bluuebunny/crossref_metadata_2025 huggingface dataset:
An interdisciplinary framework for participatory modeling design and evaluation—What makes models effective participatory decision tools?
Authors: Falconi Stefanie M. , Palmer Richard N.
Published: January 2017

Increased requirements for public involvement in water resources management (WRM) over the past century have stimulated the development of more collaborative decision‐making methods. Participatory modeling (PM) uses computer models to inform and engage stakeholders in the planning process in order to influence collaborative decisions in WRM. Past evaluations of participatory models focused on process and final outcomes, yet, were hindered by diversity of purpose and inconsistent documentation. This paper presents a two‐stage framework for evaluating PM based on mechanisms for improving model effectiveness as participatory tools. The five dimensions characterize the “who, when, how, and why” of each participatory effort (stage 1). Models are evaluated as “boundary objects,” a concept used to describe tools that bridge understanding and translate different bodies of knowledge to improve credibility, salience, and legitimacy (stage 2). This evaluation framework is applied to five existing case studies from the literature. Though the goals of participation can be diverse, the novel contribution of the two‐stage proposed framework is the flexibility it has to evaluate a wide range of cases that differ in scope, modeling approach, and participatory context. Also, the evaluation criteria provide a structured vocabulary based on clear mechanisms that extend beyond previous process‐based and outcome‐based evaluations. Effective models are those that take advantage of mechanisms that facilitate dialogue and resolution and improve the accessibility and applicability of technical knowledge. Furthermore, the framework can help build more complete records and systematic documentation of evidence to help standardize the field of PM.
Quantifying streambed advection and conduction heat fluxes
Authors: Caissie Daniel , Luce Charles H.
Published: January 2017

Groundwater and accompanying heat fluxes are particularly relevant for aquatic habitats as they influence living conditions both within the river and streambed. This study focuses on the theory and the development of new equations to estimate conduction and advection heat fluxes into and out of the bed, correcting some earlier misunderstandings and adding parameterizations that extend our understanding of timing of heat fluxes. The new heat flux equations are illustrated using Catamaran Brook (New Brunswick, Canada) stream/streambed temperature data. We show important relationships between fluxes when the surface water temperature (1) follows a sinusoidal function superimposed on a steady state condition (constant deep streambed temperature) and (2) when sinusoidal variations in stream temperature at two frequencies (annual and diel) are superimposed. When the stream temperature is used as a prescribed boundary condition, the contribution of bed fluid fluxes to stream temperature occurs through the effects of conductive thermal gradients, not through direct contribution/mixing of cold/warm water. Boundary conditions can be modified, however, to account for direct contribution of cold/warm water (e.g., localized upwelling) and consequences for the conduction heat flux. Equations developed allow for prediction of conductive fluxes to the bed during summer driven by diel and annual temperature fluctuations of the stream water and good agreement was observed between analytic solutions and field data. Results from this study provide a better insight into groundwater and heat fluxes which will ultimately result in better stream temperature models and a better management of fisheries resources.
Impact of saturation on dispersion and mixing in porous media: Photobleaching pulse injection experiments and shear‐enhanced mixing model
Authors: Jiménez‐Martínez Joaquín , Le Borgne Tanguy , Tabuteau Hervé , Méheust Yves
Published: January 2017

The dynamics of solute dispersion and mixing in unsaturated flows is analyzed from photobleaching experiments in two‐dimensional porous micromodels. This technique allows producing pulse line (delta‐Dirac) injections of a conservative tracer by bleaching a finite volume of fluorescent without disturbing the flow field. The temporal evolution of the concentration field and the spatial distribution of the air and water phases can be monitored at pore scale. We study the dispersion and mixing of a line of tracer under different water saturations. While dispersion in saturated porous media follows an approximately Fickian scaling, a shift to ballistic scaling is observed as soon as saturation is lowered. Hence, at the time scale of observation, dispersion in our unsaturated flows is dominated by the ballistic separation of tracer blobs within the water phase, between trapped clusters and preferential flow paths. While diffusion plays a minor role in the longitudinal dispersion during the time scale of the experiments, its interplay with fluid deformation is apparent in the dynamics of mixing. The scalar dissipation rates show an initial stretching regime, during which mixing is enhanced by fluid deformation, followed by a dissipation regime, during which diffusion overcomes compression induced by stretching. The transition between these two regimes occurs at the mixing time, when concentration gradients are maximum. We propose a predictive analytical model, based on shear‐enhanced diffusion, that captures the dynamics of mixing from basic unsaturated porous media parameters, suggesting that this type of model may be a useful framework at larger scales.
Water quality data for national‐scale aquatic research: The Water Quality Portal
Authors: Read Emily K. , Carr Lindsay , De Cicco Laura , Dugan Hilary A. , Hanson Paul C. , Hart Julia A. , Kreft James , Read Jordan S. , Winslow Luke A.
Published: January 2017

Aquatic systems are critical to food, security, and society. But, water data are collected by hundreds of research groups and organizations, many of which use nonstandard or inconsistent data descriptions and dissemination, and disparities across different types of water observation systems represent a major challenge for freshwater research. To address this issue, the Water Quality Portal (WQP) was developed by the U.S. Environmental Protection Agency, the U.S. Geological Survey, and the National Water Quality Monitoring Council to be a single point of access for water quality data dating back more than a century. The WQP is the largest standardized water quality data set available at the time of this writing, with more than 290 million records from more than 2.7 million sites in groundwater, inland, and coastal waters. The number of data contributors, data consumers, and third‐party application developers making use of the WQP is growing rapidly. Here we introduce the WQP, including an overview of data, the standardized data model, and data access and services; and we describe challenges and opportunities associated with using WQP data. We also demonstrate through an example the value of the WQP data by characterizing seasonal variation in lake water clarity for regions of the continental U.S. The code used to access, download, analyze, and display these WQP data as shown in the figures is included as supporting information.
Clinical and Serologic Features in Patients With Incomplete Lupus Classification Versus Systemic Lupus Erythematosus Patients and Controls
Authors: Aberle Teresa , Bourn Rebecka L. , Munroe Melissa E. , Chen Hua , Roberts Virginia C. , Guthridge Joel M. , Bean Krista , Robertson Julie M. , Sivils Kathy L. , Rasmussen Astrid , Liles Meghan , Merrill Joan T. , Harley John B. , Olsen Nancy J. , Karp David R. , James Judith A.
Published: January 2017

