bluuebunny/crossref_metadata_2025 huggingface dataset:
Reductive Amination/Cyclization of Methyl Levulinate with Aspartic Acid: Towards Renewable Polyesters with a Pendant Lactam Unit
Authors: Bernhard Yann , Pellegrini Sylvain , Bousquet Till , Favrelle Audrey , Pelinski Lydie , Cazaux Frédéric , Gaucher Valérie , Gerbaux Pascal , Zinck Philippe
Published: April 2019

Environmental regulation and depletion of fossil resources are boosting the search for new polymeric materials produced from biomass. Here, the synthesis of a new diester bearing a pendant lactam unit from methyl levulinate and aspartic acid is reported. The palladium‐catalyzed reductive amination/cyclization sequence was carefully optimized to afford the diacid with high yield (>95 %). In a second step, the compound was esterified to give the corresponding diester. The latter monomer was copolymerized with α–ω linear diols, yielding polyesters with molecular weights up to 20.5 kg mol−1.
Clinical impact of testing for mutations and microRNAs in thyroid nodules
Authors: Sistrunk John Woody , Shifrin Alexander , Frager Marc , Bardales Ricardo H. , Thomas Johnson , Fishman Norman , Goldberg Philip , Guttler Richard , Grant Edward
Published: April 2019

Background

We report results of a multicenter clinical experience study examining the likelihood of patients with indeterminate thyroid nodules to undergo surgery or have malignant outcome based on multiplatform combination mutation and microRNA testing (MPT).

Methods

MPT assessed mutations in BRAF, HRAS, KRAS, NRAS, and PIK3CA genes, PAX8/PPARγ, RET/PTC1, and RET/PTC3 gene rearrangements, and the expression of 10 microRNAs. Baseline clinical information at the time of MPT and clinical follow‐up records were reviewed for 337 patients, of which 80% had negative MPT results. Kaplan Meier analysis for cumulative probability of survival without having a surgical procedure or malignant diagnosis over the course of patient follow‐up was determined for MPT results of 180 patients, among which only 14% had malignancy.

Results

A negative MPT result in nodules with Bethesda III or IV cytology (2009) conferred a high probability of non‐surgical treatment, with only 11% expected to undergo surgery and a high probability of survival without malignancy (92%) for up to 2 years follow up. A positive MPT result conferred a 57% probability of malignancy and was an independent risk factor for undergoing surgical treatment (Hazard Ratio [HR] 9.2, 95% confidence intervals 5.4‐15.9, P < .0001) and for malignancy (HR 13.4, 95% confidence intervals 4.8‐37.2, P < .0001). For nodules with weak driver mutations, positive microRNA test results supported high risk of cancer while negative results downgraded cancer risk.

Conclusion

MPT results are predictive of real‐world decisions to surgically treat indeterminate thyroid nodules, with those decisions being appropriately aligned with a patient's risk of malignancy over time.
Reindeer turning maritime: Ice‐locked tundra triggers changes in dietary niche utilization
Authors: Hansen Brage Bremset , Lorentzen Jon Runar , Welker Jeffrey M. , Varpe Øystein , Aanes Ronny , Beumer Larissa Teresa , Pedersen Åshild Ønvik
Published: April 2019

The rapid warming of the Arctic may not only alter species’ abundances and distributions, but likely also the trophic interactions within and between ecosystems. On the high‐arctic tundra, extreme warm spells and associated rain‐on‐snow events in winter can encapsulate the vegetation entirely in ground‐ice (i.e., basal ice) and directly or indirectly affect plants, herbivores, and carnivores. However, the implications of such extreme events for trophic interactions and food‐web ecology are generally far from understood. Here, we show that wild Svalbard reindeer populations increasingly isolated by lack of sea‐ice respond to rain‐on‐snow and ice‐locked pastures by increased kelp consumption. Based on annual population surveys in late winters 2006–2015, the proportion of individual reindeer feeding along the shoreline increased the icier the winter. Stable isotope values (δ34S, δ13C, δ15N) of plants, washed‐ashore kelp, and fresh reindeer feces collected along coast‐inland gradients, confirmed ingestion of marine biomass by the reindeer in the shoreline habitat. Thus, even on remote islands and peninsulas increasingly isolated by sea‐ice loss, effects of climate change may be buffered in part by behavioral plasticity and increased use of resource subsidies. This marine dimension of a terrestrial herbivore's realized foraging niche adds to evidence that global warming significantly alters trophic interactions as well as meta‐ecosystem processes.
Narrow pollen diets are associated with declining Midwestern bumble bee species
Authors: Wood T. J. , Gibbs J. , Graham K. K. , Isaacs R.
Published: April 2019

Many species of bumble bee (Bombus) have declined in range and abundance across Europe, the Americas, and Asia, whereas other species have persisted and remain common and widespread. One explanation as to why some species have declined, based primarily on studies of the European bumble bee fauna, is that declining species have relatively narrow pollen‐foraging niches and are less able to use alternative host plants in the absence of their preferred hosts. Though extensively explored in Europe, this hypothesis has not been investigated in North America, in part due to incomplete information on the foraging niche of many species. We selected 12 bumble bee species found in Michigan and quantified their pollen diets using museum specimens. We also extensively resurveyed the state to understand their contemporary status and distribution. Compared to a pre‐2000 baseline, six species remain relatively common and widespread, whereas six species show range contractions of over 50%. There was a significant relationship between dietary breadth and distributional range change, with declined or declining species collecting around one‐third fewer pollen types than stable species. Though there were significant compositional differences, we found no differences in the number of pollen types collected by species with differing tongue lengths. Overall, these results support the hypothesis that species with narrower dietary niches are at greater risk of decline. However, it is not clear if narrow dietary niches are a cause of declines, or if both are driven by an underlying factor such as proximity to the edge of climatic niches. Further research is needed to improve our understanding of dietary niche in bumble bees, and how it interacts with other factors to influence population trajectories of stable and at‐risk species.
Understanding Solid‐State Phase‐Formation Processes by Using the High‐Temperature Gas Balance: The Example of Zr2PTe2
Authors: Scholz Tanja , Schöneich Michael , Schmidt Peer
Published: April 2019

