bluuebunny/crossref_metadata_2025 huggingface dataset:
Eutrophication homogenizes shallow lake macrophyte assemblages over space and time
Authors: Salgado Jorge , Sayer Carl D. , Brooks Stephen J. , Davidson Thomas A. , Goldsmith Ben , Patmore Ian R. , Baker Ambroise G. , Okamura Beth
Published: September 2018

Eutrophication is commonly implicated in the reduction in macrophyte species richness in shallow lakes. However, the extent to which other more nuanced measures of macrophyte diversity, such as assemblage heterogeneity, are impacted concurrently by eutrophication over space and time and the joint influences of other factors (e.g., species invasions and connectivity) remains relatively poorly documented. Using a combination of contemporary and paleoecological data, we examine how eutrophication influences macrophyte assemblage heterogeneity and how nutrient enrichment interacts with watercourse connectivity, lake surface area, and relative zebra mussel abundance over space (within and among lakes) and time (decades to centuries) at the landscape scale. The study system is the Upper Lough Erne, Northern Ireland, UK, which is composed of a large main lake and several smaller satellite lakes that vary in their hydrological connectivity to the main lake. By applying homogeneity analysis of multivariate dispersions and partial redundancy analysis, we demonstrate that contemporary lake macrophyte heterogeneity and species richness are reduced in lakes with intensified eutrophication but are increased in lakes with greater zebra mussel abundance and lake surface area. Watercourse connectivity positively influenced assemblage heterogeneity and explained larger proportions of the variation in assemblage heterogeneity than local environmental factors, whereas variation in species richness was better related to local abiotic factors. Macrophyte fossil data revealed within‐ and among‐lake assemblage homogenization post‐1960, with the main lake and connected sites showing the highest rates of homogenization due to progressive eutrophication. The long‐term and contemporary data collectively indicate that eutrophication reduces assemblage heterogeneity over time by overriding the importance of regional processes (e.g., connectivity) and exerts stronger pressure on isolated lakes. Our results suggest further that in connected lake systems, assemblage heterogeneity may be impacted more rapidly by eutrophication than species richness. This means that early effects of eutrophication in many systems may be underestimated by monitoring that focuses solely on species richness and is not performed at adequate landscape scales.
A linear mixed model framework for gene‐based gene–environment interaction tests in twin studies
Authors: Coombes Brandon J. , Basu Saonli , McGue Matt
Published: September 2018

Interaction between genes and environments (G×E) can be well investigated in families due to the shared genes and environment among family members. However, the majority of the current tests of G×E interaction between a set of variants and an environment are only suitable for studies with unrelated subjects. In this paper, we extend several G×E interaction tests to a linear mixed model framework to study interaction between a set of correlated environments and a candidate gene in families. The correlated environments can either be modeled separately or jointly in one model. We demonstrate theoretically that the tests developed by modeling correlated environments separately are valid and present a computationally fast alternative to detect G×E interaction in families. For either strategy, we propose treating the genetic main effects as a random effect to reduce the number of main‐effect parameters and thus improve the power to detect interactions. Additionally, we propose a generalization of a test of interaction that adaptively sums the interactions using a sequential algorithm. This generalized set of tests, referred to as the sequential algorithm for the sum of powered score (Seq‐SPU) family of tests, can be expressed as a weighted version of the SPU. We find that the adaptive version of our test, Seq‐aSPU, can outperform aSPU in cases where the interactions effects are in opposite directions. We applied these methods to the Minnesota Center for Twin and Family Research data set and found one significant gene in interaction with four psychosocial environmental factors affecting the alcohol consumption among the twins.
Weight loss, behavioral change, and structural neuroplasticity in children with obesity through a multidisciplinary treatment program
Authors: Augustijn Mireille J. C. M. , D’Hondt Eva , Leemans Alexander , Van Acker Lore , De Guchtenaere Ann , Lenoir Matthieu , Deconinck Frederik J. A. , Caeyenberghs Karen
Published: September 2018

This study evaluated the effect of a multidisciplinary treatment program for children with obesity (OB) on motor competence, executive functioning (EF), and brain structure. Nineteen children with OB (7–11 years), who attended a multidisciplinary treatment program consisting of diet restriction, cognitive behavioral therapy, and physical activity, were compared with an age‐matched control group of 24 children with a healthy weight (HW), who did not follow any treatment. For both groups, anthropometric measurements and tests of motor competence and EF were administered twice, with 5 months between pretest and posttest. Additionally, children’s brain structure was assessed by performing a magnetic resonance imaging (MRI) scan at the pretest and posttest, which included a T1 anatomical scan, diffusion MRI scan, and magnetization transfer imaging scan. Compared to HW controls, children with OB lost a considerable amount of their body mass (p ≤ .001) and significantly improved their balance skills (p ≤ .001), while no transfer effects of the program were observed for EF. Furthermore, the program resulted in a significant increase in total (p ≤ .001) and cerebellar (p ≤ .001) gray matter volume in children with OB, while no change was observed in the HW controls. Finally, only weak to moderate (nonsignificant) correlations could be observed between structural brain alterations, weight‐related changes, and behavioral improvements. Altogether, this is the first longitudinal study showing behavioral and structural brain alterations in response to a multidisciplinary weight loss program for children with OB. Our findings support the need for multidimensional intervention (and prevention) measures for children with OB to deal with this multifactorial health problem.
Separation of Xenon and Krypton in the Metal–Organic Frameworks M2(m‐dobdc) (M=Co, Ni)
Authors: Kapelewski Matthew T. , Oktawiec Julia , Runčevski Tomče , Gonzalez Miguel I. , Long Jeffrey R.
Published: September 2018

