bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis and comparative in vivo evaluation of 99mTc(CO)3‐labeled PEGylated and non‐PEGylated cRGDfK peptide monomers
Authors: Vats Kusum , Satpati Drishty , Sharma Rohit , Sarma Haladhar D. , Banerjee Sharmila 
Published: August 2016

This work aimed at studying the effect of insertion of medium PEG (PEG7) on the pharmacokinetic behavior of cRGDfK peptide in comparison with the non‐PEGylated analogue. The cRGDfK peptide has thus been derivatized at ε‐amino group of lysine by conjugation with N3–PEG7–COOH/N3–CH2–COOH to prepare a PEGylated and a non‐PEGylated analogue of cRGDfK. A tridentate chelator was then incorporated by click chemistry conjugation of the two peptide azides for radiolabeling with [99mTc(CO)3(H2O)3]+ precursor. Comparative in vivo evaluation of the two 99mTc(CO)3‐labeled radiotracers, 99mTc(CO)3–Pra–Tz–CH2–cRGDfK 5 and 99mTc(CO)3–Pra–Tz–PEG7–cRGDfK 6, was carried out in C57BL/6 mice bearing αvβ3‐positive melanoma tumors to determine their potential toward targeting integrin αvβ3 receptors. The radiotracers exhibited excellent stability in saline as well as in serum. Maximum tumor uptake for the two radiotracers was observed at 30 min p.i. (5: 3.0 ± 0.7% ID/g; 6: 4.1 ± 0.5% ID/g). The two neutral 99mTc(CO)3 radiotracers prepared exhibited receptor‐mediated uptake in melanoma tumor. The increase in the tumor uptake on introduction of PEG7 unit was accompanied by slower clearance from other organs which resulted in decreased target‐to‐background ratios. The in vivo kinetics of 99mTc(CO)3‐labeled radiotracer, 99mTc(CO)3–Pra–Tz–CH2–cRGDfK 5 with only methylene unit as the spacer, was found to be more favorable due to higher tumor/blood, tumor/liver, tumor/kidney, and tumor/lung ratios.
Gemcitabine‐(5′‐phosphoramidate)‐[anti‐IGF‐1R]: molecular design, synthetic organic chemistry reactions, and antineoplastic cytotoxic potency in populations of pulmonary adenocarcinoma (A549)
Authors: Coyne Cody P. , Narayanan Lakshmi 
Published: August 2016

One molecular‐based approach that increases potency and reduces dose‐limited sequela is the implementation of selective ‘targeted’ delivery strategies for conventional small molecular weight chemotherapeutic agents. Descriptions of the molecular design and organic chemistry reactions that are applicable for synthesis of covalent gemcitabine‐monophosphate immunochemotherapeutics have to date not been reported. The covalent immunopharmaceutical, gemcitabine‐(5′‐phosphoramidate)‐[anti‐IGF‐1R] was synthesized by reacting gemcitabine with a carbodiimide reagent to form a gemcitabine carbodiimide phosphate ester intermediate which was subsequently reacted with imidazole to create amine‐reactive gemcitabine‐(5′‐phosphorylimidazolide) intermediate. Monoclonal anti‐IGF‐1R immunoglobulin was combined with gemcitabine‐(5′‐phosphorylimidazolide) resulting in the synthetic formation of gemcitabine‐(5′‐phosphoramidate)‐[anti‐IGF‐1R]. The gemcitabine molar incorporation index for gemcitabine‐(5′‐phosphoramidate)‐[anti‐IGF‐R1] was 2.67:1. Cytotoxicity Analysis – dramatic increases in antineoplastic cytotoxicity were observed at and between the gemcitabine‐equivalent concentrations of 10−9 M and 10−7 M where lethal cancer cell death increased from 0.0% to a 93.1% maximum (100.% to 6.93% residual survival), respectively. Advantages of the organic chemistry reactions in the multistage synthesis scheme for gemcitabine‐(5′‐phosphoramidate)‐[anti‐IGF‐1R] include their capacity to achieve high chemotherapeutic molar incorporation ratios; option of producing an amine‐reactive chemotherapeutic intermediate that can be preserved for future synthesis applications; and non‐dedicated organic chemistry reaction scheme that allows substitutions of either or both therapeutic moieties, and molecular delivery platforms.
In allergic rhinitis, work, classroom and activity impairments are weakly related to other outcome measures
Authors: Devillier P. , Bousquet J. , Salvator H. , Naline E. , Grassin‐Delyle S. , de Beaumont O. 
Published: August 2016

