bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategy in Regulatory Decision‐Making for Management of Progressive Multifocal Leukoencephalopathy
Authors: Segec A , Keller‐Stanislawski B , Vermeer NS , Macchiarulo C , Straus SM , Hidalgo‐Simon A , De Bruin ML
Published: August 2015

Progressive multifocal leukoencephalopathy (PML) has been observed after the use of several medicines, including monoclonal antibodies. As these drugs play important roles in the therapeutic armamentarium, it is important to address the challenges that this severe adverse reaction poses to the safe use of medicines. Considering the need for consistent outcomes of regulatory decisions, the European Medicines Agency Pharmacovigilance Risk Assessment Committee (PRAC) used PML as an example to develop a systematic approach to labeling and risk minimization.
A smartphone‐based U‐Healthcare system for real‐time monitoring of acute myocardial infarction
Authors: Jung Jaehyo , Lee Jihoon , Lee Jihwan , Kim Youn Tae
Published: August 2015

In recent years, medical service has been evolving from systems designed around centralized hospitals to Ubiquitous Healthcare (U‐Healthcare). U‐Healthcare system can facilitate real‐time monitoring of patient states, and can provide medical checkups and management whenever and wherever the medical staff deems necessary. U‐Healthcare services can provide chronic condition monitoring in the early stages of diseases and help execute decisive medical action in emergencies. However, thus far, the application of U‐Healthcare systems has been limited to diseases such as obesity, diabetes, etc. Acute myocardial infarction (AMI) is among the most critical chronic diseases and requires early detection and treatment. In this paper, we propose an AMI diagnostic software technique and protocol that can support real‐time communication between the patient and medical personnel. Our monitoring and diagnostic system has been developed using a protocol based on ISO/IEEE 11073. When data is transferred from the patient's smartphone to a server in hospital, the medical personnel consult the patient's biosensor data to determine the status of the relevant disease and provide appropriate medical service. The relevant information is sent back to the patient's smartphone through a wireless network, and patients can view their data in graphical format through their smartphone. Copyright © 2015 John Wiley & Sons, Ltd.
Social functioning and autonomic nervous system sensitivity across vocal and musical emotion in Williams syndrome and autism spectrum disorder
Authors: Järvinen Anna , Ng Rowena , Crivelli Davide , Neumann Dirk , Arnold Andrew J. , Woo‐VonHoogenstyn Nicholas , Lai Philip , Trauner Doris , Bellugi Ursula
Published: August 2015

Both Williams syndrome (WS) and autism spectrum disorders (ASD) are associated with unusual auditory phenotypes with respect to processing vocal and musical stimuli, which may be shaped by the atypical social profiles that characterize the syndromes. Autonomic nervous system (ANS) reactivity to vocal and musical emotional stimuli was examined in 12 children with WS, 17 children with ASD, and 20 typically developing (TD) children, and related to their level of social functioning. The results of this small‐scale study showed that after controlling for between‐group differences in cognitive ability, all groups showed similar emotion identification performance across conditions. Additionally, in ASD, lower autonomic reactivity to human voice, and in TD, to musical emotion, was related to more normal social functioning. Compared to TD, both clinical groups showed increased arousal to vocalizations. A further result highlighted uniquely increased arousal to music in WS, contrasted with a decrease in arousal in ASD and TD. The ASD and WS groups exhibited arousal patterns suggestive of diminished habituation to the auditory stimuli. The results are discussed in the context of the clinical presentation of WS and ASD. © 2015 Wiley Periodicals, Inc. Dev Psychobiol 58:17–26, 2016.
Rfx2 is required for spermatogenesis in the mouse
Authors: Shawlot William , Vazquez‐Chantada Mercedes , Wallingford John B. , Finnell Richard H.
Published: August 2015

RFX transcription factors are key regulators of ciliogenesis in vertebrates. In Xenopus and zebrafish embryos, knockdown of Rfx2 causes defects in neural tube closure and in left–right axis patterning. To determine the essential role of the Rfx2 gene in mammalian development, we generated Rfx2‐deficient mice using an embryonic stem cell clone containing a lacZ gene trap reporter inserted into the first intron of the Rfx2 gene. We found that the Rfx2 lacZ reporter is expressed in ciliated tissues during mouse development including the node, the floor plate and the dorsal neural tube. However, mice homozygous for the Rfx2 gene trap mutation did not have defects in neural tube closure or in organ situs. The gene trap insertion appears to create a null allele as Rfx2 mRNA was not detected in Rfx2gt/gt embryos. Although Rfx2‐deficient mice do not have an obvious embryonic phenotype, we found that Rfx2gt/gt males are infertile because of a defect in spermatid maturation at or before the round and elongating spermatid stage. Our results indicate that Rfx2 is not essential for embryonic development in the mouse but is required for spermatogenesis. genesis 53:604–611, 2015. © 2015 Wiley Periodicals, Inc.
Individual variation in parental workload and breeding productivity in female European starlings: is the effort worth it?
Authors: Fowler Melinda A. , Williams Tony D.
Published: August 2015

