bluuebunny/crossref_metadata_2025 huggingface dataset:
ChemInform Abstract: Facile, One‐Pot, and Gram‐Scale Synthesis of 3,4,5‐Triiodoanisole Through a C—H Iodination/ipso‐Iododecarboxylation Strategy: Potential Application Towards 3,4,5‐Trisubstituted Anisoles.
Authors: Al‐Zoubi Raed M. , Al‐Mughaid Hussein , Al‐Zoubi Mariam A. , Jaradat Khaled T. , McDonald Robert
Published: December 2015

The reaction can be performed on a multigram scale in good yield and is catalytic, scalable, and efficient with simple work‐up and purification processes.
ChemInform Abstract: Selective Radical—Radical Cross‐Couplings: Design of a Formal β‐Mannich Reaction.
Authors: Jeffrey Jenna L. , Petronijevic Filip R. , MacMillan David W. C.
Published: December 2015

γ‐Aminoketones are obtained by direct coupling of cyclic ketones with imines using DABCO as both a base and an electron transfer agent.
ChemInform Abstract: One‐Pot Unsymmetrical Ketone Synthesis Employing a Pyrrole‐Bearing Formal Carbonyl Dication Linchpin Reagent.
Authors: Heller Stephen T. , Newton James N. , Fu Tingting , Sarpong Richmond
Published: December 2015

A wide range of ketones and Weinreb amides are synthesized from various organolithium and Grignard reagents in one‐pot without the need of a transition‐metal catalyst.
ChemInform Abstract: P(NMe2)3‐Mediated Umpolung Alkylation and Nonylidic Olefination of α‐Keto Esters.
Authors: Wang Sunewang Rixin , Radosevich Alexander T.
Published: December 2015

The phosphorus reagent promotes the umpolung alkylation of methyl aroylformates with benzylic and allylic bromides.
ChemInform Abstract: Ligandless C—C Bond Formation via Suzuki—Miyaura Reaction in Micelles or Water—Ethanol Solution Using PdPtZn and PdZn Nanoparticle Thin Films.
Authors: Hoseini S. Jafar , Zarei Atiyeh , Rafatbakhsh Iran Hajar
Published: December 2015

Slightly better yields are obtained using PdPtZn nanoparticles in a mixture of water and cetrimide.
ChemInform Abstract: Lewis Acid Catalyzed Cyclizations of Epoxidized Baylis—Hillman Products: A Straightforward Synthesis of Octahydrobenzo[e]azulenes.
Authors: Konopacki Donald B. , Shortsleeves Kelley C. , Turnbull Mark M. , Wikaira Jan L. , Hobson Adrian D.
Published: December 2015

The title azulene derivatives are obtained by a linear three‐step route involving the coupling of 2‐cyclopentenone with various aldehydes, stereoselective epoxidation, and Lewis acid catalyzed cyclization.
ChemInform Abstract: Diastereo‐ and Enantioselective Synthesis of Chiral Pyrrolidine‐Fused Spirooxindoles via Organocatalytic [3 + 2] 1,3‐Dipolar Cycloaddition of Azomethine Ylides with Maleimides.
Authors: Zhao Hong‐Wu , Yang Zhao , Meng Wei , Tian Ting , Li Bo , Song Xiu‐Qing , Chen Xiao‐Qin , Pang Hai‐Liang
Published: December 2015

In the presence of the Cinchona alkaloid‐based squaramide organocatalyst QSQ, the [3+2] cycloaddition of isatin‐derived azomethine ylides with maleimides proceeds readily to deliver pyrrolidine‐fused spirooxindoles.
ChemInform Abstract: An Efficient One‐Pot Approach to the Construction of Chiral Nitrogen‐Containing Heterocycles under Mild Conditions.
Authors: Feng Huan‐Xi , Tan Rui , Liu Yan‐Kai
Published: December 2015

The two‐step procedure shown in the presence of chiral catalyst PBP renders possible the access to a broad spectrum of functionalized pyrroles and some analogues such as quinoline (VII).
ChemInform Abstract: A New Synthesis of Versatile Indolyl‐3‐carbonylnitriles.
Authors: Veale Clinton G. L.
Published: December 2015

A mild, simple, and high‐yielding access to indolyl‐3‐carbonylnitriles is developed proceeding via dehydration of α‐oxoacetamides which are easily accessible from the corresponding indoles and oxalyl chloride.
ChemInform Abstract: Metal‐Free One‐Pot Sequential Direct Diarylation of Pyrazolin‐5‐ones with Diaryliodonium Salts.
Authors: Huang Tao , Ji Xinfei , Wu Wei , Liang Fang , Cao Song
Published: December 2015

A wide range of symmetrical or unsymmetrical C4‐diarylated pyrazolin‐5‐one derivatives are efficiently obtained under mild reaction conditions.
ChemInform Abstract: Sequential SNAr Reaction/Suzuki—Miyaura Coupling/C—H Direct Arylations Approach for the Rapid Synthesis of Tetraaryl‐Substituted Pyrazoles.
Authors: Morita Taiki , Kobayashi Daisuke , Matsumura Keisuke , Johmoto Kohei , Uekusa Hidehiro , Fuse Shinichiro , Takahashi Takashi
Published: December 2015

The title pyrazoles bearing four different aryl groups are regioselectively obtained by a protection/deprotection‐free, divergent synthesis employing readily available substrates and reagents.
ChemInform Abstract: Facile One‐Pot Clean Synthesis of Benzimidazole Motifs: Exploration on Bismuth Nitrate Accelerated Subtle Catalysis.
Authors: Mahire Vilas N. , Mahulikar Pramod P.
Published: December 2015

2‐Substituted benzimidazole derivatives (III) are efficiently synthesized by reaction of o‐phenylenediamine (I) with aromatic aldehydes (II), whereas the reaction with aldehydes (IV) affords only 1,2‐disubstituted benzimidazole derivatives (V).
ChemInform Abstract: A Rapid and Novel Method for the Synthesis of 5‐Substituted 1H‐Tetrazole Catalyzed by Exceptional Reusable Monodisperse Pt NPs@AC under the Microwave Irradiation.
Authors: Erken Esma , Esirden Ibrahim , Kaya Muharrem , Sen Fatih
Published: December 2015

