline Ligands for Palladium‐Catalyzed Asymmetric Allylic Alkylation.
Authors: Hao Xin‐Qi , Dong Ya‐Nan , Gao Biao , Li Ke , Zhao Xue‐Mei , Xu Yan , Song Mao‐Ping
Published: April 2016

A variety of bis‐imidazolines are synthesized and evaluated as ligands in Pd‐catalyzed asymmetric allylic alkylation reactions of 1,3‐diarylpropenyl acetates (I) with malonates.
ChemInform Abstract: Alkaline Earth Metal Catalyzed, One‐Pot, Multi‐Component Approach for the Synthesis of Dihydropyridine, Acridine and Xanthene Derivatives in Water.
Authors: Yaragorla Srinivasarao , Singh Garima , Pareek Abhishek
Published: April 2016

An environmentally benign Ca(II)‐catalyst and water as green solvent are used.
ChemInform Abstract: Tandem Claisen Rearrangement/6‐endo Cyclization Approach to Allylated and Prenylated Chromones.
Authors: Schmidt Bernd , Riemer Martin , Schilde Uwe
Published: April 2016

Allyl, dimethylallyl, and prenyl ethers of ortho‐acylphenols react upon microwave irradiation to form C‐allylated or ‐prenylated chromones.
ChemInform Abstract: Development of a Phase‐Transfer‐Catalyzed, [2,3]‐Wittig Rearrangement.
Authors: Denmark Scott E. , Cullen Lindsey R.
Published: April 2016

The asymmetric [2,3]‐sigmatropic rearrangement of cyclic (allyloxy)carbonyl compounds (II) and (IV) in the presence of chiral phase transfer catalysts such as (I) is presented.
ChemInform Abstract: Reactions of Carbonyl Compounds with Phosphorus Ylide Generated from Tribromofluoromethane and Tris(dimethylamino)phosphine.
Authors: Hirai Go , Nishizawa Eri , Kakumoto Daiki , Morita Masaki , Okada Mitsuaki , Hashizume Daisuke , Nagashima Sayoko , Sodeoka Mikiko
Published: April 2016

Reaction of the title ylide with simple aldehydes and ketones affords the expected Wittig products as mixtures of EIZ‐isomers.
ChemInform Abstract: Highly Regioselective Palladium‐Catalyzed Carboxylation of Allylic Alcohols with CO2.
Authors: Mita Tsuyoshi , Higuchi Yuki , Sato Yoshihiro
Published: April 2016

Allylic alcohols are carboxylated in the presence of a catalytic amount of PdCl2 and PPh3 using stoichiometric ZnEt2 as transmetalation agent under CO2 atmosphere.
ChemInform Abstract: Palladium‐Catalyzed Benzylic C—H Arylation of Azaarylmethylamines.
Authors: Kim Byeong‐Seon , Jimenez Jacqueline , Gao Feng , Walsh Patrick J.
Published: April 2016

Azaarylmethyl amines with cyclic or acyclic amino groups efficiently react with aryl and hetarylbromides or chlorides to form the corresponding aryl or hetaryl substituted azaarylmethylamines in high yields.
ChemInform Abstract: Selective Liquid‐Phase Hydrogenation of a Nitro Group in Substituted Nitrobenzenes over Au/Al2O3 Catalyst in a Packed‐Bed Flow Reactor.
Authors: Nuzhdin Alexey L. , Moroz Boris L. , Bukhtiyarova Galina A. , Reshetnikov Sergey I. , Pyrjaev Pavel A. , Aleksandrov Pavel V. , Bukhtiyarov Valerii I.
Published: April 2016

Nitrobenzenes are reduced to the corresponding anilines with nearly full conversion and excellent selectivities while reduction‐sensitive substituents (e.
ChemInform Abstract: Deep Eutectic Solvent Catalyzed Eco‐Friendly Synthesis of Imines and Hydrobenzamides.
Authors: Azizi Najmedin , Edrisi Mahtab
Published: April 2016

Imines (II) and hydrobenzamides (V) are synthesized using an urea—choline chloride‐based deep eutectic solvent as an efficient catalyst and reaction medium in good to high yields.
ChemInform Abstract: Unexpected Squaramide‐Induced Cleavage of Benzils: Synthesis and Characterization of Mono‐Aroyl Squarimides.
Authors: Sanna Elena , Lopez Carlos , Ballester Pablo , Rotger Carmen , Costa Antoni
Published: April 2016

An unprecedented cleavage of the inter‐carbonyl single bond of benzils is promoted by squaramide anions.
ChemInform Abstract: Indium‐Catalyzed Amide Allylation of N‐Carbonyl Imides: Formation of Azaspiro‐γ‐lactones via Ring Opening—Reclosure.
Authors: Sengoku Tetsuya , Murata Yusuke , Aso Yuwa , Kawakami Ai , Inuzuka Toshiyasu , Sakamoto Masami , Takahashi Masaki , Yoda Hidemi
Published: April 2016