The separation of Xe and Kr from air is challenging owing both to the very low atmospheric concentrations of these gases and the need for their distillation at cryogenic temperatures. Alternatively, separation processes based on adsorption could provide a less energy‐intensive route to the isolation of these gases. Here, we demonstrate that the metal–organic frameworks M2(m‐dobdc) (M=Co, Ni; m‐dobdc4−=4,6‐dioxido‐1,3‐benzenedicarboxylate) effectively separate Xe and Kr at ambient temperatures based on the different adsorption enthalpies of each gas at the coordinatively‐unsaturated M2+ sites in each material. In situ Xe‐ and Kr‐dosed powder X‐ray diffraction studies further reveal key differences in the binding of Xe and Kr within the materials. In particular, while both gases adsorb near the framework open metal sites at 200 K, much higher Xe occupancies are observed at these sites relative to Kr, corroborating a stronger interaction of the polarizing M2+ cations with Xe. Further, while krypton is only found located above the open metal sites, two additional adsorption sites are observed for xenon, correlating with the stronger adsorption of Xe over Kr in these materials. These results suggest the possible utility of employing M2(m‐dobdc) materials in the adsorptive separation of Xe and Kr.
Modulation of immune response to induced‐arthritis by low‐level laser therapy
Authors: dos Anjos Lúcia Mara J. , Salvador Pollyanna A. , de Souza Álvaro C. , de Souza da Fonseca Adenilson , de Paoli Flávia , Gameiro Jacy
Published: September 2018

As low‐level laser therapy immune cells responses are not always clarified, this study aimed to evaluate cytokines and immune cells profile after low‐level laser therapy (LLLT) on arthritis‐induced model. Arthritis was induced in C57BL/6 mice divided into five groups: euthanized 5 hours after inflammation induction; untreated; dexamethasone treated; LLLT at 3 Jcm−2; LLLT at 30 Jcm−2. Cytokine measurements by enzyme‐linked immunosorbent assay and mRNA cytokine relative levels by real‐time quantitative polymerase chain reaction were performed with arthritic ankle (IL‐1β, IL‐6, TNF‐α, IL‐10 and TGF‐β). Macrophages, dendritic cells, natural killer cells, lymphocytes CD4+, CD8+, Treg and costimulatory proteins were quantified in proximal lymph node by flow cytometry. Data showed decrease in all cytokine levels after LLLT and alteration in mRNA relative levels, depending on the energy density used. LLLT was able to increase of immune cell populations analyzed in the lymph node as well as costimulatory proteins expression on macrophages and dendritic cells. Treg TCD4+ and TCD8+ population enrichment were observed in LLLT at 3 and 30 Jcm−2 groups, respectively. Furthermore, Treg TCD8+ cells expressing higher levels of CD25 were observed at LLLT at 30 Jcm−2 group. Our results indicate that LLLT could change the inflammatory course of arthritis, tending to accelerate its resolution through immune cells photobiostimulation.
Perfectionism and School Counselors: Differences in Stress, Coping, and Burnout
Authors: Fye Heather J. , Gnilka Philip B. , McLaulin Sarah E.
Published: September 2018

The authors examined perfectionism and its association with perceived stress, coping processes, and burnout in a sample of 298 practicing school counselors. Latent profile analysis based on measures of perfectionism supported a 3‐class model made up of adaptive perfectionists, maladaptive perfectionists, and nonperfectionists. Among these groups, the authors found significant differences in perceived stress, coping processes, and burnout. Implications for the school counseling profession are discussed.
Effects of a Motivational Interviewing–Based Counseling Program on Classroom Behavior of Children in a Disciplinary Alternative Education Program
Authors: Ratanavivan Wannigar , Ricard Richard J.
Published: September 2018

A multiple single‐case research design was used to explore changes in teacher‐reported behaviors of 15 children who completed a motivational interviewing–based counseling program in a disciplinary alternative education school. Findings indicated that 7 children made a moderate to large improvement in their classroom behaviors while participating in the program. Students’ self‐motivational statements and self‐reported readiness to change were related to actual teacher‐rated behavioral changes. Implications for future research and counseling practice were discussed.
Implications for Wellness‐Based Supervision and Professional Quality of Life
Authors: Callender Karisse A. , Lenz A. Stephen
Published: September 2018

