bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytochrome P450 metabolism of the post-lanosterol intermediates explains enigmas of cholesterol synthesis
Authors: Ačimovič Jure , Goyal Sandeep , Košir Rok , Goličnik Marko , Perše Martina , Belič Ales , Urlep Žiga , Guengerich F. Peter , Rozman Damjana
Published: June 2016

Cholesterol synthesis is among the oldest metabolic pathways, consisting of the Bloch and Kandutch-Russell branches. Following lanosterol, sterols of both branches are proposed to be dedicated to cholesterol. We challenge this dogma by mathematical modeling and with experimental evidence. It was not possible to explain the sterol profile of testis in cAMP responsive element modulator tau (Crem τ) knockout mice with mathematical models based on textbook pathways of cholesterol synthesis. Our model differs in the inclusion of virtual sterol metabolizing enzymes branching from the pathway. We tested the hypothesis that enzymes from the cytochrome P450 (CYP) superfamily can participate in the catalysis of non-classical reactions. We show that CYP enzymes can metabolize multiple sterols in vitro, establishing novel branching points of cholesterol synthesis. In conclusion, sterols of cholesterol synthesis can be oxidized further to metabolites not dedicated to production of cholesterol. Additionally, CYP7A1, CYP11A1, CYP27A1, and CYP46A1 are parts of a broader cholesterol synthesis network.
Human Bocavirus NS1 and NS1-70 Proteins Inhibit TNF-α-Mediated Activation of NF-κB by targeting p65
Authors: Liu Qingshi , Zhang Zhenfeng , Zheng Zhenhua , Zheng Caishang , Liu Yan , Hu Qinxue , Ke Xianliang , Wang Hanzhong
Published: June 2016

Human bocavirus (HBoV), a parvovirus, is a single-stranded DNA etiologic agent causing lower respiratory tract infections in young children worldwide. Nuclear factor kappa B (NF-κB) transcription factors play crucial roles in clearance of invading viruses through activation of many physiological processes. Previous investigation showed that HBoV infection could significantly upregulate the level of TNF-α which is a strong NF-κB stimulator. Here we investigated whether HBoV proteins modulate TNF-α–mediated activation of the NF-κB signaling pathway. We showed that HBoV NS1 and NS1-70 proteins blocked NF-κB activation in response to TNF-α. Overexpression of TNF receptor-associated factor 2 (TRAF2)-, IκB kinase alpha (IKKα)-, IκB kinase beta (IKKβ)-, constitutively active mutant of IKKβ (IKKβ SS/EE)-, or p65-induced NF-κB activation was inhibited by NS1 and NS1-70. Furthermore, NS1 and NS1-70 didn’t interfere with TNF-α-mediated IκBα phosphorylation and degradation, nor p65 nuclear translocation. Coimmunoprecipitation assays confirmed the interaction of both NS1 and NS1-70 with p65. Of note, NS1 but not NS1-70 inhibited TNF-α-mediated p65 phosphorylation at ser536. Our findings together indicate that HBoV NS1 and NS1-70 inhibit NF-κB activation. This is the first time that HBoV has been shown to inhibit NF-κB activation, revealing a potential immune-evasion mechanism that is likely important for HBoV pathogenesis.
Structural basis for autoinhibition and its relief of MOB1 in the Hippo pathway
Authors: Kim Sun-Yong , Tachioka Yuka , Mori Tomoyuki , Hakoshima Toshio
Published: June 2016

MOB1 protein is a key regulator of large tumor suppressor 1/2 (LATS1/2) kinases in the Hippo pathway. MOB1 is present in an autoinhibited form and is activated by MST1/2-mediated phosphorylation, although the precise mechanisms responsible for autoinhibition and activation are unknown due to lack of an autoinhibited MOB1 structure. Here, we report on the crystal structure of full-length MOB1B in the autoinhibited form and a complex between the MOB1B core domain and the N-terminal regulation (NTR) domain of LATS1. The structure of full-length MOB1B shows that the N-terminal extension forms a short β-strand, the SN strand, followed by a long conformationally flexible positively-charged linker and α-helix, the Switch helix, which blocks the LATS1 binding surface of MOB1B. The Switch helix is stabilized by β-sheet formation of the SN strand with the S2 strand of the MOB1 core domain. Phosphorylation of Thr12 and Thr35 residues structurally accelerates dissociation of the Switch helix from the LATS1-binding surface by the “pull-the-string” mechanism, thereby enabling LATS1 binding.
Carboxyl-Terminal Modulator Protein Positively Acts as an Oncogenic Driver in Head and Neck Squamous Cell Carcinoma via Regulating Akt phosphorylation
Authors: Chang Jae Won , Jung Seung-Nam , Kim Ju-Hee , Shim Geun-Ae , Park Hee Sung , Liu Lihua , Kim Jin Man , Park Jongsun , Koo Bon Seok
Published: June 2016

The exact regulatory mechanisms of carboxyl-terminal modulator protein (CTMP) and its downstream pathways in cancer have been controversial and are not completely understood. Here, we report a new mechanism of regulation of Akt serine/threonine kinase, one of the most important dysregulated signals in head and neck squamous cell carcinoma (HNSCC) by the CTMP pathway and its clinical implications. We find that HNSCC tumor tissues and cell lines had relatively high levels of CTMP expression. Clinical data indicate that CTMP expression was significantly associated with positive lymph node metastasis (OR = 3.8, P = 0.033) and correlated with poor prognosis in patients with HNSCC. CTMP was also positively correlated with Akt/GSK-3β phosphorylation, Snail up-regulation and E-cadherin down-regulation, which lead to increased proliferation and epithelial-to-mesenchymal transition, suggesting that CTMP expression results in enhanced tumorigenic and metastatic properties of HNSCC cells. Moreover, CTMP suppression restores sensitivity to cisplatin chemotherapy. Intriguingly, all the molecular responses to CTMP regulation are identical regardless of p53 status in HNSCC cells. We conclude that CTMP promotes Akt phosphorylation and functions as an oncogenic driver and prognostic marker in HNSCC irrespective of p53.
Distinct and developmentally regulated activity-dependent plasticity at descending glutamatergic synapses on flexor and extensor motoneurons
Authors: Lenschow Constanze , Cazalets Jean-René , Bertrand Sandrine S.
Published: June 2016