Monodispers platinum nanoparticles on activated carbon are found to be a superior, reusable, environmentally benign, and highly efficient heterogenous catalyst for the synthesis of the title tetrazoles by [3+2] cycloaddition reaction of aromatic nitriles with sodium azide.
ChemInform Abstract: The Modified Trifluoromethylation Protocol Applicable to Electronically Deficient Iodopyridinones.
Authors: Kawasaki‐Takasuka Tomoko , Yamazaki Takashi
Published: December 2015

The utility of this method is demonstrated in the synthesis of pharmaceutically interesting pirfenidone analogue (XVI).
ChemInform Abstract: A Novel and Facile Synthesis of 4‐Arylquinolin‐2(1H)‐ones under Metal‐Free Conditions.
Authors: Sun Bin , Mai Wen‐Peng , Yang Liang‐Ru , Mao Pu , Yuan Jin‐Wei , Xiao Yong‐Mei
Published: December 2015

Title compounds (II) are conveniently synthesized under metal‐free conditions and using inexpensive reagents.
ChemInform Abstract: A Unified Approach to the Four Azaindoline Families by Inter‐/Intramolecular Annulative Diamination of Vinylpyridines.
Authors: Danneman Michael W. , Hong Ki Bum , Johnston Jeffrey N.
Published: December 2015

The metal‐free oxidative amination procedure allows access to a series of products which include all azaindoline structures bearing an amino function at C‐3.
ChemInform Abstract: Ultrasound‐Promoted Green Approach for the Synthesis of Thiazoloquinolines Using Gold(III) Dipyridine Complex Immobilized on SBA‐15 as Nano Catalysts at Room Temperature.
Authors: Sadeghzadeh Seyed Mohsen
Published: December 2015

The new eco‐friendly catalyst can be easily recovered by filtration and reused for several times without significant loss of activity.
ChemInform Abstract: A Novel Method for the Synthesis of Imidazo[1,5‐b]pyridazines.
Authors: Vandyshev Dmitriy Yu. , Shikhaliyev Khidmet S. , Potapov Andrei Yu. , Krysin Mikhail Yu.
Published: December 2015

The title pyridazine derivatives are synthesized through a regioselective intramolecular cyclization mechanism.
ChemInform Abstract: Palladium‐Catalyzed Oxalyl Amide Directed Silylation and Germanylation of Amine Derivatives.
Authors: Chen Changpeng , Guan Mingyu , Zhang Jingyu , Wen Zhenkang , Zhao Yingsheng
Published: December 2015

Conditions for the ortho‐selective trimethylsilylation of oxalyl amide protected benzylamine and phenylethylamine derivatives are developed which tolerate a diverse range of functional groups.
ChemInform Abstract: Palladium‐Catalyzed Phosphonylation of Pyrazoles Substituted by Electron‐Withdrawing Groups
Authors: Huang Qi , Tran Gael , Gomez Pardo Domingo , Tsuchiya Tomoki , Hillebrand Stefan , Vors Jean‐Pierre , Cossy Janine
Published: December 2015

19 examples
ChemInform Abstract: Fabrication and Application of Non‐Rare Earth Red Phosphors for Warm White‐Light‐Emitting Diodes.
Authors: Zhou Qiang , Zhou Yayun , Wang Zhengliang , Liu Yong , Chen Guo , Peng Jinhui , Yan Jing , Wu Mingmei
Published: December 2015

Red phosphors K2XF6:Mn4+ (X: Si, Ti, Ge) are precipitated from a 40% aq.
ChemInform Abstract: Nano‐Array Based Monolithic Catalysts: Concept, Rational Materials Design and Tunable Catalytic Performance
Authors: Ren Zheng , Guo Yanbing , Gao Pu‐Xian
Published: December 2015

Review: 41 refs.
ChemInform Abstract: Facet‐Controlled Synthetic Strategy of Cu2O‐Based Crystals for Catalysis and Sensing
Authors: Shang Yang , Guo Lin
Published: December 2015

Review: 173 refs.
ChemInform Abstract: Design, Synthesis, and Applications of Highly Phosphorescent Cyclometalated Platinum Complexes
Authors: Huo Shouquan , Carroll Jeffrey , Vezzu Dileep A. K.
Published: December 2015

Review: [88 refs.
ChemInform Abstract: Lanthanides and Actinides: Annual Survey of Their Organometallic Chemistry Covering the Year 2014
Authors: Edelmann Frank T.
Published: December 2015

Review: 169 refs.
ChemInform Abstract: 1,2,4‐Triazine Chemistry. Part 4. Synthesis and Chemical Behavior of 3‐Functionalized 5,6‐Diphenyl‐1,2,4‐triazines Towards Some Nucleophilic and Electrophilic Reagents
Authors: Abdel‐Rahman Reda M. , Makki Mohamed S. T. , Ali Tarik E. , Ibrahim Magdy A.
Published: December 2015

Review: 80 refs.
ChemInform Abstract: Enantioselective Nickel‐Catalyzed Cycloaddition Reactions
Authors: Pellissier Helene
Published: December 2015

Review: [66 refs.
ChemInform Abstract: Supramolecular Polymerization Engineered with Molecular Recognition
Authors: Haino Takeharu
Published: December 2015

Review: [54 refs.
ChemInform Abstract: Toward Greener Oxidative Transformations: Base‐Metal Catalysts and Metal‐Free Reactions
Authors: Wu Xiao‐Feng
Published: December 2015

Review: [37 refs.
ChemInform Abstract: Preparation of O‐Protected Glyceraldehydes as Building Blocks in Organic Synthesis
Authors: Dibello E. , Gamenara D. , Seoane G.
Published: December 2015

