bluuebunny/crossref_metadata_2025 huggingface dataset:
Chiral control of enantiomers through crystallization: Moving from ternary phase diagrams to design spaces
Authors: Lovette Michael A.
Published: May 2018

Although chiral purity is a critical quality attribute for many synthetic drugs, current industrial strategies for establishing chiral purity control are underdeveloped. Such strategies have relied on the construction of ternary phase diagrams, system classification, and case‐specific operating policies. These policies have been developed to provide enantiopure solids, regardless of product specification or target. In this article, new operating policies are developed for obtaining solids that meet, but do not exceed, chiral purity specifications for arbitrary systems. These policies can provide significant yield improvements over the current practice. Additionally, this work provides an approach for the creation of design spaces based on the collection of limited, small scale data. This approach has been extended to sequential re‐crystallizations and can be used to determine “global” optimal policies within a synthetic route. © 2018 American Institute of Chemical Engineers AIChE J, 64: 3323–3331, 2018
Assessing the value of information of data‐centric activities in the chemical processing industry 4.0
Authors: Reis Marco S. , Kenett Ron
Published: May 2018

The quality of information generated in data‐driven empirical studies is of central importance in Industry 4.0. However, despite the undeniable and widely accepted importance, not sufficient attention has been devoted to its rigorous assessment and analysis. Consequently, if information quality cannot be measured, it also cannot be improved, and therefore current efforts for extracting value from big data empirical studies and data collectors are exposed to the risk of generating limited findings and insights, leading to suboptimal solutions. In this article, we describe and apply a framework for evaluating, analyzing and improving the quality of information generated in empirical studies called InfoQ, in the context of the Chemical Processing Industry (CPI). This systematic framework can be used by anyone involved in data‐driven activities, irrespectively of the context and specific goals. The application of InfoQ framework to several case studies is described in detail, to illustrate its practical relevance. © 2018 American Institute of Chemical EngineersAIChE J, 64: 3868–3881, 2018
Heterogeneous production of Cl2 from particulate chloride: Effects of composition and relative humidity
Authors: Faxon Cameron B. , Dhulipala Surya Venkatesh , Allen David T. , Hildebrandt Ruiz Lea
Published: May 2018

Reactions initiated by chlorine atoms can enhance the formation of ozone (O3) and secondary organic aerosol (SOA) in the troposphere. Environmental chamber experiments were conducted to quantify heterogeneous Cl2 production from NH4Cl and NaCl particles exposed to O3 and hydroxyl radicals (•OH). Observations are inconsistent with models of Cl2 production resulting solely from surface‐mediated reactions of •OH and suggest that O3 plays a significant role. The production of Cl2 increased with relative humidity and decreased in the presence of SOA or nitric oxides (NOx). Heterogeneous reactive uptake coefficients for the production of Cl2 from O3 on pure NH4Cl (
) averaged 1.4 ± 1.0 × 10−3. Cl2 production was six times more efficient on NH4Cl aerosol than on NaCl aerosol. Model calculations under atmospheric conditions suggest this heterogeneous Cl2 production could increase peak daily O3 concentrations by over 10%. © 2018 American Institute of Chemical Engineers AIChE J, 64: 3151–3158, 2018
Aufwärtskonvertierende NaYF4:Yb,Er/NaYF4‐Kern/Schale‐Nanokristalle mit hoher Lumineszenzquantenausbeute
Authors: Homann Christian , Krukewitt Lisa , Frenzel Florian , Grauel Bettina , Würth Christian , Resch‐Genger Ute , Haase Markus
Published: May 2018

Eine modifizierte Syntheseroute auf der Basis wasserfreier Seltenerdacetate wurde zur Synthese aufwärtskonvertierender Kern/Schale‐Nanokristalle mit mittleren Größen zwischen 15 bis 45 nm eingesetzt. Die nahezu monodispersen Partikel bestehen aus einem NaYF4:Yb,Er‐Kern, dotiert mit 18 % Yb3+ und 2 % Er3+, und einer inerten Schale aus NaYF4, wobei die Dicke der Schale dem jeweiligen Radius des Kernpartikels entspricht. Absolutmessungen der Photolumineszenz‐Quantenausbeuten bei verschiedenen Anregungsleistungsdichten zeigen, dass die Quantenausbeuten von 45 nm Kern/Schale‐Partikeln schon fast an die Quantenausbeute des mikrokristallinen aufwärtskonvertierenden Leuchtstoffs heranreichen. Kleinere Kern/Schale‐Partikel, die nach der gleichen Methode hergestellt wurden, zeigen nur eine moderate Abnahme der Quantenausbeute. Beispielsweise ist die Quantenausbeute von 15 nm großen Kern/Schale‐Partikeln bei hohen Leistungsdichten (100 W cm−2) nur um einen Faktor drei kleiner als die des mikrokristallinen Leuchtstoffpulvers und um ungefähr einen Faktor 10 kleiner bei niedrigen Leistungsdichten (1 W cm−2).
Two Amphoteric Silver Carbene Clusters
Authors: Tskhovrebov Alexander G. , Goddard Richard , Fürstner Alois
Published: May 2018

Two highly labile silver carbene cluster complexes are described, which are unique in that they mark the transition point at which the carbene center transmutes from a fairly common NHC‐like nucleophilic behavior to an electrophilic character befitting reactive silver carbene intermediates of relevance in various catalytic transformations. This amphoteric character is the distinguishing attribute of a μ‐bridged donor/donor carbene entity that connects two silver atoms of triangular or tetrahedral metallic core units.
Nondestructive measurement of layer thickness in water‐assisted coinjection‐molded product by ultrasonic technology
Authors: Xia Neng , Zhao Peng , Kuang Tangqing , Zhao Yao , Zhang Jianfeng , Fu Jianzhong
Published: May 2018