Activity-dependent synaptic plasticity (ADSP) is paramount to synaptic processing and maturation. However, identifying the ADSP capabilities of the numerous synapses converging onto spinal motoneurons (MNs) remain elusive. Using spinal cord slices from mice at two developmental stages, 1–4 and 8–12 postnatal days (P1–P4; P8–P12), we found that high-frequency stimulation of presumed reticulospinal neuron axons in the ventrolateral funiculus (VLF) induced either an NMDA receptor-dependent-long-term depression (LTD), a short-term depression (STD) or no synaptic modulation in limb MNs. Our study shows that P1–P4 cervical MNs expressed the same plasticity profiles as P8–P12 lumbar MNs rather than P1–P4 lumbar MNs indicating that ADSP expression at VLF-MN synapses is linked to the rostrocaudal development of spinal motor circuitry. Interestingly, we observed that the ADSP expressed at VLF-MN was related to the functional flexor or extensor MN subtype. Moreover, heterosynaptic plasticity was triggered in MNs by VLF axon tetanisation at neighbouring synapses not directly involved in the plasticity induction. ADSP at VLF-MN synapses specify differential integrative synaptic processing by flexor and extensor MNs and could contribute to the maturation of spinal motor circuits and developmental acquisition of weight-bearing locomotion.
Pathway Analyses Identify Novel Variants in the WNT Signaling Pathway Associated with Tuberculosis in Chinese Population
Authors: Hu Xuejiao , Zhou Juan , Chen Xuerong , Zhou Yanhong , Song Xingbo , Cai Bei , Zhang Jingya , Lu Xiaojun , Ying Binwu
Published: June 2016

Tuberculosis remains a global public health problem, and its immunopathogenesis is still poorly understood. In this study, 25 single nucleotide polymorphisms (SNPs) in the WNT pathway were evaluated in relation to tuberculosis risk in a Chinese Han discovery set, and 6 candidate susceptible SNPs were further validated in a Chinese Tibetan cohort. Luciferase reporter assay, RT-qPCR and Western blot were used to assess the functionality of the important WNT polymorphisms. Five polymorphisms were associated with tuberculosis susceptibility after Bonferroni correction: SFRP1 rs4736958, CTNNB1 rs9859392, rs9870255 and rs3864004 showed decreased tuberculosis risk; SFRP1 rs7832767 was related to an increased risk (OR = 1.81, 95% CI = 1.30–2.52, p = 0.010). Patients with TT genotype of rs4736958 and rs7832767 correlated with higher CRP concentrations (p = 0.003, <0.001, respectively). Functional assays revealed that mutant alleles of rs9859392 (G), rs9870255 (C) and rs3864004 (A) were associated with significantly decreased transcriptional activity, lower CTNNB1 mRNA expression and p-β-catenin level, which were consistent with their effects of decreasing TB risk. Our results provide evidences that WNT pathway polymorphisms influence tuberculosis susceptibility and host immune response to Mycobacterium tuberculosis, suggesting that these variations may serve as novel markers for identifying the risk of developing tuberculosis.
7-dehydrocholesterol efficiently supports Ret signaling in a mouse model of Smith-Opitz-Lemli syndrome
Authors: Gou-Fàbregas Myriam , Macià Anna , Anerillas Carlos , Vaquero Marta , Jové Mariona , Jain Sanjay , Ribera Joan , Encinas Mario
Published: June 2016

Smith-Lemli-Opitz syndrome (SLOS) is a rare disorder of cholesterol synthesis. Affected individuals exhibit growth failure, intellectual disability and a broad spectrum of developmental malformations. Among them, renal agenesis or hypoplasia, decreased innervation of the gut, and ptosis are consistent with impaired Ret signaling. Ret is a receptor tyrosine kinase that achieves full activity when recruited to lipid rafts. Mice mutant for Ret are born with no kidneys and enteric neurons, and display sympathetic nervous system defects causing ptosis. Since cholesterol is a critical component of lipid rafts, here we tested the hypothesis of whether the cause of the above malformations found in SLOS is defective Ret signaling owing to improper lipid raft composition or function. No defects consistent with decreased Ret signaling were found in newborn Dhcr7−/− mice, or in Dhcr7−/− mice lacking one copy of Ret. Although kidneys from Dhcr7−/− mice showed a mild branching defect in vitro, GDNF was able to support survival and downstream signaling of sympathetic neurons. Consistently, GFRα1 correctly partitioned to lipid rafts in brain tissue. Finally, replacement experiments demonstrated that 7-DHC efficiently supports Ret signaling in vitro. Taken together, our findings do not support a role of Ret signaling in the pathogenesis of SLOS.
Hydration Repulsion between Carbohydrate Surfaces Mediated by Temperature and Specific Ions
Authors: Chen Hsieh , Cox Jason R. , Ow Hooisweng , Shi Rena , Panagiotopoulos Athanassios Z.
Published: June 2016