We analyzed individual variation in work load (nest visit rate) during chick‐rearing, and the consequences of this variation in terms of breeding productivity, in a highly synchronous breeder, the European starling (Sturnus vulgaris) focusing on female birds. There was marked (10‐ to 16‐fold) variation in total, female and male nest visit rates, among individuals, but individual variation in female nest visit rate was independent of environment (rainfall, temperature) and metrics of individual quality (laying date, clutch size, amount of male provisioning help), and was only weakly associated with chick demand (i.e., day 6 brood size). Female nest visit rate was independent of date and experimentally delayed birds provisioned at the same rate as peak‐nesting birds; supporting a lack of effect of date per se. Brood size at fledging was positively but weakly related to total nest visit rate (male + female), with >fivefold variation in nest visit rate for any given brood size, and in females brood size at fledging and chick mass at fledging were independent of female nest visit rate, that is, individual variation in workload was not associated with higher productivity. Nevertheless, nest visit rate in females was repeatable among consecutive days (6–8 posthatching), and between peak (first) and second broods, but not among years. Our data suggest that individual females behave as if committed to a certain level of parental care at the outset of their annual breeding attempt, but this varies among years, that is, behavior is not fixed throughout an individual's life but represents an annually variable decision. We suggest females are making predictable decisions about their workload during provisioning that maximizes their overall fitness based on an integration of information on their current environment (although these cues currently remain unidentified).
The Catalytic Role of Extra Molecules in the Aminolysis or Heterolytic Cleavage of an Iridium Alkoxycarbene Complex
Authors: Talavera María , Bolaño Sandra , Bravo Jorge , García‐Fontán Soledad , Hermida‐Ramón Jose M.
Published: August 2015

A theoretical analysis was performed on reactions involving iridium alkoxycarbene complex [IrCp*Cl{=C(OCH3)CHCPh2}(PPh2Me)]PF6 (Cp* = pentamethylcyclopentadienyl), which can undergo aminolysis or heterolytic cleavage of the carbon(sp3)–oxygen bond. The energy barriers of these pathways were estimated and the reasons for the reactivity of the system evaluated. Aminolysis or heterolytic cleavage of the carbon(sp3)–oxygen bond is the result of a subtle equilibrium between electronic, steric, and cooperative effects. Cooperative effects facilitate the proton transfer that occurs in aminolysis through formation of a bridge by one or several molecules. These molecules act as catalysts that decrease the energy barrier and change the favored pathway, so that the environment is a key factor in the reactivity of this complex.
A Family of Dinuclear Iron(II) SCO Compounds Based on a 1,3,4‐Thiadiazole Bridging Ligand
Authors: Herold Christian F. , Carrella Luca M. , Rentschler Eva
Published: August 2015

Invited for the cover of this issue is the group of Eva Rentschler at the Gutenberg University, Mainz, Germany. The cover image shows a new dinuclear iron(II) SCO compound as a molecular switch illustrating temperature‐dependent spin state switching upon cooling or heating. The 1,3,4‐thiadiazole backbone of the bridging ligand was necessary to achieve the diamagnetic [LS–LS] ground state, so far not observed in related systems.
Curbing thermo‐oxidative degradation of frying oils: Current knowledge and challenges
Authors: Aladedunye Felix A.
Published: August 2015

Deep fat frying is an ancient process with a lot of open questions. This deceptively simple food preparation technique is immensely complicated by the stringent conditions applied during the process, coupled with the inherent lability of the frying medium and the unavoidable meddling from the food materials and other minor components. The various factors affecting frying stability and performance of oil can be broadly categorized into two groups: (1) The external factors, which include frying temperature, frying time, presence of oxygen, and type of fryers, among others, are factors that can be manipulated by the frying operators; (2) the internal or endogenous factors are oil‐specific and include fatty acid composition and their distribution on triacylglycerols, and the amounts and composition of the minor components. Limiting thermo‐oxidative degradation and consequently extending the useful life of frying oils often involves deliberate optimization and control of some of these factors. Available techniques for curbing thermo‐oxidative decomposition of frying oils and the inherent challenges are discussed.

Practical applications: This review provides updates to our current knowledge of the salient factors affecting frying performance of oils/fats and specifically highlights both the opportunities for optimization and the accompanying daunting challenges. With this information, institutional frying operators can practically extend the discard point of their frying oils and deliver healthier fried products, while ensuring the safety of the frying facility and the technicians.

A trigonal bipyramid model showing the three basic optimizable parameters of frying. The base (striped) represents the optimized region for highest stability of the frying oil and the best quality fried product (operator's target). Higher values (bold lines) tapers off stability while lower values (dotted lines) decrease food quality.
Synthesis of 2‐Arylphenol Derivatives through a One‐Pot Suzuki–Miyaura Cou­pling/Dehydrogenative Aromatization Sequence with Pd/C Catalysis
Authors: Kikushima Kotaro , Nishina Yuta
Published: August 2015

One‐pot synthesis of 2‐arylphenols starting from 2‐iodo‐2‐cyclohexen‐1‐one and arylboronic acids through sequential Suzuki–Miyaura coupling/dehydrogenative aromatization with Pd/C catalysis has been developed. A range of arylboronic acids serve as substrates, including those containing electron‐donating or electron‐withdrawing groups. Additionally, one‐pot synthesis of di‐ or trisubstituted phenols bearing a phenyl group at the ortho position are also generated by using 2‐iodo‐2‐cyclohexen‐1‐one derivatives as substrate. In the present method, commercially available and easily removable Pd/C was employed as a catalyst without any ligands. The operationally simple procedure and accessible conditions were used to provide modified phenols as the sole product in moderate to high yields.
Enantiomeric separation of 1,3‐dimethylamylamine by capillary electrophoresis with indirect UV detection using a dual‐selector system
Authors: Přibylka Adam , Švidrnoch Martin , Ševčík Juraj , Maier Vítězslav
Published: August 2015

