bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuropathology of childhood‐onset basal ganglia degeneration caused by mutation of VAC14
Authors: Stutterd Chloe , Diakumis Peter , Bahlo Melanie , Fanjul Fernandez Miriam , Leventer Richard J. , Delatycki Martin , Amor David , Chow Chung W. , Stephenson Sarah , Meisler Miriam H. , Mclean Catriona , Lockhart Paul J.
Published: November 2017

Objective

To characterize the clinical features and neuropathology associated with recessive VAC14 mutations.

Methods

Whole‐exome sequencing was used to identify the genetic etiology of a rapidly progressive neurological disease presenting in early childhood in two deceased siblings with distinct neuropathological features on post mortem examination.

Results

We identified compound heterozygous variants in VAC14 in two deceased siblings with early childhood onset of severe, progressive dystonia, and neurodegeneration. Their clinical phenotype is consistent with the VAC14–related childhood‐onset, striatonigral degeneration recently described in two unrelated children. Post mortem examination demonstrated prominent vacuolation associated with degenerating neurons in the caudate nucleus, putamen, and globus pallidus, similar to previously reported ex vivo vacuoles seen in the late‐endosome/lysosome of VAC14‐deficient neurons. We identified upregulation of ubiquitinated granules within the cell cytoplasm and lysosomal‐associated membrane protein (LAMP2) around the vacuole edge to suggest a process of vacuolation of lysosomal structures associated with active autophagocytic‐associated neuronal degeneration.

Interpretation

Our findings reveal a distinct clinicopathological phenotype associated with recessive VAC14 mutations.
Relationships between grip strength, myotonia, and CTG expansion in myotonic dystrophy type 1
Authors: Hogrel Jean‐Yves , Ollivier Gwenn , Ledoux Isabelle , Hébert Luc J. , Eymard Bruno , Puymirat Jack , Bassez Guillaume
Published: November 2017

In myotonic dystrophy type 1, several studies have suggested causal relationships between CTG repeat length and the severity of symptoms, such as weakness or myotonia. We aimed to explore these relationships in a large population of 144 DM1 patients. All patients underwent clinical and functional assessments using a standardized test for grip strength and myotonia assessment. Myotonia was assessed using a fully automatic software based on mathematical modeling of relaxation force curve. CTG repeat length was statistically correlated with both myotonia and grip strength, which are two major primary neuromuscular symptoms of DM1 patients. However, these relationships are not clinically meaningful and not predictive at the individual level.
Spatially Configuring Wrinkle Pattern and Multiscale Surface Evolution with Structural Confinement
Authors: Wang Ding , Cheewaruangroj Nontawit , Li Yifan , McHale Glen , Jiang Yinzhu , Wood David , Biggins John Simeon , Xu Ben Bin
Published: November 2017

Surface elastic instabilities, such as wrinkling and creasing, can enable a convenient strategy to impart reversible patterned topography to a surface. Here the classic system of a stiff layer on a soft substrate is focused, which famously produces parallel harmonic wrinkles at modest uniaxial compression that period‐double repeatedly at higher compressions and ultimately evolve into deep folds and creases. By introducing micrometer‐scale planar Bravais lattice holes to spatially pattern the substrate, these instabilities are guided into a wide variety of different patterns, including wrinkling in parallel bands and star shape bands, and radically reduce the threshold compression. The experimental patterns and thresholds are enabled to understand by considering a simple plane‐strain model for the patterned substrate‐deformation, decorated by wrinkling on the stiff surface layer. The experiments also show localized wrinkle‐crease transitions at modest compression, yielding a hierarchical surface with different generations of instability mixed together. By varying the geometrical inputs, control over the stepwise evolution of surface morphologies is demonstrated. These results demonstrate considerable control over both the patterns and threshold of the surface elastic instabilities, and have relevance to many emerging applications of morphing surfaces, including in wearable/flexible electronics, biomedical systems, and optical devices.
Non‐Equilibrium Self‐Assembly of Monocomponent and Multicomponent Tubular Structures in Rotating Fluids
Authors: Lee Taehoon , Gizynski Konrad , Grzybowski Bartosz A.
Published: November 2017

When suspended in a denser rotating fluid, lighter particles experience a cylindrically symmetric confining potential that drives their crystallization into either monocomponent or unprecedented binary tubular packing. These assemblies form around the fluid's axis of rotation, can be dynamically interconverted (upon accelerating or decelerating the fluid), can exhibit preferred chirality, and can be made permanent by solidifying the fluid. The assembly can be extended to fluids forming multiple concentric interfaces or to systems of bubbles forming both ordered and “gradient” structures within curable polymers.
Macroporous Catalytic Carbon Nanotemplates for Sodium Metal Anodes
Authors: Yoon Hyeon Ji , Kim Na Rae , Jin Hyoung‐Joon , Yun Young Soo
Published: November 2017