Stabilizing colloids or nanoparticles in solution involves a fine balance between surface charges, steric repulsion of coating molecules and hydration forces against van der Waals attractions. At high temperature and electrolyte concentrations, the colloidal stability of suspensions usually decreases rapidly. Here, we report a new experimental and simulation discovery that the polysaccharide (dextran) coated nanoparticles show ion-specific colloidal stability at high temperature, where we observed enhanced colloidal stability of nanoparticles in CaCl2 solution but rapid nanoparticle-nanoparticle aggregation in MgCl2 solution. The microscopic mechanism was unveiled in atomistic simulations. The presence of surface bound Ca2+ ions increases the carbohydrate hydration and induces strongly polarized repulsive water structures beyond at least three hydration shells which is farther-reaching than previously assumed. We believe leveraging the binding of strongly hydrated ions to macromolecular surfaces represents a new paradigm in achieving absolute hydration and colloidal stability for a variety of materials, particularly under extreme conditions.
Future prospects of luminescent nanomaterial based security inks: from synthesis to anti-counterfeiting applications
Authors: Kumar Pawan , Singh Satbir , Gupta Bipin Kumar
Published: June 2016

The present review provides modern strategies for various kinds of luminescent nanomaterial based security inks for high end anti-counterfeiting applications.
Enantioselective sulfoxidation reaction catalyzed by a G-quadruplex DNA metalloenzyme
Authors: Cheng Mingpan , Li Yinghao , Zhou Jun , Jia Guoqing , Lu Sheng-Mei , Yang Yan , Li Can
Published: June 2016

Enantioselective sulfoxidation reaction is achieved for the first time by a human telomeric G-quadruplex DNA based biocatalyst.
Comparison of N-acetylcysteine and cysteine in their ability to replenish intracellular cysteine by a specific fluorescent probe
Authors: He Xinyuan , Wu Xiaofeng , Shi Wen , Ma Huimin
Published: June 2016

NAC can increase the intracellular Cys level more effectively than Cys as revealed by a specific fluorescent probe.
Organic photoredox catalysis for the oxidation of silicates: applications in radical synthesis and dual catalysis
Authors: Lévêque Christophe , Chenneberg Ludwig , Corcé Vincent , Ollivier Cyril , Fensterbank Louis
Published: June 2016

Metal free photooxidation of alkyl bis(catecholato)silicates with the organic dye 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyano-benzene (4CzIPN) allows the smooth formation of alkyl radicals.
A first-principles study of pressure-induced phase transformation in a rare-earth formate framework
Authors: Bhat Soumya S. , Li Wei , Cheetham Anthony K. , Waghmare Umesh V. , Ramamurty Upadrasta
Published: June 2016

The reversible pressure-induced phase transformation associated with bond rearrangement in a rare-earth formate framework was explored using first-principles calculations, which complement and help understand its experimental observations.
A first-principles study of the thermodynamic and electronic properties of Mg and MgH2nanowires
Authors: Wu Xinxing , Zhang Ruiqi , Yang Jinlong
Published: June 2016

The thermodynamic mechanism of MgH2nanowires being good hydrogen storage materials is revealed.
Substrate and cofactor binding to nitrile reductase: a mass spectrometry based study
Authors: Gjonaj Lorina , Pinkse Martijn , Fernández-Fueyo Elena , Hollmann Frank , Hanefeld Ulf
Published: June 2016

Reduction is coupled to weight gain. One nitrile group of the substrate PreQ0 couples covalently per subunit of the dimeric nitrile reductase from E. coli.
Direct synthesis of dicarbonyl PCP-iron hydride complexes and catalytic dehydrogenative borylation of styrene
Authors: Jiang Shi , Quintero-Duque Samuel , Roisnel Thierry , Dorcet Vincent , Grellier Mary , Sabo-Etienne Sylviane , Darcel Christophe , Sortais Jean-Baptiste
Published: June 2016

An efficient method based on the simple metalating reagent Fe(CO)5 leads to the synthesis of cyclometalled PCP iron carbonyl pincer complexes which are active catalytic precursors for the selective dehydrogenative borylation of styrene.
Ba-filled Ni–Sb–Sn based skutterudites with anomalously high lattice thermal conductivity
Authors: Paschinger W. , Rogl G. , Grytsiv A. , Michor H. , Heinrich P. R. , Müller H. , Puchegger S. , Klobes B. , Hermann R. P. , Reinecker M. , Eisenmenger-Sitter Ch. , Broz P. , Bauer E. , Giester G. , Zehetbauer M. , Rogl P. F.
Published: June 2016

Novel filled skutterudites BayNi4Sb12−xSnx(ymax= 0.93) have been prepared and thoroughly characterized, which show anomalously high lattice thermal conductivity.
Transition metal mediated formation of dicationic diselenides stabilised by N-heterocyclic carbenes: designed synthesis
Authors: Yadav Sangeeta , Manjare Sudesh T. , Singh Harkesh B. , Butcher Ray J.
Published: June 2016

Designed syntheses of dicationic diselenides have been developed by (i) reduction of dihaloselones (routes A and B) and (ii) by oxidation of selone adducts of metal halides (route C).
Influence of structural defects of Ge-imogolite nanotubes on their toxicity towards Pseudomonas brassicacearum
Authors: Avellan A. , Levard C. , Rose J. , Auffan M. , Bertrand M. , Olivi L. , Santaella C. , Achouak W. , Masion A.
Published: June 2016

Designing the crystallinity of Ge-imogolite nanotubes modulates toxic effects towards bacteria.
Porous carbon derived from rice husks as sustainable bioresources: insights into the role of micro-/mesoporous hierarchy in hosting active species for lithium–sulphur batteries
Authors: Rybarczyk Maria K. , Peng Hong-Jie , Tang Cheng , Lieder Marek , Zhang Qiang , Titirici Maria-Magdalena
Published: June 2016

A series of carbon materials with hierarchical micro-/mesopores from a very cheap and abundant lignocellulosic bio-waste are achieved as host materials for Li–S batteries.
A DFT study of endocyclic allenes: unprecedentedly superbasic hydrocarbons
Authors: Margetić Davor , Antol Ivana
Published: June 2016