The CE method employing an indirect UV detection for the enantioseparation of 1,3‐dimethylamylamine (DMAA), widely used in various preworkout and dietary supplements labeled as a constituent of geranium extract has been developed. The dual‐selector system consisting of negatively charged sulfated α‐CD (1.1% w/v) and sulfated β‐CD (0.2% w/v) in 5 mM phosphate/Tris buffer (pH 3.0) containing the addition of 10 mM benzyltriethylammonium chloride (BTEAC) as the chromophoric additive was used for the enantiomeric separation of DMAA stereoisomers with the LODs in the range of 7.82–9.24 μg/mL. The method was partly validated and applied for the determination of the stereoisomeric composition of DMAA in commercial dietary supplements to verify the potential natural origin of DMAA.
Predicting the effects of copper on local population decline of 2 marine organisms, cobia fish and whiteleg shrimp, based on avoidance response
Authors: Araújo Cristiano V.M. , Cedeño-Macías Luís A. , Vera-Vera Victoria C. , Salvatierra David , Rodríguez Elizabeth N.V. , Zambrano Ufredo , Kuri Samir
Published: August 2015

The present study focuses on avoidance response to predict population decline of the marine fish Rachycentron canadum (cobia) and larvae of the estuarine shrimp Litopenaeus vannamei (whiteleg shrimp). Avoidance of approximately 60% was recorded for the cobia fry exposed to 1.0 mg Cu/L, 1.60 mg Cu/L, and 1.80 mg Cu/L. For the shrimp larvae, avoidance was approximately 80% for all Cu concentrations. The population decline of cobia fry was conditioned by avoidance in lower concentrations. However, in higher concentrations mortality begins to play an important role. The displacement toward uncontaminated habitats might determine shrimp population decline. A Cu-contaminated environment can determine the habitat selection of both species and, therefore, their local population decline. Environ Toxicol Chem 2016;35:405–410. © 2015 SETAC
Neuroinflammation in the peripheral nerve: Cause, modulator, or bystander in peripheral neuropathies?
Authors: Martini Rudolf , Willison Hugh
Published: August 2015

The role of innate and adaptive inflammation as a primary driver or modifier of neuropathy in premorbidly normal nerves, and as a critical player in amplifying neuropathies of other known causes (e.g., genetic, metabolic) is incompletely understood and under‐researched, despite unmet clinical need. Also, cellular and humoral components of the adaptive and innate immune system are substantial disease modifying agents in the context of neuropathies and, at least in some neuropathies, there is an identified tight interrelationship between both compartments of the immune system. Additionally, the quadruple relationship between Schwann cell, axon, macrophage, and endoneurial fibroblast, with their diverse membrane bound and soluble signalling systems, forms a distinct focus for investigation in nerve diseases with inflammation secondary to Schwann cell mutations and possibly others. Identification of key immunological effector pathways that amplify neuropathic features and associated clinical symptomatology including pain should lead to realistic and timely possibilities for translatable therapeutic interventions using existing immunomodulators, alongside the development of novel therapeutic targets. GLIA 2016;64:475–486
High priority for hepatitis C screening in safety net hospitals: Results from a prospective cohort of 4582 hospitalized baby boomers
Authors: Turner Barbara J. , Taylor Barbara S. , Hanson Joshua , Liang Yuanyuan , Veerapaneni Poornachand , Villarreal Roberto , Perez Mary , Hernandez Ludivina , Sandhu Jasdeep , Fiebelkorn Kristin
Published: August 2015

Low‐income populations are disproportionately affected by hepatitis C virus (HCV) infection. Thus, implementing baby boomer screening (born 1945‐1965) for HCV may be a high priority for safety net hospitals. We report the prevalence and predictors of HCV infection and advanced fibrosis or cirrhosis based on the Fibrosis‐4 score plus imaging for a baby boomer cohort admitted to a safety net hospital over a 21‐month interval with >9 months of follow‐up. Anti‐HCV antibody testing was performed for 4582, or 90%, of all never‐screened patients, of whom 312 (6.7%) tested positive. Adjusted odds ratios of testing anti‐HCV‐positive were 2.66 for men versus women (P < 0.001), 1.25 for uninsured versus insured (P = 0.06), 0.70 for Hispanics versus non‐Hispanic whites (P = 0.005), and 0.93 per year of age (P < 0.001). Among 287 patients tested for HCV RNA (91% of all anti‐HCV‐positive cases), 175 (61%) were viremic (3.8% overall prevalence in cohort), which was 5% less likely per year of age (P < 0.03). Noninvasive staging of 148 (84.6%) chronic HCV patients identified advanced fibrosis or cirrhosis in 50 (33.8%), with higher adjusted odds ratios of 3.21 for Hispanics versus non‐Hispanic whites/Asians (P = 0.02) and 1.18 per year of age (P = 0.001). Other factors associated with significantly higher adjusted odds ratios of advanced fibrosis or cirrhosis were alcohol abuse/dependence, obesity, and being uninsured. Conclusion: In this low‐income, hospitalized cohort, 4% of 4582 screened baby boomers were diagnosed with chronic HCV, nearly twice the rate in the community; one‐third had noninvasive testing that indicated advanced fibrosis or cirrhosis, which was significantly more likely for Hispanics, those of older age, those with obesity, those with alcohol abuse/dependence, and those who lacked insurance. (Hepatology 2015;62:1388–1395)
Teaching children with autism to respond to conversation partners’ interest
Authors: Peters Lindsay C. , Thompson Rachel H.
Published: August 2015