Layer thickness is an important factor in judging the quality of a water‐assisted coinjection molding (WACIM) part. Here, a novel nondestructive method for measuring layer thickness via ultrasonic technology is proposed. The reflected signals from the interface of a WACIM part were measured by an immersed pulse‐echo method and calculated using a transfer function of the medium. Two objective functions were employed to describe the nonsimilarity between the measured signals and the calculated signals. By solving a multiobjective optimization problem, the optimum parameter was obtained and used to calculate the thickness of each layer in a WACIM part. The proposed method was employed to measure the layer thickness of WACIM specimens with different cross sections along the flow direction. Experimental results showed that the proposed method can correctly measure the variation in layer thickness of each layer of a WACIM part. The proposed method has broad application prospects in nondestructively measuring the layer thickness of polymeric parts. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46540.
Crystallization kinetics, morphology, and hydrolytic degradation of novel bio‐based poly(lactic acid)/crystalline silk nano‐discs nanobiocomposites
Authors: Patwa Rahul , Kumar Amit , Katiyar Vimal
Published: May 2018

In this work, novel biodegradable crystalline silk nano‐discs (CSNs) having a disc‐like morphology have been utilized for fabrication of poly(lactic acid) (PLA) nanocomposites by melt‐extrusion. The main focus is to investigate the effect of CSN on isothermal melt crystallization kinetics, spherulitic growth rates, morphology, and hydrolytic degradation of PLA. Spherulitic morphology and growth rates are examined over a wide range of crystallization temperatures (90–120 °C). With incorporation of CSN, the isothermal crystallization kinetics of PLA/CSN increases, however, the crystallization mechanism remains unaltered. The apparent activation energy and surface energy barrier for crystallization process decreases upon addition of CSNs. At lower isothermal crystallization temperatures (Tc) viz. (90–100 °C), reduced growth rates of PLA spherulites is observed. Both PLA and PLA/CSN exhibit highest crystallization rates at around ∼107 °C. The hydrolytic degradation rates calculated from molecular weight reduction shows that PLA/CSN nanocomposites' degradation rates are lower as compared to PLA in acidic, neutral, and alkaline media at pH = 2, 7, and 12, respectively, due to hydrophobic nature of CSN. Scanning electron microscopy study demonstrated the surface erosion mechanism of hydrolytic degradation of PLA and PLA/CSN nanocomposites. This work provides valuable insight for the application and reclamation of PLA/CSN bionanocomposites in moist and wet working environments. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46590.
PANI/PPY blend thin films electrodeposited for use in EGFET sensors
Authors: Mello Hugo José Nogueira Pedroza Dias , Mulato Marcelo
Published: May 2018

Galvanostatic electrodeposited thin films of polyaniline (PANI)/polypyrrole (PPY) blend were tested as chemical sensors and evaluated according to the relative monomer concentration in polymerization solution aiming to obtain a reliable reference field‐effect transistor able to be used as contrast sensing film. The blend material presented properties that can be controlled by the polymerization process. The films were produced using aniline (0.25 M) and pyrrole (0.25 M) mixed in five different proportions (90/10, 70/30, 50/50, 30/70, 10/90) with HCl (1.0 M) in an aqueous solution. The current density was 1 mA/cm2 for 300 s. The films were analyzed by their chronopotentiometric curves, thickness, reflectance spectroscopy, optical color parameters, and surface morphology. The characteristics and properties analyzed were correlated to the relative monomer concentration in the polymerization solution. The polymerization of PANI is favorable in aqueous acid solution compared to PPY, which resulted in thin films with properties varying from PANI down to PPY. The blend films presented controllable sensitivity when applied as sensing stage in field‐effect transistor devices as function of the relative monomer concentration. The sensitivity varied from 57 ± 1 mV/pH for the PANI sample, down to 25 ± 1 mV/pH for the PPY sample, presenting an exponential behavior. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46625.
Improvement of Lotus japonicus hairy root induction and development of a mycorrhizal symbiosis system
Authors: Xu Yunjian , Liu Fang , Han Guomin , Wang Wei , Zhu Suwen , Li Xiaoyu
Published: May 2018

Premise of the Study

We describe a highly efficient in vitro Lotus japonicus hairy root transformation system that is useful for the investigation of mycorrhizal symbiosis.

Methods and Results

The Agrobacterium rhizogenes–mediated transformation method was improved based on the binary plasmid (pCAMBIA1304) harboring green fluorescent protein and β‐glucuronidase genes for rapid detection. Transgenic hairy roots were grown within 13 days. These in vitro–cultured hairy roots can be inoculated with Rhizophagus irregularis, thus facilitating the investigation of the symbiosis between L. japonicus and arbuscular mycorrhizal fungi.

Conclusions

Compared with existing techniques, our protocol provides a simple and efficient A. rhizogenes–mediated transformation system for L. japonicus. The rapid induction of hairy roots can shorten the experimental time by at least one week.
Risk Factors and Biomarkers for the Occurrence of Uveitis in Juvenile Idiopathic Arthritis
Authors: Tappeiner Christoph , Klotsche Jens , Sengler Claudia , Niewerth Martina , Liedmann Ina , Walscheid Karoline , Lavric Miha , Foell Dirk , Minden Kirsten , Heiligenhaus Arnd
Published: May 2018

Objective

To analyze the prognostic value of demographic, clinical, and therapeutic factors and laboratory biomarkers and to assess their role in predicting uveitis occurrence in patients with juvenile idiopathic arthritis (JIA).