Extremely high basicities were predicted for allenes incorporated in seven-membered rings.
AIE-caused luminescence of a thermally-responsive supramolecular organogel
Authors: Ma Xinxian , Xie Jusheng , Tang Ning , Wu Jincai
Published: June 2016

A two-stage-assembly of a supramolecular gel (B-gel) can emit brilliant blue light due to the strong AIEE effect depending on the multiple hydrogen-bonding and coordination bonds between gelator L and Cd2+.
A mechanistic study on the inhibition of α-chymotrypsin by a macrocyclic peptidomimetic aldehyde
Authors: Zhang X. , Bruning J. B. , George J. H. , Abell A. D.
Published: June 2016

NMR and X-ray crystallography reveals covalent attachment of the macrocyclic aldehyde to serine195 of α-chymotrypsin and that its backbone binds as a β-strand.
Intramolecular olefin metathesis as a robust tool to synthesize single-chain nanoparticles in a size-controlled manner
Authors: Watanabe Kodai , Tanaka Ryoto , Takada Kenji , Kim Myung-Jin , Lee Jae-Suk , Tajima Kenji , Isono Takuya , Satoh Toshifumi
Published: June 2016

A comprehensive investigation of ruthenium-catalyzed intramolecular olefin metathesis was conducted for establishing a general approach to synthesize size-controlled SCNPs.
Heterostructure consists of monolayer MoS2 and arsenene with novel electronic and optical conductivity
Authors: Su Jie , Feng Liping , Liu Zhengtang
Published: June 2016

The carrier effective masses and optical conductivity of As–MoS2 heterostructures with different geometries are presented using the density functional theory.
Template synthesis of metal tungsten nanowire bundles with high field electron emission performance
Authors: Liu Yong , Lan Kun , Es-Saheb Mahir H. , Elzatahry Ahmed A. , Zhao Dongyuan
Published: June 2016

A H2 reduction-assisted hard-templating approach is demonstrated to synthesize metallic W nanowire bundles. The W nanowire bundles show a low turn-on field of 4.1 V μm−1, a high field enhancement factor up to 3563 and good field emission stability.
Room-temperature phosphorescence probe based on Mn-doped ZnS quantum dots for the sensitive and selective detection of selenite
Authors: Chen Jialing , Zhu Yaxian , Zhang Yong
Published: June 2016

Selenite was selectively and sensitively detected based on the room-temperature phosphorescence quenching of Mn–ZnS QDs caused by HSe− from the reaction of selenite and glutathione.
The effect of NiO on the conductivity of BaZr0.5Ce0.3Y0.2O3−δ based electrolytes
Authors: Bu Junfu , Jönsson Pär Göran , Zhao Zhe
Published: June 2016

1 wt% NiO was added by different methods for preparing dense BZCY532 based electrolytes. Dense BZCY(Ni)532 and BZCY532 ceramics showed no electronic conduction at 600 °C, while dense BZCY532(Ni) ceramics revealed an obvious electronic conduction.
TPD-based polythiophene derivatives with higher Vocfor polymer solar cells
Authors: Wang Kun , Xu Zhuo , Guo Bing , Guo Xia , Zhang Maojie , Li Yongfang
Published: June 2016

A new D–A copolymer photovoltaic donor material,PTPD-DFDT, with a simpler structure and easier synthesis, was synthesized, and the PSCs based onPTPD-DFDT/PC71BM demonstrate a higherVocof 0.96 V and a PCE of 5.52%.
Design of a nanoporous interfacial SiO2layer in polysiloxane–graphene oxide nanocomposites for efficient stress transmission
Authors: Wang Hualan , Wu Jirong , Gong Kai , Hao Qingli , Wang Xin , Jiang Jianxiong , Li Zhifang , Lai Guoqiao
Published: June 2016

The formation process of nanoporous surface of GEOS (left), the enhanced mechanical performance for PDMS-OH (right). Nanoporous interfacial layer SiO2is an important contributing factor for enhanced stress transmission between GEO and polysiloxane.
Synthesis and optoelectronic investigations of triarylamines based on naphtho[2,3-f]quinoxaline-7,12-dione core as donor–acceptors for n-type materials
Authors: Shaikh Azam M. , Sharma Bharat K. , Chacko Sajeev , Kamble Rajesh M.
Published: June 2016

We have synthesized a new series of fully characterized donor–acceptor systems (2–7) involving electron donor triarylamines and electron acceptor naphtho[2,3-f]quinoxaline-7,12-dione by employing palladium catalyzed C–N bond forming amination reactions in good yields.
Copper and triphenylphosphine-promoted sulfenylation of quinones with arylsulfonyl chlorides
Authors: Yu Xiaoli , Wu Qiujin , Wan Huida , Xu Zhaojun , Xu Xingle , Wang Dawei
Published: June 2016

The copper and triphenylphosphine-promoted sulfenylation of quinones with arylsulfonyl chlorides has been developed under mild conditions with moderate to good yields. This is the first time to prepare arylthioquinones with arylsulfonyl chlorides.
Non-invasive monitoring of the osteogenic differentiation of human mesenchymal stem cells on a polycaprolactone scaffold using Raman imaging
Authors: Gao Yu , Xu Chenjie , Wang Lianhui
Published: June 2016

Raman imaging allows the non-invasive and label-free monitoring of the preferred osteogenic differentiation of human mesenchymal stem cells on the polycaprolactone scaffolds.
Solder-reflow resistant solid-state micro-supercapacitors based on ionogels
Authors: Brachet Mylène , Gaboriau Dorian , Gentile Pascal , Fantini Sébastien , Bidan Gérard , Sadki Saïd , Brousse Thierry , Le Bideau Jean
Published: June 2016