Because of its remarkably high theoretical capacity and favorable redox voltage (−2.71 V vs the standard hydrogen electrode), Na is a promising anode material for Na ion batteries. In this study, macroporous catalytic carbon nanotemplates (MC‐CNTs) based on nanoweb‐structured carbon nanofibers with various carbon microstructures are prepared from microbe‐derived cellulose via simple heating at 800 or 2400 °C. MC‐CNTs prepared at 800 °C have amorphous carbon structures with numerous topological defects, and exhibit a lower voltage overpotential of ≈8 mV in galvanostatic charge/discharge testing. In addition, MC‐CNT‐800s exhibit high Coulombic efficiencies of 99.4–99.9% during consecutive cycling at current densities ranging from 0.2 to 4 mA cm−2. However, the carbon structures of MC‐CNTs prepared at 800 °C are gradually damaged by cycling. This results in significant capacity losses after about 200 cycles. In contrast, MC‐CNTs prepared at 2400 °C exhibit well‐developed graphitic structures, and maintain predominantly stable cycling behaviors over 1000 cycles with Coulombic efficiencies of ≈99.9%. This study demonstrates the superiority of catalytic carbon nanotemplates with well‐defined pore structures and graphitic microstructures for use in Na metal anodes.
High Performance Thermoelectric Materials: Progress and Their Applications
Authors: Yang Lei , Chen Zhi‐Gang , Dargusch Matthew S. , Zou Jin
Published: November 2017

Thermoelectric (TE) materials have the capability of converting heat into electricity, which can improve fuel efficiency, as well as providing robust alternative energy supply in multiple applications by collecting wasted heat, and therefore, assisting in finding new energy solutions. In order to construct high performance TE devices, superior TE materials have to be targeted via various strategies. The development of high performance TE devices can broaden the market of TE application and eventually boost the enthusiasm of TE material research. This review focuses on major novel strategies to achieve high‐performance TE materials and their applications. Manipulating the carrier concentration and band structures of materials are effective in optimizing the electrical transport properties, while nanostructure engineering and defect engineering can greatly reduce the thermal conductivity approaching the amorphous limit. Currently, TE devices are utilized to generate power in remote missions, solar–thermal systems, implantable or/wearable devices, the automotive industry, and many other fields; they are also serving as temperature sensors and controllers or even gas sensors. The future tendency is to synergistically optimize and integrate all the effective factors to further improve the TE performance, so that highly efficient TE materials and devices can be more beneficial to daily lives.
Hairy cell leukemia 2018: Update on diagnosis, risk‐stratification, and treatment
Authors: Troussard Xavier , Cornet Edouard
Published: November 2017

Disease overview

Hairy cell leukemia (HCL) and HCL‐like disorders, including HCL variant (HCL‐V) and splenic diffuse red pulp lymphoma (SDRPL), are a very heterogeneous group of mature lymphoid B‐cell disorders, characterized by the identification of hairy cells, a specific genetic profile, a different clinical course and the need for appropriate treatment.

Diagnosis

Diagnosis of HCL is based on morphological evidence of hairy cells, an HCL immunologic score of 3 or 4 based on the CD11C, CD103, CD123, and CD25 expression, the trephine biopsy which makes it possible to specify the degree of tumoral medullary infiltration and the presence of BRAF V600E somatic mutation.

Risk stratification

Progression of patients with HCL is based on a large splenomegaly, leukocytosis, a high number of hairy cells in the peripheral blood and the immunoglobulin heavy chain variable region gene mutational status. VH4‐34 positive HCL cases are associated with poor prognosis

Risk adapted therapy

Purine analogs (PNA) are indicated in symptomatic first line HCL patients. The use of PNA followed by rituximab represents an alternative option.

Management of progressive or refractory disease

It is based on the use of BRAF inhibitors associated or not with MEK inhibitors, recombinant immunoconjugates targeting CD22 or BCR inhibitors.
N‐Heterocyclic‐Carbene‐Catalyzed Reactions of Nitroalkenes: Synthesizing Important Building Blocks
Authors: Maji Biswajit
Published: November 2017

The recent developments of N‐heterocyclic carbene (NHC)‐catalyzed acyl anion equivalent (Stetter reaction), homoenolate, and enolate reactions with reactive nitroalkenes as Michael acceptors are described. The unique strategies for NHC‐catalyzed C−C bond‐forming reactions using nitroalkenes for the synthesis of synthetic building blocks, in particular asymmetric approaches, are systematically presented. Advances in the single‐electron‐transfer reaction combined with the use of NHCs as organocatalysts are also discussed, with nitroalkenes acting as important coupling partners. This Focus Review brings together both the accomplishments and the future work needed in this important area.
Stability of Residual Oxides in Oxide‐Derived Copper Catalysts for Electrochemical CO2 Reduction Investigated with 18O Labeling
Authors: Lum Yanwei , Ager Joel W.
Published: November 2017

Oxide‐derived (OD) Cu catalysts have high selectivity towards the formation of multi‐carbon products (C2/C3) for aqueous electrochemical CO2 reduction (CO2R). It has been proposed that a large fraction of the initial oxide can be surprisingly resistant to reduction, and these residual oxides play a crucial catalytic role. The stability of residual oxides was investigated by synthesizing 18O‐enriched OD Cu catalysts and testing them for CO2R. These catalysts maintain a high selectivity towards C2/C3 products (ca. 60 %) for up to 5 h in 0.1 m KHCO3 at −1.0 V vs. RHE. However, secondary‐ion mass spectrometry measurements show that only a small fraction (<1 %) of the original 18O content remains, showing that residual oxides are not present in significant amounts during CO2R. Furthermore, we show that OD Cu can reoxidize rapidly, which could compromise the accuracy of ex situ methods for determining the true oxygen content.
Dynamic delayed controllers for recycling systems with internal delays and complex poles
Authors: Vazquez‐Guerra R. J. , Marquez‐Rubio J. F. , Hernández‐Pérez M. A. , del Muro‐Cuéllar B. , Sánchez‐García J. C.
Published: November 2017