This study evaluated the efficacy of the wellness model of supervision (WELMS; Lenz & Smith, ) for promoting changes across the perceptions of counselors‐in‐training (CITs) regarding professional quality of life. Three female participants (1 Caucasian, 2 Hispanic) were enrolled in a program accredited by the Council for Accreditation of Counseling and Related Educational Programs. Results of a single‐case research design with multiple baselines indicated that the WELMS was efficacious across client–CIT interactions on professional quality of life.
Study of the mechanisms of crocetin‐induced differentiation and apoptosis in human acute promyelocytic leukemia cells
Authors: Moradzadeh Maliheh , Ghorbani Ahmad , Erfanian Saiedeh , Mohaddes Seyedeh Tahereh , Rahimi Hossein , karimiani Ehsan Ghayoor , Mashkani Baratali , Chiang Shih‐Chieh , El‐Khamisy Sherif F. , Tabarraei Alijan , Sadeghnia Hamid Reza
Published: September 2018

Crocetin, the major carotenoid in saffron, exhibits potent anticancer effects. However, the antileukemic effects of crocetin are still unclear, especially in primary acute promyelocytic leukemia (APL) cells. In the current study, the potential antipromyelocytic leukemia activity of crocetin and the underlying molecular mechanisms were investigated. Crocetin (100 µM), like standard anti‐APL drugs, all‐trans retinoic acid (ATRA, 10 µM) and As2O
3 (arsenic trioxide, 50 µM), significantly inhibited proliferation and induced apoptosis in primary APL cells, as well as NB4 and HL60 cells. The effect was associated with the decreased expressions of prosurvival genes Akt and BCL2, the multidrug resistance (MDR) proteins, ABCB1 and ABCC1 and the inhibition of tyrosyl‐DNA phosphodiesterase 1 (TDP1), while the expressions of proapoptotic genes
CASP3,
CASP9, and
BAX/BCL2 ratio were significantly increased. In contrast, crocetin at relatively low concentration (10 µM), like ATRA (1 µM) and As
2O
3 (0.5 µM), induced differentiation of leukemic cells toward granulocytic pattern, and increased the number of differentiated cells expressing CD11b and CD14, while the number of the immature cells expressing CD34 or CD33 was decreased. Furthermore, crocetin suppressed the expression of clinical marker promyelocytic leukemia/retinoic acid receptor‐α (
PML/RARα) in NB4 and primary APL cells, and reduced the expression of histone deacetylase 1 (
HDAC1) in all leukemic cells. The results suggested that crocetin can be considered as a candidate for future preclinical and clinical trials of complementary APL treatment.
Comprehensive analysis of novel three‐long noncoding RNA signatures as a diagnostic and prognostic biomarkers of human triple‐negative breast cancer
Authors: Fan Chun‐Ni , Ma Lei , Liu Ning
Published: September 2018

Currently, traditional predictors of prognosis (tumor size, nodal status, progesterone receptor [PR], estrogen receptor [ER], or human epidermal growth factor receptor‐2 [HER2]) are insufficient for precise survival prediction for triple‐negative breast cancer (TNBC). Long noncoding RNAs (lncRNAs) have been observed to exert critical functions in cancer, including in TNBC. Nevertheless, systematically tracking expression‐based lncRNA biomarkers based on the sequence data for the prediction of prognosis in TNBC has not yet been investigated. To ascertain whether biomarkers exist that can distinguish TNBC from adjacent normal tissue or nTNBC, we implemented a comprehensive analysis of lncRNA expression profiles and clinical data of 1097 BC samples from The Cancer Genome Atlas database. A total of 1510 differentially expressed lncRNAs in normal and TNBC samples were extracted. Similarly, 672 differentially expressed lncRNAs between nTNBC and TNBC samples were detected. The receiver operating characteristic curve analysis indicated that three upregulated lncRNAs (AC091043.1, AP000924.1, and FOXCUT) may be of strong diagnostic value for predicting the existence of TNBC in the training and validation sets (area under the curve (AUC > 0.85). Kaplan‐Meier analysis demonstrated that the other three lncRNAs (AC010343.3, AL354793.1, and FGF10‐AS1) were associated with the prognosis of TNBC patients (P < 0.05). We used the three overall survival (OS)‐related lncRNAs to establish a three‐lncRNA signature. Multivariate Cox regression analysis suggested that the three‐lncRNA signature was a prognostic factor independent of other clinical variables (
P < 0.01) for predicting OS in TNBC patients that could be utilized to classify patients into high‐ or low‐risk subgroups. Our results might provide efficient signatures for clinical diagnosis and prognostic evaluation of TNBC.
S100A7, Jab1, and p27kip1 expression in psoriasis and S100A7 CRISPR‐activated human keratinocyte cell line
Authors: Granata Mariagrazia , Skarmoutsou Evangelia , Gangemi Pietro , Mazzarino Maria C. , D’Amico Fabio
Published: September 2018