All-solid-state micro-supercapacitors with silicon nanowire electrodes and ionogel thin film electrolyte showed improved frequency response and a sustained solder reflow process.
Effective conjugation in conjugated polymers with strongly twisted backbones: a case study on fluorinated MEHPPV
Authors: Milad Rim , Shi Junqing , Aguirre Aranzazu , Cardone Antonio , Milián-Medina Begoña , Farinola Gianluca M. , Abderrabba Manef , Gierschner Johannes
Published: June 2016

Strongly twisted conjugated polymers demand a redefinition of the ‘effective conjugation length’, extracted here graphically by a facile method.
Calibration of pipeline ADC with pruned Volterra kernels
Authors: Centurelli F. , Monsurrò P. , Rosato F. , Ruscio D. , Trifiletti A.
Published: June 2016

A Volterra model is used to calibrate a pipeline ADC simulated in Cadence Virtuoso using the STMicroelectronics CMOS 45 nm process. The ADC was designed to work at 50 MSps, but it is simulated at up to 125 MSps, proving that calibration using a Volterra model can significantly increase sampling frequency. Equivalent number of bits (ENOB) improves by 1–2.5 bits (6–15 dB) with 37–101 model parameters. The complexity of the calibration algorithm is reduced using different lengths for each Volterra kernels and performing iterative pruning. System identification is performed by least squares techniques with a set of sinusoids at different frequencies spanning the whole Nyquist band. A comparison with simplified Volterra models proposed in the literature shows better performance for the pruned Volterra model with comparable complexity, improving linearity by as much as 1.5 bits more than the other techniques.
Reconstruction of a Combined Maxillectomy and Segmental Mandibulectomy Defect in a Seven-Year-Old with a Single Free Fibula Osteocutaneous Flap
Authors: Joseph Shawn T. , Thankappan Krishnakumar , Iyer Subramania
Published: June 2016

Combined upper alveolectomy and segmental mandibulectomy are complex defects. Reconstruction of these defects is usually suboptimal. We describe the case of a pediatric patient with vessel-depleted neck with recurrent vascular malformation involving the ramus and coronoid process of mandible and a previous history of maxillectomy and a reconstruction with anterolateral thigh flap. The patient underwent wide resection. The defects involving the upper alveolus and mandible were simultaneously reconstructed with a single free fibula flap.
Changes in habitat use and distribution of mouflon in the Kahuku Unit of Hawai‘i Volcanoes National Park
Authors: Palupe Bronson , Leopold Christina R. , Hess Steven C. , Faford Jonathan K. , Pacheco Dexter , Judge Seth W.
Published: June 2016

European mouflon sheep (Ovis gmelini musimon) were introduced to Kahuku Ranch on Hawai‘i Island in 1968 and 1974 for trophy hunting and have been detrimental to the native ecosystem by trampling, bark stripping, and browsing vegetation. In 2003, Hawai‘i Volcanoes National Park acquired Kahuku Ranch and managers began removing mouflon. The objective of this project was to determine whether hunting has changed the distribution of mouflon in Kahuku, to better understand mouflon behaviour and to expedite eradication efforts. Locations from hunting and GPS telemetry data during 2007–14 were used to determine the effect of hunting on mouflon distribution by examining distance to roads and habitat use. Mouflon seemed to avoid roads after hunting pressure increased and their distribution within vegetation types changed over time. Mouflon without hunting pressure were detected in native shrub habitat in 68% of all observations. Hunted mouflon were encountered less in native shrub habitat and more in other habitats including open forest, closed forest, and areas with no vegetation. These changes suggest that hunting has influenced the distribution of mouflon over time away from native shrub and into other vegetation types where they may be more difficult to control.
Natural Habitat Conditions in a Captive Environment Lead to Spawning of Spotted Gar
Authors: Frenette Bryan D. , Snow Richard
Published: June 2016

Gars are often spawned by means of hormone injection for aquaculture purposes, but unassisted captive spawning is less common. In May of 2014, Spotted Gars Lepisosteus oculatus spawned while being held in a large research pond at the University of Oklahoma's Aquatic Research Facility. Holding conditions were similar to natural conditions required for these fish to reproduce, and viable offspring were produced. The Spotted Gar is a species of conservation concern at the periphery of its range and can benefit from studies describing aspects of its biology. This description of captive gar spawning may have important implications for both aquaculture and restoration efforts.

Received October 28, 2015; accepted March 8, 2016 Published online June 22, 2016
Dualising activation. Responses to unemployment and mental health-related disability retirement in Finland at the turn of the millennium
Authors: Alanko Anna , Outinen Sami
Published: June 2016

‘Activation’, referring to measures that increase the labour supply, has recently been a key concept in discussing employment in the developed countries. This paper analyses the motivations behind activation measures targeted at the unemployed as well as persons disabled due to mental health problems, as expressed through legislation and national policy documents following the 1990s recession in Finland. The analysis points out that the activation measures implemented in Finland at the turn of the millennium have had a tendency to reinforce ‘dualisation’, that is, to polarise citizens as either labour market insiders or outsiders. The analysis shows that activation also involves labels that fix blame on the people themselves for their situation. Hence, the activation measures have increased the risk of exclusion for many of the persons they were supposed to help. The results are discussed in the context of the broader literature on the Nordic welfare and labour market model.
A novel chromosome segregation mechanism during female meiosis
Authors: McNally Karen Perry , Panzica Michelle T. , Kim Taekyung , Cortes Daniel B. , McNally Francis J.
Published: June 2016

In a wide range of eukaryotes, chromosome segregation occurs through anaphase A, in which chromosomes move toward stationary spindle poles, anaphase B, in which chromosomes move at the same velocity as outwardly moving spindle poles, or both. In contrast, Caenorhabditis elegans female meiotic spindles initially shorten in the pole-to-pole axis such that spindle poles contact the outer kinetochore before the start of anaphase chromosome separation. Once the spindle pole-to-kinetochore contact has been made, the homologues of a 4-μm-long bivalent begin to separate. The spindle shortens an additional 0.5 μm until the chromosomes are embedded in the spindle poles. Chromosomes then separate at the same velocity as the spindle poles in an anaphase B–like movement. We conclude that the majority of meiotic chromosome movement is caused by shortening of the spindle to bring poles in contact with the chromosomes, followed by separation of chromosome-bound poles by outward sliding.
Integrative review of clinical decision support for registered nurses in acute care settings
Authors: Dunn Lopez Karen , Gephart Sheila M , Raszewski Rebecca , Sousa Vanessa , Shehorn Lauren E , Abraham Joanna
Published: June 2016

Objective: To report on the state of the science of clinical decision support (CDS) for hospital bedside nurses.

