bluuebunny/crossref_metadata_2025 huggingface dataset:
Lyophilization of Bdellovibrio bacteriovorus 109J for Long‐Term Storage
Authors: Boileau Mélanie J. , Mani Rinosh , Clinkenbeard Kenneth D.
Published: May 2017

Bdellovibrio bacteriovorus 109J is a Gram‐negative predatory bacterium with obligate host dependency on other Gram‐negative bacteria. This bacteriolytic predator collides with, enters, and establishes growth within the prey (host) periplasm, eventually lysing the prey cell wall to release fresh, motile B. bacteriovorus progeny. Laboratory maintenance of B. bacteriovorus has been previously described by other investigators. The protocols included in this unit deal with the technique required to lyophilize or freeze dry host‐dependent B. bacteriovorus. This is an alternative means to frozen glycerol stocks for the long‐term storage of B. bacteriovorus. It includes the cultivation process and methods to lyophilize B. bacteriovorus as well as recommended storage conditions. In addition, this unit provides insight on the formulation's shelf‐life including the time to active culture after reviving lyophilized stocks of B. bacteriovorus following short‐, medium‐, and long‐term storage. © 2017 by John Wiley & Sons, Inc.
Human Umbilical Cord Mesenchymal Stromal Cell Isolation, Expansion, Cryopreservation, and Characterization
Authors: Smith J. Robert , Cromer Adrienne , Weiss Mark L.
Published: May 2017

Revised methods to derive, expand, and characterize mesenchymal stromal cells (MSCs) from the umbilical cord are provided. Several considerations are taken for GMP compliance including using a closed system isolation method and eliminating several xenogenic components. With this method cells are isolated using mechanical and enzymatic digestion and then expanded with high viabilities that retain >90% viability after cryopreservation. Lastly, characterization methods have been optimized to identify these cells as MSCs according to the ISCT minimal criteria. This method standardizes the process for isolating, expanding, cryopreserving, and characterizing MSCs from the umbilical cord. © 2017 by John Wiley & Sons, Inc.
Reactive Precipitation of Anhydrous Alkali Sulfide Nanocrystals with Concomitant Abatement of Hydrogen Sulfide and Cogeneration of Hydrogen
Authors: Li Xuemin , Zhao Yangzhi , Brennan Alice , McCeig Miranda , Wolden Colin A , Yang Yongan
Published: May 2017

Anhydrous alkali sulfide (M2S, M=Li or Na) nanocrystals (NCs) are important materials central to the development of next generation cathodes and solid‐state electrolytes for advanced batteries, but not commercially available at present. This work reports an innovative method to directly synthesize M2S NCs through alcohol‐mediated reactions between alkali metals and hydrogen sulfide (H2S). In the first step, the alkali metal is complexed with alcohol in solution, forming metal alkoxide (ROM) and releasing hydrogen (H2). Next, H2S is bubbled through the ROM solution, where both chemicals are completely consumed to produce phase‐pure M2S NC precipitates and regenerate alcohol that can be recycled. The M2S NCs morphology may be tuned through the choice of the alcohol and solvent. Both synthetic steps are thermodynamically favorable (ΔGmo<−100 kJ mol−1), proceeding rapidly to completion at ambient temperature with almost 100 % atom efficiency. The net result, H2S+2 m→M2S+H2, makes good use of a hazardous chemical (H2S) and delivers two value‐added products that naturally phase separate for easy recovery. This scalable approach provides an energy‐efficient and environmentally benign solution to the production of nanostructured materials required in emerging battery technologies.
Accelerated precomputation points–based scalar reduction on elliptic curve cryptography for wireless sensor networks
Authors: Faye Youssou , Guyennet Hervé , Yanbo Shou , Niang Ibrahima
Published: May 2017

Sensor devices are limited resource power and energy, thus providing security services for sensor networks is very difficult. Elliptic curve cryptography (ECC) is one of the most famous asymmetric cryptographic schemes, which offers the same level of security with much shorter keys compared to the other widely used asymmetric cryptographic algorithm, RSA (Rivest, Shamir, and Adleman). In ECC, the main and most‐heavily used operation is the scalar multiplication kP, where the scalar value k is a private integer and must be secured. In this work, we present a new approach to accelerate the main scalar multiplication on ECC over prime fields for sensor networks. This approach uses an equivalent representation of points and can act as a support for existing schemes in a selected interval. The simulation results showed that the proposed technique increases the efficiency of the computation time. For example, on this scalar multiplication, we obtain a gain of 4 bits in 161 bits for 6.25% of the scalars. This gain can sometimes reach 100% in some cases. After this significant reduction of the scalar k, we present a fast precomputation algorithm in a distributed scalar multiplication on kP to avoid storage of precomputation points, which requires extra memory.
Detection of cytological changes in oral mucosa among users of smokeless tobacco (shamma) in the KSA
Authors: Brima Eid I.
Published: May 2017

Background and aim

Smokeless tobacco (ST) use is a major cause of cytological changes in the oral mucosa. ST products, such as shamma, which is prevalent in southern Saudi Arabia, raise concerns about the adverse health effects among its users. We evaluated the cytological changes in the oral mucosa of users and nonusers of shamma in the city of Najran, using Papanicolaou staining.

Materials and methods

We designed questionnaires and consent forms for this study that were administered to a total of 397 participants, comprising 250 nonusers of shamma (controls) and 147 shamma users (cases). Buccal cell smears were collected from all participants, fixed, and Papanicolaou stained. Photomicrographs were taken of all stained smears, and samples were subsequently diagnosed.