Inorganic solid‐state synthesis with phosphorus and tellurium requires a careful control of the reaction parameters because of the high volatility of the components. This initial disadvantage can be used as a benefit for the investigation of phase‐formation mechanisms by analyzing the individual vapor pressure behavior. The high‐temperature gas balance is introduced as a device for detection of heterogeneous solid‐gas equilibria in closed reaction systems. The experimentally challenging synthesis of the phosphide telluride Zr2PTe2 is examined as a model system: optimized synthesis runs at lower temperatures (ϑ = 650 °C) in a faster time, while the quantity as well as the crystalline powder quality is increased. A stepwise solid‐solid reaction of zirconium and tellurium according to Ostwald's rule of stages and the shrinking core model is revealed while phosphorus sublimes and subsequently condenses to react to the ternary compound. Additional phenomena such as melting, expansion, and mechanical instabilities can be observed that broaden the possibilities of the gas balance.
Characterization of an AX Compound Derived from Ti2SC MAX Phase
Authors: Hasegawa George , Kawahara Kei , Shima Kazunari , Inada Miki , Enomoto Naoya , Hayashi Katsuro
Published: April 2019

Extraction of M elements from MAX phases results in “AX” compounds in contrast to the well‐defined two‐dimensional (2D) materials known as MXene, which are prepared by the selective etching of A elements. Despite the extensive studies on MXene from both experimental and computational aspects, the nature of the AX compounds still remains elusive, because the electrochemical etching of M atoms from MAX significantly spoils the crystal structure, predominantly resulting in amorphous AX products. Here, we demonstrate the characterization of an S/C complex prepared by the electrochemical etching of Ti2SC. The spark plasma sintering (SPS) technique affords a well‐sintered Ti2SC disk with high purity, which can be directly utilized as a binder‐free Ti2SC electrode. It is found that the electrochemically extracted Ti elements in NH4F electrolyte are partially crystallized into the monoclinic titanium oxynitride, TiO0.34N0.74. The formed amorphous S/C compound is classified into three components: acetone‐soluble volatiles including elemental sulfur, acetone‐insoluble volatiles, and non‐volatile species carbonizable into S‐doped carbon.
Reduced Graphene Oxide Coated Hollow Polyester Fibers for Efficient Solar Steam Generation
Authors: Wang Fei , Mu Peng , Zhang Zheng , Chen Tao , Li Yuanzhen , Sun Hanxue , Zhu Zhaoqi , Liang Weidong , Li An
Published: April 2019

Solar steam generation based on photothermal materials has emerged as a green and efficient technology for a broad variety of applications, such as solar energy harvesting, desalination, power generation, wastewater treatment, and so on. Herein, the fabrication of a kind of a novel photothermal material that is prepared by simple coating of reduced graphene oxide (rGO) onto commercial hollow polyester fibers (HPFs) for efficient solar steam generation is reported. The as‐resulted rGO‐wrapped HPFs possess a porous structure, low thermal conductivity (0.042 W m−1 k−1), and broad light absorption (85%), which satisfies the criterion for construction of ideal photothermal materials. As expected, a high solar‐thermal efficiency of ≈81% is obtained at 1 kW m−2 irradiation, showing great potential for practical applications based on high solar energy conversion efficiency and a simple and, in particular, scalable manufacturing process.
Coupling finite difference method with finite particle method for modeling viscous incompressible flows
Authors: Huang C. , Long T. , Liu M.B.
Published: April 2019

A hybrid approach to couple finite difference method (FDM) with finite particle method (FPM) (ie, FDM‐FPM) is developed to simulate viscous incompressible flows. FDM is a grid‐based method that is convenient for implementing multiple or adaptive resolutions and is computationally efficient. FPM is an improved smoothed particle hydrodynamics (SPH), which is widely used in modeling fluid flows with free surfaces and complex boundaries. The proposed FDM‐FPM leverages their advantages and is appealing in modeling viscous incompressible flows to balance accuracy and efficiency. In order to exchange the interface information between FDM and FPM for achieving consistency, stability, and convergence, a transition region is created in the particle region to maintain the stability of the interface between two methods. The mass flux algorithm is defined to control the particle creation and deletion. The mass is updated by N‐S equations instead of the interpolation. In order to allow information exchange, an overlapping zone is defined near the interface. The information of overlapping zone is obtained by an FPM‐type interpolation. Taylor‐Green vortices and lid‐driven shear cavity flows are simulated to test the accuracy and the conservation of the FDM‐FPM hybrid approach. The standing waves and flows around NACA airfoils are further simulated to test the ability to deal with free surfaces and complex boundaries. The results show that FDM‐FPM retains not only the high efficiency of FDM with multiple resolutions but also the ability of FPM in modeling free surfaces and complex boundaries.
Nutritional composition and acceptability of biscuits fortified with palm weevil larvae (Rhynchophorus phoenicis Fabricius) and orange‐fleshed sweet potato among pregnant women
Authors: Ayensu Jessica , Lutterodt Herman , Annan Reginald Adjetey , Edusei Anthony , Loh Su Peng
Published: April 2019