Objective

Incomplete lupus erythematosus (ILE) involves clinical and/or serologic manifestations consistent with but insufficient for systemic lupus erythematosus (SLE) classification. Because the nature of ILE is poorly understood and no treatment recommendations exist, we examined the clinical manifestations, medication history, and immunologic features in a diverse collection of ILE and SLE patients.

Methods

Medical records of subjects enrolled in the Lupus Family Registry and Repository were reviewed for medication history and American College of Rheumatology (ACR) classification criteria to identify ILE patients (3 ACR criteria; n = 440) and SLE patients (≥4 ACR criteria; n = 3,397). Participants completed the Connective Tissue Disease Screening Questionnaire. Anticardiolipin and plasma B lymphocyte stimulator (BLyS) were measured by enzyme‐linked immunosorbent assay, antinuclear antibodies (ANAs) by indirect immunofluorescence, and 13 autoantibodies by bead‐based assays.

Results

On average, ILE patients were older than SLE patients (46.2 years versus 42.0 years; P < 0.0001), and fewer ILE patients were African American (23.9% versus 32.2%; P < 0.001). ILE patients exhibited fewer autoantibody specificities than SLE patients (1.3 versus 2.6; P < 0.0001) and were less likely to have ANA titers ≥1:1,080 (10.5% versus 19.5%; P < 0.0001). BLyS levels were intermediate in ILE patients (controls < ILE; P = 0.016; ILE < SLE; P = 0.008). Pericarditis, renal, or neurologic manifestations occurred in 12.5% of ILE patients and were associated with non–European American race/ethnicity (P = 0.012). Hydroxychloroquine use increased over time, but was less frequent in ILE than SLE patients (65.2% versus 83.1%; P < 0.0001).

Conclusion

Although usually characterized by milder symptoms, ILE manifestations may require immunomodulatory treatments. Longitudinal studies are necessary to understand how ILE affects organ damage and future SLE risk, and to delineate molecular pathways unique to ILE.
Multicomponent Injectable Hydrogels for Antigen‐Specific Tolerogenic Immune Modulation
Authors: Verbeke Catia S. , Gordo Susana , Schubert David A. , Lewin Sarah A. , Desai Rajiv M. , Dobbins Jessica , Wucherpfennig Kai W. , Mooney David J.
Published: January 2017

Biomaterial scaffolds that enrich and modulate immune cells in situ can form the basis for potent immunotherapies to elicit immunity or reëstablish tolerance. Here, the authors explore the potential of an injectable, porous hydrogel to induce a regulatory T cell (Treg) response by delivering a peptide antigen to dendritic cells in a noninflammatory context. Two methods are described for delivering the BDC peptide from pore‐forming alginate gels in the nonobese diabetic mouse model of type 1 diabetes: encapsulation in poly(lactide‐co‐glycolide) (PLG) microparticles, or direct conjugation to the alginate polymer. While particle‐based delivery leads to antigen‐specific T cells responses in vivo, PLG particles alter the phenotype of the cells infiltrating the gels. Following gel‐based peptide delivery, transient expansion of endogenous antigen‐specific T cells is observed in the draining lymph nodes. Antigen‐specific T cells accumulate in the gels, and, strikingly, ≈60% of the antigen‐specific CD4+ T cells in the gels are Tregs. Antigen‐specific T cells are also enriched in the pancreatic islets, and administration of peptide‐loaded gels does not accelerate diabetes. This work demonstrates that a noninflammatory biomaterial system can generate antigen‐specific Tregs in vivo, which may enable the development of new therapies for the treatment of transplant rejection or autoimmune diseases.
Microstructured Blood Vessel Surrogates Reveal Structural Tropism of Motile Malaria Parasites
Authors: Muthinja Mendi J. , Ripp Johanna , Hellmann Janina K. , Haraszti Tamas , Dahan Noa , Lemgruber Leandro , Battista Anna , Schütz Lucas , Fackler Oliver T. , Schwarz Ulrich S. , Spatz Joachim P. , Frischknecht Friedrich
Published: January 2017

Plasmodium sporozoites, the highly motile forms of the malaria parasite, are transmitted naturally by mosquitoes and traverse the skin to find, associate with, and enter blood capillaries. Research aimed at understanding how sporozoites select blood vessels is hampered by the lack of a suitable experimental system. Arrays of uniform cylindrical pillars can be used to study small cells moving in controlled environments. Here, an array system displaying a variety of pillars with different diameters and shapes is developed in order to investigate how Plasmodium sporozoites associate to the pillars as blood vessel surrogates. Investigating the association of sporozoites to pillars in arrays displaying pillars of different diameters reveals that the crescent‐shaped parasites prefer to associate with and migrate around pillars with a similar curvature. This suggests that after transmission by a mosquito, malaria parasites may use a structural tropism to recognize blood capillaries in the dermis in order to gain access to the blood stream.
Ligand‐Controlled Palladium‐Catalyzed Pyridylation of 1‐tert‐Butoxycarbonyl‐3‐iodoazetidine: Regioselective Synthesis of 2‐ and 3‐Heteroarylazetidines
Authors: Zhang Yudan , Geng Zhiyue , Li Jingya , Zou Dapeng , Wu Yangjie , Wu Yusheng
Published: January 2017

The first efficient regioselective pyridylation of 1‐tert‐butoxycarbonyl‐3‐iodoazetidine to produce 2‐ and 3‐heteroarylazetidines under palladium‐catalyzed conditions has been developed. The established direct pyridylation of azetidines affords 2‐ vs. 3‐heteroarylazetidines in moderate to good yields (up to 92%) and with good regioselectivity (up to 98:2) by using different ligands.