Results

Various cytological changes were detected among both cases and controls: atypia (2.0%, 1.2%, respectively), keratinisation (0.7%, 0%, respectively), inflammation (13.6%, 10.8%, respectively), and infection (4.1%, 3.6%, respectively).

Conclusion

The results showed higher percentages of cytological changes among shamma users compared with nonusers; however, the differences were not statistically significant. Habitual use of other substances in the control group could be a confounding factor given this geographic region and the cytological changes we detected in both cases and controls. Diagn. Cytopathol. 2017;45:693–699. © 2017 Wiley Periodicals, Inc.
Postglacial dispersal patterns and mitochondrial genetic structure of the Pyrenean desman (Galemys pyrenaicus) in the northwestern region of the Iberian Peninsula
Authors: Querejeta Marina , Fernández‐González Angel , Romero Rafael , Castresana Jose
Published: May 2017

The genetic structure of small semiaquatic animals may be influenced by dispersal across both rivers and land. The relative importance of these two modes of dispersal may vary across different species and with ecological conditions and evolutionary periods. The Pyrenean desman (Galemys pyrenaicus) is an endemic mammal of the Iberian Peninsula with a strong phylogeographic structure and semiaquatic habits, thus making it an ideal model to study the effects of river and overland dispersal on its genetic structure. Thanks to different types of noninvasive samples, we obtained an extensive sampling of the Pyrenean desman from the northwestern region of the Iberian Peninsula and sequenced two mitochondrial DNA fragments. We then analyzed, using an isolation‐by‐distance approach, the correlation between phylogenetic distances and geographical distances measured along both river networks and land to infer the relative importance of river and overland dispersal. We found that the correlations in the whole area and in a large basin were consistent with an effect of overland dispersal, which may be due to the postglacial colonization of new territories using terrestrial corridors and, possibly, a more extensive fluvial network that may have been present during the Holocene. However, in a small basin, likely to be less influenced by the impact of ancient postglacial dispersal, the correlations suggested significant overall effects of both overland and river dispersal, as expected for a semiaquatic mammal. Therefore, different scales and geographical regions reflect different aspects of the evolutionary history and ecology of this semiaquatic species using this isolation‐by‐distance method. The results we obtained may have crucial implications for the conservation of the Pyrenean desman because they reinforce the importance of interbasin dispersal for this species in the studied area and the need to protect the whole riverine ecosystem, including rivers, upland streams and terrestrial corridors between basins.
A Simple Method to Determine Synchronous Machine Quantities Using Frequency Characteristics of Operational Impedances
Authors: TANAKA AKIRA , YAMAMOTO SHU , ARA TAKAHIRO , SAKAI KAZUTO , KOMURO SHUJI
Published: May 2017

This paper presents a simple method for determining synchronous machine quantities: d‐ and q‐axes time constants and reactances. This method determines them only by drawing additional lines in the frequency characteristics of operational impedances. A new systematic drawing strategy for determining transient/subtransient open‐circuit time constants and the d‐axis transient reactance is proposed. The frequency characteristics of operational impedances are obtained by the standstill dc test using a small dc power supply. Since the rotational test becomes unnecessary, the proposed method is suitable for tests in a factory. The validity of the proposed method was demonstrated with a numerical calculation example on a large‐capacity machine (800 MVA, 25 kV, two poles, 60 Hz) and an implementation test on a small‐capacity machine (10 kVA, 200 V, 31.9 A, four poles, 50 Hz).
Satellite glial cells in human trigeminal ganglia have a broad expression of functional Toll‐like receptors
Authors: Mitterreiter Johanna G. , Ouwendijk Werner J. D. , van Velzen Monique , van Nierop Gijsbert P. , Osterhaus Albert D. M. E. , Verjans Georges M. G. M.
Published: May 2017

Toll‐like receptors (TLRs) orchestrate immune responses to a wide variety of danger‐ and pathogen‐associated molecular patterns. Compared to the central nervous system (CNS), expression profile and function of TLRs in the human peripheral nervous system (PNS) are ill‐defined. We analyzed TLR expression of satellite glial cells (SGCs) and microglia, glial cells predominantly involved in local immune responses in ganglia of the human PNS and normal‐appearing white matter (NAWM) of the CNS, respectively. Ex vivo flow cytometry analysis of cell suspensions obtained from human cadaveric trigeminal ganglia (TG) and NAWM showed that both SGCs and microglia expressed TLR1–5, TLR7, and TLR9, although expression levels varied between these cell types. Immunohistochemistry confirmed expression of TLR1–TLR4 and TLR9 by SGCs in situ. Stimulation of TG‐ and NAWM‐derived cell suspensions with ligands of TLR1–TLR6, but not TLR7 and TLR9, induced interleukin 6 (IL‐6) secretion. We identified CD45LOWCD14POS SGCs and microglia, but not CD45HIGH leukocytes and CD45NEG cells as the main source of IL‐6 and TNF‐α upon stimulation with TLR3 and TLR5 ligands. In conclusion, human TG‐resident SGCs express a broad panel of functional TLRs, suggesting their role in initiating and orchestrating inflammation to pathogens in human sensory ganglia.
Synthesis, Structure and Antitumoural Activity of Triazole‐Functionalised NHC–Metal Complexes
Authors: Monticelli Marco , Bellemin‐Laponnaz Stéphane , Tubaro Cristina , Rancan Marzio
Published: May 2017