Recycling systems are a challenging problem from the control viewpoint due to their detrimental effects. This paper proposes a simple way to stabilize and control a class of high‐order recycling systems with time delays, internal instability, and possible complex conjugate poles. The strategy proposes P/PI/PD/PID‐like delayed controllers. Conditions to guarantee the stability of the controlled closed‐loop system are stated. The performance of the proposed delayed controllers is illustrated via numerical simulations of a high‐order unstable recycling system and an industrial chemical process.
Loading rate sensitivity of liquid nitrogen conditioned glass fiber reinforced polymeric composites: An emphasis on tensile and thermal responses
Authors: Mahato Kishore Kumar , Dutta Krishna , Ray Bankim Chandra
Published: November 2017

Glass fiber reinforced polymeric (GFRP) composites are being accepted as potential materials for ultra‐low temperature applications. The current investigation is to evaluate effect of liquid nitrogen (LN2) conditioning (for different intervals of time) on the loading rate sensitivity of tensile response of GFRP composites. In order to assess this, tensile tests of the unconditioned and conditioned specimens were carried out at different crosshead speeds viz. 1, 10, 100, 500, and 1000 mm/min. At 1 mm/min crosshead speed, an improvement of 3.33% and 7.3% ultimate tensile strength (UTS) value was observed in case of 0.25 and 1 h conditioned GFRP composites, respectively, as compared to unconditioned GFRP composites. Similarly, the specimens tested at 1000 mm/min show an improvement of 11.39% and 12.02% UTS for 0.25 and 1 h LN2 conditioned GFRP composites, respectively, as compared to unconditioned GFRP composites. Effect of LN2 conditioning on crosshead speed sensitivity of modulus and strain at break are also reported. The in‐service temperature of the GFRP composite was measured using temperature modulated differential scanning calorimetry. Furthermore, dynamic mechanical thermal analyzer was used in the temperature range (40–200 °C) to correlate the mechanical and thermomechanical response of the GFRP composites. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45856.
Strengthening of electromechanical properties for poly(vinylidene fluoride‐trifluoroethylene) films under tailored electric cycling
Authors: Jing W.Q. , Fang F. , Yang W.
Published: November 2017

Copolymers of polyvinylidene fluoride and trifluorethylene [P(VDF‐TrFE)] have potential applications in wearable and implantable electromechanical devices since they are mechanically flexible, and biocompatible. A tailored electric cyclic process is employed to enhance both electrical and mechanical properties in P(VDF‐TrFE) 65/35 mol % copolymer films. The films are subjected to lower and higher field magnitude electric cycling successively. For electrical properties, enhancement in remnant polarization, dielectric and piezoelectric constants occurs. From mechanical point of view, strengthening in the fracture strength happens. Wide‐angle X‐ray diffraction techniques examine changes of the orientation of the molecular chains, grain size, and crystallinity after electric cycling for the copolymer films. Scanning electron microscopy reveals evolutions of the microstructure, including rod‐like textures and fractography of the films. The results indicate that electric cycling causes the molecular chains to orient gradually along the direction perpendicular to the applied electric field. Consequently, an enhancement of 12.2% and 45% is realized for the remnant polarization and fracture strength, respectively for P(VDF‐TrFE) 65/35 copolymer film. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45926.
Nanoencapsulation of intercalated montmorillonite‐urea within PVA nanofibers: Hydrogel fertilizer nanocomposite
Authors: Azarian Mohammad Hossein , Kamil Mahmood Wan Ahmad , Kwok Eunice , Bt Wan Fathilah Wan Farahhanim , Binti Ibrahim Nor Fazilah
Published: November 2017

This study describes the preparation and characterization of nanofibers with poly(vinyl alcohol) (PVA) as the wall matrix to encapsulate montmorillonite (MMT) clay and intercalated MMT‐urea nanocomposite using an electrospinning technique. Nanofibers encapsulated with (1–5%, w/w) MMT clay were successfully produced and characterized in relation to morphological, spectroscopic, structural, surface, and thermal properties. The electrospinning conditions for voltage, flow‐rate, and emitter to collector distance were 20 kV, 0.5, and 0.25 mL/h, and 10 cm, respectively. The surface roughness increased from 43.5 (empty fibers) to 56 nm in the PVA/MMT‐3% and bead‐less nanofibers were formed with the maximum diameter distribution and mean diameter value of 45–80 and 62 nm, respectively. The d‐spacing was increased significantly from 1.004 in MMT to 1.684 nm in MMT‐urea, indicating the intercalation of urea occurred successfully. Furthermore, elemental analysis results showed that the intercalated MMT‐urea contained 30.4% nitrogen. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45957.
Preparation and characterization of a superabsorbent slow‐release fertilizer with sodium alginate and biochar
Authors: Baki M. , Abedi‐Koupai J.
Published: November 2017