Methods

Patients with JIA were enrolled within the first year after JIA diagnosis. Demographic and clinical parameters were documented. Serum samples were collected at study enrollment, at 3‐month follow‐up visits within the first year, and then every 6 months. A multivariable Cox regression analysis was performed to evaluate the impact of demographic, clinical, laboratory, and therapeutic parameters on uveitis onset.

Results

We included 954 JIA patients (67.2% female, 54.2% antinuclear antibody [ANA] positive, mean ± SD age at onset 7.1 ± 4.6 years). Uveitis occurred in 133 patients (observation period 44.5 months). Young age at JIA onset and ANA positivity were significantly associated with the onset of uveitis (both P < 0.001). Treatment of arthritis with methotrexate alone (hazard ratio [HR] 0.18 [95% confidence interval (95% CI) 0.12–0.29], P < 0.001) or combined with etanercept (HR 0.10 [95% CI 0.04–0.23], P < 0.001) or adalimumab (HR 0.09 [95% CI 0.01–0.61], P = 0.014) reduced the risk of uveitis onset and the occurrence of uveitis‐related complications. Predictors of uveitis onset included elevated erythrocyte sedimentation rate at baseline (HR 2.36 [95% CI 1.38–4.02], P = 0.002) and continuing moderate or high disease activity during follow‐up as measured by the 10‐joint clinical Juvenile Arthritis Disease Activity Score (HR 4.30 [95% CI 2.51–7.37], P < 0.001). Additionally, S100A12 levels ≥250 ng/ml at baseline were significantly associated with the risk of uveitis (HR 2.10 [95% CI 1.15–3.85], P = 0.016).

Conclusion

Apart from demographic risk factors and treatment modalities, JIA disease activity scores and laboratory biomarkers could be used to better define the group of JIA patients at high risk of uveitis onset.
Functional Characterization of the Osteoarthritis Genetic Risk Residing at ALDH1A2 Identifies rs12915901 as a Key Target Variant
Authors: Shepherd Colin , Zhu Dongxing , Skelton Andrew J. , Combe Jennifer , Threadgold Harrison , Zhu Linyi , Vincent Tonia L. , Stuart Paul , Reynard Louise N. , Loughlin John
Published: May 2018

Objective

To identify the functional single‐nucleotide polymorphisms (SNPs) and mechanisms conferring increased risk of hand osteoarthritis (OA) at the ALDH1A2 locus, which is a retinoic acid regulatory gene.

Methods

Tissue samples from 247 patients with knee, hip, or hand OA who had undergone joint surgery were included. RNA‐sequencing analysis was used to investigate differential expression of ALDH1A2 and other retinoic acid signaling pathway genes in cartilage. Expression of ALDH1A2 in joint tissues obtained from multiple sites was quantified using quantitative reverse transcription–polymerase chain reaction. Allelic expression imbalance (AEI) was measured by pyrosequencing. The consequences of ALDH1A2 depletion by RNA interference were assessed in primary human chondrocytes. In silico and in vitro analyses were used to pinpoint which, among 62 highly correlated SNPs, could account for the association at the locus.

Results

ALDH1A2 expression was observed across multiple joint tissue samples, including osteochondral tissue from the hand. The expression of ALDH1A2 and of several retinoic acid signaling genes was different in diseased cartilage compared to non‐diseased cartilage, with ALDH1A2 showing lower levels in OA cartilage. Experimental depletion of ALDH1A2 resulted in changes in the expression levels of a number of chondrogenic markers, including SOX9. In addition, reduced expression of the OA risk–conferring allele was witnessed in a number of joint tissues, with the strongest effect in cartilage. The intronic SNP rs12915901 recapitulated the AEI observed in patient tissues, while the Ets transcription factors were identified as potential mediators of this effect.

Conclusion

The ALDH1A2 locus seems to increase the risk of hand OA through decreased expression of ALDH1A2 in joint tissues, with the effect dependent on rs12915901. These findings indicate a mechanism that may now be targeted to modulate OA risk.
Consensus‐based journal rankings: A complementary tool for bibliometric evaluation
Authors: Aledo Juan A. , Gámez Jose A. , Molina David , Rosete Alejandro
Published: May 2018

Annual journal rankings are usually considered a tool for the evaluation of research and researchers. Although they are an objective resource for such evaluation, they also present drawbacks: (a) the uncertainty about the definite position of a target journal in the corresponding annual ranking when selecting a journal, and (b) in spite of the nonsignificant difference in score (for instance, impact factor) between consecutive journals in the ranking, the journals are strictly ranked and eventually placed in different terciles/quartiles, which may have a significant influence in the subsequent evaluation. In this article we present several proposals to obtain an aggregated consensus ranking as an alternative/complementary tool to standardize annual rankings. To illustrate the proposed methodology we use as a case study the Journal Citation Reports, and in particular the category of Computer Science: Artificial Intelligence (CS:AI). In the context of the consensus rankings obtained by the different methods, we discuss the convenience of using one or the other procedure according to the corresponding framework. In particular, our proposals allow us to obtain consensus rankings that avoid crisp frontiers between similarly ranked journals and consider the longitudinal/temporal evolution of the journals.
Modeling citation dynamics of “atypical” articles
Authors: He Zhongyang , Lei Zhen , Wang Dashun
Published: May 2018