Silver(I), gold(I), copper(I) and ruthenium(II) N‐heterocyclic carbene (NHC) complexes have been synthesised and their cytotoxic activities towards various cancer cell lines have been evaluated. The N‐heterocyclic carbene ligand has been functionalised with a 1,2,3‐triazole moiety tethered in the backbone of the ligand. The molecular structure of the silver(I) and gold(I) complexes has been solved by X‐ray diffraction analysis. The AgI, AuI and RuII complexes display good stability in aqueous conditions and show cytotoxic activities comparable or slightly superior to those of similar unfunctionalised complexes.
Phase Equilibria, Crystal Structure, and Properties of Intermediate Oxides in the Sm2O3–SrO–CoO System
Authors: Volkova Nadezhda E. , Maklakova Anastasia V. , Gavrilova Ludmila Ya. , Cherepanov Vladimir A.
Published: May 2017

The phase equilibria in the 1/2Sm2O3–SrO–CoO system were systematically studied at 1100 °C in air. Single‐phase Sr1–xSmxCoO3–δ and Sr2–ySmyCoO4+δ solid solutions were obtained within the ranges of 0.05 ≤ x ≤ 0.50 and 0.9 ≤ y ≤ 1.3, respectively. XRD patterns of the single‐phase samples were refined by the Rietveld method within the tetragonal structure (space group I4/mmm). Gradual substitution of strontium by samarium leads to a decrease of the unit‐cell parameters and the unit‐cell volume that can be explained by the size factor. An introduction of samarium into strontium cobaltite increases the oxygen content in Sr1–xSmxCoO3–δ. The variation of the electrical conductivity, Seebeck coefficient, and thermal expansion of Sr1–xSmxCoO3–δ and Sr2–ySmyCoO4+δ oxides vs. temperature were measured in air. The chemical reactivity of Sr1–xSmxCoO3–δ and Sr2–ySmyCoO4+δ, in contact with the solid electrolyte materials Ce0.8Sm0.2O2 and Zr0.85Y0.15O2, was examined. The projection of the isothermal–isobaric phase diagram (1100 °C, air) to the compositional triangle 1/2Sm2O3–SrO–CoO has been constructed.
Migraine prevalence in inflammatory bowel disease patients: A tertiary‐care centre cross‐sectional study
Authors: Moisset X. , Bommelaer G. , Boube M. , Ouchchane L. , Goutte M. , Dapoigny M. , Dallel R. , Guttmann A. , Clavelou P. , Buisson A.
Published: May 2017

Background

Inflammatory bowel diseases (IBD) are systemic, chronic inflammatory conditions that predominately affect the gastrointestinal tract and can induce abdominal pain. Besides, many IBD patients complain about headaches in daily practice. The objective was to assess the prevalence of headaches, including migraines and pain with neuropathic characteristics (NC), in IBD patients compared to historical controls from the general population.

Methods

Overall, 203 consecutive tertiary‐care centre patients completed validated self‐administered questionnaires and benefitted from a clinical evaluation performed by an IBD physician at the same time.

Results

In our cohort, 75% of the patients experienced pain in the previous 3 months. Migraine prevalence was two‐fold higher in IBD patients compared to the general population (41% vs. 21.3%, p < 0.001). Migraine was associated with a younger age, female gender and higher depression scores. Although migraine impact was very important for 30% of the patients (61/203), specific acute therapeutics were prescribed in only 22% of cases (18/83). Chronic pain with NC was more frequent than in the general population (11.3% vs. 6.9%, p = 0.012) and was strongly associated with the presence of extra‐intestinal manifestations (p < 0.001). Abdominal pain concerned 19% of the patients during the previous week and was, as expected, associated with disease activity.

Conclusions

Migraine prevalence is strongly increased in IBD patients followed in tertiary care. A systematic screening for migraine should be done by IBD physicians in daily practice to provide adequate therapeutics. Further studies are needed to confirm whether migraine should be classified as IBD extra‐intestinal manifestations.

Significance

Migraine prevalence was two‐fold higher in IBD patients compared to the general population, was generally poorly treated and a systematic screening for migraine should be done by IBD physicians in daily practice to provide adequate therapeutics.
Determination of Manganese in Whole Blood by Cathodic Stripping Voltammetry with Indium Tin Oxide
Authors: Rusinek Cory A. , Kang Wenjing , Nahan Keaton , Hawkins Megan , Quartermaine Cooper , Stastny Angela , Bange Adam , Papautsky Ian , Heineman William R.
Published: May 2017

Manganese (Mn) is a required trace metal in the body. In recent years however, it has garnered significant attention as a developmental neurotoxin in children with chronic exposure. It has been linked to complications such as memory loss with negatively associated IQ scores, attention deficit hyperactivity disorder (ADHD), and in extreme cases, the development of a Parkinson's disease analogue‐manganism. Cathodic stripping voltammetry (CSV) has proven to be a suitable method for electroanalytical determination of Mn. We have established Mn CSV using indium tin oxide (ITO) as the working electrode for the determination of Mn in bovine whole blood after an acid digestion. Reliable, accurate, and precise results were obtained, as only 9 % variation in the digested blood was observed. The CSV results were compared with graphite‐furnace atomic absorption spectroscopy (GF‐AAS) and inductively coupled plasma‐ mass spectrometry (ICP‐MS) and favorable agreement across the methods was observed. Due to ITO's excellent positive potential window and stability under harsh environments, this method could be applied to other oxide‐forming transition metals detectable by CSV.
The sequence stratigraphy and depositional characteristics of fan‐delta complexes in the Upper Bayingebi Member (Lower Cretaceous) in Chagan Sag, Inner Mongolia, China
Authors: Tan Mingxuan , Zhu Xiaomin , Wei Wei , Wu Chenbingjie , Pan Rong
Published: May 2017

The Chagan Sag is a small Early Cretaceous intracontinental passive rift subbasin in the Yingen‐Ejinaqi Basin Group generated on the Tianshan‐Xingmeng Orogenic Belt. The Lower Cretaceous strata contain the Bayingebi, Suhongtu, and Yingen formations deposited during the syn‐rift phase. The Wuliji Structural Zone bounded by a high‐dip syn‐sedimentary fault is an intensively studied area with an extent of ~300 km2 having abundant available subsurface dataset and great hydrocarbon potential. According to well‐ and seismic‐based sequence stratigraphic study, the Upper Bayingebi Member generally corresponds to a complete third‐order transgressive–regressive sequence in the Wuliji Structural Zone. The transgressive system tract gradually thins towards the north, but the regressive system tract covers the entire study area in this third‐order sequence. Further investigations reveal that tectonic subsidence and climate change are two predominant allogenic factors for controlling stratigraphic development in the Wuliji Structural Zone.