The novel facile approach provides a new class of succinimide or phthalimide‐derived azaspiro‐γ‐lactones with an exo‐methylene lactam ring as potential drug candidates.
ChemInform Abstract: Stereo‐ and Chemodivergent NHC‐Promoted Functionalisation of Arylalkylketenes with Chloral.
Authors: Douglas James J. , Churchill Gwydion , Slawin Alexandra M. Z. , Fox David J. , Smith Andrew D.
Published: April 2016

Stereo‐ and chemodivergent enantioselective reaction pathways are observed upon treatment of alkylarylketenes and trichloroacetaldehyde (chloral) with N‐heterocyclic carbenes, giving selectively either β‐lactones or α‐chloro esters.
ChemInform Abstract: Divergent C—H Insertion—Cyclization Cascades of N‐Allyl Ynamides.
Authors: Adcock Holly V. , Chatzopoulou Elli , Davies Paul W.
Published: April 2016

The reaction N‐allyl ynamides in the presence of Au(picolinate)Cl2 gives polycyclic heterocycles.
ChemInform Abstract: An Efficient One‐Pot Two Catalyst System in the Construction of 2‐Substituted Benzimidazoles: Synthesis of Benzimidazo[1,2‐c]quinazolines.
Authors: Cimarelli Cristina , Di Nicola Matteo , Diomedi Simone , Giovannini Riccardo , Hamprecht Dieter , Properzi Roberta , Sorana Federico , Marcantoni Enrico
Published: April 2016

A Ce(III)/Cu(I)‐catalytic system mediates the reaction of aryl‐ and alkylaldehydes (I) and (IV) with o‐phenylenediamine (II) to the title compounds in good yields.
ChemInform Abstract: Iodine Mediated Synthesis of Coumarins from Chromenes.
Authors: Sharma Himanshu , Mourya Mohini , Soni Lokesh K. , Guin Debanjan , Joshi Yogesh C. , Dobhal Mahaveer P. , Basak Ashok K.
Published: April 2016

The presence of water is essential for the iodine‐mediated conversion of chromenes into coumarin derivatives.
ChemInform Abstract: Copper‐Promoted Tandem Reaction of Azobenzenes with Allyl Bromides via N=N Bond Cleavage for the Regioselective Synthesis of Quinolines.
Authors: Yi Xiangli , Xi Chanjuan
Published: April 2016

Operationally simple conditions for the reaction of azobenzenes with allyl bromides to quinolines are reported which tolerate diversely substituted substrates.
ChemInform Abstract: Novel Exocyclic Enamides: Synthesis and Evaluation of the Fungicidal Activities of 5‐Methylene‐2‐(trifluoromethyl)morpholin‐3‐one Derivatives.
Authors: Tian Lei , Cui Can , Zhu Cong , Yang Hui‐Hui , Li Jian‐Qiang , Zhao Wei‐Guang
Published: April 2016

The novel exocyclic enamides are efficiently obtained by reaction of various trifluoroatrolactamides with propargyl bromide.
ChemInform Abstract: Organocatalytic Synthesis of Fused Bicyclic 2,3‐Dihydro‐1,3,4‐oxadiazoles Through an Intramolecular Cascade Cyclization.
Authors: Fugard Alison J. , Thompson Bethany K. , Slawin Alexandra M. Z. , Taylor James E. , Smith Andrew D.
Published: April 2016

The reaction tolerates various hydrazone‐carboxylic acid based substrates, and depending on the functional groups present the products are obtained in moderate to very high yields.
ChemInform Abstract: A Catalyst‐Free Synthesis of Phosphinic Amides Using O‐Benzoylhydroxylamines.
Authors: Zhu Rui , Pan Chongqing , Gu Zhenhua
Published: April 2016

In contrast to conventional methods the novel protocol tolerates a broad range of secondary phosphine oxides and O‐benzoylhydroxylamines while providing the products in moderate to very high yields.
ChemInform Abstract: New Acylated Flavonol Glycosides and a Phenolic Profile of Pritzelago alpina, a Forgotten Edible Alpine Plant
Authors: Corradi Elisabetta , De Mieri Maria , Cadisch Larissa , Abbet Christian , Hamburger Matthias , Potterat Olivier
Published: April 2016