A novel hydrogel was synthesized through the graft copolymerization of acrylic acid (AA) and acrylamide (AM) onto sodium alginate with ammonium persulfate as the initiator, methylene bisacrylamide as the crosslinking agent, and calcium chloride as the precipitating agent. Rapeseed meal biochar made at 300 °C was also used. A series of graft copolymers with various molar ratio of AA to AM was prepared. The structures of the hydrogels were characterized by Fourier transform infrared spectroscopy and scanning electron microscopy. The free absorbency and rate of release were investigated. The grafting efficiency increased as the concentration of AM increased. There was a considerable percentage of nitrogen in the graft copolymers, and the release rate of nitrogen from fertilizer in soil and water decreased with increasing concentration of AM. The water retention of soil without hydrogel remained at 63 and 53.4% on the 10th and 20th days, but with the hydrogels, it was above 70% even on the last day. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45966.
Fabrication of ceramic nanofibers using polydimethylsiloxane and polyacrylonitrile polymer blends
Authors: Al‐Ajrah Saja , Lafdi Khalid , Liu Yufei , Le Coustumer Philippe
Published: November 2017

Nanofibers with several hundred of nanometers were successfully fabricated using electrospinning process and a mixture of two types of polymers which are: polydimethylsiloxane and polyacrylonitrile as precursors. After stabilization and carbonization at 1000 °C, three phases which are: silicon carbide (SiC), carbon, and oxy‐SiC were presented. Spectroscopic and microscopic techniques had confirmed the presence of nanocrystalline SiC and turbostratic carbons. These phases formed an intertwined network at the nanometric scale. In addition, the resulted fibers showed a core‐skin effect with skin richer in carbon and a core mainly dominated by silicon‐based phases in the form SiC or SiOC ceramics. A significant improvement was observed in both tensile strength and elastic modulus in these hybrid fibers. In term of crystallography, these nanofibers seem to exhibit similar microstructure that was observed in Nicalon fiber. However, it was difficult to determine the ratio of these phases and their influence on the physical properties of these hybrid fibers. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45967.
Synthesis, Biological Evaluation, and Molecular Modeling Study of Substituted Benzyl Benzamides as CETP Inhibitors
Authors: Abu Khalaf Reema , Sabbah Dima , Al‐Shalabi Eveen , Bishtawi Samar , Albadawi Ghadeer , Abu Sheikha Ghassan
Published: November 2017

Cardiovascular disease is the most common cause for mortality and morbidity in the developed world; its risk is inversely related to the high‐density lipoprotein (HDL) cholesterol levels. Therefore, there is a great interest in developing new cholesteryl ester transfer protein (CETP) inhibitors capable of raising HDL as a novel approach for the prevention of cardiovascular disease. Herein, the synthesis and characterization of ten benzyl benzamides 8a–j that aim at CETP inhibition was performed. The in vitro CETP inhibition bioassay revealed that benzamide 8j had the best activity, with a percent inhibition of 82.2% at 10 μM concentration and an IC50 value of 1.3 μM. The docking study shows that the verified compounds accommodate the binding cleft of CETP and are enclosed by a hydrophobic lining. Furthermore, the scaffold of 8a–j matches the pharmacophoric points of CETP inhibitors, particularly in its hydrophobic and aromatic functionalities.
Exploring anatomy and physiology using iPad applications
Authors: Chakraborty Tandra R. , Cooperstein Deborah F.
Published: November 2017

This study examined the use of iPads with anatomy applications (apps) in the laboratory sections of the largest undergraduate course at the university, Anatomy and Physiology, serving more than 300 students. The majority of these students were nursing, exercise science/physical education and biology majors. With a student survey (student opinion) and student practicum grades as metrics, this study determined whether the introduction of this novel mobile technology improved student grades and aided the students in learning the course material. The results indicated that students’ grades improved with the introduction of the iPads, and 78% of the students reported that the iPads facilitated their ability to learn the course material. There was a positive association between frequency of app use and standardized mastery of the course material, as students who used the apps more frequently scored higher and indicated that they felt as though they had learned the material more comprehensively. Owning or having an iPad at home did not have a significant effect on the learning of the material. The general consensus by students was that iPad anatomy apps should be used frequently to better develop student understanding of the course material. Anat Sci Educ 11: 336–345. © 2017 American Association of Anatomists.
Cover Image, Volume 11, Issue 6
Authors: Woolf Dominic , Lehmann Johannes , Joseph Stephen , Campbell Christopher , Christo Farid C. , Angenent Largus T.
Published: November 2017

The cover image, by Dominic Woolf et al., is based on the In the Field An open‐source biomass pyrolysis reactor, DOI: 10.1002/bbb.1814.

image
Asymptotic distributions of kappa statistics and their differences with many raters, many rating categories and two conditions
Authors: Grassano Luca , Pagana Guido , Daperno Marco , Bibbona Enrico , Gasparini Mauro
Published: November 2017

In clinical research and in more general classification problems, a frequent concern is the reliability of a rating system. In the absence of a gold standard, agreement may be considered as an indication of reliability. When dealing with categorical data, the well‐known kappa statistic is often used to measure agreement. The aim of this paper is to obtain a theoretical result about the asymptotic distribution of the kappa statistic with multiple items, multiple raters, multiple conditions, and multiple rating categories (more than two), based on recent work. The result settles a long lasting quest for the asymptotic variance of the kappa statistic in this situation and allows for the construction of asymptotic confidence intervals. A recent application to clinical endoscopy and to the diagnosis of inflammatory bowel diseases (IBDs) is shortly presented to complement the theoretical perspective.
Anticancer Activity of 2‐Amino‐substituted‐1,4‐naphthoquinone Derivatives in Ovarian Cancer Cells
Authors: Shin Sujeong , Lee Haneul , Jeon Cheolmin , Preya Umma Hafsa , Choi Jung‐Hye , Park Jeong Ho
Published: November 2017