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Dual‐drug release from chitin‐based core–shell microspheres fabricated by coaxial electrospray
Authors: Shang Yu , Ding Fuyuan , Liu Jian , Xiao Ling , Deng Hongbing , Du Yumin , Shi Xiaowen
Published: January 2017

Polymeric core–shell microspheres have been widely applied in dual‐drug release system for their convenience to treat diseases through multiple therapies. In this contribution, acrylamide‐modified chitin (AMC)/chitosan (CS) core–shell microspheres were prepared by a coaxial electrospray method under mild conditions. The dimension of the microspheres and thickness of the layer can be delicately controlled by changing the feed rate of spray solutions and the applied voltage. The core–shell structure of the microspheres was characterized by Fourier transform infrared spectra (FT‐IR), scanning electron microscope (SEM), and stereo fluorescence microscope. To investigate the dual‐drug release behavior of the core–shell microspheres, small molecular FITC‐dextran and macromolecular dextran blue 2000 were chosen as model drugs. The release rate of small molecular FITC‐dextran was higher than macromolecular dextran blue 2000 regardless of the location of FITC‐dextran in the microspheres. The biocompatibility, biodegradability, and dual‐drug release behavior of the core–shell microspheres endow it with potential applications in combination therapies.
Porous Ionic Membrane Based Flexible Humidity Sensor and its Multifunctional Applications
Authors: Li Tie , Li Lianhui , Sun Hongwei , Xu Yan , Wang Xuewen , Luo Hui , Liu Zheng , Zhang Ting
Published: January 2017

A highly flexible porous ionic membrane (PIM) is fabricated from a polyvinyl alcohol/KOH polymer gel electrolyte, showing well‐defined 3D porous structure. The conductance of the PIM changes more than 70 times as the relative humidity (RH) increases from 10.89% to 81.75% with fast and reversible response at room temperature. In addition, the PIM‐based sensor is insensitive to temperature (0–95 °C) and pressure (0–6.8 kPa) change, which indicates that it can be used as highly selective flexible humidity sensor. A noncontact switch system containing PIM‐based sensor is assembled, and results show that the switch responds favorably to RH change caused by an approaching finger. Moreover, an attachable smart label using PIM‐based sensor is explored to measure the water contents of human skin, which shows a great linear relationship between the sensitivity of the sensor and the facial water contents measured by a commercial reference device.
Fruit availability drives the distribution of a folivorous–frugivorous primate within a large forest remnant
Authors: Camaratta Danielle , Chaves Óscar M. , Bicca‐Marques Júlio César
Published: January 2017

Understanding the ecological factors that influence the presence, abundance, and distribution of species within their habitats is critical for ensuring their long‐term conservation. In the case of primary consumers, such as most primates, the availability and richness of plant foods are considered key drivers of population density at these variables influence the spatial distribution of social units within a finer, habitat patch level scale. We tested the hypothesis that the spatiotemporal availability and richness of plant foods, drive the spatial distribution of brown howler monkeys (Alouatta guariba clamitans) at a fine spatial scale. We established five line transects (2.6–4.3 km long) to census the population of brown howlers in Morro São Pedro, a 1,200 ha Atlantic forest remnant in southern Brazil, every 2 weeks from January to June 2015. We used data from tree inventories performed in sighting and control plots, and phenological surveys of 17 top food tree species to estimate bi‐weekly food availability. We recorded a total of 95 sightings. The number of sightings per sampling period ranged from 2 to 12. The availability of fruit (ripe and unripe) was higher in sighting than in control plots, whereas leaf availability and the richness of food tree species was similar. We conclude that the spatial distribution of fruiting trees and the availability of fruit drive the pattern of habitat use, and spacing of brown howler groups in Morro São Pedro.
Total energy expenditure in captive capuchins (Sapajus apella)
Authors: Edwards Wren , Lonsdorf Elizabeth V. , Pontzer Herman
Published: January 2017

Primates have markedly lower total energy expenditure (TEE; kcal/day) than other placental mammals, expending approximately 50% less energy for their mass than non‐primate eutherians. However, little is known regarding interspecific variation of energy expenditure within platyrrhine primates. We investigated TEE in captive tufted capuchins (Sapajus apella, n = 8, ages 7–36), a frugivorous platyrrhine, to compare TEE with other placental mammals and primates. We tested the hypothesis that large‐brained capuchins would exhibit greater TEE than other platyrrhines that are less encephalized. We used the doubly labeled water (DLW) method to measure TEE over 7–11 days, during which physical activity data were recorded via focal observation. TEE was strongly correlated with fat free mass, but sex, age, and rates of walking and climbing were not correlated with variation in TEE in multivariate analyses controlling for fat free mass. We found evidence that daily physical activity was negatively correlated with body fat percentage. Capuchin TEE was similar (P = 0.67) to other, less encephalized platyrrhines (Callithrix and Alouatta) and 54% lower than other placental mammals, in analyses controlling for body mass. These results suggest that brain size and physical activity do not necessarily influence variation in daily energy expenditure across primate species.
Steep pH Gradients and Directed Colloid Transport in a Microfluidic Alkaline Hydrothermal Pore
Authors: Möller Friederike M. , Kriegel Franziska , Kieß Michael , Sojo Victor , Braun Dieter
Published: January 2017

