bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of childhood nutrition by dietary survey and stable isotope analyses of hair and breath
Authors: Valenzuela Luciano O. , O'Grady Shannon P. , Enright Lindsey E. , Murtaugh Maureen , Sweeney Carol , Ehleringer James R.
Published: February 2018

Objectives

The natural abundances of carbon, nitrogen, and sulfur stable isotopes in hair, and of carbon isotopes in breath serve as quantitative biomarkers of protein and carbohydrate sources, but applicability of isotopes for evaluating children's diet has not been demonstrated. In this study, we sought to describe the stable isotope patterns observed in the hair and breath of children and to assess dietary variations in relation to age and ethnicity, hypothesizing that these would reflect dietary differences across age and ethnic groups and would correlate with intake variables derived from a Food Frequency Questionnaire.

Methods

Data were obtained from a cross‐sectional study of non‐Hispanic white (N = 115) and Hispanic (N = 97) children, aged 9–16 years, in Salt Lake City, Utah. Sampling included a hair sample, breath samples (AM and PM), and a youth/adolescent food questionnaire (YAQ). Hair was analyzed for carbon (δ13C), nitrogen (δ15N), and sulfur (δ34S) isotopes, and breath samples for δ13CAM/PM of respired CO2.

Results

Non‐Hispanic whites had lower δ13C, δ15N, δ13CAM, and δ13CPM values than Hispanics. Hair δ13C and δ15N values were correlated with protein sources, particularly for non‐Hispanics. Breath δ13C values were correlated with carbohydrate sources, particularly for Hispanic students. Non‐Hispanic white students reported greater intake of total protein, animal protein, dairy, and grain than Hispanic students. Hispanic students reported higher intake of carbohydrates, particularly sweetened beverages.

Conclusion

While YAQ and stable isotope data reflected strong cultural influences in diet, no significant gender‐based nor age‐based differences were detected. Significant covariation between YAQ and isotopes existed and demonstrate the potential of stable isotopes for characterizing children's diet.
Early history of the different forms of neurofibromatosis from ancient Egypt to the British Empire and beyond: First descriptions, medical curiosities, misconceptions, landmarks, and the persons behind the syndromes
Authors: Ruggieri Martino , Praticò Andrea D. , Caltabiano Rosario , Polizzi Agata
Published: February 2018

The earliest examples ofneurofibromatosis(in this casetype 1, NF1) can be traced in the Ebers Papyrus (Ancient Egypt, 1.500 B.C.), in a Hellenistic statuette (Smyrna, 323 B.C.), in the coinage of the Parthians kings (247 B.C.) and in some 13th century monks' drawings. These earlier examples are somewhat less well defined as compared to the most recent better defined reports credited as having NF1 including an Inca child mummy (1480—1650 AD),Ulisse Aldrovandi's homuncio(“Monstrorum Historia”, 1592 A.D.) withmosaic NF1or the illustrations seen in the 18th century “Buffon's Histoire Naturelle” and “Cruveilhier's Anatomie Pathologique du Corps Human”. The first English language report on NF1 was made byAkensidein 1768 and the first systematic review byRobert William Smithin 1849, while Virchow's pupil,Friedrich Daniel von Recklinghausen, in 1882, was the first to understand the origin of skin tumors and to name them neurofibromas. The touching story ofJoseph C. Merrick(the “Elephant man,” (who had Proteus syndrome and not NF1), in 1884, played an important role in the later misconception of NF1, as did the novel by Vicotr Hugo on the hunchbackQuasimodo. The studies by van der Hoeve (1921), Yakovlev and Guthrie (1931), and Van Bogaert (1935), categorized “von Recklinghausen's” neurofibromatosis among the phakomatoses and the neurocutaneous syndromes. The first known mention of an acoustic neuroma (at autopsy) is attributed toEduard Sandifort(1777 AD) whileJohn H. Wishartmade the earliest autoptic description ofneurofibromatosis type 2(NF2), in 1822, in a 21‐year‐old man with bilateral acoustic neuromas, who manifested signs since his infancy (Wishart subtype NF2).Smithlikely described the first case ofschwannomatosisin 1849.Older, Virchow, von Recklinghausen, andVerocayfirst classified “neuromas” andMassonandPenfieldfirst used the word “schwannoma” taking it fromTheodore Schwann'sworks. In 1903HennebergandKochdescribed NF2 in detail.Young, Eldridge, andGardner, in the late ‘70, established NF2 as a distinct familial entity (Gardner subtype NF2).Schwannomatosis, the late entry of the different forms of neurofibromatosis, was credited in the middle ‘90.
Clinical heterogeneity of mitochondrial NAD kinase deficiency caused by a NADK2 start loss variant
Authors: Pomerantz Daniel J. , Ferdinandusse Sacha , Cogan Joy , Cooper David N. , Reimschisel Tyler , Robertson Amy , Bican Anna , McGregor Tracy , Gauthier Jackie , Millington David S. , Andrae Jaime L. W. , Tschannen Michael R. , Helbling Daniel C. , Demos Wendy M. , Denis Simone , Wanders Ronald J. A. , Newman John N. , Hamid Rizwan , Phillips John A. ,   Collaborators of UDN
Published: February 2018