Psoriasis, a chronic immune‐mediated inflammatory skin disease, is characterized by dysregulated keratinocyte proliferation. The EF‐hand calcium binding protein S100A7 has been found to be overexpressed in psoriatic keratinocytes. It is know that S100A7 may interact with Jab1, a cofactor that stabilizes c‐Jun. Jab1 is known to downregulate the expression of the cell cycle inhibitor p27Kip1 in some cancer models. In this study, we aimed to investigate the possible interaction between S100A7 and Jab1 and the downstream effects on p27
Kip1 expression in normal human keratinocyte cells transfected with S100A7 CRISPR activation plasmid and in archival psoriatic skin samples. Our results showed that the upregulated S100A7 colocalizes with Jab1 at the nuclear level in transfected cells and psoriatic skin samples. We also showed a differential protein expression of Jab1 between cytoplasmic and nuclear compartments, thus suggesting Jab1 translocation from nucleus to cytoplasm. p27
Kip1 protein expression patterns would imply a translocation from nucleus and a subsequent degradation of this protein. The upregulation of S1007 and its interaction with Jab1 would contribute to the p27
Kip1‐dependent impaired proliferation that characterizes psoriatic skin.
Association between the −11377 C/G and −11391 G/A polymorphisms of adiponectin gene and adiponectin levels with susceptibility to type 1 and type 2 diabetes mellitus in population from the west of Iran, correlation with lipid profile
Authors: Nomani Hamid , Hesami Osman , Vaisi‐Raygani Asad , Tanhapour Maryam , Bahrehmand Fariborz , Rahimi Zohreh , Kiani Amir , Shakiba Ebrahim , Pourmotabbed Tayebeh
Published: September 2018

Adipose tissue, an endocrine organ, secretes bioactive factors including adiponectin. Adiponectin is a protein hormone that enhances insulin sensitivity through increased fatty acid oxidation and inhibition of hepatic glucose production. We assessed the association of the adiponectin promoter region polymorphisms −11391 G/A and −11377 C/G with susceptibility to type 1 (T1DM) and type 2 (T2DM) diabetes mellitus in the population of west Iran. Also, we investigated the effect of adiponectin level and lipid profile on T1DM and T2DM development. In this case‐control study, we recruited 189 patients with diabetes (100 T2DM and 89 T1DM) and 161 sex and age‐matched unrelated healthy controls. Adiponectin mutations were detected by polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP), and the protein level was measured by the enzyme‐linked immunosorbent assay. Other biochemical parameters were determined by routine laboratory methods. The G allele of adiponectin gene at −11377 position (C/G) significantly increased the risk of T1DM. With respect to genotype models, codominant (2.97 times), dominant (3.6‐fold), and over‐codominant (2.9‐fold) patients with T1DM who carried −11377 C > G single‐nucleotide polymorphisms were significantly susceptible to the development of the disease. A significantly higher level of adiponectin in T1DM was oberved compared with the control group. In contrast, patients with T2DM had lower adiponectin levels compared with healthy controls. The genotype distributions of −11391 G/A polymorphisms were the same for patients with diabetes and control groups. The presence of G allele at −11377 C/G adiponectin gene significantly increased serum adiponectin level and may be a risk factor for T1DM susceptibility among the western Iranian population.
Estrogen inhibits osteoclasts formation and bone resorption via microRNA‐27a targeting PPARγ and APC
Authors: Guo Lei , Chen Kaizhe , Yuan Jun , Huang Ping , Xu Xing , Li Changwei , Qian Niandong , Qi Jin , Shao Zhiliang , Deng Lianfu , He Chuan , Xu Jiping
Published: September 2018

Inhibition of osteoclasts formation and bone resorption by estrogen is very important in the etiology of postmenopausal osteoporosis. The mechanisms of this process are still not fully understood. Recent studies implicated an important role of microRNAs in estrogen‐mediated responses in various cellular processes, including cell differentiation and proliferation. Thus, we hypothesized that these regulatory molecules might be implicated in the process of estrogen‐decreased osteoclasts formation and bone resorption. Western blot, quantitative real‐time polymerase chain reaction, tartrate‐resistant acid phosphatase staining, pit formation assay and luciferase assay were used to investigate the role of microRNAs in estrogen‐inhibited osteoclast differentiation and bone resorption. We found that estrogen could directly suppress receptor activator of nuclear factor B ligand/macrophage colony‐stimulating factor‐induced differentiation of bone marrow‐derived macrophages into osteoclasts in the absence of stromal cell. MicroRNA‐27a was significantly increased during the process of estrogen‐decreased osteoclast differentiation. Overexpressing of microRNA‐27a remarkably enhanced the inhibitory effect of estrogen on osteoclast differentiation and bone resorption, whereas which were alleviated by microRNA‐27a depletion. Mechanistic studies showed that microRNA‐27a inhibited peroxisome proliferator‐activated receptor gamma (PPARγ) and adenomatous polyposis coli (APC) expression in osteoclasts through a microRNA‐27a binding site within the 3′‐untranslational region of PPARγ and APC. PPARγ and APC respectively contributed to microRNA‐27a‐decreased osteoclast differentiation and bone resorption. Taken together, these results showed that microRNA‐27a may play a significant role in the process of estrogen‐inhibited osteoclast differentiation and function.
Liposomal nanocarriers for statins: A pharmacokinetic and pharmacodynamics appraisal
Authors: Askarizadeh Anis , Butler Alexandra E. , Badiee Ali , Sahebkar Amirhossein
Published: September 2018