2‐Amino‐substituted‐1,4‐naphthoquinone derivatives (10–17) were synthesized from coupling reaction between 1,4‐dihydroxynaphthalene and amines in the presence of catalyst CeCl3.7H2O. Their anticancer activity was evaluated by using three ovarian cancer cells (A2780, SKOV3, and OVCAR3). Among the eight compounds, compound 13 containing metal chelating moiety had a relatively potent cytotoxic activity (IC50 < 10 μM) on all three ovarian cancer cells.
Massive hemorrhage following definitive esophageal chemoradiation: teaching case of a fatal aortoesophageal fistula and lessons learned
Authors: McGinnis Gwendolyn J. , Holland John M. , Thomas Charles R. , Nabavizadeh Nima
Published: November 2017

Key Clinical Message

Esophageal self‐expandable metal stents and radiotherapy are valuable in combination for palliation and definitive treatment of esophageal cancer. However, risk of aortoesophageal fistula is significant in patients with evidence of malignant aortic invasion. Use of thoracic endovascular repair may represent an approach to early intervention in high‐risk patients.
Accidental knotting and subsequent removal of a catheter from the epidural space in an adult cow: a case report
Authors: Doodnaught Graeme M. , Constant Caroline , Desrochers André , Pang Daniel S. J.
Published: November 2017

Key Clinical Message

This is the first reported case in the veterinary literature of a knot in an epidural catheter. The report reviews this very rare complication and describes options for investigation and retrieval of catheters entrapped in the epidural space of any species.
Interfering with DNA High‐Order Structures using Chiral Ruthenium(II) Complexes
Authors: Zou Shanshan , Li Guanying , Rees Thomas W. , Jin Chengzhi , Huang Juanjuan , Chen Yu , Ji Liangnian , Chao Hui
Published: November 2017

In this work, it was found that DNA can undergo B‐Z transformational changes and compaction in the presence of DNA intercalators such as ruthenium(II) polypyridyl complexes. The link between B‐Z transition and condensation is weak but can be strengthened under certain circumstances with slight alterations to the structures of the ruthenium(II) complexes. Here, following on from previous research, this work reports a series of ruthenium(II) complexes with imidazophenanthroline ligands, which vary in size and planarity. The complexes exhibit distinct effects on DNA structures, ranging from little impact to the transformation of DNA secondary structures to the formation of higher‐order DNA structures. Further studies on DNA morphological changes induced by chiral ruthenium(II) complexes are observed by atomic force microscopy and transmission electron microscopy.
From Peptide Fragments to Whole Protein: Copper(II) Load and Coordination Features of IAPP
Authors: Magrì Antonio , Pietropaolo Adriana , Tabbì Giovanni , La Mendola Diego , Rizzarelli Enrico
Published: November 2017

The copper‐binding features of rat islet amyloid polypeptide (r‐IAPP) are herein disclosed through the determination of the stability constants and spectroscopic properties of its copper complex species. To mimic the metal binding sites of the human IAPP (h‐IAPP), a soluble, single‐point mutated variant of r‐IAPP, having a histidine residue in place of Arg18, was synthesized, that is, r‐IAPP(1–37; R18H). The peptide IAPP(1–8) was also characterized to have deeper insight into the N‐terminus copper(II)‐binding features of r‐IAPP as well as of its mutated form. A combined experimental (thermodynamic and spectroscopic) and computational approach allowed us to assess the metal loading and the coordination features of the whole IAPP. At physiological pH, the N‐terminal amino group is the Cu2+ main binding site both of entire r‐IAPP and of its mutated form that mimics h‐IAPP. The histidine residue present in this mutated polypeptide accounts for the second Cu2+ binding. We can speculate that the copper driven toxicity of h‐IAPP in comparison to that of r‐IAPP can be attributed to the different metal loading and the presence of a second metal anchoring site, the His18, whose role is usually invoked in the process of h‐IAPP aggregation.
Global and targeted circulating microRNA profiling of colorectal adenoma and colorectal cancer
Authors: Zhang Jinhua , Raju Gottumakkala S. , Chang David W. , Lin Shu‐Hong , Chen Zhinan , Wu Xifeng
Published: November 2017

BACKGROUND

Circulating microRNAs (miRNAs) are emerging as promising biomarkers for cancer. The objective of the current study was to investigate the potential of circulating cell‐free miRNAs as biomarkers for colorectal cancer (CRC) and its precursor lesion, colorectal adenoma.

METHODS

The serum levels of 800 miRNAs were assessed in a discovery set of 21 patients with CRC, 19 patients with adenoma, and 21 healthy controls using the NanoString miRNA analysis platform. Significantly differentially expressed miRNAs were examined further in a validation cohort of 34 patients with CRC, 33 patients with adenoma, and 35 healthy controls using Fluidigm quantitative polymerase chain reaction assays.