All life on earth depends on the generation and exploitation of ionic and pH gradients across membranes. One theory for the origin of life proposes that geological pH gradients were the prebiotic ancestors of these cellular disequilibria. With an alkaline interior and acidic exterior, alkaline vents match the topology of modern cells, but it remains unknown whether the steep pH gradients persist at the microscopic scale. Herein, we demonstrate the existence of 6 pH‐unit gradients across micrometer scales in a microfluidic vent replicate. Precipitation of metal sulfides at the interface strengthens the gradients, but even in the absence of precipitates laminar flow sustains the disequilibria. The gradients drive directed transport at the fluid interface, leading to colloid accumulation or depletion. Our results confirm that alkaline vents can provide an exploitable pH gradient, supporting their potential role at the emergence of chemiosmosis and the origin of life.
Peficitinib, a JAK Inhibitor, in Combination With Limited Conventional Synthetic Disease‐Modifying Antirheumatic Drugs in the Treatment of Moderate‐to‐Severe Rheumatoid Arthritis
Authors: Genovese Mark C. , Greenwald Maria , Codding Christine , Zubrzycka‐Sienkiewicz Anna , Kivitz Alan J. , Wang Annie , Shay Kathyjo , Wang Xuegong , Garg Jay P. , Cardiel Mario H.
Published: January 2017

Objective

To evaluate the efficacy and safety of orally administered once‐daily peficitinib in combination with limited conventional synthetic disease‐modifying antirheumatic drugs (csDMARDs) in patients with moderate‐to‐severe rheumatoid arthritis (RA).

Methods

In this randomized, double‐blind, phase IIb trial, patients with RA (n = 289) were treated with peficitinib 25 mg, 50 mg, 100 mg, or 150 mg or matching placebo once daily for 12 weeks. The primary end point was the percentage of patients who met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) at week 12.

Results

ACR20 response rates at week 12 were 22.0%, 36.8%, 48.3% (P < 0.05), 56.3% (P < 0.01), and 29.4% in the peficitinib 25 mg, 50 mg, 100 mg, 150 mg, and placebo groups, respectively. Patients in the peficitinib 100 mg and 150 mg groups achieved a rapid and statistically significant ACR20 response compared with those in the placebo group (P < 0.05), reaching statistical significance by week 2. Overall, the incidence of adverse events (AEs) was similar between patients receiving peficitinib and those receiving placebo. The most common AEs were upper respiratory tract infection (5% [n = 15]), nausea (4% [n = 12]), and urinary tract infection (4% [n = 10]). There was 1 case of herpes zoster in the placebo group, and 1 serious infection (limb abscess) in the peficitinib 25 mg group. There were no incidences of grade 2 or higher neutropenia or lymphopenia.

Conclusion

In patients with moderate‐to‐severe RA, orally administered once‐daily peficitinib in combination with limited csDMARDs resulted in a dose‐dependent ACR20 response rate over 12 weeks with satisfactory tolerability.
Cerebrospinal Fluid Cytokines Correlate With Aseptic Meningitis and Blood–Brain Barrier Function in Neonatal‐Onset Multisystem Inflammatory Disease: Central Nervous System Biomarkers in Neonatal‐Onset Multisystem Inflammatory Disease Correlate With Central Nervous System Inflammation
Authors: Rodriguez‐Smith Jackeline , Lin Yen‐Chih , Tsai Wanxia Li , Kim Hanna , Montealegre‐Sanchez Gina , Chapelle Dawn , Huang Yan , Sibley Cailin H. , Gadina Massimo , Wesley Robert , Bielekova Bibiana , Goldbach‐Mansky Raphaela
Published: January 2017

Objective

To evaluate proinflammatory cytokines and leukocyte subpopulations in the cerebrospinal fluid (CSF) and blood of patients with neonatal‐onset multisystem inflammatory disease (NOMID) after treatment, and to compare inflammatory cytokines in the CSF and blood in 6 patients treated with 2 interleukin‐1 (IL‐1) blockers—anakinra and canakinumab.

Methods

During routine follow‐up visits between December 2011 and October 2013, we immunophenotyped the CSF of 17 pediatric NOMID patients who were treated with anakinra, and analyzed CSF cytokine levels in samples obtained at baseline and at 3–5‐year follow‐up visits and compared them to samples from healthy controls.

Results

CSF levels of IL‐6, interferon‐γ–inducible 10‐kd protein (IP‐10/CXCL10), and IL‐18 and monocyte and granulocyte counts significantly decreased with anakinra treatment but did not normalize to levels in the controls, even in patients fulfilling criteria for clinical remission. CSF IL‐6 and IL‐18 levels significantly correlated with measures of blood–brain barrier function, specifically CSF protein (r = 0.75 and r = 0.81, respectively) and albumin quotient (r = 0.79 and r = 0.68, respectively). When patients were treated with canakinumab versus anakinra, median CSF white blood cell counts and IL‐6 levels were significantly higher with canakinumab treatment (10.2 cells/mm3 versus 3.7 cells/mm3 and 150.7 pg/ml versus 28.5 pg/ml, respectively) despite similar serum cytokine levels.