Mitochondrial NAD kinase deficiency (NADK2D, OMIM #615787) is a rare autosomal recessive disorder of NADPH biosynthesis that can cause hyperlysinemia and dienoyl‐CoA reductase deficiency (DECRD, OMIM #616034). NADK2 deficiency has been reported in only three unrelated patients. Two had severe, unremitting disease; one died at 4 months and the other at 5 years of age. The third was a 10 year old female with CNS anomalies, ataxia, and incoordination. In two cases mutations in NADK2 have been demonstrated. Here, we report the fourth known case, a 15 year old female with normal intelligence and a mild clinical and biochemical phenotype presumably without DECRD. Her clinical symptoms, which are now stable, became evident at the age of 9 with the onset of decreased visual acuity, bilateral optic atrophy, nystagmus, episodic lower extremity weakness, peripheral neuropathy, and gait abnormalities. Plasma amino acid levels were within normal limits except for mean lysine and proline levels that were 3.7 and 2.5 times the upper limits of normal. Whole exome sequencing (WES) revealed homozygosity for a g.36241900 A>G p. Met1Val start loss mutation in the primary NADK2 transcript (NM_001085411.1) encoding the 442 amino acid isoform. This presumed hypomorphic mutation has not been previously reported and is absent from the v1000GP, EVS, and ExAC databases. Our patient's normal intelligence and stable disease expands the clinical heterogeneity and the prognosis associated with NADK2 deficiency. Our findings also clarify the mechanism underlying NADK2 deficiency and suggest that this disease should be ruled out in cases of hyperlysinemia, especially those with visual loss, and neurological phenotypes.
Small Molecules Targeting Mycobacterium tuberculosis Type II NADH Dehydrogenase Exhibit Antimycobacterial Activity
Authors: Harbut Michael B. , Yang Baiyuan , Liu Renhe , Yano Takahiro , Vilchèze Catherine , Cheng Bo , Lockner Jonathan , Guo Hui , Yu Chenguang , Franzblau Scott G , Petrassi H. Mike , Jacobs William R. , Rubin Harvey , Chatterjee Arnab K. , Wang Feng
Published: February 2018

The generation of ATP through oxidative phosphorylation is an essential metabolic function for Mycobaterium tuberculosis (Mtb), regardless of the growth environment. The type II NADH dehydrogenase (Ndh‐2) is the conduit for electrons into the pathway, and is absent in the mammalian genome, thus making it a potential drug target. Herein, we report the identification of two types of small molecules as selective inhibitors for Ndh‐2 through a multicomponent high‐throughput screen. Both compounds block ATP synthesis, lead to effects consistent with loss of NADH turnover, and importantly, exert bactericidal activity against Mtb. Extensive medicinal chemistry optimization afforded the best analogue with an MIC of 90 nm against Mtb. Moreover, the two scaffolds have differential inhibitory activities against the two homologous Ndh‐2 enzymes in Mtb, which will allow precise control over Ndh‐2 function in Mtb to facilitate the assessment of this anti‐TB drug target.
Combinatorial Probes for High‐Throughput Electrochemical Analysis of Circulating Nucleic Acids in Clinical Samples
Authors: Das Jagotamoy , Ivanov Ivaylo , Safaei Tina S. , Sargent Edward H. , Kelley Shana O.
Published: February 2018

The analysis of circulating tumour nucleic acids (ctNAs) provides a minimally invasive way to assess the mutational spectrum of a tumour. However, effective and practical methods for analyzing this emerging class of markers are lacking. Analysis of ctNAs using a sensor‐based approach has notable challenges, as it is vital to differentiate nucleic acids from normal cells from mutation‐bearing sequences emerging from tumours. Moreover, many genes related to cancer have dozens of different mutations. Herein, we report an electrochemical approach that directly detects genes with mutations in patient serum by using combinatorial probes (CPs). The CPs enable detection of all of the mutant alleles derived from the same part of the gene. As a proof of concept, we analyze mutations of the EGFR gene, which has more than 40 clinically relevant alterations that include deletions, insertions, and point mutations. Our CP‐based approach accurately detects mutant sequences directly in patient serum.
Disassembly of Multicompartment Polymer Micelles in Spatial Sequence Using an Electrostatic Field and Its Application for Release in Chronological Order
Authors: Wu Ming , Zhu Yutian , Jiang Wei
Published: February 2018

Multicompartment micelles (MCPs), comprising sequences of repeated elemental discoid parts connected by fasciculus, were formed by self‐assembly of polystyrene‐block‐poly(2‐vinyl pyridine)‐block‐poly(ethylene oxide). Using an electrostatic field, the MCPs can be disassembled through consequent release of small spherical micelles. During this disassembly process, release of loaded species can be achieved from the micelles in chronological order. Two location‐selected cargos (mitoxantrone (MTNT) and fluorescein isothiocyanate (FITC)) in the outer and inner compartments of the micelles can be released in chronological order. Under the applied electrostatic field (intensity: 16 kV cm−1), the loaded MTNT was rapidly released with more than 80 % release, whereas the loaded FITC was slowly released with less than 20 % release in 12 h. At a later stage (after more than 12 h), the loaded MTNT was slowly released with less than 20 % release, while the loaded FITC was rapidly released with more than 80 % release.
Titanium Phosphonate Based Metal–Organic Frameworks with Hierarchical Porosity for Enhanced Photocatalytic Hydrogen Evolution
Authors: Li Hui , Sun Ying , Yuan Zhong‐Yong , Zhu Yun‐Pei , Ma Tian‐Yi
Published: February 2018