RESULTS

The ratios between the expression values of the differentially expressed miRNAs were computed. Three miRNA ratios (miR‐17‐5p/miR‐135b, miR‐92a‐3p/miR135b, and miR‐451a/miR‐491‐5p) were validated for discriminating patients with adenoma and those with CRC from the healthy control group, and 5 miRNA ratios (let‐7b/miR‐367‐3p, miR‐130a‐3p/miR‐409‐3p, miR‐148‐3p/miR‐27b, miR‐148a‐3p/miR‐409‐3p, and miR‐21‐5p/miR‐367‐3p) were validated for discriminating patients with CRC from those with adenoma and healthy controls. The area under the receiver operating characteristic curve values for the 3 miRNA ratios in discriminating patients with adenoma from healthy controls were 0.831 and 0.735, respectively, in the discovery and validation sets. The area under the receiver operating characteristic curve values for the 5 miRNA ratios in discriminating patients with CRC from those with adenoma were 0.797 and 0.732, respectively, in the discovery and validation sets. Pathway analysis revealed that target genes regulated by the miRNAs from the miRNA ratios were enriched mainly in metabolism‐related and inflammation‐related pathways.

CONCLUSIONS

The data from the current study suggest that circulating miRNAs can distinguish patients with CRC and those with adenoma and may represent novel biomarkers for the early, noninvasive detection of CRC. Cancer 2018;124:785‐96. © 2017 American Cancer Society.
Neuroendocrine tumors and fibrosis: An unsolved mystery?
Authors: Laskaratos Faidon‐Marios , Rombouts Krista , Caplin Martyn , Toumpanakis Christos , Thirlwell Christina , Mandair Dalvinder
Published: November 2017

Neuroendocrine tumors are a heterogeneous group of slow‐growing neoplasms arising mainly from the enterochromaffin cells of the digestive and respiratory tract. Although they are relatively rare, their incidence is rising. It has long been observed that they often are associated with the development of fibrosis, both local and distant. Fibrotic complications, such as carcinoid heart disease and mesenteric desmoplasia, may lead to considerable morbidity or even affect prognosis. The elucidation of the pathophysiology of fibrosis would be of critical importance for the development of targeted therapeutic strategies. In this article, the authors review the available evidence regarding the biological basis of fibrosis in neuroendocrine tumors. They explore the role of the tumor microenvironment and the interplay between tumor cells and fibroblasts as a key factor in fibrogenesis and tumor development/progression. They also review the role of serotonin, growth factors, and other peptides in the development of carcinoid‐related fibrotic reactions. Cancer 2017;123:4770‐90. © 2017 American Cancer Society.
Longitudinal analysis of quality‐of‐life outcomes in children during treatment for acute lymphoblastic leukemia: A report from the Children's Oncology Group AALL0932 trial
Authors: Zheng Daniel J. , Lu Xiaomin , Schore Reuven J. , Balsamo Lyn , Devidas Meenakshi , Winick Naomi J. , Raetz Elizabeth A. , Loh Mignon L. , Carroll William L. , Sung Lillian , Hunger Stephen P. , Angiolillo Anne L. , Kadan‐Lottick Nina S.
Published: November 2017

BACKGROUND

Children with average‐risk acute lymphoblastic leukemia (AR‐ALL) face many challenges that can adversely affect their quality of life (QOL). However, to the authors' knowledge, patterns and predictors of QOL impairment during therapy have not been well characterized to date.

METHODS

Patients with AR‐ALL who were enrolled on the Children's Oncology Group AALL0932 trial were offered participation in this prospective cohort study if they were aged ≥4 years at the time of diagnosis and had an English‐speaking parent. At approximately 2 months, 8 months, 17 months, 26 months, and 38 months (boys only) after diagnosis, parents completed the Pediatric Quality of Life Inventory Generic Core Scales Version 4.0 (PedsQL4.0) and McMaster Family Assessment Device instruments for QOL (physical, emotional, and social functioning) and family functioning, respectively. The proportions of individuals scoring in the impaired range (2 standard deviations below the population mean) were calculated at each time point. Longitudinal impairment patterns and predictors were examined.

RESULTS

A total of 594 participants with AR‐ALL were diagnosed at a mean age of 6.0 years (standard deviation, 1.6 years). At 2 months, a substantial proportion of participants had impaired scores for physical (36.5%; 95% confidence interval [95% CI], 32.3%‐40.8%) and emotional (26.2%; 95% CI, 22.5%‐30.2%) functioning compared with population norms of 2.3%. These elevations persisted at 26 months. Emotional impairment at 2 months (odds ratio, 3.4; 95% CI, 1.5‐7.7) was found to significantly predict emotional impairment at 26 months. In repeated measures analysis with multivariate modeling, unhealthy family functioning (odds ratio, 1.5; 95% CI, 1.1‐2.1) significantly predicted emotional impairment controlling for age and sex. QOL outcomes were similar between sexes at the end of therapy (26 months for girls and 38 months for boys).

CONCLUSIONS

Many children with AR‐ALL experience physical and emotional functioning impairment that begins early in treatment and persists. Early screening may identify high‐risk patients who might benefit from family‐based interventions. Cancer 2018;124:571‐9. © 2017 American Cancer Society.
Individualized outcome prognostication for patients with laryngeal cancer
Authors: Hoban Connor W. , Beesley Lauren J. , Bellile Emily L. , Sun Yilun , Spector Matthew E. , Wolf Gregory T. , Taylor Jeremy M. G. , Shuman Andrew G.
Published: November 2017

BACKGROUND

Accurate prognostication is essential to the optimal management of laryngeal cancer. Predictive models have been developed to calculate the risk of oncologic outcomes, but extensive external validation of accuracy and reliability is necessary before implementing them into clinical practice.