Conclusion

CSF leukocyte subpopulations and cytokine levels significantly improve with optimized IL‐1 blocking treatment, but do not normalize. The correlation of CSF IL‐6, IP‐10/CXCL10, and IL‐18 levels with clinical laboratory measures of inflammation and blood–brain barrier function suggests that they may have a role as biomarkers in central nervous system (CNS) inflammation. The difference in inhibition of CSF biomarkers between 2 IL‐1 blocking agents, anakinra and canakinumab, suggests differences in efficacy in the intrathecal compartment, with anakinra being more effective. Our data indicate that intrathecal immune responses shape CNS inflammation and should be assessed in addition to blood markers.
Examining the epistemology of impact and success of educational interventions using a reflective case study of university bursaries
Authors: Harrison Neil , McCaig Colin
Published: January 2017

This paper engages with the continuing emphasis given to evidence‐based policy and ‘what works’ approaches in educational research, highlighting some of the continuing epistemological challenges from a post‐positivist perspective. To illustrate these, it uses the case of bursaries awarded by universities to improve outcomes for students from disadvantaged backgrounds as an example of an education intervention designed to address structural inequality. The paper then discusses critical reflections arising from a project commissioned by the Office for Fair Access in England, which aimed to enable universities to evaluate the impact of the bursaries that they award. These reflections provide a lens to explore the limitations of experimental and quasi‐experimental designs in complex social fields. The paper concludes that we lack a strong understanding of the relationship between financial and educational disadvantage prior to and during higher education, and this undermines efforts to ‘prove’ that certain interventions will ‘level the playing field’.
Synthesis and Structures of 1D and 2D ZnGd Coordination Polymers: [ZnGd(L)(NO3)2(4‐ppa)(EtOH)] and [ZnGd(L)(NO3)2(4‐pca)] (H2L = 1,3‐bis((3‐methoxysalicylidene)amino)propane); 4‐Hppa = 4‐pyridinepropionic acid; 4‐Hpca = 4‐pyridinecarboxylic acid
Authors: Lee Ji Hun , Lee Soon W.
Published: January 2017

This paper reports the synthesis, crystal structures, and thermal behavior of two zinc–gadolinium (3d–4f) coordination polymers by adjusting the connectivity of a secondary building unit (SBU) with two pyridyl–carboxylic acids as linkers. As a SBU, the Zn–Gd compartment compound, [ZnGd(L)(NO3
)(CH3CN)(H2O)4](NO3
)2(H2O) (H2L = 1,3‐bis((3‐methoxysalicylidene)amino)propane), was used. Under microwave heating conditions, the SBU reacted with 4‐pyridinepropionic acid (4‐Hppa) and 4‐pyridinecarboxylate (4‐Hpca) to create a 1D polymer, [ZnGd(L)(NO3
)2(4‐ppa)(EtOH)], and a 2D polymer, [ZnGd(L)(NO3
)2(4‐pca)], respectively. Dimensionality of the products appeared to depend on the continuity of π conjugation of the external linking ligand.
Evaluation of the Chemical Reporter Analog PNP‐6AzGlcNAc as an O‐GlcNAcase Substrate
Authors: Kim Eun J. , Bond Michelle R. , Nam Ghilsoo , Hanover John A.
Published: January 2017

6‐Azido‐6‐deoxy‐N‐acetylglucosamine (6AzGlcNAc) was recently introduced as a new selective metabolic chemical reporter (MCR) for labeling O‐GlcNAc‐modified proteins in cells. To investigate whether O‐6AzGlcNAc is readily cleaved by O‐GlcNAcase (OGA), the enzyme responsible for removing the O‐GlcNAc modification, we synthesized PNP‐6AzGlcNAc. This analog mimics O‐GlcNAc and can be used in vitro to define the kinetic parameters for OGA thereby defining whether O‐6AzGlcNAc can be employed as an appropriate tool to monitor O‐GlcNAc dynamics in cells. Both PNP‐6AzGlcNAc and PNP‐GlcNAc were efficiently hydrolyzed by OGA with similar kinetics suggesting that an azido‐modification at the GlcNAc C6 position does not significantly interfere with the β‐hexosaminidase activity of OGA.
Apply Euclid's First Axiom to work with people with different views
Authors: Skipworth Stan
Published: January 2017

Over the past few weeks, I have joined many across our country as we process and consider the result and future brought forth from our recent presidential election. I have seen a variety of news accounts, many depicting deep levels of emotions of many people from across our country, ranging from great pride and celebration to a seemingly unprecedented form of fear and anxiety.
Long‐term outcomes following mini‐crush versus culotte stenting for the treatment of unprotected left main disease: Insights from the milan and New‐Tokyo (MITO) registry
Authors: Kawamoto Hiroyoshi , Takagi Kensuke , Chieffo Alaide , Ruparelia Neil , Yusuke Fujino  , Yabushita Hiroto , Watanabe Yusuke , Latib Azeem , Carlino Mauro , Montorfano Matteo , Nakamura Sunao , Colombo Antonio
Published: January 2017

Objectives

This study aimed to investigate the long‐term outcomes following mini‐crush versus culotte stenting with drug‐eluting stents (DES) for the treatment of unprotected left main coronary artery (LMCA) disease.

Background

Both mini‐crush and culotte stenting are considered efficacious treatment options when a planned 2‐stent strategy is deemed necessary for unprotected LMCA disease. However, there are limited data available with regard to the long‐term clinical outcomes of each strategy in this setting.

Methods

Between July 2002 and November 2013, 225 patients were identified. 135 patients were treated with the mini‐crush technique, and 90 patients with culotte stenting. The median follow‐up period was 1,263 (IQR 820–1,847) days.

Results

The mini‐crush group had worse lesion and procedural characteristics when compared to the culotte group. There were no significant differences in major adverse cardiac events (MACE) at 5 years (mini‐crush 36.0% vs. culotte 41.4%, P = 0.57). Myocardial infarction (MI) and definite stent thrombosis (ST) occurred significantly higher (MI; 0 vs. 11.3%, log‐rank P = 0.003, and definite ST; 0 vs. 6.3%, log‐rank P = 0.02, respectively) in the culotte group. Cox regression analysis indicated that full stent coverage of the LMCA and SYNTAX score were independent predictors for MACE.