Review: 114 refs.
ChemInform Abstract: Fast Hybrid Multi‐dimensional NMR Methods Based on Ultrafast 2D NMR
Authors: Akoka Serge , Giraudeau Patrick
Published: December 2015

Review: 52 refs.
ChemInform Abstract: Recent Developments in Androgen Receptor Antagonists
Authors: Ran Fansheng , Xing Hualu , Liu Yang , Zhang Daoguang , Li Pengzhan , Zhao Guisen
Published: December 2015

Review: 78 refs.
ChemInform Abstract: Bioavailability of Heavy Metals in Soils: Definitions and Practical Implementation — A Critical Review
Authors: Kim Rog‐Young , Yoon Jeong‐Ki , Kim Tae‐Seung , Yang Jae E. , Owens Gary , Kim Kwon‐Rae
Published: December 2015

Review: 183 refs.
ChemInform Abstract: Employing TiO2 Photocatalysis to Deal with Landfill Leachate: Current Status and Development
Authors: Hassan Muhammad , Zhao Yaping , Xie Bing
Published: December 2015

Review: 113 refs.
ChemInform Abstract: A Comprehensive Review on the Molecular Dynamics Simulation of the Novel Thermal Properties of Graphene
Authors: Zhang Jingchao , Xu Fei , Hong Yang , Xiong Qingang , Pan Jianming
Published: December 2015

Review: 97 refs.
STAT3‐Interacting Proteins as Modulators of Transcription Factor Function: Implications to Targeted Cancer Therapy
Authors: Yeh Jennifer E. , Frank David A.
Published: December 2015

The oncogenic transcription factor STAT3 is inappropriately activated in multiple hematopoietic and solid malignancies, in which it drives the expression of genes involved in cell proliferation, differentiation, survival, and angiogenesis. Thus far, strategies to inhibit the function of STAT3 have focused on blocking the function of its activating kinases or sequestering its DNA binding ability. A less well‐explored aspect of STAT3 function is its interaction with other proteins, which can modulate the oncogenic activity of STAT3 via its subcellular localization, DNA binding ability, and recruitment of transcriptional machinery. Herein we summarize what is currently known about STAT3‐interacting proteins and describe the utility of a proteomics‐based approach for successfully identifying and characterizing novel STAT3‐interacting proteins that affect STAT3 transcriptional activity and oncogenic function.
EPR Studies of V‐ATPase with Spin‐Labeled Inhibitors DCC and Archazolid: Interaction Dynamics with Proton Translocating Subunit c
Authors: Gölz Jan Philipp , Bockelmann Svenja , Mayer Kerstin , Steinhoff Heinz‐Jürgen , Wieczorek Helmut , Huss Markus , Klare Johann P. , Menche Dirk
Published: December 2015

Vacuolar‐type H+‐ATPases (V‐ATPases) have gained recent attention as highly promising anticancer drug targets, and therefore detailed structural analyses and studies of inhibitor interactions are very important research objectives. Spin labeling of the V‐ATPase holoenzyme from the tobacco hornworm Manduca sexta and V‐ATPase in isolated yeast (Saccharomyces cerevisiae) vacuoles was accomplished by two novel methods involving the covalent binding of a (2,2,6,6‐tetramethylpiperidin‐1‐yl)oxyl (TEMPO) derivative of N,N′‐dicyclohexylcarbodiimide (DCC) to the essential glutamate residue in the active site and the noncovalent interaction of a radical analogue of the highly potent inhibitor archazolid, a natural product from myxobacteria. Both complexes were evaluated in detail by electron paramagnetic resonance (EPR) spectroscopic studies and double electron–electron resonance (DEER) measurements, revealing insight into the inhibitor binding mode, dynamics, and stoichiometry as well as into the structure of the central functional subunit c of these medicinally important hetero‐multimeric proton‐translocating proteins. This study also demonstrates the usefulness of natural product derived spin labels as tools in medicinal chemistry.
Analytical and diagnostic validation of a flow cytometric strategy to quantify blood and marrow infiltration in dogs with large B‐cell lymphoma
Authors: Riondato Fulvio , Miniscalco Barbara , Poggi Alessia , Aricò Arianna , Aresu Luca , Comazzi Stefano , Martini Valeria
Published: December 2015

Background

Lymph node (LN), peripheral blood (PB), and bone marrow (BM) samples are commonly analyzed by flow cytometry (FC) for the immunophenotyping and staging of canine lymphomas. A prognostic value for FC BM infiltration in dogs with large B‐cell lymphoma (LBCL) was demonstrated. Aim of this study was to define the analytical performances of this technique, and to establish a cutoff suitable to safely discriminate between infiltrated and noninfiltrated PB and BM samples.

Methods

Large B‐cells were added to control PB and BM samples, to achieve twelve different large B‐cells concentrations, ranging from 0 to 50%. The percentage of large B‐cells was recorded for each dilution, using a BD Accuri C6 FC. Accuracy was evaluated by Passing‐Bablok regression analysis. Intra‐assay precision was assessed at 0%, 1, 3, and 10% dilutions evaluating the CVs of 10 repeated acquisitions. ROC curves were drawn to identify the cutoffs most suitable to discriminate between 25 infiltrated (PARR‐positive) and 25 noninfiltrated (PARR‐negative) PB and BM samples, respectively.

Results

Optimal analytical accuracy and precision were achieved. Almost all CVs were <10%. Negative controls had up to 0.5% large B‐cells, with 50 and 22% CV in PB and BM samples, respectively, 0.56 and 2.45% cutoffs were selected based on the ROC curves for PB and BM samples, respectively.