Modeling and predicting citation dynamics of individual articles is important due to its critical role in a wide range of decisions in science. While the current modeling framework successfully captures citation dynamics of typical articles, there exists a nonnegligible, and perhaps most interesting, fraction of atypical articles whose citation trajectories do not follow the normal rise‐and‐fall pattern. Here we systematically study and classify citation patterns of atypical articles, finding that they can be characterized by awakened articles, second‐acts, and a combination of both. We propose a second‐act model that can accurately describe the citation dynamics of second‐act articles. The model not only provides a mechanistic framework to understand citation patterns of atypical articles, separating factors that drive impact, but it also offers new capabilities to identify the time of exogenous events that influence citations.
Dynamics and Noncollocated Model‐Free Position Control for a Space Robot with Multi‐Link Flexible Manipulators
Authors: Yang Xinxin , Ge Shuzhi Sam , Liu Jinkun
Published: May 2018

In this paper, both the dynamics and noncollocated model‐free position control (NMPC) for a space robot with multi‐link flexible manipulators are developed. Using assumed modes approach to describe the flexible deformation, the dynamic model of the flexible space robotic system is derived with Lagrangian method to represent the system dynamic behaviors. Based on Lyapunov's direct method, the robust model‐free position control with noncollocated feedback is designed for position regulation of the space robot and vibration suppression of the flexible manipulators. The closed‐loop stability of the space robotic system can be guaranteed and the guideline of choosing noncollocated feedback is analyzed. The proposed control is easily implementable for flexible space robot with both uncertain complicated dynamic model and unknown system parameters, and all the control signals can be measured by sensors directly or obtained by a backward difference algorithm. Numerical simulations on a two‐link flexible space robot are provided to demonstrate the effectiveness of the proposed control.
Using machine learning to identify patterns of lifetime health problems in decedents with autism spectrum disorder
Authors: Bishop‐Fitzpatrick Lauren , Movaghar Arezoo , Greenberg Jan S. , Page David , DaWalt Leann S. , Brilliant Murray H. , Mailick Marsha R.
Published: May 2018

Very little is known about the health problems experienced by individuals with autism spectrum disorder (ASD) throughout their life course. We retrospectively analyzed diagnostic codes associated with de‐identified electronic health records using a machine learning algorithm to characterize diagnostic patterns in decedents with ASD and matched decedent community controls. Participants were 91 decedents with ASD and 6,186 sex and birth year matched decedent community controls who had died since 1979, the majority of whom were middle aged or older adults at the time of their death. We analyzed all ICD‐9 codes, V‐codes, and E‐codes available in the electronic health record and Elixhauser comorbidity categories associated with those codes. Diagnostic patterns distinguished decedents with ASD from decedent community controls with 75% sensitivity and 94% specificity solely based on their lifetime ICD‐9 codes, V‐codes, and E‐codes. Decedents with ASD had higher rates of most conditions, including cardiovascular disease, motor problems, ear problems, urinary problems, digestive problems, side effects from long‐term medication use, and nonspecific lab tests and encounters. In contrast, decedents with ASD had lower rates of cancer. Findings suggest distinctive lifetime diagnostic patterns among decedents with ASD and highlight the need for more research on health outcomes across the lifespan as the population of individuals with ASD ages. As a large wave of individuals with ASD diagnosed in the 1990s enters adulthood and middle age, knowledge about lifetime health problems will become increasingly important for care and prevention efforts. Autism Res 2018, 11: 1120–1128. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.

Lay Summary

This study looked at patterns of lifetime health problems to find differences between people with autism who had died and community controls who had died. People with autism had higher rates of most health problems, including cardiovascular, urinary, respiratory, digestive, and motor problems, in their electronic health records. They also had lower rates of cancer. More research is needed to understand these potential health risks as a large number of individuals with autism enter adulthood and middle age.
Typical use of inverse dynamics in perceiving motion in autistic adults: Exploring computational principles of perception and action
Authors: Takamuku Shinya , Forbes Paul A. G. , Hamilton Antonia F. de C. , Gomi Hiroaki
Published: May 2018

There is increasing evidence for motor difficulties in many people with autism spectrum condition (ASC). These difficulties could be linked to differences in the use of internal models which represent relations between motions and forces/efforts. The use of these internal models may be dependent on the cerebellum which has been shown to be abnormal in autism. Several studies have examined internal computations of forward dynamics (motion from force information) in autism, but few have tested the inverse dynamics computation, that is, the determination of force‐related information from motion information. Here, we examined this ability in autistic adults by measuring two perceptual biases which depend on the inverse computation. First, we asked participants whether they experienced a feeling of resistance when moving a delayed cursor, which corresponds to the inertial force of the cursor implied by its motion—both typical and ASC participants reported similar feelings of resistance. Second, participants completed a psychophysical task in which they judged the velocity of a moving hand with or without a visual cue implying inertial force. Both typical and ASC participants perceived the hand moving with the inertial cue to be slower than the hand without it. In both cases, the magnitude of the effects did not differ between the two groups. Our results suggest that the neural systems engaged in the inverse dynamics computation are preserved in ASC, at least in the observed conditions. Autism Res 2018, 11: 1062–1075. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.