Successful conversation requires that the speaker's behavior is sensitive to nonvocal listener responses. We observed children with autism spectrum disorder during conversation probes in which a listener periodically displayed nonvocal cues that she was uninterested in the conversation. We used behavioral skills training to teach conversation skills. First, we taught participants to tact nonvocal listener behavior (interested or uninterested), but this was insufficient to improve responding aimed at regaining listener interest. Participants were then taught to ask a question (Experiments 1 and 2) or change the topic (Experiment 2) when the listener was uninterested. Responding persisted over time and with changes in the stimulus conditions. The behavior change was also deemed socially valid by blind observers. In Experiment 3, participants learned to shift to the other trained response when exposed to extinction. This study illustrates a set of procedures for bringing speaker behavior under control of nonvocal listener cues.
Teaching discriminated social approaches to individuals with Angelman syndrome
Authors: Fichtner Caitlin S. , Tiger Jeffrey H.
Published: August 2015

Angelman syndrome is a neurogenetic disorder characterized by intellectual and developmental disability. Common behavioral characteristics of this disorder include a heightened interest in social interactions and frequent bids to initiate interaction. These bids can be problematic, for instance, when a child attempts to hug strangers in public places. The current study evaluated a discrimination training program to teach 3 boys with Angelman syndrome to discriminate appropriate from inappropriate times to initiate interactions. During baseline, we alternated periods in which attention was delivered following social initiations on a continuous reinforcement schedule with periods in which initiations were placed on extinction. We then implemented discrimination training by presenting a salient discriminative stimulus, prompting the occurrence of initiations, and providing reinforcement during reinforcement periods and withdrawing the stimulus during extinction periods. This resulted in discriminated approaches for each of the 3 participants; these results were replicated across caregivers and extended to the participants' homes.
Degradable poly(apigenin) polymer inhibits tumor cell adhesion to vascular endothelial cells
Authors: Cochran David B. , Gray Lindsay N. , Anderson Kimberly W. , Dziubla Thomas D.
Published: August 2015

Cancer and the inflammatory system share a complex intertwined relationship. For instance, in response to an injury or stress, vascular endothelial cells will express cell adhesion molecules as a means of recruiting leukocytes. However, circulating tumor cells (CTCs) have been shown to highjack this expression for the adhesion and invasion during the metastatic cascade. As such, the initiation of endothelial cell inflammation, either by surgical procedures (cancer resection) or chemotherapy can inadvertently increase the metastatic potential of CTCs. Yet, systemic delivery of anti‐inflammatories, which weaken the entire immune system, may not be preferred in some treatment settings. In this work, we demonstrate that a long‐term releasing flavone‐based polymer and subsequent nanoparticle delivery system can inhibit tumor cell adhesion, through the suppression of endothelial cell adhesion molecule expression. The degradation of a this anti‐inflammatory polymer provides longer term, localized release profile of active therapeutic drug in nanoparticle form as compared with that of the free drug, permitting more targeted anti‐metastatic therapies. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1438–1447, 2016.
Biofunctionalization of conductive hydrogel coatings to support olfactory ensheathing cells at implantable electrode interfaces
Authors: Hassarati Rachelle T. , Marcal Helder , John L. , Foster R. , Green Rylie A.
Published: August 2015

Mechanical discrepancies between conventional platinum (Pt) electrodes and neural tissue often result in scar tissue encapsulation of implanted neural recording and stimulating devices. Olfactory ensheathing cells (OECs) are a supportive glial cell in the olfactory nervous system which can transition through glial scar tissue while supporting the outgrowth of neural processes. It has been proposed that this function can be used to reconnect implanted electrodes with the target neural pathways. Conductive hydrogel (CH) electrode coatings have been proposed as a substrate for supporting OEC survival and proliferation at the device interface. To determine an ideal CH to support OECs, this study explored eight CH variants, with differing biochemical composition, in comparison to a conventional Pt electrodes. All CH variants were based on a biosynthetic hydrogel, consisting of poly(vinyl alcohol) and heparin, through which the conductive polymer (CP) poly(3,4‐ethylenedioxythiophene) was electropolymerized. The biochemical composition was varied through incorporation of gelatin and sericin, which were expected to provide cell adherence functionality, supporting attachment, and cell spreading. Combinations of these biomolecules varied from 1 to 3 wt %. The physical, electrical, and biological impact of these molecules on electrode performance was assessed. Cyclic voltammetry and electrochemical impedance spectroscopy demonstrated that the addition of these biological molecules had little significant effect on the coating's ability to safely transfer charge. Cell attachment studies, however, determined that the incorporation of 1 wt % gelatin in the hydrogel was sufficient to significantly increase the attachment of OECs compared to the nonfunctionalized CH. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 104B: 712–722, 2016.
GeauxDock: A novel approach for mixed‐resolution ligand docking using a descriptor‐based force field
Authors: Ding Yun , Fang Ye , Feinstein Wei P. , Ramanujam Jagannathan , Koppelman David M. , Moreno Juana , Brylinski Michal , Jarrell Mark
Published: August 2015