Conclusions

Quantification of large B‐cells in PB and BM samples by FC is reliable and analytical performances met the acceptance criteria. Assessment of performances of different instruments and protocols is warranted. © 2016 International Clinical Cytometry Society
Simultaneous measurement of human hematopoietic stem and progenitor cells in blood using multicolor flow cytometry
Authors: Cimato Thomas R. , Furlage Rosemary L. , Conway Alexis , Wallace Paul K.
Published: December 2015

Hematopoietic stem cells are the source of all inflammatory cell types. Discovery of specific cell surface markers unique to human hematopoietic stem (HSC) and progenitor (HSPC) cell populations has facilitated studies of their development from stem cells to mature cells. The specific marker profiles of HSCs and HSPCs can be used to understand their role in human inflammatory diseases.

The goal of this study is to simultaneously measure HSCs and HSPCs in normal human venous blood using multicolor flow cytometry. Our secondary aim is to determine how G‐CSF mobilization alters the quantity of each HSC and HSPC population. Here we show that cells within the CD34+ fraction of human venous blood contains cells with the same cell surface markers found in human bone marrow samples. Mobilization with G‐CSF significantly increases the quantity of total CD34+ cells, blood borne HSCs, multipotent progenitors, common myeloid progenitors, and megakaryocyte erythroid progenitors as a percentage of total MNCs analyzed. The increase in blood borne common lymphoid and granulocyte macrophage progenitors with G‐CSF treatment did not reach significance. G‐CSF treatment predominantly increased the numbers of HSCs and multipotent progenitors in the total CD34+ cell population; common myeloid progenitors and megakaryocyte erythroid progenitors were enriched relative to total MNCs analyzed, but not relative to total CD34+ cells. Our findings illustrate the utility of multicolor flow cytometry to quantify circulating HSCs and HSPCs in venous blood samples from human subjects. © 2016 International Clinical Cytometry Society
Exploring the Colour of 3d Transition‐Metal Ions in Trigonal Bipy­ramidal Coordination: Identification of Purple‐Blue (CoO5) and Beige‐Red (NiO5) Chromophores in LiMgBO3Host
Authors: Tamilarasan Subramani , Laha Sourav , Natarajan Srinivasan , Gopalakrishnan Jagannatha
Published: December 2015

In an attempt to develop new coloured inorganic oxides, we have investigated the substitution of 3d transition‐metal ions in LiMgBO3host [where MgIIhas a trigonal bipyramidal (TBP) oxygen coordination]. We find that single‐phase materials are formed for LiMg1–xCoIIxBO3(0 <x≤ 1.0), LiMg1–xNiIIxBO3(0 <x≤ 0.1), LiMg1–xCuIIxBO3(0 <x≤ 0.1) and also Li1–xMg1–xFeIIIxBO3(0 <x≤ 0.1) of which the CoIIand NiIIderivatives are strongly coloured, purple‐blue and beige‐red, respectively, thus identifying TBP CoO5and NiO5as new chromophores for these colours.
Synthesis of 3‐Substituted 2‐Indol­inones by a Multicomponent Coupling Isocyanide‐Dependent Microwave‐Assisted Intramolecular Transamidation Process
Authors: Maddirala Amarendar Reddy , Andreana Peter R.
Published: December 2015

A small‐molecule library synthesis of 3‐substituted 2‐indolinones using methyl isocyanide and a microwave‐assisted intramolecular transamidation process with 10 % TFA in dichloroethane has been achieved in 3 steps. A modified Fe0 Bechamp‐type reduction of a substituted bifunctional substrate, o‐nitrobenzaldehyde, renders 3‐substituted 2‐indolinones in yields ranging from 76–91 % (21 examples). Furthermore, it has been determined that symmetrical 2o N‐alkyl or aryl substituents, as a component of the amine starting material, suppresses 3‐substituted 2‐indolinone rotameric mixtures and allows for facile compound 1H NMR characterization. In the absence of methyl isocyanide, 3,4‐dihydroquinazolines or transamidation products predominate under both Brønsted or Lewis acid conditions in reasonable yields.
Research‐on‐Evaluation Articles Published in the American Journal of Evaluation, 1998–2014
Authors: Vallin Lisa M. , Philippoff Joanna , Pierce Sena , Brandon Paul R.
Published: December 2015

Prominent evaluators have advocated over the years for research on evaluation (RoE), yet to our knowledge, studies about the number and percentage of RoE studies that have been published do not exist. In this chapter, we present a summary of the RoE articles, categorized by several descriptive characteristics, that have been published in the American Journal of Evaluation (AJE), the flagship journal of the American Evaluation Association. We show that (a) about half of AJE articles can be considered RoE, (b) the percentage per year tended to increase through 2011, (c) half of the RoE articles addressed evaluation independent of a professional domain, (d) about one‐third were single case studies or surveys, and (e) the topics of the research have varied considerably. We conclude by arguing for continued documentation of RoE and for the development of an electronic database for evaluators seeking empirical evidence to address common evaluation issues.
Research on Evaluation Ethics: Reflections and an Agenda
Authors: Morris Michael
Published: December 2015

Research on evaluation ethics has grown over the past two and a half decades, enabling practitioners to view with greater precision the ethical terrain they will encounter in their work. This chapter presents an overview of the relevant literature and offers suggestions for making ethics research more useful for evaluation practice.
Advancing Research on Evaluation Through the Study of Context
Authors: Vo Anne T. , Christie Christina A.
Published: December 2015

The importance of context in shaping evaluation practice is broadly accepted. Still, there is much to be learned about context, and we remain at the early stages of this process. In this chapter, we describe a framework for organizing and focusing ideas for conducting research on evaluation context. We hope that this tool will be a source of inspiration for future studies of context, thus contributing to a deeper and higher quality evaluation knowledge base.
Evaluators’ Perspectives on Research on Evaluation
Authors: Lewis Nicole R. , Harrison George M. , Ah Sam Anna F. , Brandon Paul R.
Published: December 2015