Photocatalytic hydrogen production is crucial for solar‐to‐chemical conversion process, wherein high‐efficiency photocatalysts lie in the heart of this area. A photocatalyst of hierarchically mesoporous titanium phosphonate based metal–organic frameworks, featuring well‐structured spheres, a periodic mesostructure, and large secondary mesoporosity, are rationally designed with the complex of polyelectrolyte and cathodic surfactant serving as the template. The well‐structured hierarchical porosity and homogeneously incorporated phosphonate groups can favor the mass transfer and strong optical absorption during the photocatalytic reactions. Correspondingly, the titanium phosphonates exhibit significantly improved photocatalytic hydrogen evolution rate along with impressive stability. This work can provide more insights into designing advanced photocatalysts for energy conversion and render a tunable platform in photoelectrochemistry.
Development of pH‐sensitive nanogels for cancer treatment using crosslinked poly(aspartic acid‐graft‐imidazole)‐block‐poly(ethylene glycol)
Authors: Sim Taehoon , Lim Chaemin , Cho Young Hun , Lee Eun Seong , Youn Yu Seok , Oh Kyung Taek
Published: February 2018

pH‐sensitive nanogels (NGs) based on poly(aspartic acid‐graft‐imidazole)‐poly(ethylene glycol) were developed using linear PEG with different molecular weights (2000 and 4000 Da) as crosslinkers. The pH‐sensitive NGs showed reversible size changes during continuously alternating pH changes. The anticancer treatment potential of pH‐sensitive NGs was studied using a model drug, irinotecan (IRI). IRI‐loaded NGs (ILNs) showed different drug release kinetics in acidic versus neutral pH, in addition to pH‐dependent cytotoxicity. Due to its longer crosslinker, ILN 4 (crosslinked with PEG 4000) showed faster IRI release and a greater magnitude of IRI release than ILN 2 (crosslinked with PEG 2000), resulting in greater cytotoxicity against HCT 116 colorectal cancer cells. These pH‐sensitive NGs could potentially be used in cancer treatment by mediating the accumulation and release of IRI from ILNs in the acidic tumor environment and by reducing systemic toxicity due to reversible swelling–shrinkage. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46268.
Covalent immobilization of halohydrin dehalogenase for efficient synthesis of epichlorohydrin in an integrated bioreactor
Authors: Zou Shu‐Ping , Gu Kai , Zheng Yu‐Guo
Published: February 2018

Halohydrin dehalogenase (HHDH)‐mediated dehalogenation of 1,3‐dichloro‐2‐propanol (1,3‐DCP) is a key step in the chemoenzymatic synthesis of epichlorohydrin (ECH) from glycerol. In this study, a covalent immobilization strategy was employed to enhance the stability of Agrobacterium tumefaciens HHDH using epoxy resin ES‐103B as a carrier. Under optimal conditions, the activity recovery of ES‐103B‐immobilized HHDH (HHDH@ES‐103B) was 62.4% and the specific activity was 1604 U/g. The HHDH@ES‐103B exhibited excellent thermostability, with a half‐life of 68.6 days at 40°C, which is 8.0‐times higher than that of the free HHDH. A semicontinuous biotransformation of 1,3‐DCP to ECH was performed using HHDH@ES‐103B as biocatalyst in a recirculating packed bed reactor (RPBR), resulting in an ECH yield of 94.2%, with an average productivity of 5.2 g/L/h. The RPBR system exhibited a high operational stability and even after 50 cycles of reaction, it retained > 90% of the initial conversion. Furthermore, an integrated bioprocess based on in situ product recovery (ISPR) was developed in RPBR to overcome product inhibition. The integrated bioreactor equipped with an external macroporous adsorption resin HZD‐9 column led to another 1.6‐fold increase in ECH productivity to 8.46 g/L/h. This improved stability and reusability of HHDH@ES‐103B demonstrated its potential for the biotransformation of 1,3‐DCP to ECH. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:784–792, 2018
Directed evolution of an endoinulinase from Talaromyces purpureogenus toward efficient production of inulooligosaccharides
Authors: Afriat‐Jurnou Livnat , Cohen Rami , Paluy Irina , Ben‐Adiva Ran , Yadid Itamar
Published: February 2018

Inulinases are fructofuranosyl hydrolases that target the β‐2,1 linkage of inulin and hydrolyze it into fructose, glucose and inulooligosaccharides (IOS), the latter are of growing interest as dietary fibers. Inulinases from various microorganisms have been purified, characterized and produced for industrial applications. However, there remains a need for inulinases with increased catalytic activity and better production yields to improve the hydrolysis process and fulfill the growing industrial demands for specific fibers. In this study, we used directed enzyme evolution to increase the yield and activity of an endoinulinase enzyme originated from the filamentous fungus Talaromyces purpureogenus (Penicillium purpureogenum ATCC4713). Our directed evolution approach yielded variants showing up to fivefold improvements in soluble enzyme production compared to the starting point which enabled high‐yield production of highly purified recombinant enzyme. The distribution of the enzymatic reaction products demonstrated that after 24 h of incubation, the main product (57%) had a degree of polymerization of 3 (DP3). To the best of our knowledge, this is the first application of directed enzyme evolution to improve inulooligosaccharide production. The approach enabled the screening of large genetic libraries within short time frames and facilitated screening for improved enzymatic activities and properties, such as substrate specificity, product range, thermostability and pH optimum. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:868–877, 2018
CK 20‐positive and CK 7‐negative Merkel cell carcinoma of the cheek
Authors: Rai Manoj Ponadka , Bedi Prabhjot S , Singh Jeevandeep , Marinas Edwin B.
Published: February 2018

Key Clinical Message

Merkel cell carcinomas (MCCs) are uncommon, highly malignant skin tumors that develop in sun‐exposed areas of the skin. Most of the MCCs are CK 20‐positive and CK 7‐negative such as our case. About 80% of Merkel cell carcinoma is associated with Merkel cell polyomavirus.
From Water and Ni Foam to a Ni(OH)2@Ni Foam Binder‐Free Supercapacitor Electrode: A Green Corrosion Route
Authors: Liu Xu , Yang Yue , Xing Xinxin , Zou Tong , Wang Zidong , Wang Yude
Published: February 2018