Edible insects are currently being promoted as an inexpensive alternative source of protein in underdeveloped countries due to the rising cost of conventional animal protein and the foreseen future deficit in its supply. A supplemental palm weevil larvae and orange‐fleshed sweet potato biscuit was developed as part of efforts to understand the nutritional benefits of edible insects and to predict whether these benefits will contribute to better nutrition among pregnant women in Ghana. The palm weevil larvae flour and the orange‐fleshed sweet potato flour were mixed with wheat flour in three formulations that had 0, 35, and 70% of palm weevil larvae flour, before being made into biscuits. The biscuits were subjected to proximate and mineral content analysis and sensory evaluation. Proximate and mineral composition of the biscuits increased with increasing levels of palm weevil larvae flour substitution. Among the blends, biscuits containing 70% palm weevil larvae had the highest energy and fat content, and protein content also increased by 45% compared with biscuits made from 100% wheat flour. Calcium, iron, and zinc levels also increased with increasing levels of palm weevil larvae flour substitution. However, carbohydrate and crude fiber concentrations of the biscuits decreased with increasing substitution. The overall acceptability of the biscuits as determined by sensory evaluation using pregnant women was high. Biscuits fortified with palm weevil larvae can be a nutritious snack for pregnant women.
Jump variance risk: Evidence from option valuation and stock returns
Authors: Chang Hsuan‐Ling , Chang Yen‐Cheng , Cheng Hung‐Wen , Peng Po‐Hsiang , Tseng Kevin
Published: April 2019

We study jump variance risk by jointly examining both stock and option markets. We develop a GARCH option pricing model with jump variance dynamics and a nonmonotonic pricing kernel featuring jump variance risk premium. The model yields a closed‐form option pricing formula and improves in fitting index options from 1996 to 2015. The model‐implied jump variance risk premium has predictive power for future market returns. In the cross‐section, heterogeneity in exposures to jump variance risk leads to a 6% difference in risk‐adjusted returns annually.
The significance of tumor budding in oral cancer survival and its relevance to the eighth edition of the American Joint Committee on Cancer staging system
Authors: Ho Yi‐Yun , Wu Tzu‐Ying , Cheng Han‐Chieh , Yang Cheng‐Chieh , Wu Cheng‐Hsien
Published: April 2019

Background

To explore the clinicopathological significance of tumor budding (TB) on oral squamous cell carcinoma (OSCC) prognosis.

Methods

Data of 200 patients with OSCC were retrieved from the cancer registration database in Taipei Veterans General Hospital. Clinicopathological characteristics and survival relevant to TB were analyzed.

Results

The data showed that TB was predominant in the tongue and floor of the mouth in younger patients with OSCC and correlated with several pathological factors, such as perineural invasion and lymphovascular invasion. Patients with TB have significantly lower recurrence‐free survival (P ≤ .0001). TB was significantly associated with lymph node metastasis in patients with early cancer stage (P = .042). Multivariate analysis demonstrated extranodal extension and TB as independent predictors of lymph node recurrence (adjusted hazard ratio = 9.90 and 3.89, respectively).

Conclusion

TB is a significant predictor of tumor aggression with locoregional failure even in the revised 8th American Joint Committee on Cancer staging system.
Detecting recurrent head and neck cancer using electronic nose technology: A feasibility study
Authors: van de Goor Rens M. G. E. , Hardy Joey C. A. , van Hooren Michel R. A. , Kremer Bernd , Kross Kenneth W.
Published: April 2019

Background

The aim of this feasibility study was to assess the diagnostic performance of an electronic nose (e‐nose) as a noninvasive diagnostic tool in detecting locoregional recurrent and/or second (or third) primary head and neck squamous cell carcinoma (HNSCC) after curative treatment.

Methods

Using an e‐nose (Aeonose, The eNose Company, Zutphen, The Netherlands), breath samples were collected from patients after curative treatment of an HNSCC with a locoregional recurrence or second (or third) primary tumor (N = 20) and from patients without evidence of recurrent disease (N = 20). Analyses were performed utilizing artificial neural networking based on patterns of volatile organic compounds.

Results

A diagnostic accuracy of 83% was observed in differentiating follow‐up patients with locoregional recurrent or second (or third) primary HNSCC from those without evidence of disease.

Conclusion

This study has demonstrated the feasibility of using an e‐nose to detect locoregional recurrent and/or second (or third) primary HNSCC.
Synthesis of mesoporous silica/polyglutamic acid peptide dendrimer with dual targeting and its application in dissolving thrombus
Authors: Huang Mengjie , Zhang Shao‐Fei , Lü Shaoyu , Qi Taomei , Yan Jia , Gao Chunmei , Liu Mingzhu , Li Tao , Ji Yanzheng
Published: April 2019