During the deposition of the Upper Bayingebi Member, transverse gravity flow dominated fan‐delta complexes sourced from the Maodun Subuplift are well developed in the Wuliji Structural Zone. The retrogradational conical fan deltas are mainly located in the southern sector during the transgressive system tract stage, but the progradational Gilbert‐type fan deltas are widely developed during the regressive system tract stage. The sedimentary evolution and stratigraphic architecture are directly linked with preexisting topography, accommodation, and sediment supply. In addition, climate change and vegetation types are thought to be critical controls for fluid properties originated from feeder drainage systems and depositional processes of the construction of fan‐delta complexes in the distinct system tracts.
Amyloid is essential but insufficient for Alzheimer causation: addition of subcellular cofactors is required for dementia
Authors: Fessel Jeffrey
Published: May 2017

Objective

The aim of this study is to examine the hypotheses stating the importance of amyloid or of its oligomers in the pathogenesis of Alzheimer's disease (AD).

Methods

Published studies were examined.

Results

The importance of amyloid in the pathogenesis of AD is well established, yet accepting it as the main cause for AD is problematic, because amyloid‐centric treatments have provided no clinical benefit and about one‐third of cognitively normal, older persons have cerebral amyloid plaques. Also problematic is the alternative hypothesis that, instead of amyloid plaques, it is oligomers of amyloid precursor protein that cause AD.Evidence is presented suggesting amyloid/oligomers as necessary but insufficient causes of the dementia and that, for dementia to develop, requires the addition of cofactors known to be associated with AD. Those cofactors include several subcellular processes: mitochondrial impairments; the Wnt signaling system; the unfolded protein response; the ubiquitin proteasome system; the Notch signaling system; and tau, calcium, and oxidative damage.

Conclusions

A modified amyloid/oligomer hypothesis for the pathogenesis of AD is that activation of one or more of the aforementioned cofactors creates a burden of functional impairments that, in conjunction with amyloid/oligomers, now crosses a threshold of dysfunction that results in clinical dementia. Of considerable importance, several treatments that might reverse the activation of some of the subcellular processes are available, for example, lithium, pioglitazone, erythropoietin, and prazosin; they should be given in combination in a clinical trial to test their safety and efficacy. © 2017 John Wiley & Sons, Ltd.
Measuring change in perceived well‐being of family caregivers: validation of the Spanish version of the Perceived Change Index (PCI‐S) in Chilean dementia caregivers
Authors: Aravena José M. , Albala Cecilia , Gitlin Laura N.
Published: May 2017

Objective

Few instruments evaluate family caregiver perceptions of challenges caring for persons with dementia and improvement or worsening in these areas. To address this measurement gap, we examine psychometric properties of a Spanish version of the 13‐item Perceived Change Index (PCI‐S), originally validated with English‐speaking caregivers.

Methods

Cross‐sectional study with 94 caregivers of persons with mild to moderate dementia in Chile. Interviews included caregiver demographics, burden, health perception, distress with behaviours, dementia severity, behavioural symptoms and functionality.

Results

Caregiver mean age was 55.9 (SD ± 14.14) years and mean years caregiving was 3 (SD ± 2.60). The scale had strong internal consistency (Cronbach α = 0.94), and inter‐observer consistency (CCI = 0.99; 95% CI = 0.95–0.99). Two factors were identified: Management skills (α = 0.89), and somatic well‐being and affects (α = 0.92), explaining 63% of scale variance. Significant associations supporting convergent validity were observed for PCI‐S and subscales with caregiver burden (p < 0.01), health perceptions (p < 0.01), depressive symptoms (p < 0.01) and distress with behaviours (p < 0.01); and in persons with dementia, functionality (p < 0.05), dementia severity (p < 0.05) and behavioural symptoms (p < 0.01) in expected directions. In logistic regression models, perceived worsening (PCI‐S and subscale scores) was associated with more behavioural symptoms (OR = 1.07; 95% CI = 1.03–1.15) and caregiver burden (OR = 1.48; 95% CI = 1.18–1.86); whereas perceived improvement was associated with higher physical functioning (OR = 0.95; 95% CI = 0.91–0.99) in persons with dementia. PCI‐S scores were not associated with socio‐demographic characteristics reflecting divergent validity.

Conclusions

Spanish version of the 13‐item Perceived Change Index and its two‐factor solution is a valid and reliable measure with clinical utility to detect improvement or worsening in caregivers concerning daily care challenges. Copyright © 2017 John Wiley & Sons, Ltd.
The influence of vascular risk factors on cognitive function in early Parkinson's disease
Authors: Doiron Maxime , Langlois Mélanie , Dupré Nicolas , Simard Martine
Published: May 2017

Objectives

Hypertension, dyslipidemia, diabetes, and obesity are well‐established risk factors for cognitive impairment and dementia in older adults. In contrast, previous studies that have assessed the impact of vascular risk factors (VRFs) on cognition in Parkinson's disease (PD) have had methodological limitations and reported conflicting findings. We address this question in a large well‐characterized cohort of de novo PD patients.