The front cover artwork is provided by Mr. Xu Liu and Prof. Yude Wang from Yunnan University (Kunming, P.R. China). The image shows the green corrosion route from water and Ni foam to a Ni(OH)2@Ni foam binder‐free supercapacitor electrode. Read the full text of the Article at 10.1002/celc.201701094.
Linear discriminant analysis, partial least squares discriminant analysis, and soft independent modeling of class analogy of experimental and simulated near‐infrared spectra of a cultivation medium for mammalian cells
Authors: Szabó Éva , Gergely Szilveszter , Salgó András
Published: February 2018

Currently, the qualification and control of medium formulations are performed based on simple methods (eg, pH and osmolality measurement of medium solutions), expensive and time‐consuming cell culture tests, and the quantification of certain critical compounds by liquid chromatography. In addition to traditional medium qualification tools, relatively new spectroscopic techniques, such as fluorescence spectroscopy, nuclear magnetic resonance, Raman and near‐infrared spectroscopies, and combinations of these techniques are increasingly being applied to medium powder investigation. A chemically defined medium powder for Chinese hamster ovary cell cultivation was investigated in this study to determine its response to heat treatments at different temperatures (30°C, 50°C, and 70°C). Because the low availability and high costs of medium powders limit the sample sizes for such experiments, 5 groups of simulated data sets were generated based on the experimental spectra to compare the efficiencies of 3 classification methods: linear discriminant analysis (LDA) based on principal component analysis (PCA), partial least squares discriminant analysis (PLS‐DA), and soft independent modeling of class analogy (SIMCA). In case of these data sets, PCA‐LDA showed better results for the classification of experimental spectra than PLS‐DA and SIMCA. Moreover, the PLS‐DA and SIMCA models yielded different results for different training set groups, while the PCA‐LDA model yielded similar results for all training sets.
Waste Water Treatment with Reeds in a Mobile Root Space Treatment Plant
Authors: Zehnsdorf Andreas , Scherber Anja , Schmidt Steffen , Ebersbach Anna Theresia , Bernhard Katy , Jentzsch Daniel , Schlenker Uwe
Published: February 2018

Für temporäre Einsätze zur Behandlung kommunaler Abwässer wurde eine mobile Wurzelraumkläranlage getestet, deren Reaktionsraum ausschließlich aus Schilfwurzeln als Aufwuchsfläche für Mikroorganismen besteht. Die Anlage wurde in der Vegetationsperiode 2016 mit vorgeklärtem kommunalem Abwasser einer Großkläranlage beschickt. Bei einem Zulaufvolumenstrom von 1200 L d−1 wurden die Ablaufgrenzwerte für den chemischen Sauerstoffbedarf und den biochemischen Sauerstoffbedarf zuverlässig eingehalten. Kurzzeitige Belastungsspitzen bis 1800 L d−1 führten nicht zur Überlastung der Anlage.
Two‐level multi‐block operating performance optimality assessment for plant‐wide processes
Authors: Zou Xiaoyu , Wang Fuli , Chang Yuqing , Zhao Luping , Zheng Wei
Published: February 2018

A process operating performance optimality assessment (POPOA) consists of an optimal degree online assessment and non‐optimal cause identification, which contribute to maintaining a high comprehensive economic index (CEI) of the production. However, two main problems limit the application of the traditional POPOA methods, i.e., the plant‐wide process characteristics and the coexistence of both the quantitative and qualitative variables. To overcome the two problems for POPOA, a novel two‐level multi‐block assessment method based on the fuzzy probabilistic rough set (FPRS) is proposed in this research. The operating performance grade of both the global and sub‐block level are properly defined, where the sub‐block assessment indices, which are difficult to obtain, are not required. Different from traditional multi‐block methods due to the novel offline modelling method, an explicit global model is unnecessary. The global performance grade is directly determined by the sub‐block performance grades. When the process is operating at a non‐optimal performance grade, the responsible sub‐block can be rapidly identified through online assessment. The proposed non‐optimal cause identification technique is carried out in the non‐optimal sub‐blocks, based on a newly‐defined matching degree function. The identified non‐optimal causes also contribute to the actual production adjustment to obtain the optimal performance. Finally, the proposed POPOA method is successfully applied to a gold hydrometallurgy process, which is a typical plant‐wide process with hybrid types of variables.
Internally Reuse Waste: Catalytic Asymmetric One‐Pot Strecker Reaction of Fluoroalkyl Ketones, Anilines and TMSCN by Sequential Catalysis
Authors: Liu Yun‐Lin , Yin Xiao‐Ping , Zhou Jian
Published: February 2018

We report a highly enantioselective one‐pot facile synthesis of fluorinated Cα‐tetrasubstituted amino nitriles from α‐fluoroalkyl α‐aryl ketones, anilines, and TMSCN through a sequential p‐TsOH catalyzed ketimine formation and chiral bifunctional tertiary amine mediated asymmetric Strecker reaction. This one‐pot approach has two important advantages. First, it greatly improves the overall yield of the synthesis of chiral Cα‐tetrasubstituted fluorinated aminonitriles from ketones, because the purification of α‐fluorinated ketimines by column chromatography suffers from great yield loss. Second, it represents the first example of asymmetric tandem reactions that can simultaneously reuse the by‐product and catalyst from the upstream step as a promoter and an additive to improve the reactivity and enantioselectivity of the subsequent catalytic enantioselective reaction, respectively. It could utilize the by‐product H2O generated in‐situ from the ketimine formation step to activate TMSCN to form HCN, and concurrently reuse the remaining p‐TsOH acid as an additive to improve enantioselectivity.
Interview with David A. Case: On force fields, biomolecular modeling, and NMR
Authors: Case David A. , Skrynnikov Nikolai R.
Published: February 2018

Prof. David Case is based in the Department of Chemistry and Chemical Biology at Rutgers University. In this interview he speaks about force field development and validation, predictive power of MD models, combining physics‐based force fields with empirical scoring functions, MD modeling of disordered proteins and RNA, synergies between MD simulations and NMR measurements, and chemical shift calculations. The video of this interview is available on the YouTube site (URL https://www.youtube.com/watch?v=bumGM1CWA7Y).
Satisfaction with cancer care, self‐efficacy, and health‐related quality of life in Latino cancer survivors
Authors: Moreno Patricia I. , Ramirez Amelie G. , San Miguel‐Majors Sandra L. , Fox Rina S. , Castillo Leopoldo , Gallion Kipling J. , Munoz Edgar , Estabrook Ryne , Perez Arely , Lad Thomas , Hollowell Courtney , Penedo Frank J.
Published: February 2018

BACKGROUND

The objective of the current study was to examine how modifiable factors such as satisfaction with cancer care and self‐efficacy impact health‐related quality of life (HRQOL) among Latino cancer survivors.