Conclusions

The incidence of MACE and overall TLR were comparable between groups. However, the rates of MI and definite ST were significantly higher in the culotte group. Full stent coverage of the LMCA may reduce the incidence of MACE when a two‐stent strategy is used for the treatment of unprotected LMCA disease. © 2016 Wiley Periodicals, Inc.
PFO closure: End of an era or beginning of a new chapter?
Authors: Traina Mahmoud I. , Tuzcu E. Murat
Published: January 2017

Key Points

This large long‐term retrospective cohort study shows that percutaneous patent foramen ovale (PFO) closure is safe.

Higher rates of recurrent stroke or TIA were noted in older patients (age>55) and those with diabetes and hypertension

Randomized trials have failed to show significant benefit from PFO closure for cryptogenic stroke though pooled analyses and longer‐term follow‐up have revealed significant reduction in recurrent strokes. Future studies and longer‐term follow‐up will need to elucidate which subgroups of patients will benefit from closure.
Addressing the needs of treating congenital heart disease: The influence of deficient retro‐aortic rim on technical success and early adverse events following device closure of secundum atrial septal defects: An analysis of the IMPACT registry®
Authors: M. Tobis Jonathan
Published: January 2017

Key Points

For secundum ASD, a deficient retro‐aortic rim is common (40% of cases)

However, the deficient retro‐aortic rim had no effect on ASD device placement success or immediate outcome

The IMPACT Registry does not track long‐term outcome, so there is no information provided about long‐term complications, such as erosion.
BVS for bifurcation lesions: To Do or Not to Do Is No more the question!
Authors: Seth Ashok
Published: January 2017

Key Points

Presents the intermediate term results of BVS in bifurcation lesions from a large database.

Emphasizes the optimal technique of BVS implantation in this lesion subset which may influence outcomes.

Prospective, large, protocol driven registries would define the role of BVS in bifurcation lesion.
Unprotected Left Main Disease and Percutaneous Intervention: A Prototype for Precision Medicine
Authors: Chatterjee Arka , Hillegass William B.
Published: January 2017

Key Points

The SYNTAX Score based on angiographic findings is an actionable risk prediction model helping guide treatment for significant unprotected left main disease.

Adding the clinical factor based EuroSCORE to SYNTAX improves outcome prediction for percutaneous coronary intervention of unprotected left main disease.

Prediction models are an increasingly useful tool permitting cardiologists to optimize patient outcomes through “personalized” or precision medicine.
Spraying Coagulation‐Assisted Hydrothermal Synthesis of MoS2/Carbon/Graphene Composite Microspheres for Lithium‐Ion Battery Applications
Authors: Liu Jine , Fu Aiping , Wang Yiqian , Guo Peizhi , Feng Hongbin , Li Hongliang , Zhao Xiu Song
Published: January 2017

Composite microspheres consisting of molybdenum disulfide, amorphous carbon, and reduced graphene oxide (named MoS2‐AC‐RGO) were prepared by using a hydrothermal approach combined with the spraying coagulation process and calcinations step. Intercalation compound cellulose−MoS2 was obtained after the spraying coagulation‐assisted hydrothermal treatment, which then converts to MoS2‐AC‐RGO after calcination. Graphene oxide and cellulose were utilized as the precursors of RGO and AC, respectively. Thiourea was adopted as both the species for cellulose dissolution and the sulfur precursor for MoS2. The suspension of GO and sodium molybdate also played the role of the coagulation bath. The influence of cellulose on the structure, morphology, and electrochemical performance of the resultant MoS2‐AC‐RGO microspheres was investigated based on XRD, SEM, TEM, Raman spectra, TGA, and N2 adsorption−desorption technique as well as electrochemical measurements. The composite microspheres show superior electrochemical properties as anode materials for lithium‐ion batteries and exhibit a high reversible capacity of 910 mAhg−1 at a current density of 200 mA g−1, excellent rate capability, and superior cyclic stability with a capacity of 86% after 70 cycles. The roles of the graphene and the cellulose in improving the electrochemical properties of the MoS2‐AC‐RGO composites are discussed based on the morphology, structure, phase, and electrochemical performance studies.
Coupling Activity‐Based Detection, Target Amplification, Colorimetric and Fluorometric Signal Amplification, for Quantitative Chemosensing of Fluoride Generated from Nerve Agents
Authors: Sun Xiaolong , Reuther James F. , Phillips Scott T. , Anslyn Eric V.
Published: January 2017

The G‐class nerve agents, which include sarin, soman, and cyclosarin, react readily with nucleophilic reagents to produce fluoride. Thus, a chemosensing protocol has been designed for these agents that pairs the nucleophilic reactivity of oximates for generating fluoride with an autoinductive target amplification reaction to amplify the quantity of fluoride for facile colorimetric and fluorescent optical quantification. The chemosensing protocol was demonstrated by using the nerve agent surrogate diisopropyl fluorophosphate (DFP) and benzaldoxime as the nucleophile. Autoinductive fluoride amplification responds to fluoride released from DFP by amplifying the fluoride concentration and a yellow reporter molecule. The reporter is a conjugated oligomer with a nominal repeating unit that originates from 4‐aminobenzaldehyde. Exposure of the amplified fluoride to a fluoride‐specific ratiometric fluorescent reporter provides a fluorescent readout, in which three fluorophores are generated per fluoride. Both colorimetric and fluorescent readouts enable quantitative assays with low micromolar limits of detection for fluoride resulting from DFP. More importantly, this work demonstrates the successful merging of multiple complex reactions for achieving selective, sensitive, and quantitative chemosensing.
Pentagonal Bipyramid FeII Complexes: Robust Ising‐Spin Units towards Heteropolynuclear Nanomagnets
Authors: Bar Arun Kumar , Gogoi Nayanmoni , Pichon Céline , Goli V. M. L. Durga Prasad , Thlijeni Mehrez , Duhayon Carine , Suaud Nicolas , Guihéry Nathalie , Barra Anne‐Laure , Ramasesha S. , Sutter Jean‐Pascal
Published: January 2017