METHOD

Four published prognostic calculators that predict 5‐year overall survival for patients with laryngeal cancer were evaluated using patient information from a prospective epidemiology study cohort (n = 246; median follow‐up, 60 months) with previously untreated, stage I through IVb laryngeal squamous cell carcinoma.

RESULTS

Different calculators yielded substantially different predictions for individual patients. The observed 5‐year overall survival was significantly higher than the averaged predicted 5‐year overall survival of the 4 calculators (71.9%; 95% confidence interval [CI], 65%‐78%] vs 47.7%). Statistical analyses demonstrated the calculators' limited capacity to discriminate outcomes for risk‐stratified patients. The area under the receiver operating characteristic curve ranged from 0.68 to 0.72. C‐index values were similar for each of the 4 models (range, 0.66‐0.68). There was a lower than expected hazard of death for patients who received induction (bioselective) chemotherapy (hazard ratio, 0.46; 95% CI, 0.24‐0.88; P = .024) or primary surgical intervention (hazard ratio, 0.43; 95 % CI, 0.21‐0.90; P = .024) compared with those who received concurrent chemoradiation.

CONCLUSIONS

Suboptimal reliability and accuracy limit the integration of existing individualized prediction tools into routine clinical decision making. The calculators predicted significantly worse than observed survival among patients who received induction chemotherapy and primary surgery, suggesting a need for updated consideration of modern treatment modalities. Further development of individualized prognostic calculators may improve risk prediction, treatment planning, and counseling for patients with laryngeal cancer. Cancer 2018;124:706‐16. © 2017 American Cancer Society.
A randomized study of cyclosporine and methotrexate with or without methylprednisolone for the prevention of graft‐versus‐host disease: Improved long‐term survival with triple prophylaxis
Authors: Ruutu Tapani , Nihtinen Anne , Niittyvuopio Riitta , Juvonen Eeva , Volin Liisa
Published: November 2017

BACKGROUND

In a previously published study, the authors randomized 108 adult patients with a malignant hematologic disorder undergoing allogeneic bone marrow transplantation from a human leukocyte antigen‐identical sibling to receive methylprednisolone (53 patients; MP+) or not to receive methylprednisolone (55 patients; MP‐) as a part of graft‐versus‐host disease (GVHD) prophylaxis. All patients received cyclosporine and methotrexate. The cumulative incidence of acute GVHD was found to be significantly lower among the patients given MP.

METHODS

In the current study, the authors performed a long‐term follow‐up to discover possible late effects of the intensified GVHD prophylaxis.

RESULTS

The median follow‐up for surviving patients was 24.5 years. In the MP+ group, the overall survival and recurrence‐free survival were higher (P = .021 and P = .028, respectively) and the nonrecurrence mortality was lower (P = .003) than in the MP‐ group. There was a trend toward a lower cumulative incidence and a significantly lower prevalence (P = .031) of chronic GVHD in the MP+ group. There was no difference noted with regard to the rate of disease recurrence or in the incidence of secondary malignancies. Eleven patients in the MP‐ group but none in the MP+ group died >15 years after transplantation. At the end of follow‐up, the overall survival rates in the MP+ and MP‐ groups were 55% and 20%, respectively, and the recurrence‐free survival rates were 49% and 15%, respectively.

CONCLUSIONS

Long‐term survival was found to be higher among the patients given MP in addition to cyclosporine and methotrexate. There was marked late nonrecurrence mortality observed in the group not given MP. No adverse late effects caused by the addition of corticosteroid were observed. Cancer 2018;124:727‐33. © 2017 American Cancer Society.
Performance of Ensemble Kalman Filters in Large Dimensions
Authors: Majda Andrew J. , Tong Xin T.
Published: November 2017

Contemporary data assimilation often involves more than a million prediction variables. Ensemble Kalman filters (EnKF) have been developed by geoscientists. They are successful indispensable tools in science and engineering, because they allow for computationally cheap low‐ensemble‐state approximation for extremely large‐dimensional turbulent dynamical systems. The practical finite ensemble filters like EnKF necessarily involve modifications such as covariance inflation and localization, and it is a genuine mystery why they perform so well with small ensemble sizes in large dimensions. This paper provides the first rigorous stochastic analysis of the accuracy and covariance fidelity of EnKF in the practical regime where the ensemble size is much smaller than the large ambient dimension for EnKFs with random coefficients. A challenging issue overcome here is that EnKF in huge dimensions introduces unavoidable bias and model errors that need to be controlled and estimated. © 2017 the Authors. Communications on Pure and Applied Mathematics is published by the Courant Institute of Mathematics and Wiley Periodicals, Inc.
Quantum Chemical Analyses of BH4− and BH3OH− Hydride Transfers to CO2 in Aqueous Solution with Potentials of Mean Force
Authors: Groenenboom Mitchell C. , Keith John A.
Published: November 2017

The front cover artwork is provided by the authors. The image shows two very different energy profiles for the same aqueous phase hydride transfer from a hydride donor (BH3OH−) to a CO2 molecule as modeled at 0 K and 300 K. Read the full text of the article at 10.1002/cphc.201700608.
Marine subsidies change short‐term foraging activity and habitat utilization of terrestrial lizards
Authors: Kenny Heather V. , Wright Amber N. , Piovia‐Scott Jonah , Yang Louie H. , Spiller David A. , Schoener Thomas W.
Published: November 2017