With the frequent occurrence of thrombus diseases, thrombus has become a factor endangering human health. Nattokinase (NK) is a new generation of thrombolytic drug with efficient thrombolytic effect and no major side effects. However, it is easily inactivated in external environment due to its sensitivity, which is still a challenge for its generalized application. Herein, a mesoporous silica/polyglutamic acid peptide dendrimer (M‐MSNs‐G3‐RGD) nanoparticle was prepared to protect and transport NK. First, magnetic mesoporous silica nanoparticles (M‐MSNs) were prepared as the core of the whole nanoparticle, then polyglutamic acid peptide dendrimer (G3) was bonded to form M‐MSNs‐G3. At last, arginine‐glycine‐aspartic peptide (RGD) was grafted onto the M‐MSNs‐G3 to obtain M‐MSNs‐G3‐RGD. The physical and chemical characteristics and biological toxicity of M‐MSNs‐G3‐RGD were studied. Thrombus‐targeting nanocomposites M‐MSNs‐G3‐RGD/NK were prepared by loading the thrombolytic drug NK via electrostatic interaction. In vitro and in vivo targeted thrombolytic experiments showed that the nanoparticles exhibited significant thrombolysis ability. These results suggested the potential application of M‐MSNs‐G3‐RGD/NK in dual targeted thrombolysis.
Mathematical predictions of oxygen availability in micro‐ and macro‐encapsulated human and porcine pancreatic islets
Authors: Cao Rui , Avgoustiniatos Efstathios , Papas Klearchos , de Vos Paul , Lakey Jonathan R. T.
Published: April 2019

Optimal function of immunoisolated islets requires adequate supply of oxygen to metabolically active insulin producing beta‐cells. Using mathematical modeling, we investigated the influence of the pO2 on islet insulin secretory capacity and evaluated conditions that could lead to the development of tissue anoxia, modeled for a 300 μm islet in a 500 μm microcapsule or a 500 μm planar, slab‐shaped macrocapsule. The pO2 was used to assess the part of islets that contributed to insulin secretion. Assuming a 500 μm macrocapsule with a 300 μm islet, with oxygen consumption rate (OCR) of 100–300 nmol min−1 mg−1 DNA, islets did not develop any necrotic core. The nonfunctional zone (with no insulin secretion if pO2 < 0.1 mmHg) was 0.3% for human islets (OCR ~100 nmol/min/mg DNA) and 35% for porcine islets (OCR ~300 nmol/min/mg DNA). The OCR of the islet preparation is profoundly affected by islet size, with optimal size of <250 μm in diameter (human) or <150 μm (porcine). Our data suggest that microcapsules afford superior oxygen delivery to encapsulated islets than macrocapsules, and optimal islet function can be achieved by encapsulating multiple, small (<150 μm) islets with OCR of ~100 nmol min−1 mg−1 DNA (human islets) or ~200 nmol min−1 mg−1 DNA (porcine islets).
Low dose 100 cGy irradiation as a potential therapy for pulmonary hypertension
Authors: Egan Pamela C. , Liang Olin D. , Goldberg Laura R. , Aliotta Jason M. , Pereira Mandy , Borgovan Theodor , Dooner Mark , Camussi Giovanni , Klinger James R. , Quesenberry Peter J.
Published: April 2019

Pulmonary hypertension (PH) is an incurable disease characterized by pulmonary vascular remodeling and ultimately death. Two rodent models of PH include treatment with monocrotaline or exposure to a vascular endothelial growth factor receptor inhibitor and hypoxia. Studies in these models indicated that damaged lung cells evolve extracellular vesicles which induce production of progenitors that travel back to the lung and induce PH. A study in patients with pulmonary myelofibrosis and PH indicated that 100 cGy lung irradiation could remit both diseases. Previous studies indicated that murine progenitors were radiosensitive at very low doses, suggesting that 100 cGy treatment of mice with induced PH might be an effective PH therapy. Our hypothesis is that the elimination of the PH‐inducing marrow cells by low dose irradiation would remove the cellular influences creating PH. Here we show that low dose whole‐body irradiation can both prevent and reverse established PH in both rodent models of PH.
Altered Glycemic Control Associated With Polymorphisms in the SLC22A1 (OCT1) Gene in a Mexican Population With Type 2 Diabetes Mellitus Treated With Metformin: A Cohort Study
Authors: Reséndiz‐Abarca Carlos Alberto , Flores‐Alfaro Eugenia , Suárez‐Sánchez Fernando , Cruz Miguel , Valladares‐Salgado Adán , del Carmen Alarcón‐Romero Luz , Vázquez‐Moreno Miguel Alexander , Wacher‐Rodarte Niels Agustín , Gómez‐Zamudio Jaime Héctor
Published: April 2019

The organic cation transporters OCT1 and OCT2 and the multidrug and toxin extrusion transporter MATE1, encoded by the SLC22A1, SLC22A2, and SLC47A1 genes, respectively, are responsible for the absorption of metformin in enterocytes, hepatocytes, and kidney cells. The aim of this study was to evaluate whether genetic variations in the SLC22A1, SLC22A2, and SLC47A1 genes could be associated with an altered response to metformin in patients with type 2 diabetes mellitus. A cohort study was conducted in 308 individuals with a diagnosis of type 2 diabetes mellitus of less than 3 years and who had metformin monotherapy. Three measurements of blood glycated hemoglobin (HbA1c) were obtained at the beginning of the study and after 6 and 12 months. Five polymorphisms were analyzed in the SLC22A1 (rs622342, rs628031, rs594709), SLC22A2 (rs316019), and SLC47A1 (rs2289669) genes by real‐time polymerase chain reaction. The results showed a significant association among genotypes CC‐rs622342 (β = 1.36; P < .001), AA‐rs628031 (β = 0.98; P = .032), and GG‐rs594709 (β = 1.21; P = .016) in the SLC22A1 gene with an increase in HbA1c levels during the follow‐up period. Additionally, a significant association was found in the CGA and CAG haplotypes with an increase in HbA1c levels compared to the highest‐frequency haplotype (AGA). In conclusion, the genetic variation in the SLC22A1 gene was significantly related to the variation of the HbA1c levels, an important indicator of glycemic control in diabetic patients. This information may contribute to identifying patients with an altered response to metformin before starting their therapy.
Sulfur trioxide removal performance of alkaline sorbents injection in the temperature range 400–705 °C: a pilot‐scale study
Authors: Xie Dong , Wang Haiming , Tao Jun , Chang Dongwu , You Changfu
Published: April 2019