METHODS

Latinos previously diagnosed with breast, prostate, or colorectal cancer (N = 288) completed questionnaires (Patient Satisfaction with Cancer Care Scale, Stanford Chronic Disease Self‐Management Measures, Functional Assessment of Cancer Therapy‐General, and Short Acculturation Scale for Hispanics) within 2 years after receiving primary cancer treatment.

RESULTS

Path model analyses demonstrated that satisfaction with cancer care was associated with greater HRQOL and that this relationship was explained by several facets of self‐efficacy (ie, confidence in managing psychological distress [z = 3.81; P<.001], social support from close others [z = 2.46; P = .014], social/recreational activities [z = 3.30; P = .001], and patient‐provider communication [z = −3.72; P<.001]). Importantly, foreign‐born, less acculturated, and monolingual Spanish‐speaking survivors reported lower self‐efficacy in patient‐provider communication; however, adjusting for acculturation, language, nativity, and other covariates did not alter these results.

CONCLUSIONS

Factors that contribute to disparities in HRQOL among Latino cancer survivors compared with non‐Latino whites, such as low income, less education, and a lack of health insurance, can be difficult to address. The findings of the current study emphasize the importance of self‐efficacy within the context of patient‐centered cancer care practices (eg, patient inclusion in care decisions, sufficient time with provider, ready access to medical advice) and suggest that improving satisfaction with care may increase patients' confidence in managing important aspects of their cancer experience and, in turn, improve HRQOL among Latino cancer survivors. Cancer 2018. © 2018 American Cancer Society. Cancer 2018;124:1770–9. © 2018 American Cancer Society
Adapting the Elixhauser comorbidity index for cancer patients
Authors: Mehta Hemalkumar B. , Sura Sneha D. , Adhikari Deepak , Andersen Clark R. , Williams Stephen B. , Senagore Anthony J. , Kuo Yong‐Fang , Goodwin James S.
Published: February 2018

BACKGROUND

This study was designed to adapt the Elixhauser comorbidity index for 4 cancer‐specific populations (breast, prostate, lung, and colorectal) and compare 3 versions of the Elixhauser comorbidity score (individual comorbidities, summary comorbidity score, and cancer‐specific summary comorbidity score) with 3 versions of the Charlson comorbidity score for predicting 2‐year survival with 4 types of cancer.

METHODS

This cohort study used Texas Cancer Registry–linked Medicare data from 2005 to 2011 for older patients diagnosed with breast (n = 19,082), prostate (n = 23,044), lung (n = 26,047), or colorectal cancer (n = 16,693). For each cancer cohort, the data were split into training and validation cohorts. In the training cohort, competing risk regression was used to model the association of Elixhauser comorbidities with 2‐year noncancer mortality, and cancer‐specific weights were derived for each comorbidity. In the validation cohort, competing risk regression was used to compare 3 versions of the Elixhauser comorbidity score with 3 versions of the Charlson comorbidity score. Model performance was evaluated with c statistics.

RESULTS

The 2‐year noncancer mortality rates were 14.5% (lung cancer), 11.5% (colorectal cancer), 5.7% (breast cancer), and 4.1% (prostate cancer). Cancer‐specific Elixhauser comorbidity scores (c = 0.773 for breast cancer, c = 0.772 for prostate cancer, c = 0.579 for lung cancer, and c = 0.680 for colorectal cancer) performed slightly better than cancer‐specific Charlson comorbidity scores (ie, the National Cancer Institute combined index; c = 0.762 for breast cancer, c = 0.767 for prostate cancer, c = 0.578 for lung cancer, and c = 0.674 for colorectal cancer). Individual Elixhauser comorbidities performed best (c = 0.779 for breast cancer, c = 0.783 for prostate cancer, c = 0.587 for lung cancer, and c = 0.687 for colorectal cancer).

CONCLUSIONS

The cancer‐specific Elixhauser comorbidity score performed as well as or slightly better than the cancer‐specific Charlson comorbidity score in predicting 2‐year survival. If the sample size permits, using individual Elixhauser comorbidities may be the best way to control for confounding in cancer outcomes research. Cancer 2018;124:2018‐25. © 2018 American Cancer Society.
Systemic Pharmacokinetics, Safety, and Preliminary Efficacy of Topical AhR Agonist Tapinarof: Results of a Phase 1 Study
Authors: Bissonnette Robert , Vasist Lakshmi S. , Bullman Jonathan N. , Collingwood Therese , Chen Geng , Maeda‐Chubachi Tomoko
Published: February 2018