Resource pulses are brief periods of unusually high resource abundance. While population and community responses to resource pulses have been relatively well studied, how individual consumers respond to resource pulses has received less attention. Local consumers are often the first to respond to a resource pulse, and the form and timing of individual responses may influence how the effects of the pulse are transmitted throughout the community. Previous studies in Bahamian food webs have shown that detritivores associated with pulses of seaweed wrack provide an alternative prey source for lizards. When seaweed is abundant, lizards (Anolis sagrei) shift to consuming more marine‐derived prey and increase in density, which has important consequences for other components of the food web. We hypothesized that the diet shift requires individuals to alter their habitat use and foraging activity and that such responses may happen very rapidly. In this study, we used recorded video observations to investigate the immediate responses of lizards to an experimental seaweed pulse. We added seaweed to five treatment plots for comparison with five control plots. Immediately after seaweed addition, lizards decreased average perch height and increased movement rate, but these effects persisted for only 2 days. To explore the short‐term nature of the response, we used our field data to parametrize heuristic Markov chain models of perch height as a function of foraging state. These models suggest a “Synchronized‐satiation Hypothesis,” whereby lizards respond synchronously and feed quickly to satiation in the presence of a subsidy (causing an initial decrease in average perch height) and then return to the relative safety of higher perches. We suggest that the immediate responses of individual consumers to resource pulse events can provide insight into the mechanisms by which these consumers ultimately influence community‐level processes.
Water level affects availability of optimal feeding habitats for threatened migratory waterbirds
Authors: Aharon‐Rotman Yaara , McEvoy John , Zhaoju Zheng , Yu Hui , Wang Xin , Si Yali , Xu Zhenggang , Yuan Zeng , Jeong Wooseog , Cao Lei , Fox Anthony D.
Published: November 2017

Extensive ephemeral wetlands at Poyang Lake, created by dramatic seasonal changes in water level, constitute the main wintering site for migratory Anatidae in China. Reductions in wetland area during the last 15 years have led to proposals to build a Poyang Dam to retain high winter water levels within the lake. Changing the natural hydrological system will affect waterbirds dependent on water level changes for food availability and accessibility. We tracked two goose species with different feeding behaviors (greater white‐fronted geese Anser albifrons [grazing species] and swan geese Anser cygnoides [tuber‐feeding species]) during two winters with contrasting water levels (continuous recession in 2015; sustained high water in 2016, similar to those predicted post‐Poyang Dam), investigating the effects of water level change on their habitat selection based on vegetation and elevation. In 2015, white‐fronted geese extensively exploited sequentially created mudflats, feeding on short nutritious graminoid swards, while swan geese excavated substrates along the water edge for tubers. This critical dynamic ecotone successively exposes subaquatic food and supports early‐stage graminoid growth during water level recession. During sustained high water levels in 2016, both species selected mudflats, but also to a greater degree of habitats with longer established seasonal graminoid swards because access to tubers and new graminoid growth was restricted under high‐water conditions. Longer established graminoid swards offer less energetically profitable forage for both species. Substantial reduction in suitable habitat and confinement to less profitable forage by higher water levels is likely to reduce the ability of geese to accumulate sufficient fat stores for migration, with potential carryover effects on subsequent survival and reproduction. Our results suggest that high water levels in Poyang Lake should be retained during summer, but permitted to gradually recede, exposing new areas throughout winter to provide access for waterbirds from all feeding guilds.
Linking songbird nest predation to seedling density: Sugar maple masting as a resource pulse in a forest food web
Authors: Fiola Marie‐Line , Vernouillet Alizée , Villard Marc‐André
Published: November 2017

The ecological literature presents considerable evidence for top‐down forcing on the maintenance of species diversity. Yet, in temperate forests, bottom‐up forces often exert a strong influence on ecosystem functioning. Here, we report on the indirect influence of a pulsed resource, sugar maple (Acer saccharum) seed production, on nest survival in a migratory songbird. We hypothesized that seed production in year t would determine daily nest survival rate in year t + 1 through its effects on seed‐eating rodents. We used the density of sugar maple seedlings (with cotyledons) in year t + 1 as a proxy for seed production in year t and predicted that it would be inversely related to songbird nest survival the same year. We estimated the density of sugar maple seedlings, eastern chipmunk (Tamias striatus) activity, and daily nest survival rate in the ovenbird (Seiurus aurocapilla) over four successive years in a northern hardwood forest of New Brunswick, Canada. Seedling density varied by two orders of magnitude between years, whereas an index of chipmunk activity changed by an order of magnitude. Both variables were positively correlated and negatively correlated to daily nest survival rate. A logistic‐exposure model including only seedling density received the greatest level of support (lowest AICc). Previous studies have reported the effect of sugar maple masting on seed‐eating rodent populations, but the strong link we report between seedling density and songbird nest survival is novel. A nocturnal seed‐eating nest predator, deer mouse (Peromyscus maniculatus), was not considered in our models, which may explain why chipmunk was not the best predictor of daily nest survival rate. The trophic linkages we observed are remarkably strong for a temperate forest ecosystem and might become more prevalent in northeastern North America, at least on calcium‐rich soils, with the loss of large‐diameter beech trees as a result of beech bark disease.