isolation and structure elucidation of eleven new acylated flavonoid glycosides from the aerial parts of Pritzelago alpina (Brassicaceae)
ChemInform Abstract: Eight New Alkaloids with PTP1B and α‐Glucosidase Inhibitory Activities from the Medicinal Mushroom Hericium erinaceus
Authors: Wang Kai , Bao Li , Ma Ke , Liu Ning , Huang Ying , Ren Jinwei , Wang Wenzhao , Liu Hongwei
Published: April 2016

isolation and structure elucidation of erinacerin M (I), erinacerin N—P (II), erinacerin Q (III), erinacerin R (IV), erinacerin S (V), and erinacerin T (VI)
ChemInform Abstract: New 2‐Benzoxazolinone Derivatives with Cytotoxic Activities from the Roots of Acanthus ilicifolius.
Authors: Zhao Dan , Xie Lijun , Yu Lei , An Ni , Na Wei , Chen Feng , Li Youbin , Tan Yinfeng , Zhang Xiaopo
Published: April 2016

Four new 2‐benzoxazolinone‐type alkaloids, acanthosides A—D, are isolated along with three known ones.
ChemInform Abstract: Silica Based Superhydrophobic Coating for Long‐Term Industrial and Domestic Applications.
Authors: Mahadik Satish A. , Pedraza Fernado , Vhatkar Rajiv S.
Published: April 2016

A MeOH/H2O solution containing MeSi(O‐Et)3, HO2C‐CO2H, and NH3 is hydrolysized for 15 h at 20 °C before being sprayed on Ge, brass, steel, Cu, and glass substrates (2 min, 125 °C, 40% rel.
ChemInform Abstract: Towards High‐Efficiency Nanoelectrocatalysts for Oxygen Reduction Through Engineering Advanced Carbon Nanomaterials
Authors: Zhou Ming , Wang Hsing‐Lin , Guo Shaojun
Published: April 2016

Review: recent developments of carbon‐based noble‐metal‐free high‐efficiency oxygen reduction electrocatalysts, including heteroatom‐doped, transition metal‐based nanoparticles, and especially iron carbide (Fe3C)‐based carbon nanomaterial composites; 295 refs.
ChemInform Abstract: Chromatography with Silver Nitrate. Part 2
Authors: Mander Lewis N. , Williams Craig M.
Published: April 2016

Review: [117 refs.
ChemInform Abstract: Gold‐Catalyzed Cyclization Processes: Pivotal Avenues for Organic Synthesis
Authors: Kumar Amit , Singh Sukhdev , Sharma Sunil K. , Parmar Virinder S. , Van der Eycken Erik V.
Published: April 2016

Review: [52 refs.
ChemInform Abstract: Design of Organic Transformations at Ambient Conditions: Our Sincere Efforts to the Cause of Green Chemistry Practice
Authors: Brahmachari Goutam
Published: April 2016

Review: [efforts in designing green synthetic protocols for diverse organic transformations at room temperature and pressure reported during the last five years; 100 refs.
ChemInform Abstract: Versatile Oxidation Methods for Organic and Inorganic Substrates Catalyzed by Platinum‐Group Metals on Carbons
Authors: Sawama Yoshinari , Asai Shota , Monguchi Yasunari , Sajiki Hironao
Published: April 2016

Review: [30 refs.
ChemInform Abstract: Silica‐Supported Polyphosphoric Acid (PPA‐SiO2): An Efficient and Reusable Heterogeneous Catalyst for Ecofriendly Organic Synthesis
Authors: Vekariya Rajesh H. , Prajapati Neelam P. , Patel Hitesh D.
Published: April 2016

Review: 130 refs.
ChemInform Abstract: Advances in Click Chemistry for Silica‐Based Material Construction
Authors: Mohammadi Ziarani Ghodsi , Hassanzadeh Zahra , Gholamzadeh Parisa , Asadi Shima , Badiei Alireza
Published: April 2016

Review: 105 refs.
ChemInform Abstract: Studies on the Alkaloids of the Calycanthaceae and Their Syntheses
Authors: Xu Jin‐Biao , Cheng Ke‐Jun
Published: April 2016

Review: 70 refs.
ChemInform Abstract: Cancer Immunotherapy: Selected Targets and Small‐Molecule Modulators
Authors: Weinmann Hilmar
Published: April 2016

Review: 140 refs.
ChemInform Abstract: Some Recent Synthetic Development on Compounds with Potent Activities on Hormone‐Sensitive Breast Cancers
Authors: Wang Zheng , Gao Hui‐Lei , Chen Xu‐Dong
Published: April 2016

Review: 85 refs.
ChemInform Abstract: To Rebound or Dissociate? This Is the Mechanistic Question in C—H Hydroxylation by Heme and Nonheme Metal—Oxo Complexes
Authors: Cho Kyung‐Bin , Hirao Hajime , Shaik Sason , Nam Wonwoo
Published: April 2016