Pentagonal bipyramid FeII complexes have been investigated to evaluate their potential as Ising‐spin building units for the preparation of heteropolynuclear complexes that are likely to behave as single‐molecule magnets (SMMs). The considered monometallic complexes were prepared from the association of a divalent metal ion with pentadentate ligands that have a 2,6‐diacetylpyridine bis(hydrazone) core (H2LN3O2R). Their magnetic anisotropy was established by magnetometry to reveal their zero‐field splitting (ZFS) parameter D, which ranged between −4 and −13 cm−1 and was found to be modulated by the apical ligands (ROH versus Cl). The alteration of the D value by N‐bound axial CN ligands, upon association with cyanometallates, was also assessed for heptacoordinated FeII as well as for related NiII and CoII derivatives. In all cases, N‐coordinated cyanide ligands led to large magnetic anisotropy (i.e., −8 to −18 cm−1 for Fe and Ni, +33 cm−1 for Co). Ab initio calculations were performed on three FeII complexes, which enabled one to rationalize the role of the ligand on the nature and magnitude of the magnetic anisotropy. Starting from the pre‐existing heptacoordinated complexes, a series of pentanuclear compounds were obtained by reactions with paramagnetic [W(CN)8]3−. Magnetic studies revealed the occurrence of ferromagnetic interactions between the spin carriers in all the heterometallic systems. Field‐induced slow magnetic relaxation was observed for mononuclear FeII complexes (Ueff/kB up to 53 K (37 cm−1), τ0=5×10−9 s), and SMM behavior was evidenced for a heteronuclear [Fe3W2] derivative (Ueff/kB=35 K and τ0=4.6 10−10 s), which confirmed that the parent complexes were robust Ising‐type building units. High‐field EPR spectroscopic investigation of the ZFS parameters for a Ni derivative is also reported.
Cost‐effectiveness of sentinel node biopsy and pathological ultrastaging in patients with early‐stage cervical cancer
Authors: Brar Harinder , Hogen Liat , Covens Al
Published: January 2017

BACKGROUND

The objective of this study was to determine the cost‐effectiveness of radical hysterectomy (RH) and sentinel lymph node biopsy (SLNB) for the management of early‐stage cervical cancer (stage IA2‐IB1).

METHODS

A simple decision tree model was developed to follow a simulated cohort of patients with early‐stage cervical cancer treated with RH and 1 of 3 lymph node assessment strategies: systematic pelvic lymph node dissection (PLND), SLNB using technetium 99 (Tc99) and blue dye, and SLNB using Tc99 only. SLNB using indocyanine green (ICG) was used as an exploratory strategy. Relevant studies were identified to extract the probability data and utility parameters and to estimate quality‐adjusted life‐years (QALYs) and absolute life‐years (ALYs). Only direct medical costs were modeled, and the time horizon for the study was 5 years.

RESULTS

SLNB using Tc99 and blue dye cost $21,089 and yielded 4.54 QALYs and 4.90 ALYs. PLND cost $22,353 and yielded 4.47 QALYs and 4.91 ALYs. SLNB using blue dye and Tc99 was the most cost‐effective strategy when ALYs were considered with an incremental cost‐effectiveness ratio (ICER) of $144,531. When QALYs were considered, the SLNB technique using Tc99 and blue dye dominated all other strategies. SLNB using ICG cost $20,624 and yielded 4.90 ALYs and 4.54 QALYs. It was clinically superior to and less expensive than all other strategies when QALYs were the outcome of interest and had an ICER of $221,171 per ALY in comparison with RH plus PLND.

CONCLUSIONS

SLNB using Tc99 and blue dye with ultrastaging is considered the most cost‐effective strategy with respect to 5‐year progression‐free survival and morbidity‐free survival. Although it was included only as an exploratory strategy in this study, SLNB with ICG has the potential to be the most cost‐effective strategy. Cancer 2017;123:1751–1759. © 2017 American Cancer Society.
Age, hepatitis C virus infection, and the risk of cancer: Unlocking a complex puzzle of interactions
Authors: Li Daneng , Hurria Arti
Published: January 2017

Hepatitis C infection may increase the risk of various malignancies among older adults. A better understanding of the complex biology of the aging process and hepatitis C infection may help to unlock an important piece of the puzzle in the world of cancer development.

See also pages 1202‐11.
Hepatitis C virus infection and the risk of cancer among elderly US adults: A registry‐based case‐control study
Authors: Mahale Parag , Torres Harrys A. , Kramer Jennifer R. , Hwang Lu‐Yu , Li Ruosha , Brown Eric L. , Engels Eric A.
Published: January 2017

BACKGROUND

Hepatitis C virus (HCV) infection causes hepatocellular carcinoma (HCC) and subtypes of non‐Hodgkin lymphoma (NHL). Associations with other cancers are not established. The authors systematically assessed associations between HCV infection and cancers in the US elderly population.

METHODS

This was a registry‐based case‐control study using Surveillance, Epidemiology, and End Results (SEER)‐Medicare data in US adults aged ≥66 years. Cases (n = 1,623,538) were patients who had first cancers identified in SEER registries (1993‐2011). Controls (n = 200,000) were randomly selected, cancer‐free individuals who were frequency‐matched to cases on age, sex, race, and calendar year. Associations with HCV (documented by Medicare claims) were determined using logistic regression.