BACKGROUND

Sulfur trioxide (SO3) in coal combustion flue gas can adversely affect power plant equipment and the environment. In this work, the removal of SO3 with typical sodium (Na), magnesium (Mg) and calcium (Ca)‐based sorbents was investigated at a pilot‐scale facility in the temperature range 400–705 °C.

RESULTS

The injection of sodium bicarbonate (NaHCO3) showed the highest SO3 removal efficiency, which was ∼85% at the sorbent/SO3 molar ratio of 2 with the gas residence time of 1 s. This is much higher than that of calcium hydroxide (Ca(OH)2) (∼25%) and magnesium hydroxide (Mg(OH)2) (∼30%). The removal efficiency of Mg(OH)2 and Ca(OH)2 increased with increasing the reaction temperature from 400 to 705 °C. With the addition of 800 ppm sulfur dioxide (SO2), the adsorption of SO3 on alkaline sorbents was inhibited due to the competitive adsorption, which caused SO3 removal efficiency to decrease by 5–12.5%. When injecting the sorbents in slurry form, the removal efficiency was found to be two times higher than that in powder form.

CONCLUSION

NaHCO3 is the most effective sorbent comparing to Mg(OH)2 and Ca(OH)2. To increase the SO3 removal efficiency, the alkaline sorbents should be injected in the high temperature zone in flue gas. It is recommended to inject the sorbents in slurry form instead of injecting powders directly to achieve high removal efficiency. © 2019 Society of Chemical Industry
Demand and order‐fulfillment planning: The impact of point‐of‐sale data, retailer orders and distribution center orders on forecast accuracy
Authors: Narayanan Arunachalam , Sahin Funda , Robinson E. Powell
Published: April 2019

Industry consultants claim that investing in systems that base forecasting on point‐of‐sale (POS) data throughout the supply chain will improve forecast accuracy. We explore what actually happens to forecast accuracy for demand and order‐fulfillment planning when the forecast demand signal is based on POS, retailer orders, or distribution center (DC) orders. We begin by comparing the forecast accuracy for different demand signals using daily demand and operating data from a large consumer‐products supply chain. We then extend the analysis by varying the demand and supply‐chain parameters to evaluate their impact on demand signal performance. We find that POS data improve forecast accuracy for demand planning but not for order‐fulfillment planning. These findings thus challenge consulting‐firm claims about the ability of POS‐based forecasting systems to improve forecast accuracy across all contexts.
Modelling time‐course relationships with multiple treatments: Model‐based network meta‐analysis for continuous summary outcomes
Authors: Pedder Hugo , Dias Sofia , Bennetts Margherita , Boucher Martin , Welton Nicky J.
Published: April 2019

Background

Model‐based meta‐analysis (MBMA) is increasingly used to inform drug‐development decisions by synthesising results from multiple studies to estimate treatment, dose‐response, and time‐course characteristics. Network meta‐analysis (NMA) is used in Health Technology Appraisals for simultaneously comparing effects of multiple treatments, to inform reimbursement decisions. Recently, a framework for dose‐response model‐based network meta‐analysis (MBNMA) has been proposed that combines, often nonlinear, MBMA modelling with the statistically robust properties of NMA. Here, we aim to extend this framework to time‐course models.

Methods

We propose a Bayesian time‐course MBNMA modelling framework for continuous summary outcomes that allows for nonlinear modelling of multiparameter time‐course functions, accounts for residual correlation between observations, preserves randomisation by modelling relative effects, and allows for testing of inconsistency between direct and indirect evidence on the time‐course parameters. We demonstrate our modelling framework using an illustrative dataset of 23 trials investigating treatments for pain in osteoarthritis.

Results

Of the time‐course functions that we explored, the Emax model gave the best fit to the data and has biological plausibility. Some simplifying assumptions were needed to identify the ET50, due to few observations at early follow‐up times. Treatment estimates were robust to the inclusion of correlations in the likelihood.

Conclusions

Time‐course MBNMA provides a statistically robust framework for synthesising evidence on multiple treatments at multiple time points. The use of placebo‐controlled studies in drug‐development means there is limited potential for inconsistency. The methods can inform drug‐development decisions and provide the rigour needed in the reimbursement decision‐making process.
Progress in the Development of Intrinsically Conducting Polymer Composites as Biosensors
Authors: Prajapati Deepak G. , Kandasubramanian Balasubramanian
Published: April 2019