Methods

A total of 367 untreated and non‐demented patients aged 50 years and older with early PD (H&Y = 1.0–2.0) underwent a comprehensive clinical and neuropsychological assessment at baseline and 24 months later. A series of linear mixed models were used to determine the effects of VRFs on cognition while controlling for patient and disease characteristics. The outcomes included norm‐referenced Z‐scores of global cognition, visuospatial skills, verbal episodic memory, semantic verbal fluency, attention, and working memory tests.

Results

A longer history of hypertension and a higher pulse pressure were significant predictors of lower Z‐scores on immediate and delayed free recall, recognition, and verbal fluency tests. On average, every 10 mmHg increase in pulse pressure was associated with a 0.08 reduction on the cognitive Z‐scores. The effects were independent of age, education, disease duration, motor impairment, medication, and depressive symptoms. Other VRFs were not associated with cognitive outcomes.

Conclusions

Our results are consistent with previous studies suggesting that hypertension exerts a detrimental effect on memory and verbal fluency in early PD. Management of blood pressure and cardiovascular health may be important to reduce risk of cognitive decline in PD. Copyright © 2017 John Wiley & Sons, Ltd.
Domain‐specific cognitive impairment in non‐demented Parkinson's disease psychosis
Authors: Hinkle Jared T. , Perepezko Kate , Bakker Catherine C. , Dawson Ted M. , Johnson Vanessa , Mari Zoltan , Marvel Cherie L. , Mills Kelly A. , Pantelyat Alexander , Pletnikova Olga , Rosenthal Liana S. , Shepard Melissa D. , Stevens Daniel A. , Troncoso Juan C. , Wang Jiangxia , Pontone Gregory M.
Published: May 2017

Introduction

In Parkinson's disease (PD), psychosis is associated with cognitive impairment that may be more profound in particular cognitive domains. Our goal was to determine whether psychosis in non‐demented PD participants is associated with domain‐specific cognitive impairment on the Mini‐Mental State Exam (MMSE).

Methods

The Morris K. Udall Parkinson's Disease Research Center of Excellence Longitudinal Study at Johns Hopkins is a prospective study that was initiated in 1998. Clinical assessments are conducted at two‐year intervals at the Johns Hopkins Hospital. We analyzed data from 137 enrolled participants with idiopathic PD. Psychosis diagnoses were established by psychiatrist interview per DSM‐IV criteria. An incident dementia diagnosis resulted in exclusion from analysis for that evaluation and any future evaluations in that participant. We used logistic regression with generalized estimated equations (GEE) to model the time‐varying relationship between MMSE subscale scores and psychosis, adjusting for potential confounding variables identified through univariable analysis.

Results

Thirty‐one unique psychosis cases were recorded among non‐demented participants. Fifty total evaluations with psychosis present were analyzed. In multivariable regressions, psychosis was associated with lower scores on the orientation (relative odds ratio, rOR: 0.73; 95% CI: 0.58–0.93; p = 0.011), language (rOR: 0.64; 95% CI: 0.48–0.86; p = 0.003), and intersecting pentagon (rOR: 0.43; 95% CI: 0.20–0.92 p = 0.030) subscales of the MMSE.

Conclusions

In PD, executive dysfunction, disorientation, and impaired language comprehension may be associated with psychosis. Our findings suggest that the corresponding MMSE subscales may be useful in identifying participants with a higher likelihood of developing psychosis. Copyright © 2017 John Wiley & Sons, Ltd.
Comparison of JAK2V617F‐positive essential thrombocythaemia and early primary myelofibrosis: The impact of mutation burden and histology
Authors: Latagliata Roberto , Polverelli Nicola , Tieghi Alessia , Palumbo Giuseppe Alberto , Breccia Massimo , Sabattini Elena , Villari Loredana , Riminucci Mara , Valli Riccardo , Catani Lucia , Alimena Giuliana , Ottaviani Emanuela , Fama Angelo , Martinelli Giovanni , Perricone Margherita , Spinsanti Marco , Cavo Michele , Vianelli Nicola , Palandri Francesca
Published: May 2017

An accurate histological diagnosis may distinguish essential thrombocythaemia (ET) from early primary myelofibrosis (early‐PMF), which is associated with worse outcome. Outcome of ET is also negatively affected by the presence of the JAK2V617F mutation. To investigate the impact of JAK2V617F mutation burden and histology on outcome, we collected 475 WHO‐diagnosed ET (69.2%) or early‐PMF JAK2V617F‐positive patients followed in 4 Italian haematology centers. JAK2V617F allele burden was ≤50% in 90% and 87% of ET and early‐PMF patients, respectively (P = .34). During follow‐up, 32 (9.7%) ET and 18 (12.3%) early‐PMF patients experienced 59 thrombotic events, and 27 patients (5.6%) and 6 (1.2%) patients evolved to myelofibrosis and acute leukemia, respectively. At last contact, 28 (5.8%) patients had died. In early‐PMF compared to ET, the 10‐year mortality rates (6.7% and 4.3%, P = .73), leukemic transformation rates (1.4% and 1.2%, P = .45), and thrombosis rates (16.7% and 12.2%, P = .12) were comparable. Only progression to overt myelofibrosis at 10 years was significantly worse (11.4% and 1.5%, P = .004). In multivariate analysis, a higher (>50%) JAK2V617F burden was significantly correlated with fibrotic progression and histology. Considering JAK2V617F‐positive disease, a higher (>50%) JAK2V617F burden and histological classification are independent prognostic risk factors for disease progression. These findings reinforce the need for standardized detection of this mutation.
Temporal change of spatial heterogeneity and its effect on regional trend of annual precipitation heterogeneity indices
Authors: Zhang Runrun , Chen Xi , Wang Huimin , Cheng Qinbo , Zhang Zhicai , Shi Peng
Published: May 2017