Statins, inhibitors of 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase, are a well‐known class of drug with beneficial therapeutic effects in cardiovascular disease and lipid disorders and have potential use against cancer. However, the bioavailability of statins is hampered due to low aqueous solubility and rapid metabolism. To improve pharmacokinetic profiles of statins, development of drug delivery systems is promising. Hence, the use of liposomes for selective delivery of statins to a selected site or for bioavailability enhancement is an effective strategy to increase statin therapeutic effects. Moreover, liposomal delivery can reduce the required dose of statins especially in terms of antitumor effects. Liposomes, because of their unique properties and biphasic and amphiphilic nature, have attracted much interest and can be considered as a suitable choice for delivery of both hydrophilic and lipophilic statins. In this review article, we focus on liposomes and evaluate the effects of different liposomal delivery systems, based on differences in size, phospholipid composition, circulation half‐life, and cholesterol content, on statin function.
Downregulation of AC061961.2, LING01‐AS1, and RP11–13E1.5 is associated with dilated cardiomyopathy progression
Authors: Qiu Zhibing , Ye Bin , Yin Li , Chen Wen , Xu Yueyue , Chen Xin
Published: September 2018

This study aimed to explore long noncoding RNAs (lncRNAs) implicated in dilated cardiomyopathy (DCM). Ten samples of failing hearts collected from the left ventricles of patients with DCM undergoing heart transplants, and ten control samples obtained from normal heart donors were included in this study. After sequencing, differentially expressed genes (DEGs) and lncRNAs between DCM and controls were screened, followed with functional enrichment analysis and weighted gene coexpression network analysis (WGCNA). Five key lncNRAs were validated through real‐time polymerase chain reaction (PCR). Total 1,398 DEGs were identified, including 267 lncRNAs. WGCNA identified seven modules that were significantly correlated with DCM. The top 50 genes in the three modules (black, dark‐green, and green–yellow) were significantly correlated with DCM disease state. Four core enrichment lncRNAs, such as AC061961.2, LING01‐AS1, and RP11–557H15.4, in the green–yellow module were associated with neurotransmitter secretion. Five core enrichment lncRNAs, such as KB‐1299A7.2 and RP11–13E1.5, in the black module were associated with the functions of blood circulation and heart contraction. AC061961.2, LING01‐AS1, and RP11–13E1.5 were confirmed to be downregulated in DCM tissues by real‐time PCR. The current study suggests that downregulation of AC061961.2, LING01‐AS1, and RP11–13E1.5 may be associated with DCM progression, which may serve as key diagnostic biomarkers and therapeutic targets for DCM.
Mutant p53R248Q downregulates oxidative phosphorylation and upregulates glycolysis under normoxia and hypoxia in human cervix cancer cells
Authors: Hernández‐Reséndiz Ileana , Gallardo‐Pérez Juan Carlos , López‐Macay Ambar , Robledo‐Cadena Diana Xochiquetzal , García‐Villa Enrique , Gariglio Patricio , Saavedra Emma , Moreno‐Sánchez Rafael , Rodríguez‐Enríquez Sara
Published: September 2018