Molecular docking is an important component of computer‐aided drug discovery. In this communication, we describe GeauxDock, a new docking approach that builds on the ideas of ligand homology modeling. GeauxDock features a descriptor‐based scoring function integrating evolutionary constraints with physics‐based energy terms, a mixed‐resolution molecular representation of protein‐ligand complexes, and an efficient Monte Carlo sampling protocol. To drive docking simulations toward experimental conformations, the scoring function was carefully optimized to produce a correlation between the total pseudoenergy and the native‐likeness of binding poses. Indeed, benchmarking calculations demonstrate that GeauxDock has a strong capacity to identify near‐native conformations across docking trajectories with the area under receiver operating characteristics of 0.85. By excluding closely related templates, we show that GeauxDock maintains its accuracy at lower levels of homology through the increased contribution from physics‐based energy terms compensating for weak evolutionary constraints. GeauxDock is available at http://www.institute.loni.org/lasigma/package/dock/. © 2015 Wiley Periodicals, Inc.
Toll‐Like Receptors and Tissue Remodeling: The Pro/Cons Recent Findings
Authors: Micera Alessandra , Balzamino Bijorn Omar , Zazzo Antonio Di , Biamonte Filippo , Sica Gigliola , Bonini Stefano
Published: August 2015

The Toll‐like Receptor (TLR) family ensures prompt response towards pathogens, protecting the host against infections, and guarantees a realistic balance between protective and detrimental activities. Multiple regulating mechanisms characterize TLR activity that is not limited to innate and adaptive antimicrobial immune responses, as observed in the inflammatory (either infective, allergic, or autoimmune) responses associated with tissue remodeling. Following the insult and the arise of inflammatory response, tissue remodeling takes place and might develop in fibrosis, depending on microenvironment as a result of imbalanced fibroblasts (FBs) and myofibroblasts (myoFBs) activation/survival. The process is driven by an epithelial‐fibroblast‐immune cell cross‐talk. While the main FB function is the matrix metabolism for tissue homeostasis or repair, the myoFB differentiation represents a crucial step in attempting repair of injury. FBs/myoFBs provide more than structural support at site of injury, synthesizing and/or reacting to different cytokines, growth factors, neuromediators and soluble/lipid mediators. TLR‐bearing FBs/myoFBs might contribute at the innate immune level, providing a second line of protection/defense as well as being a target/effector cell of tissue remodeling. TLRs might also interfere with acute inflammation as well as with established fibrosis, triggering structural/functional changes in agreement with the genetic background, the site of lesion, the entity of associated infection, the poor blood circulation or the pharmacological treatments, all together strictly influencing tissue repair/remodeling process. This review will focus on the recent findings on TLRs at launch and long‐lasting tissue remodeling process, that strongly suggest TLRs as optional targets for future therapies. J. Cell. Physiol. 231: 531–544, 2016. © 2015 Wiley Periodicals, Inc.
Ca2+ Signalling in Endothelial Progenitor Cells: Friend or Foe?
Authors: Moccia Francesco , Guerra Germano
Published: August 2015

Endothelial progenitor cells (EPCs) are mobilized either from the bone marrow and/or the arterial to replace dysfunctional endothelial cells and rescue blood perfusion in ischemic tissues. In addition, they may contribute to the angiogenic switch, thereby sustaining tumour growth and metastatization. Understanding the molecular mechanisms utilized by vascular endothelial growth factor (VEGF) to stimulate EPCs might unveil novel targets to enhance their clinical outcome in regenerative medicine and to adverse tumour vascularisation. VEGF stimulates peripheral blood‐derived EPCs to undergo repetitive Ca2+ oscillations shaped by the interaction between inositol‐1,4,5‐trisphosphate (InsP3)‐dependent Ca2+ release and store‐operated Ca2+ entry (SOCE). However, the Ca2+ machinery underlying VEGF‐induced Ca2+ spikes changes in umbilical cord blood‐derived EPCs, which require TRPC3‐mediated Ca2+ entry to trigger the interplay between InsP3 and SOCE. Surprisingly, VEGF fails to elicit pro‐angiogenic Ca2+ signals when EPCs derive from renal cellular carcinoma patients, thus questioning the suitability of VEGFR‐2 as a target for anti‐angiogenic treatments in these individuals. The lack of response to VEGF is likely due to the dramatic rearrangement of the Ca2+ toolkit occurring in RCC‐derived EPCs. Finally, primary myelofibrosis‐derived EPCs display a further pattern of reorganization of the Ca2+ machinery and proliferate independently of SOCE. Thus, the Ca2+ machinery in human ECFCs is extremely plastic and may change depending on the physio‐pathological background of the donor. As a consequence, the Ca2+ toolkit could properly be used to enhance the regenerative outcome of cell‐based therapy or adverse tumor vascularisation. J. Cell. Physiol. 231: 314–327, 2016. © 2015 Wiley Periodicals, Inc.
The effect of quinidine, a strong P‐glycoprotein inhibitor, on the pharmacokinetics and central nervous system distribution of naloxegol
Authors: Bui Khanh , She Fahua , Zhou Diansong , Butler Kathleen , Al‐Huniti Nidal , Sostek Mark
Published: August 2015