Tapinarof cream is a novel topical nonsteroidal agent that represents a unique class of anti‐inflammatory molecules targeting the aryl hydrocarbon receptor. Study 201851 was an open‐label, 2‐cohort sequential study that assessed the systemic pharmacokinetics, safety, and efficacy of tapinarof in adults with moderate to severe atopic dermatitis. A total of 11 participants were enrolled: 5 received 2% cream, and 6 received 1% cream. Tapinarof was systemically absorbed, and measurable amounts were detected in both cohorts. Generally, plasma exposure was greater with the 2% cream and decreased from day 1 to day 21. Median Tmax ranged from 1 to 4 hours. Preliminary efficacy results were similar between the 1% and 2% concentrations, with the 1% cream showing better tolerability based on 3 subjects in the 2% cohort who discontinued treatment because of systemic AEs. The efficacy and safety of 1% tapinarof support results of previous positive studies that used a different formulation. However, conclusions in the present study are limited because of the open‐label design and small number of participants. The 1% cream was selected as the concentration for use in future studies because of its lower AE incidence and efficacy comparable to the 2% cream.
A High‐Performance Application Specific Integrated Circuit for Electrical and Neurochemical Traumatic Brain Injury Monitoring
Authors: Pagkalos Ilias , Rogers Michelle L. , Boutelle Martyn G. , Drakakis Emmanuel M.
Published: February 2018

This paper presents the first application specific integrated chip (ASIC) for the monitoring of patients who have suffered a Traumatic Brain Injury (TBI). By monitoring the neurophysiological (ECoG) and neurochemical (glucose, lactate and potassium) signals of the injured human brain tissue, it is possible to detect spreading depolarisations, which have been shown to be associated with poor TBI patient outcome. This paper describes the testing of a new 7.5 mm2 ASIC fabricated in the commercially available AMS 0.35 μm CMOS technology. The ASIC has been designed to meet the demands of processing the injured brain tissue's ECoG signals, recorded by means of depth or brain surface electrodes, and neurochemical signals, recorded using microdialysis coupled to microfluidics‐based electrochemical biosensors. The potentiostats use switchedcapacitor charge integration to record currents with 100 fA resolution, and allow automatic gain changing to track the falling sensitivity of a biosensor. This work supports the idea of a “behind the ear” wireless microplatform modality, which could enable the monitoring of currently non‐monitored mobile TBI patients for the onset of secondary brain injury.
Family conflict, chaos, and negative life events predict cortisol activity in low‐income children
Authors: Doom Jenalee R. , Cook Stephanie H. , Sturza Julie , Kaciroti Niko , Gearhardt Ashley N. , Vazquez Delia M. , Lumeng Julie C. , Miller Alison L.
Published: February 2018

Childhood poverty is hypothesized to increase risk for mental and physical health problems at least in part through dysregulation of the hypothalamic‐pituitary‐adrenal axis. However, less is known about the specific psychosocial stressors associated with cortisol reactivity and regulation for children living in poverty. The current study investigates negative life events, household chaos, and family conflict in preschool and middle childhood as potential predictors of cortisol regulation in low‐income 7–10 year olds (N = 242; M age = 7.9 years). Participants were assessed in preschool and participated in a follow‐up assessment in middle childhood, during which diurnal free cortisol and free cortisol reactivity to the Trier Social Stress Test for Children (TSST‐C) were assessed. Household chaos during preschool predicted a more blunted diurnal cortisol slope in middle childhood. Greater negative life events during preschool and greater concurrent family conflict were associated with increased free cortisol reactivity in middle childhood.
Synthesis of Diamond‐Like Carbon Films Deposited by the Ionization Vapor Method and Development of its Semiconductive Devices Fabricated by the Focused Ga Ion Beam Implantation
Authors: KURUMI SATOSHI , TAKAHARA YUSUKE , OHNO TAKAFUMI , MATSUDA KEN‐ICHI , SUZUKI KAORU
Published: February 2018

In this study, we have attempted to synthesize the Gallium (Ga)‐implanted diamond‐like carbon (DLC) film for new functional devices as substituting Si‐based materials. Intrinsic‐DLC (i‐DLC) films (energy gap: 1.45 eV) were deposited by the ionization vapor method with applying the negative pulsed bias voltage (frequency: 2 kHz, duty ratio: 30%, peak voltage: 500 V) to SiO2 substrates. Ga atoms were implanted to i‐DLC films as accepters utilizing by focused ion beam irradiation system. The Raman scattering spectra of i‐DLC and Ga‐DLC films showed typical DLC characteristics which consisted of I(D) and I(G) peaks. In order to evaluate working function of the Ga‐DLC film, several electrode materials (Au, Pt, Cu, Al, and Sn) were deposited on the films. Current–voltage characteristics of Au and Pt electrodes on Ga‐DLC films showed Ohmic contacts, and Cu, Al, and Sn electrodes were Schottky contacts. These results suggested that a work function of the Ga‐DLC film was in the range of 4.47 eV to 4.58 eV. To apply these contact properties to DLC semiconductive devices, we produced the DLC Schottky diode using Al and Pt electrodes deposited on the Ga‐DLC film. A current–voltage characteristic of DLC Schottky diode showed diode property in which amount of forward and backward voltage were 7.0 V and 17.0 V, respectively. The ideality factor n of produced diode was 11.3.
Complement factor H protects mice from ischemic acute kidney injury but is not critical for controlling complement activation by glomerular IgM
Authors: Goetz Lindsey , Laskowski Jennifer , Renner Brandon , Pickering Matthew C. , Kulik Liudmila , Klawitter Jelena , Stites Erik , Christians Uwe , van der Vlag Johan , Ravichandran Kameswaran , Holers V. Michael , Thurman Joshua M.
Published: February 2018