A statistical test on climate and hydrological series from different spatial resolution could obtain different regional trend due to spatial heterogeneity and its temporal variability. In this study, annual series of the precipitation heterogeneity indices of concentration index (CI) and the number of wet days (NW) along with annual total amount of precipitation were calculated based on at‐site daily precipitation series during 1962–2011 in the headwater basin of the Huaihe River, China. The regional trends of the indices were first detected based on at‐site series by using the aligned and intrablock methods, and field significance tests that consider spatial heterogeneity over sites. The detected trends were then compared with the trends of the regional index series derived from daily areal average precipitation (DAAP), which averages at‐site differences and thus neglects spatial heterogeneity. It was found that the at‐site‐based regional test shows increasing trends of CI and NW in the basin, which follows the test on individual sites that most of sites were characterized by increasing CI and NW. However, the DAAP‐derived regional series of CI and NW were tested to show a decreasing trend. The disparity of the regional trend test on at‐site‐based regional series and the DAAP‐derived regional series arises from a temporal change of the spatial heterogeneity, which was quantified by the generalized additive models for location, scale, and shape. This study highlights that compared with averaging indices, averaging at‐site daily precipitation could lead to an error in the regional trend inference on annual precipitation heterogeneity indices. More attention should be paid to temporal variability in spatial heterogeneity when data at large scales are used for regional trend detection on hydro‐meteorological events associated with intra‐annual heterogeneity.
Role of quantitative p16INK4A mRNA assay and digital reading of p16INK4A immunostained sections in diagnosis of cervical intraepithelial neoplasia
Authors: Vasiljević Nataša , Carter Paul D. , Reuter Caroline , Warman Rhian , Brentnall Adam R. , Carton James R. , Cuzick Jack , Lorincz Attila T.
Published: May 2017

Visual interpretation of cervical biopsies is subjective and variable, generally showing fair to moderate inter‐reader agreement in distinguishing high from low grade cervical intraepithelial neoplasia (CIN). We investigated the performance of two objective p16 quantitative tests in comparison with visual assessment: (i) p16‐mRNA assay and (ii) digital analysis of sections stained for p16 protein. The primary analysis considered 232 high‐risk human papilloma virus positive (HPV+) samples from diagnostic cervical specimens. A p16 RT‐qPCR (p16‐mRNA assay) was run on mRNA extracted from formalin‐fixed paraffin‐embedded sections. Two p16 immunohistochemistry (IHC) readings, a visual read by a histopathologist (Visual IHC) and a digital read of a high‐resolution scan (Digital IHC), were done on adjacent sections. The worst reviewed CIN grade (agreed by at least two histopathologists) from up to two biopsies and a loop excision was taken, with CIN2/3 as the primary endpoint. Visual IHC attained a specificity of 70% (95%CI 61–77) for 85% (95%CI 77–91%) sensitivity. The four‐point Visual IHC staining area under the curve (AUC) was 0.77 (95%CI 0.71–0.82), compared with 0.71 (95%CI 0.64–0.77) for p16‐mRNA and 0.67 (95%CI 0.60–0.74) for Digital IHC. Spearman rank‐order correlations were: visual to p16‐mRNA 0.41, visual to digital 0.49 and p16‐mRNA to digital: 0.22. The addition of p16‐mRNA assay to visual reading of p16 IHC improved the AUC from 0.77 to 0.84 (p = 0.0049). p16‐mRNA testing may be complementary to visual IHC p16 staining for a more accurate diagnosis of CIN, or perhaps a substitute in locations with a lack of skilled pathologists.
The occurrence of hepatocellular carcinoma in different risk stratifications of clinically noncirrhotic nonalcoholic fatty liver disease
Authors: Lee Teng‐Yu , Wu Jaw‐Ching , Yu Shi‐Hang , Lin Jaw‐Town , Wu Ming‐Shiang , Wu Chun‐Ying
Published: May 2017

Nonalcoholic fatty liver disease (NAFLD) may be a cause of hepatocellular carcinoma (HCC), but its high prevalence challenges current surveillance strategies. We aimed to evaluate HCC incidences in different risk stratifications for noncirrhotic NAFLD. Using Taiwan's National Health Insurance Research Database, we located 31,571 patients with NAFLD between the years 1998 and 2012. After excluding other causes of hepatitis, underlying cirrhosis or malignancy, 18,080 patients were recruited for final analysis. Cumulative incidences of HCC were analyzed after adjusting for competing mortality. With a median follow‐up duration of 6.32 years in the study cohort, the 10‐year cumulative incidence of HCC was 2.73% [95% confidence interval (CI): 1.69–3.76%]. Hepatoprotectant was used as a surrogate marker for elevated serum alanine transaminase (ALT). After adjusting for age, gender, hypertension, hypercholesterolemia, diabetes mellitus, gout, statin use, metformin use and aspirin use, elevated ALT was independently associated with an increased HCC risk [hazard ratio (HR) 6.80, 95% CI: 3.00–15.42; p < 0.001]. Multivariate stratified analysis verified this association in all subgroups (HR> 1.0). Moreover, increased age (HR 1.08 per year, 95% CI: 1.05–1.11) and statin use (HR 0.29, 95% CI: 0.12–0.68) were also identified as independent risk factors. The 10‐year cumulative HCC incidence was highest in older (age >55 years) patients with ALT elevation (12.41%, 95% CI: 5.99–18.83%), but lowest in younger patients without ALT elevation (0.36%, 95% CI: 0–1.08%). The incidence of HCC was relatively low in patients with clinically noncirrhotic NAFLD, however, HCC risk was significantly increased in older patients experiencing an elevated serum ALT.
Associations between RNA splicing regulatory variants of stemness‐related genes and racial disparities in susceptibility to prostate cancer
Authors: Wang Yanru , Freedman Jennifer A. , Liu Hongliang , Moorman Patricia G. , Hyslop Terry , George Daniel J. , Lee Norman H. , Patierno Steven R. , Wei Qingyi
Published: May 2017