Mutations in p53 are strongly associated with several highly malignant cancer phenotypes but its role in regulating energy metabolism has not been completely elucidated. The effect on glycolysis and oxidative phosphorylation (OxPhos) of mutant p53R248Q overexpression in HeLa cells (HeLa‐M) was analyzed and compared with cells overexpressing wild‐type p53 (HeLa‐H) and nontransfected cells containing negligible p53 levels (HeLa‐L). p53
R248Q overexpression induced early cell detachment during in vitro growth; however, detached HeLa‐M cells showed high viability, shorter generation time and significant diminution in the adhesion proteins E‐cadherin and β‐catenin versus HeLa‐H and HeLa‐L cells. Under normoxia, a lower growth rate of attached HeLa‐M cells correlated with decreased levels of proliferating cell nuclear antigen (PCNA), peroxisome proliferator‐activated receptor gamma coactivator 1‐α (PGC‐1α), adenosine monophosphate‐activated protein kinase (AMPK), mitochondrial proteins (20–80%) and OxPhos flux (69 ± 12%). On the contrary, HeLa‐M also showed increased contents of CDKN1A, nuclear factor κB (NF‐κB), c‐MYC, hypoxia‐inducible factor 1‐α (HIF‐1α; 1–4 times), glycolytic HIF‐1α targets (2–4 times), and glycolysis flux (2‐fold) versus HeLa‐H. In consequence, glycolysis provided ~70% of the cellular adenosine triphosphate (ATP) in HeLa‐M cells under normoxia whereas, OxPhos predominated (65–82%) in HeLa‐H and HeLa‐L cells. Pifithrin‐α, a specific p53 inhibitor, did not alter the p53
R248Q target protein contents and OxPhos and glycolytic fluxes, and a poor HIF‐1α‐p53
R248Q interaction was attained, in HeLa‐M cells. These observations suggested that p53
R248Q deficiently interacted with pifithrin‐α and HIF‐1α. Therefore, lower mitochondrial biogenesis, deficient HIF‐1α/mutant p53 interaction, and development of a pseudohypoxic state under normoxia were the apparent biochemical mechanisms underlying glycolysis activation and OxPhos downregulation in HeLa‐M cells.
Suggestions for Model‐Informed Precision Dosing to Optimize Neonatal Drug Therapy
Authors: Euteneuer Joshua C. , Kamatkar Suyog , Fukuda Tsuyoshi , Vinks Alexander A. , Akinbi Henry T.
Published: September 2018

Evidence for dosing, efficacy, and safety of most medications used to treat neonates is sparse. Thus, dosing is usually derived by extrapolation from adult and pediatric pharmacologic data with scaling by body weight or body surface area. This may lead to drug dosing that is unsafe or ineffective. However, new strategies are being developed and studied to dose medications in critically ill neonates. Mass spectroscopy technology capable of quickly analyzing drug levels is readily available. Software that integrates population pharmacokinetics and pharmacodynamics with data from sparse samples from neonates allows for timely adjustments of dosing to achieve the desired effect while minimizing adverse outcomes. Some genetic polymorphisms that affect drug response in neonates have also been reported. This review highlights aspects of drug response and how it is impacted by prematurity, assesses pharmacogenomic studies in neonates, and offers suggestions for innovative pharmacokinetic/pharmacodynamic model‐based approaches that combine population‐ or physiology‐based pharmacology data, Bayesian analysis, and electronic decision support tools for precision dosing in neonates while illustrating examples where this approach can be used to optimize medical therapy in neonates. Barriers to implementing precision dosing in neonates and how to overcome them are also discussed.
Structurally modified CuFe2O4/persulfate process for acetaminophen scavenging: high efficiency with low catalyst addition
Authors: Zhang Yuanchun , Zhang Qian , Dong Zhengyu , Wu Liying , Hong Junming
Published: September 2018

BACKGROUND

Iron (Fe)–copper (Cu) bimetallic catalysts such as CuFe2O4, CuFeO2 and CuO/Fe3O4 have been widely applied in persulfate oxidization process. Among these catalysts, CuFe2O4 has shown excellent performance in catalyzing peroxymonosulfate. However, because the catalytic effect of CuFe2O4 on persulfate (PS) is not obvious, the application of CuFe2O4 to activate persulfate has been investigated only rarely. Hence, structural modification has been applied in order to improve the catalytic activity of CuFe2O4 on persulfate.

RESULT

In this study, Oxygen (O)‐deficient CuFe2O4 was synthesized via the hydrogen reduction method and first used to activate PS for degrading acetaminophen (APAP) in aqueous solution with low catalyst concentration of 0.3 g L−1. Results reveal that high‐concentration APAP (100 mg L−1) could be efficiently removed by O‐deficient CuFe2O4‐activated PS, and 91% removal rate could be reached in 60 min using 0.8 g L−1 PS and 0.3 g L−1 catalyst under unadjusted pH. Dissolved O2 and Cl−showed inhibitory effects on the degradation process. Radical scavenger experiments, in which methanol, tert‐butyl alcohol (TBA) and nitrobenzene (NB) were used as radical trappers, indicated that SO4− and OH were the active radicals in the reaction, but the main radical was SO4−. Oxygen‐deficient CuFe2O4 showed strong reduction ability and could activate PS efficiently, and the electron transfer capability was remarkably enhanced after this structural modification.

CONCLUSIONS

Results indicated that compared to the pristine crystal, the catalytic activity of CuFe2O4 could be improved through structural modification. Additionally, the structurally modified catalyst showed high potential to treat wastewater with high antibiotic content under mild conditions. © 2018 Society of Chemical Industry
Dipyrido[1,2‐b:3′,4′‐e][1,2,4]triazine Scaffolds from Pentafluoropyridine
Authors: Ranjbar‐Karimi Reza , Darehkordi Ali , Bahadornia Fahimeh , Poorfreidoni Alireza
Published: September 2018