Materials and Methods: We performed an integrative review of qualitative and quantitative peer-reviewed original research studies using a structured search of PubMed, Embase, Cumulative Index to Nursing and Applied Health Literature (CINAHL), Scopus, Web of Science, and IEEE Xplore (Institute of Electrical and Electronics Engineers Xplore Digital Library). We included articles that reported on CDS targeting bedside nurses and excluded in stages based on rules for titles, abstracts, and full articles. We extracted research design and methods, CDS purpose, electronic health record integration, usability, and process and patient outcomes.

Results: Our search yielded 3157 articles. After removing duplicates and applying exclusion rules, 28 articles met the inclusion criteria. The majority of studies were single-site, descriptive or qualitative (43%) or quasi-experimental (36%). There was only 1 randomized controlled trial. The purpose of most CDS was to support diagnostic decision-making (36%), guideline adherence (32%), medication management (29%), and situational awareness (25%). All the studies that included process outcomes (7) and usability outcomes (4) and also had analytic procedures to detect changes in outcomes demonstrated statistically significant improvements. Three of 4 studies that included patient outcomes and also had analytic procedures to detect change showed statistically significant improvements. No negative effects of CDS were found on process, usability, or patient outcomes.

Discussion and Conclusions: Clinical support systems targeting bedside nurses have positive effects on outcomes and hold promise for improving care quality; however, this research is lagging behind studies of CDS targeting medical decision-making in both volume and level of evidence.
Significant Differences Between Local Reporting and Central Assessment of Radiographic Complications in a Prospective, Multicenter Study About Locking Plate Fixation of Proximal Humerus Fractures
Authors: Kathrein Susanne , Joeris Alexander , Kralinger Franz , Blauth Michael , Goldhahn Joerg
Published: June 2016

Objectives:

To compare reporting outcomes of radiographic complications conducted by an independent review board and the responsible on-site study personnel in a multicenter study about locking plate fixation of proximal humeral fractures.

Design:

Prospective, multicenter study; setting: 9 level I trauma centers.

Patients:

One hundred fifty patients (age 50–90) with a radiographically confirmed displaced proximal humeral fracture fixed with a locking plate were included in the study.

Intervention:

All radiographic data were reevaluated by an independent review board according to predefined criteria.

Main Outcome Measurements:

Differences in outcomes between the review board and the on-site assessment were analyzed with a paired t test. Interrater agreements between the central review board and on-site assessments were estimated by means of kappa statistics.

Results:

The review board revealed significantly more radiographic complications than the on-site assessment (P = 0.006), except for the complication “head necrosis.” The interrater agreement was slight to moderate in all calculated categories.

Conclusions:

Implementation of a complication review board using predefined criteria is recommended for clinical studies to prevent underreporting of radiographic complications by on-site assessment.
Three point fixation of pediatric proximal humerus fractures by prebent wave-shaped wires: technical notes
Authors: Stahl Ido , Eidelman Mark
Published: June 2016

Pediatric proximal humerus fractures are uncommon and mostly treated conservatively. However, surgical treatment should be considered in displaced fractures classified as Neer–Horowitz grade III–IV in children older than 11 years. We describe a three-point fixation method of applying two Kirschner wires, prebent into a wave shape, and inserted into the proximal humerus through a single cortical hole. In this minimally invasive approach, we treated four boys, obtaining accurate reduction and stable fixation, with all patients starting pendulous exercises the day after surgery. At follow-up, all patients had regained full shoulder range of motion, with no residual pain and no complications recorded.
Whole-body vibration improves neuromuscular parameters and functional capacity in osteopenic postmenopausal women
Authors: Dutra Milena C. , de Oliveira Mônica L. , Marin Rosangela V. , Kleine Hellen C.R. , Silva Orivaldo L. , Lazaretti-Castro Marise
Published: June 2016

Objective:

In this longitudinal, paired-control study, we developed special vibration platforms to evaluate the effects of low-intensity vibration on neuromuscular function and functional capacity in osteopenic postmenopausal women.

Methods:

Women in the platform group (PG; n = 62) stood still and barefoot on the platform for 20 minutes, 5 times a week for 12 months. Each platform vibrated with a frequency of 60 Hz, intensity of 0.6g, and amplitude of less than 1 mm. Women in the control group (CG; n = 60) were followed up and instructed not to modify their physical activity during the study. Every 3 months all volunteers were invited to a visit to check for any change in their lifestyle. Assessments were performed at baseline and at 12 months, and included isometric muscle strength in the hip flexors and back extensors, right handgrip strength, dynamic upper limb strength (arm curl test), upper trunk flexibility (reach test [RT]), mobility (timed up and go test), and static balance (unipedal stance test). Statistical analyses were performed using the intention-to-treat strategy.