Review: review on hydroxylation reactions where dissociative non‐rebound mechanism is shown to dominate; 50 refs.
ChemInform Abstract: Forensic Chemistry and Ambient Mass Spectrometry: A Perfect Couple Destined for a Happy Marriage?
Authors: Correa Deleon N. , Santos Jandyson M. , Eberlin Livia S. , Eberlin Marcos N. , Teunissen Sebastiaan F.
Published: April 2016

Review: 101 refs.
The challenge of being a young manager: The effects of contingent reward and participative leadership on team‐level turnover depend on leader age
Authors: Buengeler Claudia , Homan Astrid C. , Voelpel Sven C.
Published: April 2016

Effective leadership requires a leaderclaimingas well as team membersgrantingthe leadership position. Contingent reward and participative leadership may both facilitate this mutual process. However, these behaviors differ in the degree to which they require a leader to have status and be prototypical. Their effectiveness might thus depend on the status‐related characteristics of the leader. In this respect, we propose that younger leaders, by deviating from the leader prototype in terms of age, lack a natural status cue, which will determine the effectiveness of these two leadership behaviors in shaping turnover. Two pilot studies (N = 113 and 121 individuals) confirm that younger leaders are perceived as less prototypical and to have lower status than older leaders. Examining 83 work teams, we show that leader age differently moderates the effects of contingent reward and participative leadership on time‐lagged team turnover. For younger (compared with older) leaders, contingent reward was effective as illustrated by decreased voluntary turnover and increased involuntary turnover, whereas participative leadership, which was associated with increased voluntary turnover and decreased involuntary turnover, was ineffective. These findings point to the importance of incorporating natural status cues of leaders for understanding the effectiveness of different leadership behaviors. Copyright © 2016 John Wiley & Sons, Ltd.
Tendon‐derived progenitor cells improve healing of collagenase‐induced flexor tendinitis
Authors: Durgam Sushmitha S. , Stewart Allison A. , Sivaguru Mayandi , Wagoner Johnson Amy J. , Stewart Matthew C.
Published: April 2016

Tendinitis is a common and a performance‐limiting injury in athletes. This study describes the value of intralesional tendon‐derived progenitor cell (TDPC) injections in equine flexor tendinitis. Collagenase‐induced tendinitis was created in both front superficial digital flexor (SDF) tendons. Four weeks later, the forelimb tendon lesions were treated with 1 × 107autogenous TDPCs or saline. Tendinitis was also induced by collagenase in one hind SDF tendon, to study the survival and distribution of DiI‐labeled TDPCs 1, 2, 4, and 6 weeks after injection. The remaining normal tendon was used as a “control.” Twelve weeks after forelimb TDPC injections, tendons were harvested for assessment of matrix gene expression, biochemical, biomechanical, and histological characteristics. DiI‐labeled TDPCs were abundant 1 week after injection but gradually declined over time and were undetectable after 6 weeks. Twelve weeks after TDPC injection, collagens I and III, COMP and tenomodulin mRNA levels were similar (p = 0.3) in both TDPC and saline groups and higher (p < 0.05) than normal tendon. Yield and maximal stresses of the TDPC group were significantly greater (p = 0.005) than the saline group's and similar (p = 0.6) to normal tendon. However, the elastic modulus of the TDPC and saline groups were not significantly different (p = 0.32). Histological assessment of the repair tissues with Fourier transform‐second harmonic generation imaging demonstrated that collagen alignment was significantly better (p = 0.02) in TDPC group than in the saline controls. In summary, treating collagenase‐induced flexor tendon lesions with TDPCs improved the tensile strength and collagen fiber alignment of the repair tissue. Study Design © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2162–2171, 2016.
Common scientific and statistical errors in obesity research
Authors: George Brandon J. , Beasley T. Mark , Brown Andrew W. , Dawson John , Dimova Rositsa , Divers Jasmin , Goldsby TaShauna U. , Heo Moonseong , Kaiser Kathryn A. , Keith Scott W. , Kim Mimi Y. , Li Peng , Mehta Tapan , Oakes J. Michael , Skinner Asheley , Stuart Elizabeth , Allison David B.
Published: April 2016

This review identifies 10 common errors and problems in the statistical analysis, design, interpretation, and reporting of obesity research and discuss how they can be avoided. The 10 topics are: 1) misinterpretation of statistical significance, 2) inappropriate testing against baseline values, 3) excessive and undisclosed multiple testing and “P‐value hacking,” 4) mishandling of clustering in cluster randomized trials, 5) misconceptions about nonparametric tests, 6) mishandling of missing data, 7) miscalculation of effect sizes, 8) ignoring regression to the mean, 9) ignoring confirmation bias, and 10) insufficient statistical reporting. It is hoped that discussion of these errors can improve the quality of obesity research by helping researchers to implement proper statistical practice and to know when to seek the help of a statistician.
NIPT and Informed Consent: an Assessment of Patient Understanding of a Negative NIPT Result
Authors: Piechan Julie L. , Hines Karrie A. , Koller Daniel L. , Stone Kristyne , Quaid Kimberly , Torres‐Martinez Wilfredo , Wilson Mathews Divya , Foroud Tatiana , Cook Lola
Published: April 2016