Natural IgM binds to glomerular epitopes in several progressive kidney diseases. Previous work has shown that IgM also binds within the glomerulus after ischemia/reperfusion (I/R) but does not fully activate the complement system. Factor H is a circulating complement regulatory protein, and congenital or acquired deficiency of factor H is a strong risk factor for several types of kidney disease. We hypothesized that factor H controls complement activation by IgM in the kidney after I/R, and that heterozygous factor H deficiency would permit IgM‐mediated complement activation and injury at this location. We found that mice with targeted heterozygous deletion of the gene for factor H developed more severe kidney injury after I/R than wild‐type controls, as expected, but that complement activation within the glomeruli remained well controlled. Furthermore, mice that are unable to generate soluble IgM were not protected from renal I/R, even in the setting of heterozygous factor H deficiency. These results demonstrate that factor H is important for limiting injury in the kidney after I/R, but it is not critical for controlling complement activation by immunoglobulin within the glomerulus in this setting. IgM binds to glomerular epitopes after I/R, but it is not a significant source of injury.
EOMES‐positive CD4+ T cells are increased in PTPN22 (1858T) risk allele carriers
Authors: Chemin Karine , Ramsköld Daniel , Diaz‐Gallo Lina‐Marcela , Herrath Jessica , Houtman Miranda , Tandre Karolina , Rönnblom Lars , Catrina Anca , Malmström Vivianne
Published: February 2018

The presence of the PTPN22 risk allele (1858T) is associated with several autoimmune diseases including rheumatoid arthritis (RA). Despite a number of studies exploring the function of PTPN22 in T cells, the exact impact of the PTPN22 risk allele on T‐cell function in humans is still unclear. In this study, using RNA sequencing, we show that, upon TCR‐activation, naïve human CD4+ T cells homozygous for the PTPN22 risk allele overexpress a set of genes including CFLAR and 4‐1BB, which are important for cytotoxic T‐cell differentiation. Moreover, the protein expression of the T‐box transcription factor Eomesodermin (EOMES) was increased in T cells from healthy donors homozygous for the PTPN22 risk allele and correlated with a decreased number of naïve CD4+ T cells. There was no difference in the frequency of other CD4+ T‐cell subsets (Th1, Th17, Tfh, Treg). Finally, an accumulation of EOMES+CD4+ T cells was observed in synovial fluid of RA patients with a more pronounced production of Perforin‐1 in PTPN22 risk allele carriers. Altogether, we propose a novel mechanism of action of PTPN22 risk allele through the generation of cytotoxic CD4+ T cells and identify EOMES+CD4+ T cells as a relevant T‐cell subset in RA pathogenesis.
Effect of local wound infiltration with ketamine versus dexmedetomidine on postoperative pain and stress after abdominal hysterectomy, a randomized trial
Authors: Mohamed S.A. , Sayed D.M. , El Sherif F.A. , Abd El‐Rahman A.M.
Published: February 2018

Background and Objectives

Postoperative pain and stress elicit hormonal changes. We aimed at comparing the effects of wound infiltration with ketamine versus dexmedetomidine on postoperative pain and stress response.

Methods

This double‐blinded study included ninety patients scheduled for total abdominal hysterectomy and were randomly assigned into three groups to receive local wound infiltration with 40 mL of 0.25% bupivacaine (group C), plus 2 mg/kg ketamine (group K) or 2 μg/kg dexmedetomidine (group D). Primary outcome was postoperative morphine consumption; secondary outcomes included first request of analgesia, VAS scores at rest and movement (VAS–R/M) and side effects. Serum cortisol, prolactin and glucose levels at baseline, pre‐infiltration, 6 and 24 h postoperatively were measured.

Results

Rescue analgesia was less in K (6.80 ± 3.19 mg) and D (8.39 ± 3.86 mg) compared to C (13.33 ± 4.01 mg) (p < 0.05). First request of analgesia was delayed in K (7.60 ± 4.16 h) and D (6.00 ± 3.73 h) compared to C (4.20 ± 1.13 h) (p < 0.05). Both VAS and R/M were significantly lower in K (all over 24 h) and D (for 8 and 4 h, respectively) compared to C. Stress markers were significantly lower in K and D compared to C at 6 and 24 h, and in K compared to D at 24 h (p < 0.05).

Conclusions

Local wound infiltration with ketamine or dexmedetomidine added to bupivacaine had an opioid‐sparing effect, delayed first request of rescue analgesia, and attenuated postoperative stress response, especially with ketamine in patients underwent total abdominal hysterectomy.
Facile Synthesis of Cyclodextrin Functionalized Reduced Graphite Oxide with the Aid of Ionic Liquid for Simultaneous Determination of Guanine and Adenine
Authors: Wang Meiling , Cui Mingzhu , Liu Weifeng , Liu Xuguang , Xu Bingshe
Published: February 2018

Here, a facile reduction approach for synthesis of β‐cyclodextrin functionalized reduced graphite oxide with the aid of ionic liquid (βCD/IRGO) was reported. This strategy relies on the simple mixing of pre‐pared aqueous βCD/GO with ionic liquid (IL) at high temperatures, which can bring about a well dispersed βCD/RGO in the utilized IL (βCD/IRGO) with a synchronous evaporation of water. The as‐prepared βCD/IRGO product can be stably re‐dispersed in water (up to 1.0 mg/mL) after washed and dried. And the presented βCD/IRGO composites possess high supramolecular recognition capability and good conductivity for realizing enhanced electrochemical response towards simultaneous detection of guanine and adenine compared with other βCD/carbon (RGO or carbon nanotube) based composites. In the presence of one of analysts, the linear response ranges is 0.03–10.0 μM for guanine and 0.02–7.0 μM for adenine, respectively, with detection limit of 0.01 μM for both guanine and adenine (S/N=3). This ease of making the βCD/IRGO composite will open up possibilities of its diversifier applications.
Screen‐printed Gold Electrodes Functionalized with Grafted p‐Aminobenzoic Acid for the Construction of Electrochemical Immunosensors. Determination of TGF‐β1 Cytokine in Human Plasma
Authors: Guerrero Sara , Agüí Lourdes , Yáñez‐Sedeño Paloma , Pingarrón José M.
Published: February 2018