Naloxegol is a PEGylated, oral, peripherally acting μ‐opioid receptor antagonist approved in the United States for treatment of opioid‐induced constipation in patients with noncancer pain. Naloxegol is metabolized by CYP3A, and its properties as a substrate for the P‐glycoprotein (PGP) transporter limit its central nervous system (CNS) permeability. This double‐blind, randomized, 2‐part, crossover study in healthy volunteers evaluated the effect of quinidine (600 mg PO), a CYP3A/PGP transporter inhibitor, on the pharmacokinetics and CNS distribution of naloxegol (25 mg PO). In addition, the effects of quinidine on morphine (5 mg/70 kg IV)‐induced miosis and exposure to naloxegol were assessed. Coadministration of quinidine and naloxegol increased naloxegol's AUC 1.4‐fold and Cmax 2.5‐fold but did not antagonize morphine‐induced miosis, suggesting that PGP inhibition does not increase the CNS penetration of naloxegol. Naloxegol pharmacokinetics was unaltered by coadministration of morphine and either quinidine or placebo; conversely, pharmacokinetics of morphine and its metabolites (in the presence of quinidine) were unaltered by coadministration of naloxegol. Naloxegol was safe and well tolerated, alone or in combination with quinidine, morphine, or both. The observed increase in exposure to naloxegol in the presence of quinidine is primarily attributed to quinidine's properties as a weak CYP3A inhibitor.
Basic Ionic Liquid Promoted Domino Knoevenagel–Thia‐Michael Reaction: An Efficient and Multicomponent Strategy for Synthesis of 1,3‐Thiazines
Authors: Siddiqui I. R. , Rahila  , Shamim Shayna , Rai Pragati , Shireen  , Waseem Malik A. , Srivastava Arjita , Srivastava Anjali
Published: August 2015

An efficient, three‐component strategy for synthesis of 1,3‐thiazines with high atom economy in one‐pot mediated by room temperature basic ionic liquid is described here. The strategy involves basic ionic liquid, [bmim]OH‐catalyzed Knoevenagel condensation between ethyl cyanoacetate and aromatic aldehyde and subsequent thia‐Michael addition with substituted thioureas. The reaction sequence is smooth and quantitative under ambient temperature. [bmim]OH was recovered and reused four times without any appreciable decrease in its reactivity and product yield.
Synthesis and Characterization of New Heterocyclic Compounds Containing Thienylbenzo[h]Quinoline Moiety
Authors: Al‐Taifi Elham A. , Abbady Mohamed S. , Bakhite Etify A.
Published: August 2015

In this paper the reaction of 2‐(2′‐thienylmethylene)‐3,4‐dihydronaphthalen‐2(1H)‐one (1) with cyanothioacetamide gave a mixture of 3‐cyano‐5,6‐dihydro‐4‐(2′‐thienyl)‐benzo[h]quinolin‐2(1H)‐thione (2) and the related disulfide 3. Compound 2 was reacted with some halo compounds namely; ethyl chloroacetate, chloroacetamide, chloro(N‐(p‐chlorophenyl))acetamide, N1‐chloroacetylsulfanilamide, and 2‐chloromethyl‐1H‐benzimidazole to produce a series of 2‐(substituted)methylthio‐3‐cyano‐5,6‐dihydro‐4‐(2′‐thienyl)benzo[h]quinolines 4a, 4b, 4c, 4d, 4e and 11. Upon heating the latter compounds with sodium ethoxide, they underwent intramolecular Thorpe–Zeigler cyclization to furnish the corresponding 2‐(substituted)‐3‐amino‐5,6‐dihydro‐4‐(2′‐thienyl)‐benzo[h]thieno[2,3‐b]quinolines 5a, 5b, 5c, 5d, 5e and 12. (3‐Cyano‐5,6‐dihydro‐4‐(2′‐thienyl)‐benzo[h]quinolin‐2‐ylthio)acethydrazide (8) and the related isomer, 3‐amino‐5,6‐dihydro‐4‐(2′‐thienyl)thieno[2,3‐b]benzo[h]quinoline‐2‐carbohydrazide (9), were also synthesized. Most of the aforementioned compounds were used as key intermediates for synthesizing other benzo[h]quinolines, benzo[h]thieno[2,3‐b]quinolines as well as benzo[h]pyrimido[4′,5′:4,5] thieno[2,3‐b]quinolines. The structure of all synthesized compounds was confirmed by spectroscopic measurements and analytical analyses.
Seven Decades of ‘Development’, and Now What?
Authors: Koehler Gabriele
Published: August 2015

Year 2015 is slated as a year of transformation to address unprecedented political, ecological, social, gender and economic inequities. UN negotiations are underway to produce new sustainable development goals (SDGs). The paper argues that ideas matter in the conceptualisation of development agendas, which in turn depend on power constellations within and between the first UN—the member states, the second UN—the UN secretariat and agencies, and the third UN—civil society. The paper tracks past development decades and examines whether the SDGs can and will be as visionary as the UN Charter adopted in 1945, which created moral pressure for institutional and policy change. Copyright © 2015 John Wiley & Sons, Ltd.
Universality and Ambition in the Post‐2015 Development Agenda: A Comparison of Global and National Targets
Authors: Scott Andrew , Lucci Paula
Published: August 2015

The post‐2015 moment is a moment in time in which multiple efforts are being made to envision a better long‐term future for humanity and to forge, post‐2015, a new and different global development trajectory. The replacement of the Millennium Development Goals by the Sustainable Development Goals (SDGs) is occurring in the shadow of the global financial crisis and the reaching of planetary boundaries that define a safe operating space for humanity. There is thus a need not only for new global goals but also a new global development paradigm. The papers in this special issue examine the SDGs in the making and indicate the extent to which they may be associated with a new global development paradigm. They identify key weaknesses in the emerging SDGs in terms of the articulation of global and local priorities, the failure to address the synergies and trade‐offs between different goals and the lack of an underlying policy framework. They also suggest that to be effective, new global goals require new global rules. Copyright © 2015 John Wiley & Sons, Ltd.
Post‐2015 Global Governance of Official Development Finance: Harnessing the Renaissance of Public Entrepreneurship
Authors: Xu Jiajun , Carey Richard
Published: August 2015