Biosensors are analytical devices which find extensive applications in fields such as the food industry, defense sector, environmental monitoring, and in clinical diagnosis. Similarly, intrinsically conducting polymers (ICPs) and their composites have lured immense interest in bio‐sensing due to their various attributes like compatibility with biological molecules, efficient electron transfer upon biochemical reactions, loading of bio‐reagent, and immobilization of biomolecules. Further, they are proficient in sensing diverse biological species and compounds like glucose (detection limit ≈0.18 nm), DNA (≈10 pm), cholesterol (≈1 µm), aptamer (≈0.8 pm), and also cancer cells (≈5 pm mL−1) making them a potential candidate for biological sensing functions. ICPs and their composites have been extensively exploited by researchers in the field of biosensors owing to these peculiarities; however, no consolidated literature on the usage of conducting polymer composites for biosensing functions is available. This review extensively elucidates on ICP composites and doped conjugated polymers for biosensing functions of copious biological species. In addition, a brief overview is provided on various forms of biosensors, their sensing mechanisms, and various methods of immobilizing biological species along with the life cycle assessment of biosensors for various biosensing applications, and their cost analysis.
microRNA‐mRNA analysis in pituitary and hypothalamus of sterile Japanese flounder
Authors: Zhang Xiaoyan , Wang Guixing , Sun Zhaohui , Hou Jilun , Wang Yufen
Published: April 2019

Double haploidy is an advantageous situation for genetic mapping and genome sequencing studies. In the present study, the hypothalamus and pituitary gland from sterile and fertile double‐haploid (DH) Japanese flounders (aged 5 years) were used as experimental materials for studying the expression of genes in individuals with reproductive disorders, using high‐throughput sequencing technology. The results revealed abnormal levels of some hormones in sterile DHs during the breeding season. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the significantly different microRNAs and messenger RNAs were related to metabolism, signal transduction, and melanogenesis; those related to steroid hormone synthesis and secretion related pathways were not detected. Our results suggest that the key to sterility in DHs was the arrested ovary development. However, the reason for arrested ovary development was mainly related to the lower levels of expression of genes involved in steroid biosynthesis in gonads, and was not related to the pituitary. For maintaining homeostasis, the hypothalamus and pituitary would have large differences in several processes, including signal transduction, metabolism, and immune response. The present study provides primary data for further studies on sterility in fish, and even in other animals.
Steric and Electronic Effects in Gold N‐Heterocyclic Carbene Complexes Revealed by Computational Analysis
Authors: de Kock Sunel , Dillen Jan , Esterhuysen Catharine
Published: April 2019

A computational analysis of a series of cationic and neutral gold imidazolylidene and benzimidizolylidene complexes is reported. The Bond Dissociation Energies of the various ligands in the complexes calculated at the PBE0‐D3/def2‐TZVP level of theory increase with increasing ligand volume, except for those of complexes containing t‐butyl‐substituted ligands, which are anomalously low particularly for the benzimidazolylidene species. Atoms in Molecules studies show the presence of a variety of weak intramolecular interactions, characterised by the presence of bond critical points with a range of different properties. Energy Decomposition Analysis and calculation of Electrostatic Surface Potentials indicate that some interactions are weakly attractive dispersion‐type interactions, while others are repulsive. The octanol/water partition coefficients (log P values) were calculated as a measure of the lipophilicities of the complexes and were found to increase with increasing volume.
Effect of recycling and injection parameters on gloss properties of smooth colored polypropylene parts: Contribution of surface and skin layer
Authors: Mbarek Souad , Baccouch Zaineb , Eterradossi Olivier , Perrin Didier , Monasse Bernard , Garay Helene , Quantin Jean‐Cristophe
Published: April 2019

The aim of this article is to investigate the optical properties of a recycled polymer during numerous processes. The effects of different process parameters (number of grinding‐injection cycles, material temperature, mold temperature, and injection rate) on gloss and color properties of a buff‐colored polypropylene containing 2wt%/wt of pigment was considered. The variations of properties are in the same range that is observed by changing processing parameters. It is found that the roughness is not able to explicate the variation of the optical properties for these variations of conditions. In addition, the optical properties of the skin layer of the injected parts are associated with the observed gloss and color variations. Moreover, the change of spherulite dimensions is related with optical changes. POLYM. ENG. SCI., 59:1288–1299 2019. © 2019 Society of Plastics Engineers
Synthesis and characterization of a novel freeze‐dried silanated chitosan bone tissue engineering scaffold reinforced with electrospun hydroxyapatite nanofiber
Authors: Nezafati Nader , Faridi‐Majidi Raheleh , Pazouki Mohammad , Hesaraki Saeed
Published: April 2019

Novel chitosan scaffolds containing different weight ratios of electrospun hydroxyapatite nanofibers (n‐HAs) were fabricated. The fibers possessed diameters in the range 110–170 nm. A fixed concentration of glycidyloxypropyl‐trimethoxysilane (GPTMS) as a crosslinking agent was added to the chitosan solution (CG). The porosity percentage was increased when GPTMS and n‐HAs were added to the chitosan structure. The presence of GPTMS in the chitosan structure caused a decrease in the average pore size. The pores were more irregular in shape than pure chitosan and CG scaffolds when n‐HAs were added. A uniform distribution of n‐HAs was seen for a chitosan‐GPTMS hybrid scaffold containing 25 wt% n‐HAs (CGH25) using energy dispersive X‐ray spectroscopy and mapping. The best values of compressive strength and elastic modulus were achieved for CGH25. The swelling ratio was decreased on adding GPTMS to the chitosan scaffold. Different morphologies of hydroxyapatite deposits on the surface of CG and CGH25 (string‐likeversusneedle‐like precipitates) were observed after 14 days of soaking in simulated body fluid. For CGH25, the viability of MG‐63 osteoblastic cells improved with respect to CG for up to 72 h of cell culture. These results reveal the potential of the chitosan‐CGH25 scaffold for use in bone tissue engineering. © 2019 Society of Chemical Industry
Pathogen acquisition in patients with cystic fibrosis receiving ivacaftor or lumacaftor/ivacaftor
Authors: Singh Sachinkumar B. , McLearn‐Montz Amanda J. , Milavetz Francesca , Gates Levi K. , Fox Christopher , Murry Logan T. , Sabus Ashley , Porterfield Harry S. , Fischer Anthony J.
Published: April 2019

Background

The cystic fibrosis transmembrane conductance regulator (CFTR) modulators ivacaftor and lumacaftor/ivacaftor improve the status of existing infections in patients with cystic fibrosis (CF). It is unknown how well these drugs protect patients against incident infections. We hypothesized that CFTR modulator treatment would decrease new infections with Pseudomonas aeruginosa or Staphylococcus aureus.