SummaryBackgroundThe impact of grass pollen‐induced allergic rhinitis (AR) on classroom/work productivity and activities can be assessed with a specific instrument: the Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment Questions: Allergy Specific (WPAI‐AS). This study evaluated the relationships between the WPAI‐AS and other outcome measures in AR.MethodsAdolescents (aged 12–17) and adults (aged 18–65) consulting specialists for AR were enrolled in a four‐week, multicentre, observational study. The management of AR was left to the physicians’ discretion. Participants regularly rated the WPAI‐AS, their symptoms (using the Rhinoconjunctivitis Total Symptom Score (RTSS) and a 0‐ to 100‐mm visual analogue scale (VAS)) and quality of life (according to the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)).ResultsA total of 247 adolescents and 292 adults showed similar baseline impairments in classroom/work productivity and activities other than work. In both age groups, the WPAI‐AS scores were moderately correlated with the RQLQ score and, to a lesser extent, with the VAS score and the RTSS. A multiple regression analysis indicated that the RQLQ score was a weak but statistically significant predictor of both impaired work/classroom productivity and daily activities. A 50‐mm VAS cut‐off categorized patients in whom AR had the greatest impact on productivity.ConclusionsGrass pollen‐induced AR impairs work/classroom and daily activity to a similar extent in adults and adolescents. The weak‐to‐moderate correlations with AR symptom scores and quality‐of‐life scores suggest that a specific tool (such as the WPAI‐AS) should be used to assess AR's impact on word/classroom productivity and daily activities.
Antithyroid drugs during breastfeeding
Authors: Hudzik Bartosz , Zubelewicz‐Szkodzinska Barbara 
Published: August 2016

SummaryAntithyroid drugs (ATDs) are widely used for the treatment of Graves’ disease (GD) in the general population. Over the past decade, there has been an increasing awareness that several disturbances of thyroid function may occur in mothers after delivery which may be more prevalent than previously appreciated. Exacerbation of immune reactions occurs 3–12 month following delivery. Management of hyperthyroidism during lactation requires special considerations and should be implemented to prevent any adverse outcomes in mother and neonate. Continuation of breastfeeding is safe and should be encouraged in hyperthyroid mothers taking ATDs, whether these are ATDs being continued after gestation or indeed ATD treatment initiated in the postpartum period. Given PTU hepatotoxicity concerns, experts currently recommend using low‐to‐moderate MMI doses as a first‐line therapy in lactating mothers. PTU should be reserved only as a second‐line agent for cases of severe hyperthyroidism (thyroid storm) and allergic reactions to previous MMI treatment. ATD should be administered in divided doses immediately following each feeding. Evaluation of thyroid function tests is advisable at least 3–4 weeks after the initiation of breastfeeding.
Rising trends of endogenous Klebsiella pneumoniae endophthalmitis in Australia
Authors: Odouard Capucine , Ong Daini , Shah Parth R , Gin Thomas , Allen Penelope J , Downie John , Lim Lyndell L , McCluskey Peter 
Published: August 2016

AbstractBackgroundEndogenous Klebsiella pneumoniae endophthalmitis (EKPE) is a well‐known entity in South‐East Asia. We demonstrate a range of differing clinical features and outcomes of EKPE, and highlight the increasing incidence of EKPE in major centres in Sydney and Melbourne, Australia.DesignRetrospective observational case study and case series in the hospital setting.ParticipantsFour cases of EKPE.MethodsEKPE cases from 2005 to 2015 were identified through established endophthalmitis databases as well as hospital‐based microbiological searches.Main Outcome MeasuresEKPE cases were confirmed with positive K. pneumoniae intraocular samples.ResultsRising trends of EKPE were noted in major centres in Australia. Six eyes of four patients with EKPE from January 2011 to December 2015 are reported. The mean age was 49 years (range 43–58 years). Two patients had bilateral involvement. There were systemic symptoms up to 10 days prior to ocular symptoms. The source of sepsis in all cases was a hepatic abscess. Two patients had diabetes mellitus. Five eyes had hypopyon panuveitis on presentation. All eyes underwent vitrectomy. The patient with the most delayed presentation underwent enucleation following globe perforation. Final best corrected visual acuity (BCVA) in one patient with bilateral EKPE was light perception (LP) only. The other three eyes had BCVA in at least one eye of 6/24 or better.ConclusionsEKPE is an emerging condition in Australia. Although rare, EKPE is a sight‐threatening and potentially life‐threatening emergency that can initially present to ophthalmologists. One should suspect EKPE in septic patients with a B‐scan showing a vitreous or retinal abscess.
Feasibility of using high‐resolution satellite imagery to assess vertebrate wildlife populations
Authors: LaRue Michelle A. , Stapleton Seth , Anderson Morgan 
Published: August 2016