The spirit of ‘public entrepreneurship’, reignited by large‐scale and long‐term official finance from emerging economies, is now driving a process of ‘creative destruction’ in the established systems for governing official development finance primarily forged among advanced economies. In response to this burgeoning official finance from emerging economies once on the margins or outside of these established systems, potentially seismic shifts are occurring in three central governance systems—the reporting systems for official development assistance in the OECD Development Assistance Committee, OECD export credit disciplines and debt sustainability in the Bretton Woods Institutions. Emerging economies create competitive pressures that work to redress the undue rigidities in these established frameworks, opening the way to meeting vast development financing needs. If not well managed or coordinated, however, growing official finance runs the risk of further rounds of financial arms races and debt crises. To harness the processes of ‘public entrepreneurship’ as a force for good in realizing a transformative post‐2015 development agenda requires international cooperation to reshape global governance of official development finance. Copyright © 2015 John Wiley & Sons, Ltd.
Impact of gadolinium‐based contrast agent in the assessment of Crohn's disease activity: Is contrast agent injection necessary?
Authors: Quaia Emilio , Sozzi Michele , Gennari Antonio Giulio , Pontello Michele , Angileri Roberta , Cova Maria Assunta
Published: August 2015

Purpose

To determine whether magnetic resonance enterography (MRE) performed without intravenous contrast injection is diagnostically noninferior to conventional contrast‐enhanced MRE (CE‐MRE) in patients with Crohn's disease (CD).

Materials and Methods

This was an Institutional Review Board (IRB)‐approved retrospective study. Ninety‐six patients (52 male and 44 female; 47.18 years ± 13.6) with a diagnosis of CD underwent MRE at 1.5T including T2‐weighted single‐shot turbo‐spin‐echo, T2‐weighted spectral fat presaturation with inversion recovery (SPAIR), T1‐weighted balanced fast‐field‐echo MR sequences, and CE‐MRE consisting in T1‐weighted breath‐hold THRIVE 3D MRI sequences after administration of gadobenate dimeglumine (0.2 mL/kg of body weight). Unenhanced MRE, CE‐MRE, and unenhanced MRE plus CE‐MRE were reviewed in separate sessions with blinding by two readers in consensus, and subsequently by two other readers independently considering a subgroup of 20 patients. Crohn's Disease Endoscopic Index of Severity (CDEIS) and/or histologic analysis of the surgical specimen were considered as reference standards for the assessment of inflammatory activity.

Results

Patients revealed prevalently active (n = 55 patients) or quiescent CD (n = 41 patients). The agreement between unenhanced MRE vs. CE‐MRE in interpreting active bowel inflammation was 96% (123/128 bowel segments; one‐sided 95% confidence interval [CI], >94.4%). Unenhanced MRE vs. CE‐MRE vs. unenhanced MRE plus CE‐MRE revealed a diagnostic accuracy of 93% [90/96] vs. 92% [88/96] vs. 97% [93/96] (P > 0.05) in the diagnosis of active CD. Interreader agreement was very good for all variables (κ value = 0.8–0.9) except for the measurement of the length of disease (κ value = 0.45).

Conclusion

Unenhanced MRE was noninferior to CE‐MRE in diagnosing active inflammation in patients with CD. J. MAGN. RESON. IMAGING 2016;43:688–697.
Why is the Bay of Bengal experiencing a reduced rate of sea surface warming?
Authors: D'Mello Joshua Rosario , Prasanna Kumar S.
Published: August 2015

The sea surface temperature (SST) in the Bay of Bengal (BoB) during the period 1960–1995 showed a decadal cycle, riding over a warming trend. The disruption of the decadal cycle was noticed post‐1995 and was followed by a slowdown in the sea surface warming. The cause for the disruption of the SST decadal cycle was the weakening of the link between SST and sunspot number. The rising trend in the SST is due to the increasing atmospheric CO2 concentration. The post‐1995 SST slowdown was due to the increasing influence of the number of depressions, cyclones and severe cyclones in the BoB, the occurrence of which showed an upward trend. Using Price–Weller–Pinkel model we show that cyclonic systems deepen the mixed‐layer through enhanced mechanical‐mixing with cooler sub‐surface waters, thereby reducing the mixed‐layer temperature and consequently the SST. This process opposes the SST rise due to increasing atmospheric CO2 concentration. The net effect of the wind‐mixing caused by the increased number of depressions, cyclones and severe cyclones and the increased CO2 concentration is a SST slowdown in the BoB. This mechanism differs from the SST slowdown mechanisms suggested for the Atlantic and the Pacific.
The super‐heat wave in eastern China during July–August 2013: a perspective of climate change
Authors: Xia Jiangjiang , Tu Kai , Yan Zhongwei , Qi Yajie
Published: August 2015

Eastern China suffered a record‐breaking heat wave throughout almost all of summer, during 2013. Recent studies found a discernible impact of anthropogenic forcing on this extreme heat wave event. In this study, we investigate the role of multidecadal variability (MDV) in regulating the likelihood of the 2013 heat wave event. Using the ensemble empirical mode decomposition (EEMD) method, we decomposed the heat wave index series into three components: (1) a non‐linear secular trend (ST), representing the long‐term anthropogenic warming; (2) MDV; and (3) the residual high‐frequency variability. For the period 1873–2013, the linear trend of heat wave strength (HW‐S, defined as the July–August mean temperatures) was 0.06 °C per decade, mainly because of the contribution of ST. MDV plays an important role in regulating changes over decades. ST and MDV together form a changing climate background (CB) for extreme events. The 2013 heat wave event would be almost impossible under the pre‐industrial CB but becomes likely under the long‐term warming background, with a return period of longer than 103 years. When the positive phase of MDV is added to the secular warming background (the current CB), the return period of a super‐heat wave such as the 2013 event becomes about 42 (12–103) years. The Atlantic Multidecadal Oscillation (AMO) shows significant correlation with the MDV component of the HW‐S in Shanghai. The correlation pattern between the AMO and MDV of July–August temperatures over the Northern Hemisphere is analysed to explain the AMO–Shanghai relationship. It is suggested that the likelihood of such an extreme event will increase with further long‐term climate warming, modified by low‐frequency oceanic variations such as the AMO.
Long‐term trends in gale days and storminess for the Falkland Islands
Authors: Jones Philip D. , Harpham Colin , Lister David
Published: August 2015