Since becoming clinically available in 2011, the use of noninvasive prenatal testing (NIPT) to screen for fetal aneuploidy has continued to increase. However, it has been questioned whether the education of patients undergoing NIPT consistently meets informed consent standards. We sought to evaluate patients’ basic understanding of NIPT, such as conditions assessed and accuracy. In addition, we investigated patient self‐assessment of NIPT knowledge and satisfaction with the testing process. We distributed an anonymous paper survey to pregnant women during prenatal visits following a negative NIPT result. The survey assessed patient NIPT knowledge, gathered pregnancy‐specific and demographic information, and allowed respondents to rank their basic understanding of NIPT and provide written feedback about the testing process. A total of 95 completed and 3 partially completed surveys were returned. Participants scored lowest on knowledge questions involving whether a negative NIPT result ensures a healthy baby or eliminates the possibility of Down syndrome. Most perceived themselves to have a good basic understanding of NIPT and two‐thirds of the written feedback proposed no changes to NIPT administration. Overall, most patients appear satisfied with their understanding of NIPT and the testing process, yet they may not fully appreciate the limitations of this screening method.
Outcomes of Proximal Humerus Fracture Open Reduction Internal Fixation with Concomitant Ipsilateral Shoulder Girdle Injuries: A Case Control Study
Authors: Berkes Marschall B. , Little Milton T. M. , Pardee Nadine C. , Schottel Patrick C. , Lazaro Lionel E. , Lorich Dean G.
Published: April 2016

Background

Proximal humerus fractures treated in the face of ipsilateral injuries to the shoulder girdle may be predisposed to worse clinical outcomes.

Questions/Purposes

The purpose of this investigation was to examine outcomes of proximal humerus fractures treated with open reduction internal fixation (ORIF) using an endosteal augment in the presence of a concomitant shoulder girdle injury in comparison to isolated proximal humerus fractures treated with ORIF and endosteal augment.

Methods

A prospective database was used to identify proximal humerus fractures with ipsilateral shoulder girdle injuries (glenohumeral and acromioclavicular dislocation, fractures of the acromion, clavicle, scapula, or humeral diaphysis). These were compared to isolated proximal humerus fractures treated in the same fashion (ORIF with endosteal augment). Minimum of 1 year follow-up was required for inclusion. Outcomes assessed included range of motion (ROM), development of avascular necrosis (AVN), hardware-related complications, reoperation, and subjective outcome assessments including the Disabilities of Arm Shoulder and Hand questionnaire (DASH), Constant score, UCLA rating scale, and the Short Form-36 (SF-36).

Results

Fifteen ipsilateral injuries were seen in 14 patients. Seventy-seven isolated proximal humerus fractures were available for comparison. The ipsilateral injury group had significantly worse forward flexion (141 vs 156°, p = 0.02), external rotation (56 vs 64°, p = 0.03), higher rates of avascular necrosis (4 of 14, 28.6% vs 1 of 77, 1.3%, p = 0.002), and inferior SF-36 physical health scores (48.5 vs 63.5; p = .04). Despite these differences, no significant differences were seen with hardware-related complications or DASH, Constant score, or UCLA rating scale results. No patients required secondary reconstructive procedures.

Conclusion

Despite a statistically higher rate of AVN and decreased ROM, patient-based outcomes of proximal humerus fractures with ipsilateral shoulder injuries approached those seen in isolated proximal humerus fractures. This suggests that these injuries can achieve similarly good clinical results provided any associated shoulder pathology is identified and treated appropriately.
Dynamic Assessment of Functional Lipidomic Analysis in Human Urine
Authors: Rockwell Hannah E. , Gao Fei , Chen Emily Y. , McDaniel Justice , Sarangarajan Rangaprasad , Narain Niven R. , Kiebish Michael A.
Published: April 2016