Evidence suggests that cells with a stemness phenotype play a pivotal role in oncogenesis, and prostate cells exhibiting this phenotype have been identified. We used two genome‐wide association study (GWAS) datasets of African descendants, from the Multiethnic/Minority Cohort Study of Diet and Cancer (MEC) and the Ghana Prostate Study, and two GWAS datasets of non‐Hispanic whites, from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial and the Breast and Prostate Cancer Cohort Consortium (BPC3), to analyze the associations between genetic variants of stemness‐related genes and racial disparities in susceptibility to prostate cancer. We evaluated associations of single‐nucleotide polymorphisms (SNPs) in 25 stemness‐related genes with prostate cancer risk in 1,609 cases and 2,550 controls of non‐Hispanic whites (4,934 SNPs) and 1,144 cases and 1,116 controls of African descendants (5,448 SNPs) with correction by false discovery rate ≤0.2. We identified 32 SNPs in five genes (TP63, ALDH1A1, WNT1, MET and EGFR) that were significantly associated with prostate cancer risk, of which six SNPs in three genes (TP63, ALDH1A1 and WNT1) and eight EGFR SNPs showed heterogeneity in susceptibility between these two racial groups. In addition, 13 SNPs in MET and one in ALDH1A1 were found only in African descendants. The in silico bioinformatics analyses revealed that EGFR rs2072454 and SNPs in linkage with the identified SNPs in MET and ALDH1A1 (r2 > 0.6) were predicted to regulate RNA splicing. These variants may serve as novel biomarkers for racial disparities in prostate cancer risk.
A polymorphism in miR‐1262 regulatory region confers the risk of lung cancer in Chinese population
Authors: Xie Kaipeng , Chen Mengxi , Zhu Meng , Wang Cheng , Qin Na , Liang Cheng , Song Ci , Dai Juncheng , Jin Guangfu , Shen Hongbing , Lin Dongxin , Ma Hongxia , Hu Zhibin
Published: May 2017

It has been proposed that the majority of disease‐associated loci identified by genome‐wide association studies (GWAS) are enriched in non‐coding regions, such as the promoter, enhancer or non‐coding RNA genes. Thus, we performed a two‐stage case‐control study to systematically evaluate the association of genetic variants in miRNA regulatory regions (promoter and enhancer) with lung cancer risk in 7,763 subjects (discovery stage: 2,331 cases and 3,077 controls; validation stage: 1,065 cases and 1,290 controls). As a result, we identified that rs12740674 (C > T) in miR‐1262 enhancer was significantly associated with the increased risk of lung cancer (additive model in discovery stage: adjusted OR = 1.31, 95%CI = 1.13–1.53, p = 3.846 × 10−4 in Nanjing GWAS; adjusted OR = 1.20, 95%CI = 1.00–1.44, p = 0.041 in Beijing GWAS; validation stage: adjusted OR = 1.20, 95%CI = 1.03–1.41, p = 0.024). In meta‐analysis, the p value for the association between rs12740674 and lung cancer risk reached 6.204 × 10−6 (adjusted OR = 1.24, 95%CI = 1.13–1.36). Using 3DSNP database, The Cancer Genome Atlas (TCGA) data and functional assays, we observed that the risk T allele of rs12740674 reduced the expression level of miR‐1262 in lung tissue through chromosomal looping, and overexpression of miR‐1262 inhibited lung cancer cell proliferation probably through targeting the expression levels of ULK1 and RAB3D. Our findings confirmed the important role that genetic variants of noncoding sequence play in lung cancer susceptibility and indicated that rs12740674 in miR‐1262 may be biologically relevant to lung carcinogenesis.
High heparin content surface‐modified polyurethane discs promote rapid and stable angiogenesis in full thickness skin defects through VEGF immobilization
Authors: McLuckie Michelle , Schmidt Christian A. , Oosthuysen Anel , Sanchez‐Macedo Nadia , Merker Hannes , Bezuidenhout Deon , Hoerstrup Simon P. , Lindenblatt Nicole
Published: May 2017

Three‐dimensional scaffolds have the capacity to serve as an architectural framework to guide and promote tissue regeneration. Parameters such as the type of material, growth factors, and pore dimensions are therefore critical in the scaffold's success. In this study, heparin has been covalently bound to the surface of macroporous polyurethane (PU) discs via two different loading methods to determine if the amount of heparin content had an influence on the therapeutic affinity loading and release of (VEGF165) in full thickness skin defects. PU discs (5.4 mm diameter, 300 µm thickness, and interconnected pore size of 150 µm) were produced with either a low (2.5 mg/g) or high (6.6 mg/g) heparin content (LC and HC respectively), and were implanted into the modified dorsal skin chamber (MDSC) of C57BL/6 J mice with and without VEGF. Both low‐ and high‐content discs with immobilized VEGF165 (LCV and HCV, respectively) presented accelerated neovascularization and tissue repair in comparison to heparin discs alone. However, the highest angiogenetic peak was on day 7 with subsequent stabilization for HCV, whereas other groups displayed a delayed peak on day 14. We therefore attribute the superior performance of HCV due to its ability to hold more VEGF165, based on its increased heparin surface coverage, as also demonstrated in VEGF elution dynamics. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2543–2550, 2017.
The zebrafish embryo as a model to quantify early inflammatory cell responses to biomaterials
Authors: Zhang Xiaolin , Stockhammer Oliver. W. , de Boer Leonie , Vischer Norbert. O. E , Spaink Herman. P. , Grijpma Dirk. W. , Zaat Sebastian. A. J.
Published: May 2017