Weather typing, based on surface pressure charts, has been one of the principal means of analysis in synoptic climatology. Here, we use an automated scheme to derive weather types (WTs) and also calculate Lamb weather types (LWTs) for the Falkland Islands. The WTs are based on sea‐level pressure data estimated using two reanalysis products: one that extends from 1948 to 2014 and another that just uses station pressure data as input and extends back to 1871. The WTs can be used to derive counts of gale days and these will be compared with storminess estimates based on the rate of change of daily‐average pressure measurements at the principal observational site (near the capital, Port Stanley) on the islands. A particular emphasis of the paper is the reliability of the results taking into account that we are using reanalysis datasets from a very data‐sparse region of the world. More gale days are estimated during the period from about 1880 to the mid‐1910s and since the 1980s. Fewer gale days are evident during other periods, particularly from the mid‐1910s to 1947. As these changes are not evident in the storminess measure derived from the sub‐daily pressure series for the Port Stanley region, the results in terms of gale‐day counts are very suggestive of being due to differences in the quality of the reanalysis during the different periods. The reanalysis appears better the higher the number of gale days estimated. The opening of the Panama Canal in 1914 dramatically reduced the number of ships, and hence observations, rounding Cape Horn. The paper also relates seasonal counts of the LWTs and WTs to recently developed long series of temperature and precipitation for the Port Stanley region.
Elevated marrow inflammatory cells and osteoclasts in subchondral osteosclerosis in human knee osteoarthritis
Authors: Geurts Jeroen , Patel Amit , Hirschmann Michael T. , Pagenstert Geert I. , Müller‐Gerbl Magdalena , Valderrabano Victor , Hügle Thomas
Published: August 2015

Subchondral osteosclerosis, characterized by an increase of hypomineralized bone material, is a pathological hallmark of osteoarthritis. The cellular components in the subchondral marrow compartment that participate in this aberrant bone remodeling process remain to be elucidated. This study assessed the presence of marrow inflammatory cells and their relative abundance between nonsclerotic and sclerotic tissues in knee osteoarthritis. Bone samples from osteoarthritic knee tibial plateaus were stratified for histological analyses using computed tomography osteoabsorptiometry. Immunohistological analysis revealed the presence of CD20 (B‐lymphocyte) and CD68 (macrophage), but not CD3 (T‐lymphocyte) immunoreactive mononuclear cells in subchondral marrow tissues and their relative abundance was significantly increased in sclerotic compared with nonsclerotic bone samples. Multinucleated osteoclasts that stained positive for CD68 and tartrate‐resistant acid phosphatase, predominantly associated with CD34‐positive blood vessels and their abundance was strongly increased in sclerotic samples. Bone‐specific alkaline phosphatase activity in outgrowth osteoblasts was induced by conditioned medium from nonsclerotic, but not sclerotic, bone pieces. These results suggest that an interaction between bone‐resident cells and marrow inflammatory cells might play a role in aberrant bone remodeling leading to subchondral osteosclerosis. Elevated osteoclast activity in sclerotic bone suggests that bone formation and resorption activities are increased, yet uncoupled, in human knee osteoarthritis. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:262–269, 2016.
Nitrogen losses, uptake and abundance of ammonia oxidizers in soil under mineral and organo‐mineral fertilization regimes
Authors: Florio Alessandro , Felici Barbara , Migliore Melania , Dell'Abate Maria Teresa , Benedetti Anna
Published: August 2015

BACKGROUND

A laboratory incubation experiment and greenhouse studies investigated the impact of organo‐mineral (OM) fertilization as an alternative practice to conventional mineral (M) fertilization on nitrogen (N) uptake and losses in perennial ryegrass (Lolium perenne) as well as on soil microbial biomass and ammonia oxidizers.

RESULTS

While no significant difference in plant productivity and ammonia emissions between treatments could be detected, an increase in soil total N content and an average 17.9% decrease in nitrates leached were observed in OM fertilization compared with M fertilization. The microbial community responded differentially to treatments, suggesting that the organic matter fraction of the OM fertilizer might have influenced N immobilization in the microbial biomass in the short–medium term. Furthermore, nitrate contents in fertilized soils were significantly related to bacterial but not archaeal amoA gene copies, whereas in non‐fertilized soils a significant relationship between soil nitrates and archaeal but not bacterial amoA copies was found.

CONCLUSION

The application of OM fertilizer to soil maintained sufficient productivity and in turn increased N use efficiency and noticeably reduced N losses. Furthermore, in this experiment, ammonia‐oxidizing bacteria drove nitrification when an N source was added to the soil, whereas ammonia‐oxidizing archaea were responsible for ammonia oxidation in non‐fertilized soil. © 2015 Society of Chemical Industry