The development of enabling mass spectrometry platforms for the quantification of diverse lipid species in human urine is of paramount importance for understanding metabolic homeostasis in normal and pathophysiological conditions. Urine represents a non‐invasive biofluid that can capture distinct differences in an individual's physiological status. However, currently there is a lack of quantitative workflows to engage in high throughput lipidomic analysis. This study describes the development of a MS/MSALL shotgun lipidomic workflow and a micro liquid chromatography–high resolution tandem mass spectrometry (LC–MS/MS) workflow for urine structural and mediator lipid analysis, respectively. This workflow was deployed to understand biofluid sample handling and collection, extraction efficiency, and natural human variation over time. Utilization of 0.5 mL of urine for structural lipidomic analysis resulted in reproducible quantification of more than 600 lipid molecular species from over 20 lipid classes. Analysis of 1 mL of urine routinely quantified in excess of 55 mediator lipid metabolites comprised of octadecanoids, eicosanoids, and docosanoids generated by lipoxygenase, cyclooxygenase, and cytochrome P450 activities. In summary, the high‐throughput functional lipidomics workflow described in this study demonstrates an impressive robustness and reproducibility that can be utilized for population health and precision medicine applications.
Clinicopathological study of surgical margins in squamous cell carcinoma of buccal mucosa
Authors: Mohiyuddin S.M. Azeem , Padiyar B. Vageesh , Suresh T.N. , Mohammadi Kouser , Sagayaraj A. , Merchant Shuaib , Sultana Azeem Mahnaaz
Published: April 2016

Objective

To evaluate the margins of resected specimen of oral squamous cell carcinoma (SCC) and to document the surgical margin (measured at the time of resection) and margins at the time of pathological examination (after immersion of the specimen in formalin).

Methods

Patients who were diagnosed and confirmed with squamous carcinoma of buccal mucosa were included in the study. Patients underwent resection of the tumor with a margin of 1 cm. Soon after resection, the distance between outermost visible margin of the tumor and the margin of the specimen was measured and documented. Specimens were fixed in 10% formalin and submitted for gross and histopathological examination. The closest histopathologic margin was compared with the in situ margin (10 mm) to determine and document any shrinkage of the margin and the percentage of discrepancy if any.

Results

A total of 52 specimens were collected from patients between January 2014 and December 2014. All specimens were obtained from the oral cavity (n = 52) of which 43 (82.7%) were squamous cell carcinoma and 9 (17.3%) were verrucous variant of squamous cell carcinoma. The average decrease in tumor margins measured after fixation in formalin was found to be statistically significant (P < 0.05) in 65% of cases.

Conclusion

Tumor margin shrinks significantly after formalin fixation by about 25%. The operating surgeon and pathologist should be well aware of such changes while planning for further management thereby ensuring adequate margin of resection and adjuvant treatment wherever required to prevent possible local recurrence of the disease.
Subglacial processes on an Antarctic ice stream bed. 1: Sediment transport and bedform genesis inferred from marine geophysical data
Authors: LIVINGSTONE STEPHEN J. , STOKES CHRIS R. , Ó COFAIGH COLM , HILLENBRAND CLAUS-DIETER , VIELI ANDREAS , JAMIESON STEWART S. R. , SPAGNOLO MATTEO , DOWDESWELL JULIAN A.
Published: April 2016

The spatial pattern and morphometry of bedforms and their relationship to sediment thickness have been analysed in the Marguerite Bay Palaeo-ice stream Trough, western Antarctic Peninsula. Over 17 000 glacial landforms were measured from geophysical datasets, and sediment thickness maps were generated from acoustic sub-bottom profiler data. These analyses reveal a complex bedform pattern characterised by considerable spatial diversity, influenced heavily by the underlying substrate. The variability in length and density of mega-scale lineations indicates an evolving bedform signature, whereby landforms are preserved at different stages of maturity. Lineation generation and attenuation is associated with regions of thick, soft till where deformation was likely to be the greatest. The distribution of soft till and the localised extent of grounding-zone wedges (GZWs) indicate a dynamic sedimentary system characterised by considerable spatio-temporal variability in sediment erosion, transport and deposition. Formation of GZWs on the outer shelf of Marguerite Trough, within the error range of the radiocarbon dates, requires large sediment fluxes (upwards of 1000 m3a−1(m grounding line width)−1), and a >1 m thick mobile till layer, or rapid basal sliding velocities (upwards of 6 km a−1).
A possiblePararcus diepenbroekivertebra from the Vossenveld Formation (Triassic, Anisian), Winterswijk, the Netherlands
Authors: During M.A.D. , Voeten D.F.A.E. , Schulp A.S. , Reumer J.W.F.
Published: April 2016