Lay Summary

We tested the ability to estimate force information from motion information, which arises from a specific “inverse dynamics” computation. Autistic adults and a matched control group reported feeling a resistive sensation when moving a delayed cursor and also judged a moving hand to be slower when it was pulling a load. These findings both suggest that the ability to estimate force information from motion information is intact in autism.
Water Services Development and Governance in Finland
Authors: Katko Tapio S.
Published: May 2018

Water and wastewater services have developed remarkably well in Finland by following a principle of continuous development.
My Library in Practice
Authors: Janes Colton
Published: May 2018

Good books on management can inspire leadership success, which in turn helps the employees who provide water services to our communities.
Calculation of the potential production of methane and chemicals using anaerobic digestion
Authors: Dionisi Davide , Bolaji Ifeoluwa , Nabbanda Diana , Silva Igor MO
Published: May 2018

The aim of this paper is to calculate the amount of energy or chemicals that can be produced using anaerobic digestion (AD). Five feedstocks were considered: the organic fraction of municipal solid waste (OFMSW); cattle, pig and poultry manure; energy crops; agricultural residues, and sewage sludge. Carbohydrates, proteins, and lipids were assumed to be the biodegradable components of the feedstocks. Chemical oxygen demand (COD) was assumed as a basis for the calculations of the production of methane and other chemicals. Methane production was calculated assuming that AD converts the biodegradable COD to methane with a yield of 80% COD/COD. The potential production of chemicals, i.e. acetic, propionic, butyric, and lactic acids, ethanol, and hydrogen, was calculated assuming conversion yields of carbohydrates, proteins, and lipids from the literature. Globally, with the assumptions made in this study, the AD of the feedstocks considered here can potentially satisfy 17–20% of the total energy consumption and 33–39% of the electrical energy requirements. Potentially, AD can generate organic acids at rates that are hundreds or thousands of times their current production rates. Ethanol and hydrogen can be produced by AD at rates that are up to 2–3 times their current production rate. This paper also discusses the main challenges that must be overcome to achieve the potential of AD. © 2018 Society of Chemical Industry and John Wiley & Sons, Ltd
Gene variants in the folate pathway are associated with increased levels of folate receptor autoantibodies
Authors: Dong Yuqi , Wang Linlin , Lei Yunping , Yang Na , Cabrera Robert M. , Finnell Richard H. , Ren Aiguo
Published: May 2018

Background

Folate receptors (FRs) facilitate embryonic uptake of folates and are important for proper early embryonic development. There is accumulating evidence that blocking FR autoantibodies contribute to developmental diseases. However, genetic factors associated with the expression of FR autoantibodies remain unknown.

Objective

We investigated the effects of genetic polymorphisms in folate pathway genes on FR autoantibody titers in women.

Methods

We recruited 302 pregnant women in China. The FR antigen‐down immunoassay was used to measure levels of FR autoantibodies including human immunoglobulin G (IgG) and immunoglobulin M (IgM) in maternal plasma. Genotypes were identified by matrix‐assisted laser desorption/ionization time of flight mass spectrometry and polymerase chain reaction methods. General linear model was used to analyze the effects of genetic variants on FR autoantibody levels.

Results

Significant associations were observed between genotypic variations and levels of FR autoantibodies. Plasma levels of FR autoantibodies in women with the TT genotype at MTHFR rs1801133 were significantly higher than those of women with the CC genotype (IgG: β = 0.62, 95% CI 0.21–1.04; IgM: β = 0.42, 95% CI 0.12–0.72). For DNMT3A rs7560488, the level of FR autoantibody IgG significantly increased in the TT genotype compared with CC genotype (β = 0.90, 95% CI 0.20–1.59). For MTHFD2 rs828903, genotype GG was associated with elevated levels of FR autoantibody IgM compared to the AA genotype (β = 0.60, 95% CI 0.10–1.10). No association was detected between genetic variants of the DHFR gene with FR autoantibodies levels.

Conclusion

Genetic variations in MTHFR, DNMT3A, and MTHFD2 genes were associated with elevated plasma levels of FR autoantibodies.
Modeling clustered long‐term survivors using marginal mixture cure model
Authors: Niu Yi , Song Lixin , Liu Yufeng , Peng Yingwei
Published: May 2018

There is a great deal of recent interests in modeling right‐censored clustered survival time data with a possible fraction of cured subjects who are nonsusceptible to the event of interest using marginal mixture cure models. In this paper, we consider a semiparametric marginal mixture cure model for such data and propose to extend an existing generalized estimating equation approach by a new unbiased estimating equation for the regression parameters in the latency part of the model. The large sample properties of the regression effect estimators in both incidence and the latency parts are established. The finite sample properties of the estimators are studied in simulation studies. The proposed method is illustrated with a bone marrow transplantation data and a tonsil cancer data.
Protein purification by chemo‐selective precipitation using thermoresponsive polymers
Authors: Wu Yuanzi , Cai Zhen , Wu Shuigen , Xiong Wenli , Ma Shanyun
Published: May 2018

A recoverable and thermoresponsive polymer‐protein bioconjugate is synthesized and employed in the purification of protein with free sulfhydryl groups. Initiator with disulphide was modified on the cysteine residue of the target protein. Poly(N‐isopropylacrylamide) exhibiting a lower critical solution temperature was grown from the protein. The resulting protein–polymer conjugate was successfully thermoprecipitated and separated from other proteins. The approach was demonstrated with bovine serum albumin with the recycling yield of 76.4%. Enzyme activity test with papain verified the reversible polymer modification protected protein under extreme environments without affecting the functionality of the protein. This study implies the favorable potential of chemo‐selective enriching and purification of proteins.
Osteostimulation scaffolds of stem cells: BMP‐7‐derived peptide‐decorated alginate porous scaffolds promote the aggregation and osteo‐differentiation of human mesenchymal stem cells
Authors: Yang Yue , Luo Zuyuan , Zhao Ying
Published: May 2018