Annelation reaction between pentafluoropyridine and diaminodihydro substituted pyridine derivatives gave dipyrido[1,2‐b:3′,4′‐e][1,2,4]triazine systems as major products arising from the initial nucleophilic substitution of more nucleophilic N‐amino group of pyridone ring at 4‐position of the pyridine ring followed by intramolecular cyclization at 3‐position of pyridine ring. Also, 6‐amino‐2‐oxo‐1‐((perfluoropyridin‐4‐yl)amino)‐4‐aryl‐1,2‐dihydropyridine‐3,5‐dicarbonitrile derivatives were obtained as side products. The structures of all the compounds were confirmed by IR, 1H NMR, 13C NMR, and 19F NMR spectroscopy as well as elemental analysis.
Calix[4]arene‐based Multifunctional Ligand as Potent Protein Binding Agent
Authors: Esmaielzade Rostami Mahshid , Gorji Banafsheh , Zadmard Reza
Published: September 2018

In this work, a new protein binding agent based on multifunctional calix[4]arene CP has been synthesized by a one‐pot four‐component reaction. Protein binding affinity of designed ligand (CP) was investigated in physiological buffer (pH = 7.4) by fluorescence quenching method and revealed considerable binding affinity between CP and β‐lactoglobulin (BLG). The three‐dimensional (3D) fluorescence measurements indicated that binding of CP to BLG did not influence on BLG conformation. Furthermore, the effect of various biologically important metal ions on the binding constant of CP with BLG was investigated.
Hantzsch Reaction: A Greener and Sustainable Approach to 1,4‐Dihydropyridines Using Non‐commercial β‐Ketoesters
Authors: Dharma Rao G. B.
Published: September 2018

An expeditious synthesis of new series of symmetrical 1,4‐dihydropyrimidine derivatives has been developed using a four‐component reaction involving the in situ generation of non‐commercial β‐ketoesters via transesterification transformation of tert‐butyl‐β‐ketoester with corresponding alcohol followed by the one‐pot Hantzsch reaction with arylaldehyde and ammonium carbonate in aqueous medium at 70°C under catalyst‐free conditions.
Contemporary Leadership: The Perspective of a Practitioner
Authors: Vecchiotti Robert
Published: September 2018

The definition of leadership continues to evolve and has recently undergone many changes from its male‐dominated past through the contributions of women leaders, the Millennial cohort, contemporary insights from research, surveys, and informed opinion. Many qualities have been added to the list that describes a leader's behavior. It is noted that the list has become too long to be useful to a practitioner. The various movements that contributed to a contemporary definition of leadership are outlined. The importance of followers as implementers and the definition of leadership as a process are presented through the eyes of a practitioner. The leadership process offers the most promise for a useful and contemporary definition of leadership. Recommendations are made to shape future research to include the rise of servant leadership among Millennials.
Ultrasound Findings in Patients With Femoracetabular Impingement Without Radiographic Osteoarthritis: A Pilot Study
Authors: Orellana Cristóbal , Moreno Mireia , Calvet Joan , Navarro Noemí , García‐Manrique María , Gratacós Jordi
Published: September 2018

Objectives

To assess ultrasound (US) abnormalities in patients with clinical and radiographic features of femoracetabular impingement (FAI) without radiologic osteoarthritis.

Methods

This study included patients aged 50 years or younger with hip pain and clinical and radiographic signs suggestive of FAI but without radiographic hip osteoarthritis. Demographic characteristics, the symptom duration, and the radiologic type of FAI were recorded. Ultrasound examinations assessed for anterior labral abnormalities, osteophytes, bone cortex irregularities, capsular distension, and acetabulofemoral and femoral head‐to‐neck distances. A balanced group of healthy volunteers was used as control participants.

Results

Forty‐four patients with FAI were evaluated. Ultrasound changes were found in 93.2% of patients, with 63.6% showing some kind of labral abnormality, 40.9% showing articular cartilage abnormalities, 38.6% showing bone contour irregularities, and 29.5% showing osteophytes. The cartilage width and symptom duration were inferior in patients with a damaged articular surface compared with those without (P = .005 and .012, respectively). Patients showing osteophytes on US examinations were slightly older (P = .048). Patients with cam‐type FAI were more frequently male (P = .0001) and younger (P = .022) compared with those who had pincer‐type FAI and also had a shorter symptom duration (P < .05). Patients with symptoms for 2 years or less had a shorter femoral cartilage width (P = .027). Femoral head‐to‐neck distances were shorter in patients compared with controls (P = .0005). Only 1 patient in the control group showed some US abnormality.