To rapidly assess early inflammatory cell responses provoked by biomaterials in the full complexity of the living organism, we developed a zebrafish embryo model which allows real time analysis of these responses to biomaterial microspheres. Fluorescently labeled microspheres with different properties were injected into embryos of selected transgenic zebrafish lines expressing distinct fluorescent proteins in their neutrophils and macrophages. Recruitment of leukocytes and their interactions with microspheres were monitored using fluorescence microscopy. We developed a novel method using ImageJ and the plugin ObjectJ project file “Zebrafish‐Immunotest” for rapid and semi‐automated fluorescence quantification of the cellular responses. In the embryo model we observed an ordered inflammatory cell response to polystyrene and poly (ε‐caprolactone) microspheres, similar to that described for mammalian animal models. The responses were characterized by an early infiltration of neutrophils followed by macrophages, and subsequent differentially timed migration of these cells away from the microspheres. The size of microspheres (10 and 15 µm) did not influence the cellular responses. Poly (ε‐caprolactone) microspheres provoked a stronger infiltration of neutrophils and macrophages than polystyrene microspheres did. Our study shows the potential usefulness of zebrafish embryos for in vivo evaluation of biomaterial‐associated inflammatory cell responses. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2522–2532, 2017.
Characterization and quantitation of PVP content in a silicone hydrogel contact lens produced by dual‐phase polymerization processing
Authors: Hoteling Andrew J. , Nichols William F. , Harmon Patricia S. , Conlon Shawn M. , Nuñez Ivan M. , Hoff Joseph W. , Cabarcos Orlando M. , Steffen Robert B. , Hook Daniel J.
Published: May 2017

Polyvinylpyrrolidone (PVP) has been incorporated over the years into numerous hydrogel contact lenses as both a primary matrix component and an internal wetting agent to increase lens wettability. In this study, complementary analytical techniques were used to characterize the PVP wetting agent component of senofilcon A and samfilcon A contact lenses, both in terms of chemical composition and amount present. Photo‐differential scanning calorimetry (photo‐DSC), gas chromatography with a flame ionization detector (GC‐FID), and high‐resolution/accurate mass (HR/AM) liquid chromatography‐mass spectrometry (LC‐MS) techniques confirmed dual phase reaction and curing of the samfilcon A silicone hydrogel material. Gel permeation chromatography (GPC) demonstrated that high molecular weight (HMW) polymer was present in isopropanol (IPA) extracts of both lenses. High‐performance liquid chromatography (HPLC) effectively separated hydrophilic PVP from the hydrophobic silicone polymers present in the extracts. Collectively, atmospheric solids analysis probe mass spectrometry (ASAP MS), Fourier transform infrared (FTIR) spectroscopy, 1H nuclear magnetic resonance (NMR) spectroscopy, GC‐FID, and LC‐MS analyses of the lens extracts indicated that the majority of NVP is consumed during the second reaction phase of samfilcon A lens polymerization and exists as HMW PVP, similar to the PVP present in senofilcon A. GC‐FID analysis of pyrolyzed samfilcon A and senofilcon A indicates fourfold greater PVP in samfilcon A compared with senofilcon A. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1064–1072, 2018.
Immobilization of lipase B from Candida antarctica on epoxy‐functionalized silica: characterization and improving biocatalytic parameters
Authors: de Souza Stefânia P , de Almeida Rayza AD , Garcia Gabriel G , Leão Raquel AC , Bassut Jonathan , de Souza Rodrigo OMA , Itabaiana Ivaldo
Published: May 2017

BACKGROUND

In this work, lipase B from Candida antarctica (CaLB) was immobilized on Purolite® ECR8205F, Purolite® ECR8214F and Immobead® IB150 P epoxy resins with no modification to their surfaces. Biocatalysts were evaluated for thermal stability and applied in reactions of hydrolysis, esterification and the synthesis of glyceryl carbonate by transesterification with dimethyl‐carbonate both with glycerol and Macauba oil as well as dynamic kinetic resolution of α‐methylbenzylamine, all of them compared with commercial Novozyme 435®.

RESULTS

Protein desorption of the biocatalysts with Triton X‐100 showed that lipase was immobilized by covalent single‐bond type binding. The immobilization efficiencies were 55.1% for the biocatalyst 8205, 57.1% for 8214, and 14.9 for the 150P, demonstrating the intense effect of surface and material composition on lipase immobilization. The biocatalysts also showed higher initial velocities of esterification and hydrolysis reactions as well as higher thermal stability than Novozyme 435®. On glycerol carbonate synthesis, conversion of 97% and selectivity higher than 99% was demonstrated by enzyme 8214, similar to Novozyme 435®. On kinetic dynamic resolution, conversions higher than 94% and and enantiomeric excesses greater than 90% were also depicted.

CONCLUSION

Compared with commercial preparation Novozyme 435®, the novel biocatalysts obtained by immobilization on new epoxy resins demonstrated protein loads about 10‐fold lower and higher specific activity. In all reactions performed, competitive performances were found, demonstrating high potential for industrial applications. © 2017 Society of Chemical Industry