Program evaluators are giving increasing attention to research on evaluation (RoE), but little is known about their perceptions of RoE. In this chapter, we report the methods and results of a questionnaire survey that drew from the Theory of Planned Behavior and addressed a broad swath of evaluators’ attitudes toward, beliefs about, and knowledge of RoE; time and opportunities to participate in RoE; application of RoE findings; and involvement in RoE. The results show that evaluators (a) believe RoE is important, (b) report a moderate degree of access and opportunities to read or use the RoE literature, (c) have little time and few opportunities to conduct RoE, (d) report knowing enough about RoE to attend presentations but lack the knowledge to conduct RoE, and (e) describe little involvement in conducting RoE. University faculty, those with doctorates, and those with an advanced level of understanding of evaluation report the greatest participation in RoE. These results confirm our sense of current perceptions about evaluators’ participation in various RoE activities and set the stage for developing steps to encourage RoE in its various manifestations.
Longitudinal assessment of white matter abnormalities following sports‐related concussion
Authors: Meier Timothy B. , Bergamino Maurizio , Bellgowan Patrick S. F. , Teague T. K. , Ling Josef M. , Jeromin Andreas , Mayer Andrew R.
Published: December 2015

There is great interest in developing physiological‐based biomarkers such as diffusion tensor imaging to aid in the management of concussion, which is currently entirely dependent on clinical judgment. However, the time course for recovery of white matter abnormalities following sports‐related concussion (SRC) is unknown. We collected diffusion tensor imaging and behavioral data in forty concussed collegiate athletes on average 1.64 days (T1; n = 33), 8.33 days (T2; n = 30), and 32.15 days post‐concussion (T3; n = 26), with healthy collegiate contact‐sport athletes (HA) serving as controls (n = 46). We hypothesized that fractional anisotropy (FA) would be increased acutely and partially recovered by one month post‐concussion. Mood symptoms were assessed using structured interviews. FA differences were assessed using both traditional and subject‐specific analyses. An exploratory analysis of tau plasma levels was conducted in a subset of participants. Results indicated that mood symptoms improved over time post‐concussion, but remained elevated at T3 relative to HA. Across both group and subject‐specific analyses, concussed athletes exhibited increased FA in several white matter tracts at each visit post‐concussion with no longitudinal evidence of recovery. Increased FA at T1 and T3 was significantly associated with an independent, real‐world outcome measure for return‐to‐play. Finally, we observed a nonsignificant trend for reduced tau in plasma of concussed athletes at T1 relative to HA, with tau significantly increasing by T2. These results suggest white matter abnormalities following SRC may persist beyond one month and have potential as an objective biomarker for concussion outcome. Hum Brain Mapp 37:833–845, 2016. © 2015 Wiley Periodicals, Inc.
Tumor volume as a predictor of survival in human papillomavirus–positive oropharyngeal cancer
Authors: Davis Kara S. , Lim Chwee Ming , Clump David A. , Heron Dwight E. , Ohr James P. , Kim Seungwon , Duvvuri Umamaheswar , Johnson Jonas T. , Ferris Robert L.
Published: December 2015

Background

Increasing evidence exists that tumor volume may be a superior prognostic model than traditional TNM staging. It has been observed that oropharyngeal squamous cell carcinoma (oropharyngeal SCC) in the setting of human papillomavirus (HPV) positivity have a greater propensity for cystic nodal metastases, and, thus, presumably larger volume with relatively smaller primary tumors. The influence of HPV status on the predictive value of tumor volume is unknown.

Methods

Fifty‐three patients with HPV‐positive oropharyngeal SCC were treated with definitive chemotherapy and intensity‐modulated radiotherapy (IMRT).

Results

The estimated 2‐year overall survival (OS) and disease‐free survival (DFS) was 92.2% and 83.6%, respectively. Nodal classification did not predict OS (p = .096) or DFS (p = .170). Similarly, T classification did not predict OS (p = .057) or DFS (p = .309). Lower nodal volume was associated with greater DFS (p = .001).

Conclusion

Nodal tumor volume was found to be predictive of DFS. DFS was best predicted by nodal gross tumor volume (GTV) at 24 months. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1613–E1617, 2016
Sinonasal mucosal melanoma: A 12‐year experience of 58 cases
Authors: Lombardi Davide , Bottazzoli Marco , Turri–Zanoni Mario , Raffetti Elena , Villaret Andrea Bolzoni , Morassi Maria Laura , Ungari Marco , Vermi William , Battaglia Paolo , Castelnuovo Paolo , Facco Carla , Sessa Fausto , Donato Francesco , Nicolai Piero
Published: December 2015

Background

Sinonasal mucosal melanoma is a rare malignancy with poor prognosis.

Methods

Patients with sinonasal malignant melanoma who underwent surgery by different approaches were included in this study. Overall survival (OS) and event‐free survival were calculated, and statistically significant variables by univariate analysis were entered in a multivariate Cox regression model.

Results

Pathological staging was pT3, pT4a, and pT4b in 30 cases (51.7%), 17 cases (29.3%), and 11 cases (19.0%). At 3 and 5 years, OS was 43.5% and 29% and event‐free survival was 23.6% and 12.4%, respectively. At univariate analysis, OS was significantly influenced by male sex, advanced pT classification, positive margins, and surgical approach; event‐free survival was affected by positive margins. At multivariate analysis, the risk of death was independently associated with male sex (hazard ratio [HR] = 2.27; p = .04) and positive margins (HR = 2.32; p = .03).