Screen‐printed gold electrodes were modified with grafted p‐aminobezoic acid to provide scaffolds with high loading of surface confined carboxyl groups that can be used to construct electrochemical immunosensors. As a specific application, an immunosensor for the determination of the cytokine transforming growth factor beta 1 (TGF‐β1) is reported. The capture antibody (anti‐TGF) was covalently immobilized on the surface of the prepared disposable scaffold and a sandwich‐type immunoassay was implemented with biotinylated detector antibody (Biotin‐anti‐TGF) and streptavidin labeled with alkaline phosphatase (AP‐Strept). The transduction event was monitored by differential pulse voltammetry after addition of 1‐naphthyl phosphate (1‐NPP) as the enzyme substrate. The different variables affecting the preparation and the analytical behavior of the AP‐Strept‐Biotin‐anti‐TGF‐TGF‐β1‐anti‐TGF‐SPAuE immunosensor were optimized, and the functionalized gold electrodes and the prepared immunosensor were characterized using several techniques. A linear range extending between 0.05 and 3.0 ng/mL TGF‐β1, adequate for the determination of the cytokine in human plasma, and a LOD of 10 pg/mL, better than that claimed for commercial ELISA kits, were achieved. The immunosensor exhibits also a great selectivity against other proteins and an excellent storage ability. The usefulness of the immunosensor was demonstrated by analyzing human plasma spiked with TGF‐β1.
Toxicokinetics of cadmium in Palaemon varians postlarvae under waterborne and/or dietary exposure
Authors: Pavlaki Maria D. , Morgado Rui G. , Soares Amadeu M.V.M. , Calado Ricardo , Loureiro Susana
Published: February 2018

The present study assessed cadmium uptake and depuration rates in the euryhaline estuarine shrimp Palaemon varians under different exposure routes. Postlarval shrimp were exposed for 4 d under different exposure routes: contaminated water, contaminated diet, and a 2-way exposure scenario where both contaminated water and diet were used. After exposure, postlarval shrimp were transferred to a clean medium and fed a noncontaminated diet for 96 h. Bioaccumulation via the different exposure routes was modeled with a standard first-order, one-compartment toxicokinetics model and one with an additional parameter reflecting an inert fraction or storage compartment. The simultaneous 2-way exposure (through water and diet) resulted in accumulation being almost twice as high as the sum of the individual exposure routes, thus indicating that accumulation from multiple routes may be more than additive. Cadmium uptake from water was faster than uptake from food maintained for 48 h at that same cadmium concentration. Shrimp were unable to eliminate cadmium from their body, showing no depuration during 96 h after exposure via different routes, thus suggesting that a longer depuration period is needed. Model comparisons did not provide a significantly better fit when the model included the presence of an inert fraction. The present study highlights the importance of assessing accumulation using multiple exposure routes compared with individual routes because the latter may underestimate bioaccumulation. Environ Toxicol Chem 2018;37:1614–1622. © 2018 SETAC
Characterization of rammed‐earth materials from the XVIth century Badii Palace in Marrakech, Morocco to ensure authentic and reliable restoration
Authors: Daoudi L. , Rocha F. , Costa C. , Arrebei N. , Fagel N.
Published: February 2018

Thirty rammed‐earth and coating materials collected from the Badii Palace wall in Marrakech were investigated for their particle size, chemical, and mineralogical characteristics. This was done in order to assess the original methods employed—and the provenance of the earth products used—during the Saadian period (XVIth century) construction of the palace. Differences in composition between the rammed‐earth and coating materials (and comparison with the local raw materials) suggest a different origin for these two materials. A high compositional similarity between the coating material and the corresponding rammed‐ earth is observed for the samples collected from well‐preserved walls. However, incompatibility between rammed earth and coatings was observed in many parts of the wall where the original coated materials have deteriorated by natural weathering and by the corrosive action of atmospheric pollution. The composition of coating material currently used for restoration shows the same incompatibility with the substrate and this is probably related to the same degradation problems. Finally, the influence of the semiarid climate in the degradation process is discussed. This study indicates constraints on the selection of the most suitable materials for sustainable restoration of these historic buildings.
Multiscale energy reallocation during low‐frequency steady‐state brain response
Authors: Wang Yifeng , Chen Wang , Ye Liangkai , Biswal Bharat B. , Yang Xuezhi , Zou Qijun , Yang Pu , Yang Qi , Wang Xinqi , Cui Qian , Duan Xujun , Liao Wei , Chen Huafu
Published: February 2018

Traditional task‐evoked brain activations are based on detection and estimation of signal change from the mean signal. By contrast, the low‐frequency steady‐state brain response (lfSSBR) reflects frequency‐tagging activity at the fundamental frequency of the task presentation and its harmonics. Compared to the activity at these resonant frequencies, brain responses at nonresonant frequencies are largely unknown. Additionally, because the lfSSBR is defined by power change, we hypothesize using Parseval's theorem that the power change reflects brain signal variability rather than the change of mean signal. Using a face recognition task, we observed power increase at the fundamental frequency (0.05 Hz) and two harmonics (0.1 and 0.15 Hz) and power decrease within the infra‐slow frequency band (<0.1 Hz), suggesting a multifrequency energy reallocation. The consistency of power and variability was demonstrated by the high correlation (r > .955) of their spatial distribution and brain–behavior relationship at all frequency bands. Additionally, the reallocation of finite energy was observed across various brain regions and frequency bands, forming a particular spatiotemporal pattern. Overall, results from this study strongly suggest that frequency‐specific power and variability may measure the same underlying brain activity and that these results may shed light on different mechanisms between lfSSBR and brain activation, and spatiotemporal characteristics of energy reallocation induced by cognitive tasks.