Results:

Both groups were similar for all variables at baseline. At the end of intervention, the PG was significantly better than CG in all parameters but in the RT. When compared with baseline, after 12 months of vibration the PG presented statistically significant improvements in isometric and dynamic muscle strength in the hip flexors (+36.7%), back extensors (+36.5%), handgrip strength (+4.4%), arm curl test (+22.8%), RT (+9.9%), unipedal stance test (+6.8%), and timed up and go test (−9.2%), whereas the CG showed no significant differences during the same period of time. As such, there were no side effects related to the study procedures during the 12 months of intervention.

Conclusions:

Low-intensity vibration improved balance, motility, and muscle strength in the upper and lower limbs in postmenopausal women.
Orbital Recurrence of Ethmoid Sinus Malignant Meningioma: Case Study and Literature Review
Authors: Neems Leslie , Christopher Chambers
Published: June 2016

The authors describe a case of a recurrent World Health Organization grade III extradural, sinonasal meningioma that presented with epiphoria. Primary extradural meningiomas are rare, comprising only 1% to 2% of all meningiomas.
1
These tumors are diagnosed and graded histologically according to the World Health Organization criteria.
2
Grade III tumors are very malignant with high recurrence and death rates.
3
This case highlights the rarity of sinonasal tract meningiomas involving the orbit. In addition, it shows the poor prognosis of such malignant disease and the need for a multidisciplinary approach. Collection and evaluation of protected patient health information for this report was in compliance with the Health Insurance Portability and Accountability Act and approved by the Institutional Review Board of Northwestern University Feinberg School of Medicine. Research adhered to the tenets of the Declaration of Helsinki.
Three-dimensional printing and pediatric liver disease
Authors: Alkhouri Naim , Zein Nizar N.
Published: June 2016

Purpose of review

Enthusiastic physicians and medical researchers are investigating the role of three-dimensional printing in medicine. The purpose of the current review is to provide a concise summary of the role of three-dimensional printing technology as it relates to the field of pediatric hepatology and liver transplantation.

Recent findings

Our group and others have recently demonstrated the feasibility of printing three-dimensional livers with identical anatomical and geometrical landmarks to the native liver to facilitate presurgical planning of complex liver surgeries. Medical educators are exploring the use of three-dimensional printed organs in anatomy classes and surgical residencies. Moreover, mini-livers are being developed by regenerative medicine scientist as a way to test new drugs and, eventually, whole livers will be grown in the laboratory to replace organs with end-stage disease solving the organ shortage problem.

From presurgical planning to medical education to ultimately the bioprinting of whole organs for transplantation, three-dimensional printing will change medicine as we know in the next few years.
Evaluation of a Computer Application for Retrospective Detection of Vitamin K Antagonist Treatment Imbalance
Authors: Ferret Laurie , Luyckx Michel , Ficheur Grégoire , Chazard Emmanuel , Beuscart Régis
Published: June 2016

Objective

Management of vitamin K antagonists (VKAs) is difficult, and overdoses can have dramatic hemorrhagic consequences. The adverse drug event (ADE) scorecards is a tool intended for the detection and description of adverse drug reaction/ADE developed during a European computerized medical data processing project. It is used in a quality assurance process. Our objective was to evaluate the performance of the ADE scorecards in the detection of the contributing factors for VKA overdoses, among the cases where a VKA overdose is observed.

Methods

Twenty-eight rules allow the detection of VKA treatment overdose related to drug or a clinical situation. They were applied on 14,748 electronic medical records from a community hospital. Among 582 records including a VKA prescription, 59 cases of VKA overdoses (international normalized ratio ≥ 5) during the hospital stay have been identified. The ADE scorecards detected 49 of them. We evaluated the positive predictive value and sensitivity of these rules, by an expert review of the cases.

Results

The expert review confirmed the contribution of a detected risk factor to the VKA overdose in 11 cases. Therefore, the precision of the rules is 22.4%. The sensitivity is 84.6%. The risk factors were mainly infection and amiodarone introduction. The 4 cases of clinical injury related to a drug were properly designated by the rules.

Conclusions

Our study shows the great potential of the ADE scorecards for detecting cofactors of VKA overdoses and gives an argument to include complex rules in the knowledge bases used for the detection and identification of ADEs in large medical databases.
Frequency of Passive EHR Alerts in the ICU: Another Form of Alert Fatigue?
Authors: Kizzier-Carnahan Vanessa , Artis Kathryn A. , Mohan Vishnu , Gold Jeffrey A.
Published: June 2016

Objectives

The intensive care unit (ICU) is a complex environment in terms of data density and alerts, with alert fatigue, a recognized barrier to patient safety. The Electronic Health Record (EHR) is a major source of these alerts. Although studies have looked at the incidence and impact of active EHR alerts, little research has studied the impact of passive data alerts on patient safety.

Method

We reviewed the EHR database of 100 consecutive ICU patient records; within, we assessed the number of values flagged as either as abnormal or “panic” across all data domains. We used data from our previous studies to determine the 10 most commonly visited screens while preparing for rounds to determine the total number of times, an abnormal value would be expected to be viewed.

Results

There were 64.1 passive alerts/patient per day, of which only 4.5% were panic values. When accounting for the commonly used EHR screens by providers, this was increased to 165.3 patient/d. Laboratory values comprised 71% of alerts, with the remaining occurring in vitals (25%) and medications (6%). Despite the high prevalence of alerts, certain domains including ventilator settings (0.04 flags/d) were rarely flagged.

Conclusions

The average ICU patient generates a large number of passive alerts daily, many of which may be clinically irrelevant. Issues with EHR design and use likely further magnify this problem. Our results establish the need for additional studies to understand how a high burden of passive alerts impact clinical decision making and how to design passive alerts to optimize their clinical utility.
Perceptions of the PrePex Device Among Men Who Received or Refused PrePex Circumcision and People Accompanying Them
Authors: Milovanovic Minja , Taruberekera Noah , Martinson Neil , Lebina Limakatso
Published: June 2016

Background:

The PrePex medical male circumcision (MMC) device has been approved for MMC scale-up. However, the WHO has recommended that a country-specific situation analysis should be carried out before MMC device rollout.