Conclusion

Male sex and positive margins were negative prognostic factors. Endoscopic resection did not show an increased risk of death compared with more extensive surgical approaches. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1737–E1745, 2016
Deletion of CB2 cannabinoid receptors reduces synaptic transmission and long‐term potentiation in the mouse hippocampus
Authors: Li Yong , Kim Jimok
Published: December 2015

The effects of cannabinoids are mostly mediated by two types of cannabinoid receptors—CB1 receptors in the nervous system and CB2 receptors in the immune system. However, CB2 cannabinoid receptors have recently been discovered in the brain and also implicated in neurophysiological functions. The deletion of CB2 receptors in mice induces long‐term memory deficits and schizophrenia‐like behaviors, implying that endogenous activity of CB2 receptors might be involved in neuropsychiatric effects. Little is known about the cellular mechanisms by which physiological activation of CB2 receptors modulates neuronal functions. We aimed to determine how deletion of CB2 receptors in mice affects synaptic transmission and plasticity. Electrophysiological and morphological studies indicated that CB2 receptor knockout resulted in decreases in excitatory synaptic transmission, long‐term potentiation, and dendritic spine density in the hippocampus. Our data imply that endogenous activity of CB2 receptors might contribute to the maintenance of synaptic functions and the expression of normal long‐term potentiation. This study provides insights into the role of CB2 cannabinoid receptors in regulating cognitive functions such as long‐term memory. © 2016 Wiley Periodicals, Inc.
Evaluation of hepatic vascular endothelial injury during liver storage by molecular detection and targeted contrast‐enhanced ultrasound imaging
Authors: Xie Fang , Zhang Shu‐Hua , Cheng Jia , Wang Hong‐Wei , Fei Xiang , Jiao Zi‐Yu , Tang Jie , Luo Yu‐Kun
Published: December 2015

We hypothesized that lack of the high‐energy phosphates during liver storage may potentially cause persistent injury to the vascular endothelium. Biopsies were obtained from livers obtained from beating heart human donors, stored either in the standard storage solution, that is, University of Wisconsin solution (UWS) or Celsior, and examined for various markers related to progressive endothelial injury. The expression of P2Y1 receptor, the major signal transduction machinery for adenosine triphosphate/adenosine diphosphate, decreased in hepatic vascular endothelial cells over time. Despite unaltered endothelial nitric oxide synthase (eNOS) levels, serine1177‐phosphorylated eNOS, the active form of eNOS, progressively decreased with time. The production of nitric oxide enzyme decreased with time when liver tissues were examined in vitro. This also coincided with decreased interaction of eNOS with actin nucleating proteins like myristoylated alanine‐rich C kinase substrate and Rac1, which plays a role in modulating the cytoskeleton and helps position eNOS in a favorable cytosolic position for active enzymatic activity. Conversely, the interaction of eNOS with caveolin1 was significantly increased 6 H after ex vivo storage. Finally, we demonstrated by targeted contrast‐enhanced ultrasound that membrane‐bound vascular cell adhesion molecule‐1 in the hepatic vascular endothelial cell increased after 6 H of ex vivo storage. Overall, the results of this study provide evidence of a progressive hepatic vascular endothelial injury during the ex vivo storage. This may be a causative factor for ischemic cholangiopathy and delayed graft function post liver transplantation. © 2015 IUBMB Life, 68(1):51–57, 2015
Labetalol: A Review of Its Pharmacology, Pharmacokinetics, Clinical Uses and Adverse Effects
Authors: MacCarthy E. Paul , Bloomfield Saul S.
Published: December 2015

Labetalol is a combined alpha‐ and beta‐adenoceptor blocking agent for oral and intravenous use in the treatment of hypertension. It is a nonselective competitive antagonist at beta‐adrenoceptors and a competitive antagonist of postsynaptic alpha1‐adrenoceptors. Labetalol is more potent at beta than at alpha1adrenoceptors in man; the ratio of beta‐alpha antagonism is 3:1 after oral and 6.9:1 after intravenous administration.

Labetalol is readily absorbed in man after oral administration, but the drug, which is lipid soluble, undergoes considerable hepatic first‐pass metabolism and has an absolute bioavailability of approximately 25%. There are no active metabolites, and the elimination half‐life of the drug is approximately 6 hours.

Unlike conventional beta‐adrenoceptor blocking drugs without intrinsic sympathomimetic activity, labetalol, when given acutely, produces a decrease in peripheral vascular resistance and blood pressure with little alteration in heart rate or cardiac output. However, like conventional beta‐blockers, labetalol may influence the renin‐angiotensin‐aldosterone system and respiratory function.

Clinical studies have shown that the antihypertensive efficacy of labetalol is superior to placebo and to diuretic therapy and is at least comparable to that of conventional beta‐blockers, methyldopa, clonidine and various adrenergic neuronal blockers. Labetalol administered alone or with a diuretic is often effective when other antihypertensive regimens have failed. Studies have shown that labetalol is effective in the treatment of essential hypertension, renal hypertension, pheochromocytoma, pregnancy hypertension and hypertensive emergencies. In addition, preliminary studies indicate that labetalol may be of value in the management of ischemic heart disease.

The most troublesome side effect of labetalol therapy is posture‐related dizziness. Other reported side effects of the drug include gastrointestinal disturbances, tiredness, headache, scalp tingling, skin rashes, urinary retention and impotence. Side effects related to the beta‐adrenoceptor blocking effect of labetalol, including asthma, heart failure and Raynaud's phenomenon, have been reported in rare instances.
Different Testosterone and LH Relationships in Infertile Men
Authors: MORROW ANTHONY F. , BAKER H.W. GORDON , BURGER HENRY G.
Published: December 2015

In both man and animals, changes in Leydig cell structure and function accompany seminiferous tubule damage. In this study of 1745 men attending an infertility clinic, 14% of men with elevated levels of FSH also had elevated LH levels. Groups with severe seminiferous tubule failure (eg, Sertoli Cell Only syndrome or high FSH levels) showed an inverse correlation between LH and testosterone levels. In contrast, groups with milder forms of seminiferous tubule disorders (mild hypospermatogenesis, or FSH levels in the low‐normal range) showed a positive correlation between LH and testosterone. It is concluded that different mechanisms must be operative to explain the opposite relationships between LH and testosterone, and that their elucidation may point to the etiology of some forms of seminiferous tubule damage in man.
Evidence for a Role of Cyclooxygenase (Prostaglandin Synthetase) and Prostaglandins in the Sperm Acrosome Reaction and Fertilization
Authors: JOYCE CATHY L. , NUZZO NANCY A. , WILSON LAIRD , ZANEVELD LOURENS J.D.
Published: December 2015