An isolated, completely ossified vertebra tentatively ascribed to the non-cyamodontid placodontPararcus diepenbroekiis described from the Anisian Vossenveld Formation in Winterswijk, the Netherlands, and compared to other material from the same locality. This fossil is the first completely ossified vertebra of the taxon and most likely originates from an adult specimen. It was recovered c. 16 m deeper in the stratigraphy than previously described material of the species, which is thus far known only from Winterswijk. Based on the slanting angle of the transverse process, the vertebra is interpreted to originate from the dorsal region. Besides the overall agreements in morphology that warrant a tentative identification asPararcus diepenbroeki, the newly described vertebra deviates from other knownPararcusvertebrae in the presence of a longer, well-ossified neural spine and a strongly constricted, less pachyostotic and ovaloid vertebral centrum. General agreement in morphology with previously described vertebrae suggests this novel condition indicates a different anatomical position and perhaps a varied ossification pattern.
Scotopic vision in the monkey is modulated by the G protein-coupled receptor 55
Authors: BOUSKILA JOSEPH , HARRAR VANESSA , JAVADI PASHA , CASANOVA CHRISTIAN , HIRABAYASHI YOSHIO , MATSUO ICHIRO , OHYAMA JYUNPEI , BOUCHARD JEAN-FRANÇOIS , PTITO MAURICE
Published: April 2016

The endogenous cannabinoid system plays important roles in the retina of mice and monkeys via their classic CB1 and CB2 receptors. We have previously reported that the G protein-coupled receptor 55 (GPR55), a putative cannabinoid receptor, is exclusively expressed in rod photoreceptors in the monkey retina, suggesting its possible role in scotopic vision. To test this hypothesis, we recorded full-field electroretinograms (ERGs) after the intravitreal injection of the GPR55 agonist lysophosphatidylglucoside (LPG) or the selective GPR55 antagonist CID16020046 (CID), under light- and dark-adapted conditions. Thirteen vervet monkeys (Chlorocebus sabaeus) were used in this study: four controls (injected with the vehicle dimethyl sulfoxide, DMSO), four injected with LPG and five with CID. We analyzed amplitudes and latencies of the a-wave (photoreceptor responses) and the b-wave (rod and cone system responses) of the ERG. Our results showed that after injection of LPG, the amplitude of the scotopic b-wave was significantly higher, whereas after the injection of CID, it was significantly decreased, compared to the vehicle (DMSO). On the other hand, the a-wave amplitude, and the a-wave and b-wave latencies, of the scotopic ERG responses were not significantly affected by the injection of either compound. Furthermore, the photopic ERG waveforms were not affected by either drug. These results support the hypothesis that GPR55 plays an instrumental role in mediating scotopic vision.
Playing the policy game: a review of the barriers to and enablers of nutrition policy change
Authors: Cullerton Katherine , Donnet Timothy , Lee Amanda , Gallegos Danielle
Published: April 2016

Objective

To progress nutrition policy change and develop more effective advocates, it is useful to consider real-world factors and practical experiences of past advocacy efforts to determine the key barriers to and enablers of nutrition policy change. The present review aimed to identify and synthesize the enablers of and barriers to public policy change within the field of nutrition.

Design

Electronic databases were searched systematically for studies examining policy making in public health nutrition. An interpretive synthesis was undertaken.

Setting

International, national, state and local government jurisdictions within high-income, democratic countries.

Results

Sixty-three studies were selected for inclusion. Numerous themes were identified explaining the barriers to and enablers of policy change, all of which fell under the overarching category of ‘political will’, underpinned by a second major category, ‘public will’. Sub-themes, including pressure from industry, neoliberal ideology, use of emotions and values, and being visible, were prevalent in describing links between public will, political will and policy change.

Conclusions

The frustration around lack of public policy change in nutrition frequently stems from a belief that policy making is a rational process in which evidence is used to assess the relative costs and benefits of options. The findings from the present review confirm that evidence is only one component of influencing policy change. For policy change to occur there needs to be the political will, and often the public will, for the proposed policy problem and solution. The review presents a suite of enablers which can assist health professionals to influence political and public will in future advocacy efforts.
Microbial diversity arising from thermodynamic constraints
Authors: Großkopf Tobias , Soyer Orkun S
Published: April 2016

The microbial world displays an immense taxonomic diversity. This diversity is manifested also in a multitude of metabolic pathways that can utilise different substrates and produce different products. Here, we propose that these observations directly link to thermodynamic constraints that inherently arise from the metabolic basis of microbial growth. We show that thermodynamic constraints can enable coexistence of microbes that utilise the same substrate but produce different end products. We find that this thermodynamics-driven emergence of diversity is most relevant for metabolic conversions with low free energy as seen for example under anaerobic conditions, where population dynamics is governed by thermodynamic effects rather than kinetic factors such as substrate uptake rates. These findings provide a general understanding of the microbial diversity based on the first principles of thermodynamics. As such they provide a thermodynamics-based framework for explaining the observed microbial diversity in different natural and synthetic environments.
Neutrophil-specific deletion of the CARD9 gene expression regulator suppresses autoantibody-induced inflammation in vivo
Authors: Németh Tamás , Futosi Krisztina , Sitaru Cassian , Ruland Jürgen , Mócsai Attila
Published: April 2016