RESULTS

HCV prevalence was higher in cases than in controls (0.7% vs 0.5%). HCV was positively associated with cancers of the liver (adjusted odds ratio [aOR] = 31.5; 95% confidence interval [CI], 29.0‐34.3), intrahepatic bile duct (aOR, 3.40; 95% CI, 2.52‐4.58), extrahepatic bile duct (aOR, 1.90; 95% CI, 1.41‐2.57), pancreas (aOR, 1.23; 95% CI, 1.09‐1.40), and anus (aOR, 1.97; 95% CI, 1.42‐2.73); nonmelanoma nonepithelial skin cancer (aOR, 1.53; 95% CI, 1.15‐2.04); myelodysplastic syndrome (aOR, 1.56; 95% CI, 1.33‐1.83); and diffuse large B‐cell lymphoma (aOR, 1.57; 95% CI, 1.34‐1.84). Specific skin cancers associated with HCV were Merkel cell carcinoma (aOR, 1.92; 95% CI, 1.30‐2.85) and appendageal skin cancers (aOR, 2.02; 95% CI, 1.29‐3.16). Inverse associations were observed with uterine cancer (aOR, 0.64; 95% CI, 0.51‐0.80) and prostate cancer (aOR, 0.73; 95% CI, 0.66‐0.82). Associations were maintained in sensitivity analyses conducted among individuals without documented alcohol abuse, cirrhosis, or hepatitis B or human immunodeficiency virus infections and after adjustment for socioeconomic status. Associations of HCV with other cancers were not observed.

CONCLUSIONS

HCV is associated with increased risk of cancers other than HCC in the US elderly population, notably bile duct cancers and diffuse large B‐cell lymphoma. These results support a possible etiologic role for HCV in an expanded group of cancers. Cancer 2017;123:1202–1211. © 2016 American Cancer Society.
Cytogenetic risk determines outcomes after allogeneic transplantation in older patients with acute myeloid leukemia in their second complete remission: A Center for International Blood and Marrow Transplant Research cohort analysis
Authors: Michelis Fotios V. , Gupta Vikas , Zhang Mei‐Jie , Wang Hai‐Lin , Aljurf Mahmoud , Bacher Ulrike , Beitinjaneh Amer , Chen Yi‐Bin , DeFilipp Zachariah , Gale Robert Peter , Kebriaei Partow , Kharfan‐Dabaja Mohamed , Lazarus Hillard M. , Nishihori Taiga , Olsson Richard F. , Oran Betul , Rashidi Armin , Rizzieri David A. , Tallman Martin S. , de Lima Marcos , Khoury H. Jean , Sandmaier Brenda M. , Weisdorf Daniel , Saber Wael ,   for the Acute Leukemia Working Committee of the Center for International Blood and Marrow Transplant Research, aresearch collaboration between the National Marrow Donor Program/Be the Match Registry and theMedicalCollegeofWisconsin
Published: January 2017

BACKGROUND

Allogeneic hematopoietic cell transplantation (HCT) offers curative potential to a number of older patients with acute myeloid leukemia (AML) in their first complete remission. However, there are limited data in the literature concerning post‐HCT outcomes for older patients in their second complete remission (CR2).

METHODS

The purpose of the current study was to retrospectively investigate within the Center for International Blood and Marrow Transplant Research database parameters influencing posttransplant outcomes for patients 60 years of age or older undergoing HCT for AML in CR2.

RESULTS

In total, 196 patients from 78 centers were identified; the median age was 64 years (range, 60‐78 years). Seventy‐one percent had a Karnofsky performance status ≥ 90 at the time of HCT. Reduced‐intensity conditioning regimens were used in 159 patients (81%). A univariate analysis demonstrated a 3‐year overall survival (OS) rate of 42% (95% confidence interval [CI], 35%‐49%), a leukemia‐free survival rate of 37% (95% CI, 30%‐44%), a cumulative incidence of nonrelapse mortality of 25% (95% CI, 19%‐32%), and a cumulative incidence of relapse (CIR) of 38% (95% CI, 31%‐45%). A multivariate analysis demonstrated that cytogenetic risk was the only independent risk factor for OS (P = .023) with a hazard ratio (HR) of 1.14 (95% CI, 0.59‐2.19) for intermediate‐risk cytogenetics and an HR of 2.32 (95% CI, 1.05‐5.14) for unfavorable‐risk cytogenetics. For CIR, cytogenetic risk was also the only independent prognostic factor (P = .01) with an HR of 1.10 (95% CI, 0.47‐2.56) for intermediate‐risk cytogenetics and an HR of 2.98 (95% CI, 1.11‐8.00) for unfavorable‐risk cytogenetics.

CONCLUSIONS

Allogeneic HCT is a curative treatment option for older patients with AML in CR2, particularly for those with favorable or intermediate cytogenetic risk. Cancer 2017;123:2035–2042. © 2017 American Cancer Society.
Connectivity and ultrastructure of dopaminergic innervation of the inner ear and auditory efferent system of a vocal fish
Authors: Perelmuter Jonathan T. , Forlano Paul M.
Published: January 2017

Dopamine (DA) is a conserved modulator of vertebrate neural circuitry, yet our knowledge of its role in peripheral auditory processing is limited to mammals. The present study combines immunohistochemistry, neural tract tracing, and electron microscopy to investigate the origin and synaptic characteristics of DA fibers innervating the inner ear and the hindbrain auditory efferent nucleus in the plainfin midshipman, a vocal fish that relies upon the detection of mate calls for reproductive success. We identify a DA cell group in the diencephalon as a common source for innervation of both the hindbrain auditory efferent nucleus and saccule, the main hearing endorgan of the inner ear. We show that DA terminals in the saccule contain vesicles but transmitter release appears paracrine in nature, due to the apparent lack of synaptic contacts. In contrast, in the hindbrain, DA terminals form traditional synaptic contacts with auditory efferent neuronal cell bodies and dendrites, as well as unlabeled axon terminals, which, in turn, form inhibitory‐like synapses on auditory efferent somata. Our results suggest a distinct functional role for brain‐derived DA in the direct and indirect modulation of the peripheral auditory system of a vocal nonmammalian vertebrate.