The scaffolds for stem cell‐based bone tissue engineering should hold the ability to guide stem cells osteo‐differentiating. Otherwise, stem cells will differentiate into unwanted cell types or will form tumors in vivo. Alginate, a natural polysaccharide with great biocompatibility, was widely used in biomedical applications. However, the limited bioactivity and poor osteogenesis capability of pristine alginate hampered its further application in tissue engineering. In this work, a bone forming peptide‐1 (BFP‐1), derived from bone morphogenetic protein‐7, was grafted to alginate polymer chains to prepare peptide‐decorated alginate porous scaffolds (pep‐APS) for promoting osteo‐differentiation of human mesenchymal stem cells (hMSCs). SEM images of pep‐APS exhibited porous structure with about 90% porosity (pore size 100–300 μm), which was appropriate for hMSCs ingrowth. The adhesion, proliferation and aggregation of hMSCs grown on pep‐APS were enhanced in vitro. Moreover, pep‐APS promoted the alkaline phosphatase (ALP) activity of hMSCs, and the osteo‐related genes expression was obviously up‐regulated. The immunochemical staining and western blot analysis results showed high expression level of OCN and Col1a1 in the hMSCs grown on pep‐APS. This work provided a facile and valid strategy to endow the alginate polymers themselves with specific bioactivity and prepare osteopromoting scaffold with enhanced osteogenesis ability, possessing potential applications in stem cell therapy and regenerative medicine.
Combinatorial synthetic pathway fine‐tuning and comparative transcriptomics for metabolic engineering of Raoultella ornithinolytica BF60 to efficiently synthesize 2,5‐furandicarboxylic acid
Authors: Yuan Haibo , Liu Yanfeng , Li Jianghua , Shin Hyun‐dong , Du Guocheng , Shi Zhongping , Chen Jian , Liu Long
Published: May 2018

The compound 5‐hydroxymethylfurfural (HMF) has attracted much attention due to its versatility as an important bio‐based platform chemical. Here, we engineered Raoultella ornithinolytica BF60 as a whole‐cell biocatalyst for a highly efficient synthesis of 2,5‐furandicarboxylic acid (FDCA) from HMF. Specifically, various expression cassettes of key genes, such as hmfH (gene encoding HMF/furfural oxidoreductase [HmfH]) and hmfo (gene encoding HMF oxidase), were designed and constructed for fine‐tuning FDCA synthesis from HMF. The FDCA titer reached 108.9 mM with a yield of 73% when 150 mM HMF was used as the substrate. This yield was 16% higher than that without balancing key gene expression in FDCA synthetic pathways. Additionally, to strengthen HmfH expression at the translational level, ribosomal binding site (RBS) sequences, which were computationally designed using the RBS calculator, were assembled into HmfH expression cassettes. The HmfH expression in the presence of these sequences enhanced FDCA titer to 139.6 mM with a yield of 93%. Next, previously unknown candidate genes, such as aldR, dkgA, akR, AdhP1, and AdhP2, which encode enzymes that catalyze the reactions leading to the formation of the undesired product 2,5‐bis(hydroxymethyl)furan (HMF alcohol) from HMF, were identified by RNA‐sequencing‐based transcriptomics. Combinatorial deletion of these five candidate genes led to an 88% reduction in HMF alcohol formation and 12% enhancement in FDCA production (175.6 mM). Finally, FDCA synthesis was further improved by the substrate pulse‐feeding strategy, and 221.5 mM FDCA with an 88.6% yield was obtained. The combinatorial synthetic pathway fine‐tuning and comparative transcriptomics approach may be useful for improving the biocatalysis efficiency of other industrially useful compounds.
Does oral spirulina protect the cornea from formaldehyde exposure? Application to anatomy laboratories
Authors: Al‐Neklawy Ahmed Farid
Published: May 2018

In this study, the protective effect of spirulina on corneal injury after formaldehyde (FA) exposure was assessed. Thirty adult male albino rats were divided into four groups. Group I: 12 rats were divided into two subgroups: I‐a (negative control) and I‐b (positive control). Group II (spirulina group): six rats received spirulina via an oral gavage feeding needle at a daily dose of 400 mg/kg b.w. Group III (FA exposure group): six rats were subjected to 10% FA inhalation for 2 h per day for 2 weeks (5 days per week). Group IV (FA exposure group treated with spirulina): six rats were exposed to 10% FA as in group III, with co‐administration of spirulina as in group II. After 2 weeks, all the rats were sacrificed; the corneas were dissected and processed for paraffin sections. The sections were stained with hematoxylin and eosin (H&E), Masson's trichrome (MTC), or avidin‐biotin peroxidase, and examined by light microscopy. The sections of rat cornea exposed to FA (Group III) showed disorganized and compressed epithelium with erosions. Subepithelial mononuclear cell infiltration and invasion of blood vessels were also evident. Stromal collagen fibers were disorganized and widely separated. All these changes were ameliorated by administration of spirulina (Group IV). Corneal thickness was nearly normal in Group IV, statistically significantly less than in Group III. It was concluded that spirulina protects against FA‐induced corneal injury in rats. Clin. Anat. 31:830–837, 2018. © 2018 Wiley Periodicals, Inc.
An original micro‐CT study and meta‐analysis of the internal and external anatomy of maxillary molars—implications for endodontic treatment
Authors: Tomaszewska Iwona M. , Jarzębska Anna , Skinningsrud Bendik , Pękala Przemysław A. , Wroński Sebastian , Iwanaga Joe
Published: May 2018