Neutrophils are terminally differentiated cells with limited transcriptional activity. The biological function of their gene expression changes is poorly understood. CARD9 regulates transcription during antifungal immunity but its role in sterile inflammation is unclear. Here we show that neutrophil CARD9 mediates pro-inflammatory chemokine/cytokine but not lipid mediator release during non-infectious inflammation. Genetic deficiency of CARD9 suppresses autoantibody-induced arthritis and dermatitis in mice. Neutrophil-specific deletion of CARD9 is sufficient to induce that phenotype.Card9−/−neutrophils show defective immune complex-induced gene expression changes and pro-inflammatory chemokine/cytokine release but normal LTB4production and other short-term responses.In vivodeletion of CARD9 reduces tissue levels of pro-inflammatory chemokines and cytokines but not LTB4. The CARD9-mediated signalling pathway involves Src-family kinases, Syk, PLCγ2, Bcl10/Malt1 and NFκB. Collectively, CARD9-mediated gene expression changes within neutrophils play important roles during non-infectious inflammationin vivoand CARD9 acts as a divergence point between chemokine/cytokine and lipid mediator release.
Coupled molybdenum carbide and reduced graphene oxide electrocatalysts for efficient hydrogen evolution
Authors: Li Ji-Sen , Wang Yu , Liu Chun-Hui , Li Shun-Li , Wang Yu-Guang , Dong Long-Zhang , Dai Zhi-Hui , Li Ya-Fei , Lan Ya-Qian
Published: April 2016

Electrochemical water splitting is one of the most economical and sustainable methods for large-scale hydrogen production. However, the development of low-cost and earth-abundant non-noble-metal catalysts for the hydrogen evolution reaction remains a challenge. Here we report a two-dimensional coupled hybrid of molybdenum carbide and reduced graphene oxide with a ternary polyoxometalate-polypyrrole/reduced graphene oxide nanocomposite as a precursor. The hybrid exhibits outstanding electrocatalytic activity for the hydrogen evolution reaction and excellent stability in acidic media, which is, to the best of our knowledge, the best among these reported non-noble-metal catalysts. Theoretical calculations on the basis of density functional theory reveal that the active sites for hydrogen evolution stem from the pyridinic nitrogens, as well as the carbon atoms, in the graphene. In a proof-of-concept trial, an electrocatalyst for hydrogen evolution is fabricated, which may open new avenues for the design of nanomaterials utilizing POMs/conducting polymer/reduced-graphene oxide nanocomposites.
A High Affinity Red Fluorescence and Colorimetric Probe for Amyloid β Aggregates
Authors: Rajasekhar K. , Narayanaswamy Nagarjun , Murugan N. Arul , Kuang Guanglin , Ågren Hans , Govindaraju T.
Published: April 2016

A major challenge in the Alzheimer’s disease (AD) is its timely diagnosis. Amyloid β (Aβ) aggregates have been proposed as the most viable biomarker for the diagnosis of AD. Here, we demonstrate hemicyanine-based benzothiazole-coumarin (TC) as a potential probe for the detection of highly toxic Aβ42aggregates through switch-on, enhanced (~30 fold) red fluorescence (Emax = 654 nm) and characteristic colorimetric (light red to purple) optical outputs. Interestingly,TCexhibits selectivity towards Aβ42fibrils compared to other abnormal protein aggregates.TCprobe show nanomolar binding affinity (Ka = 1.72 × 107M−1) towards Aβ42aggregates and also displace ThT bound to Aβ42fibrils due to its high binding affinity. The Aβ42fibril-specific red-shift in the absorption spectra ofTCresponsible for the observed colorimetric optical output has been attributed to micro-environment change around the probe from hydrophilic-like to hydrophobic-like nature. The binding site, binding energy and changes in optical properties observed forTCupon interaction with Aβ42fibrils have been further validated by molecular docking and time dependent density functional theory studies.
Preservation Macroscopic Entanglement of Optomechanical Systems in non-Markovian Environment
Authors: Cheng Jiong , Zhang Wen-Zhao , Zhou Ling , Zhang Weiping
Published: April 2016

We investigate dynamics of an optomechanical system under the non-Markovian environment. In the weak optomechanical single-photon coupling regime, we provide an analytical approach fully taking into account the non-Markovian memory effects. When the cavity-bath coupling strength crosses a certain threshold, an oscillating memory state for the classical cavity field is formed. Due to the existence of the non-decay optical bound state, a nonequilibrium optomechanical thermal entanglement is preserved even without external driving laser. Our results provide a potential usage to generate and protect entanglement via non-Markovian environment.