Methods

We retrospectively studied a single‐center cohort of patients with CF during two time periods (2008‐2011, Era 1) and (2012‐2015, Era 2) based on the January 2012 approval of ivacaftor. Using Kaplan–Meier analysis, we compared the time to any new infection with P. aeruginosa, methicillin‐resistant
S. aureus (MRSA), or methicillin‐sensitive
S. aureus (MSSA) that was absent during a 2‐year baseline. We stratified the analysis based on whether patients received ivacaftor or lumacaftor/ivacaftor during Era 2. We used the log‐rank test and considered
P < 0.05 statistically significant.

Results

For patients receiving ivacaftor or lumacaftor/ivacaftor in Era 2, there was a statistically significant delay in the time to new bacterial acquisition in Era 2 vs. Era 1 (
P = 0.008). For patients who did not receive CFTR modulators, there was a trend toward slower acquisition of new bacterial infections in Era 2 compared to Era 1, but this was not statistically significant (
P = 0.10).

Conclusions

Patients receiving ivacaftor or lumacaftor/ivacaftor for CF had significantly delayed acquisition of
P. aeruginosa and
S. aureus after these drugs were released. This method for analyzing incident infections may be useful for future studies of CFTR modulators and bacterial acquisition in CF registry cohorts.
The impact of mannose‐binding lectin polymorphisms on lung function in primary ciliary dyskinesia
Authors: Videbæk Katja , Buchvald Frederik , Holgersen Mathias Gelderman , Henriksen Alison , Eriksson Frank , Garred Peter , Nielsen Kim Gjerum
Published: April 2019

Objective

Primary ciliary dyskinesia (PCD) is a congenital lung disease that leads to recurrent and chronic lung infection. The resulting inflammation causes lung damage and declines in lung function. Mannose‐binding lectin (MBL) is a first line host defense protein of importance for the innate immunity. Polymorphisms in the MBL gene named MBL2 result in unstable and low functional levels MBL proteins. MBL insufficiency is linked to an increased risk of lung infection and to declines in lung function in patients with cystic fibrosis. We investigated whether there is a similar link in patients with PCD.

Methods

This retrospective longitudinal study included 85 patients with PCD. Diagnostics and age at diagnosis were recorded, complete spirometry data starting at diagnosis, and Pseudomonas aeruginosa infection status over the last 2 years were collected, and the patients were grouped according to MBL2 genotype status (MBL2‐sufficient or MBL2‐deficient).

Results

MBL‐deficient patients were diagnosed almost 3 years earlier than MBL‐sufficient patients (median 6.1 vs 8.9 years, P  < 0.05). There were no differences in the first measured spirometry values, but MBL‐deficient patients showed greater declines in forced expiratory volume in one sec (FEV1) than patients with MBL sufficiency (z‐score: −0.049 per year [95% CI, −0.075; −0.021] vs −0.009 per year [95% CI, −0.033; 0.015]; P = 0.023). No differences were found in forced vital capacity (FVC), FEV1/FVC, or infection status.

Conclusion

MBL‐deficiency, which is associated with MBL2 mutations, was associated with a lower age at diagnosis and with steeper declines in FEV1 in patients with PCD. This suggests that the MBL genotype might be a disease modifier in PCD.
Recent advances in hyperspectral imaging for melanoma detection
Authors: Johansen Thomas Haugland , Møllersen Kajsa , Ortega Samuel , Fabelo Himar , Garcia Aday , Callico Gustavo M. , Godtliebsen Fred
Published: April 2019

Skin cancer is one of the most common types of cancer. Skin cancers are classified as nonmelanoma and melanoma, with the first type being the most frequent and the second type being the most deadly. The key to effective treatment of skin cancer is early detection. With the recent increase of computational power, the number of algorithms to detect and classify skin lesions has increased. The overall verdict on systems based on clinical and dermoscopic images captured with conventional RGB (red, green, and blue) cameras is that they do not outperform dermatologists. Computer‐based systems based on conventional RGB images seem to have reached an upper limit in their performance, while emerging technologies such as hyperspectral and multispectral imaging might possibly improve the results. These types of images can explore spectral regions beyond the human eye capabilities. Feature selection and dimensionality reduction are crucial parts of extracting salient information from this type of data. It is necessary to extend current classification methodologies to use all of the spatiospectral information, and deep learning models should be explored since they are capable of learning robust feature detectors from data. There is a lack of large, high‐quality datasets of hyperspectral skin lesion images, and there is a need for tools that can aid with monitoring the evolution of skin lesions over time. To understand the rich information contained in hyperspectral images, further research using data science and statistical methodologies, such as functional data analysis, scale‐space theory, machine learning, and so on, are essential.