The aim of this work was to conduct a radiological micro‐CT study and meta‐analysis to determine the morphological features of the root canal anatomy of the maxillary molars. The radiological study included micro‐CT scans of 110 maxillary first molars and 98 maxillary second molars. To identify articles eligible for inclusion in our meta‐analysis, PubMed, Embase, and Web of Science were search comprehensively. The following data were extracted: study type (cadaveric, intraoperative or imaging), Vertucci types of canal configuration, presence/number of canals, roots, apical foramina, apical deltas, and inter‐canal communications. The mesiobuccal root was the most variable with respect to canal configuration, type I being the most common configuration followed by type II and type IV. Type I was the most common canal configuration in the distobuccal and palatal root. Regarding the number of canals in the maxillary first and second molars, one canal was most prevalent in all roots of the three molars, except for the mesiobuccal root of maxillary first molar, in which two canals were most prevalent. The most prevalent number of roots in all maxillary molars was three. Knowledge of endodontic anatomy determines the parameters of root canal treatment and significantly affects the probability of success. It is therefore especially important to know the morphology of the root canal system in order to perform endodontic treatment correctly. Clin. Anat. 31:838–853, 2018. © 2018 Wiley Periodicals, Inc.
Survival analysis of adult patients with ALL in Mexico City: first report from the Acute Leukemia Workgroup (ALWG) (GTLA)
Authors: Crespo‐Solis Erick , Espinosa‐Bautista Karla , Alvarado‐Ibarra Martha , Rozen‐Fuller Etta , Pérez‐Rocha Fernando , Nava‐Gómez Chantal , Ortiz‐Zepeda Maricela , Álvarez‐Vera José Luis , Ramos‐Peñafiel Christian Omar , Meillón‐García Luis Antonio , Rodríguez‐Rodríguez Sergio , Pomerantz‐Okon Alan , Turrubiates‐Hernández Francisco Javier , Demichelis‐Gómez Roberta
Published: May 2018

Acute lymphoblastic leukemia (ALL) is a hematologic malignancy characterized by the clonal expansion of hematopoietic lymphoid progenitors. With new target therapies, the survival of adults with ALL has improved in the past few decades. Unfortunately, there are no large ALL patient series in many Latin American countries. Data from the Acute Leukemia Workgroup that includes five Mexico City referral centers were used. Survival was estimated for adult patients with ALL during 2009–2015. In total, 559 adults with ALL were included. The median age was 28 years; 67% were classified into the adolescent and young adult group. Cytogenetic information was available in 54.5% of cases. Of the 305 analyzed cases, most had a normal caryotype (70.5%) and Philadelphia‐positive was present in 16.7%. The most commonly used treatment regimen was hyper‐CVAD. In approximately 20% of cases, there was considerable delay in the administration of chemotherapy. Primarily refractory cases accounted for 13.1% of patients. At the time of analysis, 26.7% of cases had survived. The 3‐year overall survival was 22.1%. The main cause of death was disease progression in 228 (55.6%). Clinical and public health strategies are needed to improve diagnosis, treatment and survivorship care for adult with ALL. This multicentric report represents the largest series in Mexico of adult ALL patients in which a survival analysis and risk identification were obtained.
Assessment of the prognostic factors in patients with pulmonary carcinoid tumor: a population‐based study
Authors: Huang Yiwei , Yang Xiaodong , Lu Tao , Li Ming , Zhao Mengnan , Yang Xingyu , Ma Ke , Wang Shuai , Zhan Cheng , Liu Yu , Wang Qun
Published: May 2018

Previous studies have identified potential risk factors for pulmonary carcinoid tumors and evaluated the effect of various treatments; however, the results were not entirely consistent. We conducted a population‐based study to further explore relevant prognostic issues. We extracted cases with pulmonary carcinoid tumors from the Surveillance Epidemiology and End Results database. Cox proportional hazard regression was utilized to identify potential significant risk factors, which helped establish a nomogram for predicting long‐term survival. Survival analysis and a competing risk study were conducted to evaluate the value of different surgical approaches. There were 7057 cases included in the study. Univariate and multivariate analyses showed that age, sex, tumor size, stage, histology, surgical type, chemotherapy, and radiation therapy were all significant prognostic factors. A nomogram with good accuracy for predicting 10‐year survival was formulated. Furthermore, patients who had undergone surgery had a significantly better survival than those who did not undergo surgery. There was no significant prognostic difference between lobectomy and sublobectomy stratified by tumor stage; however, lobectomy was associated with a significantly better survival in atypical tumors, especially those with regional disease. Our research identified possible risk factors in a large cohort and constructed a nomogram to visually predict 10‐year survival of pulmonary carcinoid tumors. We showed that lobectomy and sublobectomy should be considered as the mainstay of treatment, especially lobectomies for atypical tumor.
Anti‐PD‐1 therapy redirects macrophages from an M2 to an M1 phenotype inducing regression of OS lung metastases
Authors: Dhupkar Pooja , Gordon Nancy , Stewart John , Kleinerman Eugenie S.
Published: May 2018