Method:

A cross-sectional survey was conducted over 12 months in 3 MMC clinics, by trained nurses and researchers, to ascertain attitudes toward PrePex MMC in 3 groups: men consenting for PrePex MMC (PrePex recipients), people accompanying men, and adolescents coming for either PrePex or surgical circumcision (MMC escorts) and men refusing the PrePex device MMC (PrePex rejecters). All participants received information on surgical and the PrePex device MMC methods.

Results:

A total of 312 PrePex recipients, 117 MMC escorts, and 21 PrePex rejecters were recruited into the study. Ninety-nine percent of PrePex recipients thought that their expectations (safe, convenient, minimal pain) were met, and they were pleased with cosmetic outcome. Fifty-nine percent of PrePex rejecters opted for surgical circumcision because they perceived PrePex to be novel and risky. All 3 groups of participants were concerned about odor, dead skin, discomfort, healing time, and wound care. Ninety-eight percent of MMC escorts, 99% of PrePex recipient, and 81% of PrePex rejecters perceived PrePex circumcision as an acceptable option for South African MMC programmes.

Conclusions:

This acceptability study suggests that PrePex MMC is considered safe and convenient and could be incorporated into existing MMC programmes. Concerns about odor, pain, wound care, and healing time suggest that the need for more research to further optimize methods and that MMC clients should be counseled on available methods to enable them to choose among options based on their preferences.
Delivering PrePex Medical Male Circumcision Services Through a Mobile Clinic: The Experience From a Pilot Project in North West Province, South Africa
Authors: Kufa Tendesayi , Chetty-Makkan Candice , Maraisane Mpho , Charalambous Salome , Chihota Violet , Toledo Carlos
Published: June 2016

We describe the implementation of a pilot project to demonstrate the safety and feasibility of providing PrePex circumcision from a mobile clinic. We analyzed available project diary entries and staff meeting minutes to identify challenges encountered. The main challenges identified were (1) daily time constraints because of setting up procedures, (2) transportation logistics for clients when the mobile clinic had moved to a different location, (3) integration and coordination of staff responsibilities, and (4) recruitment for PrePex services in the mobile clinic. The provision of PrePex device circumcision through a mobile clinic was feasible but careful planning and review of operational procedures were needed to resolve the implementation challenges.
Transdermal Rivastigmine Delivery for Alzheimer Disease: Amenability of Exposure Predictions of Rivastigmine and Metabolite, NAP226-90, by Linear Regression Model Using Limited Samples
Authors: Srinivas Nuggehally R.
Published: June 2016

Purpose

Although an optimized delivery of rivastigmine for management of Alzhiemer disease (AD) is provided by the transdermal patch, it is critical to establish a limited sampling strategy for the measurement of exposure of rivastigmine/NAP226-90.

Methods

The relationship Cmax versus AUC0–24h for rivastigmine/NAP226-90 was established by regression models. The derived regression equations enabled the prediction AUC0–24h for rivastigmine and NAP226-90. Models were evaluated using statistical criteria. Mixed model was used to predict AUC0–24h for rivastigmine/NAP226-90 from time points such as 8 (C8h), 12 (C12h), and 18 (C18h) hours.

Results

Excellent correlation was established for between Cmax and AUC0–24h for rivastigmine and NAP226-90. AUC0–24h predictions of either rivastigmine or NAP226-90 were within 0.8- to 1.25-fold difference. The RMSE in the AUC0–24h predictions ranged from 17.6% to 21.9%, and the R
2 for prediction were greater than 0.96 for both rivastigmine and NAP226-90. Use of mixed model for C8h, C12h, and C18h resulted in AUC0–24h within 1.5-fold difference for rivastigmine or NAP226-90.

Conclusions

Cmax of rivastigmine and NAP226-90 was highly correlated with the corresponding AUC0–24h values confirming the role of a time point closer to Cmax for an effective AUC measurement of rivastigmine or the metabolite.
Improvement in Symptoms of Autism Spectrum Disorder in Children With the Use of Gastrin-Releasing Peptide: An Open Trial
Authors: Becker Michele Michelin , Riesgo Rudimar S. , Roesler Rafael , Bosa Cleonice , Ohlweiler Lygia , Backes Bárbara , Endres Renata G. , Zanon Regina B. , Marchezan Josemar , Schwartsmann Gilberto
Published: June 2016

Objectives

The aim of this study was to determine the efficacy and tolerability of gastrin-releasing peptide (GRP) for core symptoms of autism spectrum disorder.

Methods

This is a prospective, open-label study with 160 pmol/kg of GRP tested in 10 children with autism. Outcome measures used were the Clinical Global Impressions-Improvement Scale, Aberrant Behavior Checklist (ABC), Childhood Autism Rating Scale, and Autism Diagnostic Interview-Revised. Positive response was defined as a score of 1 (very much improved) or 2 (much improved) on the Clinical Global Impressions-Improvement Scale and an improvement of 25% or greater on at least 1 subscale of ABC.

Results

Six (60%) of the 10 subjects responded to GRP. Improvements were observed on the ABC irritability and hyperactivity subscales in 80% of patients, and 70% exhibited improvement on the social withdrawal subscale. On the Childhood Autism Rating Scale, there was a mean reduction of 4 points (4.3 ± 2.9). Analysis of the Autism Diagnostic Interview-Revised results detected significant improvements in the domain that assesses social interaction, with a mean reduction of 2.4 points (2.4 ± 2.83). Adverse effects occurred in 3 patients.

Conclusions

Gastrin-releasing peptide was safe and well tolerated by most subjects and may be effective for core symptoms of autism.