This article is categorized under:

Applications of Computational Statistics > Health and Medical Data/Informatics
Splitting the affective atom: Divergence of valence and approach-avoidance motivation during a dynamic emotional experience
Authors: Kaczmarek Lukasz D. , Behnke Maciej , Enko Jolanta , Kosakowski Michał , Guzik Przemysław , Hughes Brian M.
Published: April 2019

Valence and approach-avoidance motivation are two distinct but closely related components of affect. However, little is known about how these two processes evolve and covary in a dynamic affective context. We formulated several hypotheses based on the Motivational Dimensional Model of Affect. We expected that anger would be a unique approach-related rather than avoidance-related negative emotion. We also expected that high-approach positive emotions (e.g., desire) would differ from low-approach positive emotions (e.g., amusement) producing a stronger link between valence and approach-avoidance motivation. We also explored other dynamic properties of discrete emotions such as the difference between approach-avoidance motivation and valence as a marker of balance within affective components. We asked 69 participants to provide continuous ratings of valence and approach-avoidance motivation for eight standardized clips representing different discrete emotions. Using multilevel modeling, we established a significant relationship between valence and approach-avoidance motivation with high-approach emotions producing a stronger link between valence and approach-avoidance motivation compared to neutral states and low-approach emotions. Contrary to expectations, we observed that individuals exhibited an avoidance response during anger elicitation. Finally, we found that awe was a distinct positive emotion where approach motivation dominated over valence. These findings are relevant to the theory and research on diverging processes within the core structure of affect.
GPA: A Microbial Genetic Polymorphisms Assignments Tool in Metagenomic Analysis by Bayesian Estimation
Authors: Li Jiarui , Du Pengcheng , Ye Adam Yongxin , Zhang Yuanyuan , Song Chuan , Zeng Hui , Chen Chen
Published: April 2019

Identifying antimicrobial resistant (AMR) bacteria in metagenomics samples is essential for public health and food safety. Next-generation sequencing (NGS) technology has provided a powerful tool in identifying the genetic variation and constructing the correlations between genotype and phenotype in humans and other species. However, for complex bacterial samples, there lacks a powerful bioinformatic tool to identify genetic polymorphisms or copy number variations (CNVs) for given genes. Here we provide a Bayesian framework for genotype estimation for mixtures of multiple bacteria, named as Genetic Polymorphisms Assignments (GPA). Simulation results showed that GPA has reduced the false discovery rate (FDR) and mean absolute error (MAE) in CNV and single nucleotide variant (SNV) identification. This framework was validated by whole-genome sequencing and Pool-seq data from Klebsiella pneumoniae with multiple bacteria mixture models, and showed the high accuracy in the allele fraction detections of CNVs and SNVs in AMR genes between two populations. The quantitative study on the changes of AMR genes fraction between two samples showed a good consistency with the AMR pattern observed in the individual strains. Also, the framework together with the genome annotation and population comparison tools has been integrated into an application, which could provide a complete solution for AMR gene identification and quantification in unculturable clinical samples. The GPA package is available at https://github.com/IID-DTH/GPA-package.
A ketogenic drink improves brain energy and some measures of cognition in mild cognitive impairment
Authors: Fortier Mélanie , Castellano Christian‐Alexandre , Croteau Etienne , Langlois Francis , Bocti Christian , St‐Pierre Valérie , Vandenberghe Camille , Bernier Michaël , Roy Maggie , Descoteaux Maxime , Whittingstall Kevin , Lepage Martin , Turcotte Éric E. , Fulop Tamas , Cunnane Stephen C.
Published: April 2019

Introduction

Unlike for glucose, uptake of the brain's main alternative fuel, ketones, remains normal in mild cognitive impairment (MCI). Ketogenic medium chain triglycerides (kMCTs) could improve cognition in MCI by providing the brain with more fuel.

Methods

Fifty‐two subjects with MCI were blindly randomized to 30 g/day of kMCT or matching placebo. Brain ketone and glucose metabolism (quantified by positron emission tomography; primary outcome) and cognitive performance (secondary outcome) were assessed at baseline and 6 months later.

Results

Brain ketone metabolism increased by 230% for subjects on the kMCT (P < .001) whereas brain glucose uptake remained unchanged. Measures of episodic memory, language, executive function, and processing speed improved on the kMCT versus baseline. Increased brain ketone uptake was positively related to several cognitive measures. Seventy‐five percent of participants completed the intervention.

Discussion

A dose of 30 g/day of kMCT taken for 6 months bypasses a significant part of the brain glucose deficit and improves several cognitive outcomes in MCI.
Hardmetal benefits for oil and gas
Authors: Nickels Liz
Published: April 2019

The increasing use of hardmetal coatings is a boon for the expanding offshore oil and gas industry. Liz Nickels spoke to coating specialist Hardide Coatings about one particular application.
A dynamical systems view of granular flow: from monoclinal flood waves to roll waves
Authors: Razis Dimitrios , Kanellopoulos Giorgos , van der Weele Ko
Published: April 2019

On the basis of the Saint-Venant equations for flowing granular matter, we study the various travelling waveforms that are encountered in chute flow for growing Froude number. Generally, for$Fr<2/3$one finds either a uniform flow of constant thickness or a monoclinal flood wave, i.e. a shock structure monotonically connecting a thick region upstream to a shallower region downstream. For$Fr>2/3$both the uniform flow and the monoclinal wave cease to be stable; the flow now organizes itself in the form of a train of roll waves. From the governing Saint-Venant equations we derive a dynamical system that elucidates the transition from monoclinal waves to roll waves. It is found that this transition involves several intermediate stages, including an undular bore that had hitherto not been reported for granular flows.