Three cyclooxygenase (prostaglandin synthetase) inhibitors, indomethacin, phenylbutazone, and oxyphenbutazone, decreased fertilization in vitro when mixed with capacitated mouse spermatozoa before addition of the treated gametes to oocytes. Fertilization was inhibited whether the oocytes were intact, follicle cell‐free, or both follicle cell‐free and zona‐free. At various concentrations of inhibitor, no effect was observed on the motility or forward progression of the spermatozoa. These cyclooxygenase inhibitors also decreased the guinea pig acrosome reaction. Inhibition of the acrosome reaction did not occur when a mixture of the prostaglandins (PGE2 or PGF2α) and one of the inhibitors was added to the spermatozoa. Alone, these prostaglandins tended to enhance the rate at which the acrosome reaction took place. Lowered calcium levels reduced the occurrence of the acrosome reaction, an effect that could be reversed at least partially by the addition of PGE2. Even in the nominal absence of calcium, some acrosome reaction took place when PGE2 was present in the medium. These results support an essential role for cyclooxygenase and arachidonic acid metabolites, including prostaglandins, in the events leading to the acrosome reaction and fertilization.
Effect of Adrenal Steroids on Testosterone and Luteinizing Hormone Secretion in the Ram
Authors: JUNIEWICZ PAUL E. , JOHNSON BRYAN H. , BOLT DOUGLAS J.
Published: December 2015

The effects of adrenal steroids on testosterone and LH secretion and changes in serum Cortisol levels in response to treatments were studied in the ram. Acute administration of synthetic ACTH(10 μg/kg BW) elevated (P < 0.01) serum Cortisol and transiently suppressed (P < 0.05) serum testosterone and LH. Acute dexamethasone treatment suppressed (P < 0.01) serum Cortisol, testosterone and LH. Administration of vehicle had no effect (P > 0.10) on serum hormone levels. These data support the contention that adrenal steroids inhibit testicular endocrine function indirectly by acting at the hypothalamic or pituitary level because both ACTH and dexamethasone treatments suppressed serum LH. To differentiate between hypothalamic and pituitary sites of action, the pituitary and testicular responses to an LHRH challenge (100 μg) were examined in rams chronically treated with dexamethasone (5 mg i.m., twice daily for 5 days). This treatment regimen suppressed (P < 0.01) serum Cortisol levels. Compared with controls, basal testosterone levels were suppressed (P < 0.05) in dexamethasone‐treated rams; however, no effect (P > 0.10) on the magnitude of the testosterone response to LHRH or on either basal or LHRH‐stimulated LH secretion was observed. Thus, although a direct testicular effect cannot be eliminated, these data suggest that, in the ram, adrenal steroids inhibit testicular endocrine function by acting at the level of the hypothalamus.
The Pituitary‐Testicular Axis at Rest and During Moderate Exercise in Males with Diabetes Mellitus and Normal Sexual Function
Authors: MURRAY FREDERICK T. , CAMERON DON F. , VOGEL ROBERT B. , THOMAS RONALD G. , WYSS HEDWIG U. , ZAUNER CHRISTIAN W.
Published: December 2015

Hormonal studies of pituitary‐testicular function in insulin‐dependent diabetes mellitus were examined at rest and during moderate exercise to assess whether diabetes per se caused abnormalities of nocturnal penile tumescence and androgen function in men with normal sexual function. The present study compared 10 healthy men and eight men with Type I diabetes mellitus in whom normal sexual function was determined by clinical history. Urinary gonadotropin excretion, semen analysis and diurnal variation of serum glucose, prolactin, testosterone and free testosterone were determined in both groups. In addition, the serum levels of testosterone, free testosterone, prolactin, follicle‐stimulating hormone (FSH) and luteinizing hormone (LH) were measured at rest, during 45 minutes of exercise on a bicycle ergometer at 50% of the subjects previously determined maximal oxygen uptake (VO2 max) and during a 30‐minute recovery period. Nocturnal penile tumescence and parameters of semen analysis were similar in both groups. Urinary FSH excretion and serum FSH were higher (P ≤ 0.01) in the diabetic subjects while urinary LH excretion was similar. Diurnal variation of serum prolactin, testosterone and free testosterone were similar in both groups. Exercise produced a significant (P ≤ 0.01) increase in maximal free and total testosterone in both groups without changes in serum FSH or LH. Prolactin increased significantly (P ≤ 0.01) during exercise in the diabetic group only. We conclude that, for the most part, the pituitary‐testicular axis and nocturnal penile tumescence under basal conditions and the pituitary‐testicular axis during moderate exercise are similar in healthy males and insulin‐dependent diabetic males with normal sexual function.
Comparison Between Human Sperm Preservation Medium and TEST‐Yolk Buffer on Protecting Chromatin and Morphology Integrity of Human Spermatozoa in Fertile and Subfertile Men After Freeze‐Thawing Procedure
Authors: HAMMADEH M. E. , GREINER S. , ROSENBAUM P. , SCHMIDT W.
Published: December 2015

ABSTRACT: The aim of this study was to identify the detrimental effect of the freeze‐thaw process on chromatin integrity and morphology of human spermatozoa, and to determine whether human sperm preservation medium (HSPM) or TEST‐yolk buffer (TYB) offers a better protection to spermatozoa from cryodamage after the freeze‐thaw procedure. Thirty‐five semen samples obtained from couples childless because of male factor infertility (subfertile men, group 1) and 25 semen samples from healthy, normal volunteers of proven fertility (group 2) were included in the study. Each semen sample was divided into 2 parts, the first part was mixed with HSPM and the other with TYB (1:1), and frozen with a controlled slow‐stage freezer, before plunging into liquid nitrogen. Twelve smears from each semen sample were made before (n = 4) and after (n = 8) the freeze‐thaw process. Chromatin structure was evaluated after staining using the acridine orange (AO) test, whereas morphology was analyzed according to strict criteria. The mean percentage of spermatozoa that exhibited normal morphology and intact chromatin structure was decreased after freeze‐thaw in all samples treated with HSPM or TYB in comparison with the value observed in the native semen samples of both groups. However, TYB preserved chromatin and morphology significantly better than HSPM did (9.3% ± 5.6% and 88.7% ± 11.2% vs. 7.8% ± 4.2% and 85.5% ± 12.5%, respectively). Therefore, TYB could be recommended as a first choice cryoprotectant for semen preservation in order to avoid extra chromatin structure damage and morphology alterations of spermatozoa not only for patients pursuing assisted reproduction, but also for donor samples.
Utility of the Nitroblue Tetrazolium Reduction Test for Assessment of Reactive Oxygen Species Production by Seminal Leukocytes and Spermatozoa
Authors: Esfandiari Navid , Sharma Rakesh K. , Saleh Ramadan A. , Thomas Anthony J. , Agarwal Ashok
Published: December 2015