AbstractAlthough remote sensing has been used for >40 years to learn about Earth, use of very high‐resolution satellite imagery (VHR) (<1‐m resolution) has become more widespread over the past decade for studying wildlife. As image resolution increases, there is a need to understand the capabilities and limitations of this exciting new path in wildlife research. We reviewed studies that used VHR to examine remote populations of wildlife. We then determined characteristics of the landscape and the life history of species that made the studies amenable to use of satellite imagery and developed a list of criteria necessary for appropriate use of VHR in wildlife research. From 14 representative articles, we determined 3 primary criteria that must be met for a system and species to be appropriately studied with VHR: open landscape, target organism's color contrasts with the landscape, and target organism is of detectable size. Habitat association, temporal exclusivity, coloniality, landscape differentiation, and ground truthing increase the utility of VHR for wildlife research. There is an immediate need for VHR imagery in conservation research, particularly in remote areas of developing countries, where research can be difficult. For wildlife researchers interested in but unfamiliar with remote sensing resources and tools, understanding capabilities and current limitations of VHR imagery is critical to its use as a conservation and wildlife research tool.
Motor Imagery Shapes Abstract Concepts
Authors: de la Fuente Juanma , Casasanto Daniel , Martínez‐Cascales Jose Isidro , Santiago Julio 
Published: August 2016

AbstractThe concepts of “good” and “bad” are associated with right and left space. Individuals tend to associate good things with the side of their dominant hand, where they experience greater motor fluency, and bad things with their nondominant side. This mapping has been shown to be flexible: Changing the relative fluency of the hands, or even observing a change in someone else's motor fluency, results in a reversal of the conceptual mapping, such that good things become associated with the side of the nondominant hand. Yet, based on prior studies, it is unclear whether space–valence associations were determined by the experience of fluent versus disfluent actions, or by the mere expectation of fluency. Here, we tested the role of expected fluency by removing motor execution and perceptual feedback altogether. Participants were asked to imagine themselves performing a psychomotor task with one of their hands impaired, after which their implicit space–valence mapping was measured. After imagining that their right hand was impaired, right‐handed participants showed the “good is left” association typical of left‐handers. Motor imagery can change people's implicit associations between space and emotional valence. Although asymmetric motor experience may be necessary to establish body‐specific associations between space and valence initially, neither motoric nor perceptual experience is needed to change these associations subsequently. The mere expectation of fluent versus disfluenct actions can drive fluency‐based effects on people's implicit spatialization of “good” and “bad.” These results suggest a reconsideration of the mechanisms and boundary conditions of fluency effects.
Orientation selectivity in rat primary visual cortex emerges earlier with low‐contrast and high‐luminance stimuli
Authors: Ghodrati Masoud , Alwis Dasuni S. , Price Nicholas S. C. 
Published: August 2016

AbstractIn natural vision, rapid and sustained variations in luminance and contrast change the reliability of information available about a visual scene, and markedly affect both neuronal and behavioural responses. The hallmark property of neurons in primary visual cortex (V1), orientation selectivity, is unaffected by changes in stimulus contrast, but it remains unclear how sustained differences in mean luminance and contrast affect the time‐course of orientation selectivity, and the amount of information that neurons carry about orientation. We used reverse correlation with characterize the temporal dynamics of orientation selectivity in rat V1 neurons under four luminance‐contrast conditions. We show that orientation selectivity and mutual information between neuronal responses and stimulus orientation are invariant to contrast or mean luminance. Critically, the time‐course of the emergence of orientation selectivity was affected by both factors; response latencies were longer for low‐ than high‐luminance gratings, and surprisingly, response latencies were also longer for high‐ than low‐contrast gratings. Modelling suggests that luminance‐modulated changes in feedforward gain, in combination with hyperpolarization caused by high contrasts can account for our physiological data. The hyperpolarization at high contrasts may increase signal‐to‐noise ratios, whereas a more depolarized membrane may lead to greater sensitivity to weak stimuli.
Synesthesia strengthens sound‐symbolic cross‐modal correspondences
Authors: Lacey Simon , Martinez Margaret , McCormick Kelly , Sathian K. 
Published: August 2016