Osteosarcoma (OS) pulmonary metastasis translates into poor patient survival. The implication of PD‐1‐PD‐L1 pathway in the context of NK cells and/or macrophages in OS is unknown. We investigated the effect of anti‐PD‐1 in OS lung metastasis and the role of NK cells and/or macrophages in anti‐PD‐1 responses. A human LM7 OS mouse model was used. Immunohistochemistry for tissues (PD‐L1, caspase‐3, Ki‐67, NK cells, macrophages), and Western blotting for OS lung tumors (p‐Stat3, p‐Erk1/2) was performed. NK and macrophages were assessed using flow cytometry. NK cell and macrophage depletion were conducted using anti‐asialo GM1 and clodrosome, respectively. PD‐L1 expression was observed in human OS cells and OS patient lung metastases. Anti‐PD1 antibody led to a significant decrease in the number of OS lung metastases, enhanced tumor apoptosis, decreased tumor cell proliferation, and p‐STAT‐3/p‐Erk1/2 signaling blockade in OS lung tumors. NK cells and macrophages in OS lung tumors expressed PD‐1 and anti‐PD1 increased NK cell and macrophage tumor infiltration. Increased numbers of antitumor M1 macrophages and decreased pro‐inflammatory M2 macrophages were seen. NK depletion did not affect therapeutic effect of anti‐PD‐1, suggesting that NK cells were not directly involved. However, macrophage depletion significantly compromised anti‐PD1 efficacy, confirming their role in efficacy of anti‐PD‐1 against OS lung metastasis. Our findings suggest that OS lung metastases regression by anti‐PD1 can be attributed to activated tumor M1 macrophages and reduced M2 macrophages. Owing to the co‐relation of M1 macrophages with OS patient outcome, we provide a novel mechanism of PD‐1 blockade and a basis for future clinical trials for anti‐PD‐1 antibodies in OS.
Contralateral prophylactic mastectomy rate and predictive factors among patients with breast cancer who underwent multigene panel testing for hereditary cancer
Authors: Elsayegh Nisreen , Webster Rachel D. , Gutierrez Barrera Angelica M. , Lin Heather , Kuerer Henry M. , Litton Jennifer K. , Bedrosian Isabelle , Arun Banu K.
Published: May 2018

Although multigene panel testing is increasingly common in patients with cancer, the relationship between its use among breast cancer patients with non‐BRCAmutations or variants of uncertain significance (VUS) and disease management decisions has not been well described. This study evaluated the rate and predictive factors of CPM patients who underwent multigene panel testing. Three hundred and fourteen patients with breast cancer who underwent multigene panel testing between 2014 and 2017 were included in the analysis. Of the 314 patients, 70 elected CPM. Election of CPM by gene status was as follows:BRCAcarriers (42.3%), non‐BRCAcarriers (30.1%), and VUS (10.6%). CPM election rates did not differ between non‐BRCAcarriers andBRCAcarriers (P = 0.6205). Among non‐BRCAcarriers, negative hormone receptor status was associated with CPM (P = 0.0115). For those with a VUS, hormone receptor status was not associated with CPM (P = 0.1879). Although the rate of CPM betweenBRCAcarriers and non‐BRCAcarriers was not significantly different, the predictors of CPM were different in each group. Our analyses shed the light on the increasing use of CPM among patients who are non‐BRCAcarriers as well those with a VUS. Our study elucidates the differing predictive factors of CPM election amongBRCAcarriers, non‐BRCAcarries, and those with a VUS. Our findings reveal the need for providers to be cognizant that non‐BRCAgenes and VUS drive women to elect CPM despite the lack of data for contralateral breast cancer risk associated with these genes.
MiRNA‐545 negatively regulates the oncogenic activity of EMS1 in gastric cancer
Authors: Ma Min , Zhao Juanxia , Wu Qunfeng , Xiao Ke , Li Shuang , Zhu Haizhen , Liu Chen , Xie Hailong , Zuo Chaohui
Published: May 2018

Gastric cancer (GC) is a common malignant tumor of the digestive system. In addition, GC metastasis is an extremely complicated process. In this article, high expression levels of EMS1 mRNA and protein were found to be positively correlated with an enhanced malignant potential of GC cells and a poor clinical prognosis of GC patients. Interestingly, the expression levels of EMS1 mRNA and protein in GC cells were inhibited by microRNA‐545 (miR‐545), which was identified by a bioinformatics analysis. The expression level of miR‐545 in carcinoma tissues was significantly lower than that in para‐carcinoma tissues. The proliferation and epithelial‐mesenchymal transition (EMT) of GC cells were suppressed by exogenous oligonucleotides of miR‐545 mimics. In addition, the expression levels of EMT‐associated markers were altered with the expression of miR‐545. Notably, the growth rates of tumors in nude mice were seriously restrained by an intratumoral injection of oligonucleotides of the miR‐545 mimics. These results suggest a negative regulatory role of miR‐545 on the oncogenic activity of EMS1. In addition, EMS1 and miR‐545 may be potential biomarkers for GC diagnosis. Synthesized oligonucleotides of miR‐545 mimics may be developed as important gene medicines for GC therapy in the future.
Radiotherapy vs surgery for T1‐2N0M0 laryngeal squamous cell carcinoma: A population‐based and propensity score matching study
Authors: Zhan Cheng , Yang Xiaodong , Song Xinmao , Yan Li
Published: May 2018

There are conflicting reports about whether radiotherapy or surgery is optimal for early‐stage laryngeal squamous cell carcinoma (LSCC), although both have recently been recommended. Patients with T1‐2N0M0 LSCC in the population‐based SEER database who underwent radiotherapy or surgery were reviewed. Propensity score matching was used to eliminate the baseline variations. After matching, 1913 pairs of patients were included. Overall, patients who received radiotherapy had worse cancer‐specific survival than patients with surgery. After stratification, the survival in patients who received radiotherapy was worse with respect to the following characteristics: ≤60 years of age; T1a glottis cancer; well‐differentiated tumors; and with married status. In other patients, survival outcomes were similar in patients who received radiotherapy and underwent surgery. Our results indicate that radiotherapy is not preferable in early‐stage LSCC patients who are ≤60 years of age, have T1a glottis cancer or well‐differentiated tumors, or are married. In other patients, both radiotherapy and surgery are comparable. However, our results cannot be a reference before controlled, prospective trials are performed.