ABSTRACT: The purpose of this study was to evaluate the ability of spermatozoa and leukocytes in semen to produce reactive oxygen species (ROS) by using nitroblue tetrazolium (NBT) staining and to examine the association between NBT staining and levels of ROS as measured by chemiluminescence. Twenty‐one infertility patients (leukocytospermia; n = 8; nonleukocytospermia, n = 13) and 9 healthy donors were included. Standard semen analysis and density gradient centrifugation were performed to test NBT staining, ROS, and total antioxidant capacity. A ROS‐total antioxidant capacity (ROS‐TAC) score was calculated by using principal component analysis. In the leukocytospermic group, after separation on a density gradient, the percentage of NBT‐positive staining was significantly higher in sperm suspensions contaminated with leukocytes (median [25th, 75th percentiles]; 70% [61%, 79%]) compared to the nonleukocytospermic group (14.5% [9%, 25.5%]; P = .03) and donors (7% [3%, 11%]; P = .02), respectively. A strong positive correlation was seen between levels of ROS in whole ejaculates and NBT‐positive staining in leukocytes (r = 0.59; P < .0006) and in leukocyte fractions (r = 0.72; P < .0001) after density gradient separation. Similarly, ROS was positively correlated with excessive cytoplasmic retention in spermatozoa from whole ejaculates and abnormal spermatozoa after separation on density gradients (r = 0.72; P < .0001). The ROS‐TAC score was inversely correlated with NBT staining in leukocytes in whole ejaculates (r = −0.960, P < .0007) and in both leukocyte fractions (r = −0.39; P < .04) and spermatozoa with cytoplasmic retention (r = −0.38; P < .04). Our results indicate that the NBT reduction test can be used to assess the contribution of seminal leukocytes and defective spermatozoa towards ROS generation in semen. Levels of ROS assessed by chemiluminescence assay are strongly correlated with the results of NBT staining.
Insulin‐Dependent Diabetes Affects Testicular Function by FSH‐ and LH‐Linked Mechanisms
Authors: Ballester Joan , Muñoz M. Carmen , Domínguez Jorge , Rigau Teresa , Guinovart Joan J. , Rodríguez‐Gil Joan E.
Published: December 2015

ABSTRACT: A study was conducted to form a unified hypothesis regarding the gonadotropin‐related mechanisms that underlie alterations in the male reproductive system in individuals with diabetes. Streptozotocin‐induced diabetes resulted in reduced fertility, prolificacy, and libido. Testes showed a marked decrease in the number and function of Leydig cells, the latter manifested as changes in the expression of biochemical markers, including the GLUT‐3 hexose transporter, c‐kit, insulin‐like growth factor I (IGF‐I), androgen receptors, and overall tyrosine phosphorylation, as assessed by Western blot and immunocytochemical analyses. The expression of c‐kit, IGF‐I, insulin, and follicle‐stimulating hormone (FSH) receptors in the seminiferous tubules was also affected. Serum levels of luteinizing hormone (LH), FSH, and testosterone significantly decreased. There was a significant (P < .05) correlation between the serum levels of insulin and FSH. No significant correlation was found between the serum levels of insulin or glucose and LH. On the basis of our results, we conclude that, in insulin‐dependent diabetes, 1) Leydig cell function and testosterone production decrease because of the absence of the stimulatory effect of insulin on these cells and an insulin‐dependent decrease in FSH, which, in turn, reduces LH levels; and 2) sperm output and fertility are reduced because of a decrease in FSH caused by a reduction in insulin.
Accuracy of fetal sex determination on ultrasound examination in the first trimester of pregnancy
Authors: Manzanares Sebastián , Benítez Adara , Naveiro‐Fuentes Mariña , López‐Criado María Setefilla , Sánchez‐Gila Mar
Published: December 2015

Purpose

The aim of this study was to evaluate the feasibility and success rate of sex determination on transabdominal sonographic examination at 11–13 weeks' gestation and to identify factors influencing accuracy.

Methods

In this prospective observational evaluation of 672 fetuses between 11 weeks' and 13 weeks + 6 days' gestational age (GA), we determined fetal sex according to the angle of the genital tubercle viewed on the midsagittal plane. We also analyzed maternal, fetal, and operator factors possibly influencing the accuracy of the determination.

Results

Fetal sex determination was feasible in 608 of the 672 fetuses (90.5%), and the prediction was correct in 532 of those 608 cases (87.5%). Fetal sex was more accurately predicted as the fetal crown–rump length (CRL), and GA increased and was less accurately predicted as the maternal body mass index increased. A CRL greater than 55.7 mm, a GA more than 12 weeks + 2 days, and a body mass index below 23.8 were identified as the best cutoff values for sex prediction. None of the other analyzed factors influenced the feasibility or accuracy of sex determination.

Conclusions

The sex of a fetus can be accurately determined on sonographic examination in the first trimester of pregnancy; the accuracy of this prediction is influenced by the fetal CRL and GA and by the maternal body mass index. © 2015 Wiley Periodicals, Inc. J Clin Ultrasound 44:272–277, 2016