AbstractSynesthesia is a phenomenon in which an experience in one domain is accompanied by an involuntary secondary experience in another, unrelated domain; in classical synesthesia, these associations are arbitrary and idiosyncratic. Cross‐modal correspondences refer to universal associations between seemingly unrelated sensory features, e.g., auditory pitch and visual size. Some argue that these phenomena form a continuum, with classical synesthesia being an exaggeration of universal cross‐modal correspondences, whereas others contend that the two are quite different, since cross‐modal correspondences are non‐arbitrary, non‐idiosyncratic, and do not involve secondary experiences. Here, we used the implicit association test to compare synesthetes’ and non‐synesthetes’ sensitivity to cross‐modal correspondences. We tested the associations between auditory pitch and visual elevation, auditory pitch and visual size, and sound‐symbolic correspondences between auditory pseudowords and visual shapes. Synesthetes were more sensitive than non‐synesthetes to cross‐modal correspondences involving sound‐symbolic, but not low‐level sensory, associations. We conclude that synesthesia heightens universally experienced cross‐modal correspondences, but only when these involve sound symbolism. This is only partly consistent with the idea of a continuum between synesthesia and cross‐modal correspondences, but accords with the idea that synesthesia is a high‐level, post‐perceptual phenomenon, with spillover of the abilities of synesthetes into domains outside their synesthesias. To our knowledge, this is the first demonstration that synesthetes, relative to non‐synesthetes, experience stronger cross‐modal correspondences outside their synesthetic domains.
A comparative transcriptomic analysis of astrocytes differentiation from human neural progenitor cells
Authors: Magistri Marco , Khoury Nathalie , Mazza Emilia Maria Cristina , Velmeshev Dmitry , Lee Jae K. , Bicciato Silvio , Tsoulfas Pantelis , Faghihi Mohammad Ali 
Published: August 2016

AbstractAstrocytes are a morphologically and functionally heterogeneous population of cells that play critical roles in neurodevelopment and in the regulation of central nervous system homeostasis. Studies of human astrocytes have been hampered by the lack of specific molecular markers and by the difficulties associated with purifying and culturing astrocytes from adult human brains. Human neural progenitor cells (NPCs) with self‐renewal and multipotent properties represent an appealing model system to gain insight into the developmental genetics and function of human astrocytes, but a comprehensive molecular characterization that confirms the validity of this cellular system is still missing. Here we used an unbiased transcriptomic analysis to characterize in vitro culture of human NPCs and to define the gene expression programs activated during the differentiation of these cells into astrocytes using FBS or the combination of CNTF and BMP4. Our results demonstrate that in vitro cultures of human NPCs isolated during the gliogenic phase of neurodevelopment mainly consist of radial glial cells (RGCs) and glia‐restricted progenitor cells. In these cells the combination of CNTF and BMP4 activates the JAK/STAT and SMAD signaling cascades, leading to the inhibition of oligodendrocytes lineage commitment and activation of astrocytes differentiation. On the other hand, FBS‐derived astrocytes have properties of reactive astrocytes. Our work suggests that in vitro culture of human NPCs represents a valuable cellular system to study human disorders characterized by impairment of astrocytes development and function. Our datasets represent an important resource for researchers studying human astrocytes development and might set the basis for the discovery of novel human‐specific astrocyte markers.
Virally delivered, constitutively active NFκB improves survival of injured retinal ganglion cells
Authors: Dvoriantchikova Galina , Pappas Steve , Luo Xueting , Ribeiro Marcio , Danek Dagmara , Pelaez Daniel , Park Kevin K. , Ivanov Dmitry 
Published: August 2016

AbstractAs axon damage and retinal ganglion cell (RGC) loss lead to blindness, therapies that increase RGC survival and axon regrowth have direct clinical relevance. Given that NFκB signaling is critical for neuronal survival and may regulate neurite growth, we investigated the therapeutic potential of NFκB signaling in RGC survival and axon regeneration. Although both NFκB subunits (p65 and p50) are present in RGCs, p65 exists in an inactive (unphosphorylated) state when RGCs are subjected to neurotoxic conditions. In this study, we used a phosphomimetic approach to generate DNA coding for an activated (phosphorylated) p65 (p65mut), then employed an adeno‐associated virus serotype 2 (AAV2) to deliver the DNA into RGCs. We tested whether constitutive p65mut expression prevents death and facilitates neurite outgrowth in RGCs subjected to transient retinal ischemia or optic nerve crush (ONC), two models of neurotoxicity. Our data indicate that RGCs treated with AAV2‐p65mut displayed a significant increase in survival compared to controls in ONC model (77 ± 7% vs. 25 ± 3%, P‐value = 0.0001). We also found protective effect of modified p65 in RGCs of ischemic retinas (55 ± 12% vs. 35 ± 6%), but not to a statistically significant degree (P‐value = 0.14). We did not detect a difference in axon regeneration between experimental and control animals after ONC. These findings suggest that increased NFκB signaling in RGCs attenuates retinal damage in animal models of neurodegeneration, but insignificantly impacts axon regeneration.
Modulation of physiological mirror activity with transcranial direct current stimulation over dorsal premotor cortex
Authors: Beaulé Vincent , Tremblay Sara , Lafleur Louis‐Philippe , Ferland Marie C. , Lepage Jean‐François , Théoret Hugo 
Published: August 2016

AbstractHumans have a natural tendency towards symmetrical movements, which rely on a distributed cortical network that allows for complex unimanual movements. Studies on healthy humans using rTMS have shown that disruption of this network, and particularly the dorsal premotor cortex (dPMC), can result in increased physiological mirror movements. The aim of the present set of experiments was to further investigate the role of dPMC in restricting motor output to the contralateral hand and determine whether physiological mirror movements could be decreased in healthy individuals. Physiological mirror movements were assessed before and after transcranial direct current stimulation (tDCS) over right and left dPMC in three conditions: bilateral, unilateral left and unilateral right stimulation. Mirror EMG activity was assessed immediately before, 0, 10 and 20 min after tDCS. Results show that physiological mirroring increased significantly in the hand ipsilateral to cathodal stimulation during bilateral stimulation of the dPMC, 10 and 20 min after stimulation compared to baseline. There was no significant modulation of physiological mirroring in the hand ipsilateral to anodal stimulation in the bilateral condition or following unilateral anodal or unilateral cathodal stimulation. The present data further implicate the dPMC in the control of unimanual hand movements and show that physiological mirroring can be increased but not decreased with dPMC tDCS.
Hippocampal malrotation is an anatomic variant and has no clinical significance in MRI‐negative temporal lobe epilepsy
Authors: Tsai Meng‐Han , Vaughan David N. , Perchyonok Yuliya , Fitt Greg J. , Scheffer Ingrid E. , Berkovic Samuel F. , Jackson Graeme D. 
Published: August 2016

SummaryObjectiveThere is considerable difficulty in diagnosing hippocampal malrotation (HIMAL), with different criteria of variable reliability. Here we assess qualitative and quantitative criteria in HIMAL diagnosis and explore the role of HIMAL in magnetic resonance imaging (MRI)–negative temporal lobe epilepsy (TLE).MethodsWe studied the MRI of 155 adult patients with MRI‐negative TLE and 103 healthy volunteers, and we asked (1) what are the qualitative and quantitative features that allow a reliable diagnosis of HIMAL, (2) how common is HIMAL in a normal control population, and (3) is HIMAL congruent with the epileptogenic side in MRI‐negative TLE.ResultsWe found that the features that are most correlated with the expert diagnosis of HIMAL are hippocampal shape change with hippocampal diameter ratio > 0.8, lack of normal lateral convex margin, and a deep dominant inferior temporal sulcus (DITS) with DITS height ratio > 0.6. In a blinded analysis, a consensus diagnosis of unilateral or bilateral HIMAL was made in 25 of 103 controls (24.3% of people, 14.6% of hippocampi—14 left, six right, 10 bilateral) that did not differ from 155 lesion‐negative TLE patients where 25 had HIMAL (16.1% of patients, 11.6% of hippocampi—12 left, two right, 11 bilateral). Of the 12 with left HIMAL only, 9 had seizures arising from the left temporal lobe, whereas 3 had right‐sided seizures. Of the two with right HIMAL only, both had seizures arising from the left temporal lobe.SignificanceHIMAL is an anatomic variant commonly found in controls. HIMAL is also an incidental nonpathologic finding in adult MRI‐negative TLE and should not influence surgical decision making.