Conclusions

Ultrasound showed detected abnormalities in a significant proportion of patients with symptomatic FAI in early phases of the disease. Additional longitudinal studies are warranted to establish the prognostic importance of these US changes.© 2018 by the American Institute of Ultrasound in Medicine
Passive experimental warming decouples air and sediment temperatures in a salt marsh
Authors: Carey Joanna C. , Kroeger Kevin D. , Zafari Babak , Tang Jianwu
Published: September 2018

Open top chambers (OTCs) are a commonly used passive warming technique in experimental warming studies. OTCs have been shown to be effective in multiple types of terrestrial systems, but their utility in wetland environments remains uncertain. The objective of this work was to evaluate the effectiveness of using OTCs to warm a temperate salt marsh across diurnal and seasonal cycles. We found that OTCs are effective at warming air temperatures on the marsh, with average air temperatures 1.6 ± 0.007°C and 1.1 ± 0.006°C warmer within the high and low marsh, respectively over a 16‐month period. In contrast, OTCs were ineffective at warming sediments, especially during the day. In fact, sediment temperatures within the OTC were cooler during the day relative to ambient conditions. Such daytime warming of air, but cooling of sediments relative to ambient conditions resulted in a significant decoupling of above and belowground temperatures in the marsh (r = −0.99 and −0.82 on low and high marsh, respectively). Our data indicate that shading by OTCs was responsible for the daytime sediment cooling relative to ambient conditions during most of the year, as incoming solar radiation was reduced by 30% within OTCs. Wet sediments require more energy to heat than the air due to their higher specific heat capacity. Thus, reductions in radiation by OTCs prevented effective warming of sediments, but still allowed for the warming of air. In turn, we conclude that OTCs are not an effective method to experimentally warm tidal marsh sediments.
Involvement of calpain in the neuropathogenesis of Alzheimer’s disease
Authors: Mahaman Yacoubou Abdoul Razak , Huang Fang , Kessete Afewerky Henok , Maibouge  Tanko Mahamane Salissou , Ghose Bishwajit , Wang Xiaochuan
Published: September 2018

Alzheimer’s disease (AD) is the most common (60% to 80%) age‐related disease associated with dementia and is characterized by a deterioration of behavioral and cognitive capacities leading to death in few years after diagnosis, mainly due to complications from chronic illness. The characteristic hallmarks of the disease are extracellular senile plaques (SPs) and intracellular neurofibrillary tangles (NFTs) with neuropil threads, which are a direct result of amyloid precursor protein (APP) processing to Aβ, and τ hyperphosphorylation. However, many indirect underlying processes play a role in this event. One of these underlying mechanisms leading to these histological hallmarks is the uncontrolled hyperactivation of a family of cysteine proteases called calpains. Under normal physiological condition calpains participate in many processes of cells’ life and their activation is tightly controlled. However, with an increase in age, increased oxidative stress and other excitotoxicity assaults, this regulatory system becomes impaired and result in increased activation of these proteases involving them in the pathogenesis of various diseases including neurodegeneration like AD. Reviewed here is a pool of data on the implication of calpains in the pathogenesis of AD, the underlying molecular mechanism, and the potential of targeting these enzymes for AD therapeutics.
Oral Glucose Tolerance is Associated with Neuroelectric Indices of Attention Among Adults with Overweight and Obesity
Authors: Niemiro Grace M. , Skinner Sarah K. , Walk Anne M. , Edwards Caitlyn G. , De Lisio Michael , Holscher Hannah D. , Burd Nicholas A. , Khan Naiman A.
Published: September 2018

Objective

This study aimed to elucidate the relationship between glucose levels and insulin resistance and sensitivity obtained from oral glucose tolerance tests and neurophysiological indices of attention among adults with overweight and obesity.

Methods

Forty adults with overweight or obesity (BMI ≥ 25 kg/m2) underwent dual‐energy x‐ray absorptiometry to assess visceral adipose tissue. Repeated venous blood samples were collected during an oral glucose tolerance test to measure insulin resistance (homeostatic model assessment of insulin resistance) and indices of insulin sensitivity (Matsuda index and Stumvoll metabolic clearance rate). Attention was assessed using event‐related brain potentials recorded during a visual oddball task. Amplitude and latency of the P3 wave form in a central‐parietal region of interest were used to index attentional resource allocation and information processing speed.

Results

Following adjustment for visceral adipose tissue, reduced values of Matsuda index and Stumvoll metabolic clearance rate (indicating poor insulin sensitivity) were correlated with longer peak latency, whereas insulin area under the curve was positively related to peak latency, indicating slower information processing. Individuals with decreased insulin sensitivity (Matsuda index < 4.3) had significantly longer P3 latencies compared with individuals with normal insulin sensitivity.

Conclusions

Higher fasting glucose, but not homeostatic model assessment of insulin resistance, and reduced indices of glucose sensivity are associated with decrements in attention characterized by slower reaction time and slower information processing speed among adults with overweight and obesity.
Tributyl citrate as an effective plasticizer for biodegradable polymers: effect of plasticizer on free volume and transport and mechanical properties
Authors: Chaos Ana , Sangroniz Ainara , Gonzalez Alba , Iriarte Marian , Sarasua Jose‐Ramon , del Río Javier , Etxeberria Agustin
Published: September 2018

The effectiveness of tributyl citrate (TbC) as a plasticizer for polylactide and polyhydroxybutyrate was analysed in order to improve the ductility of these polymers and make them good candidates for food packaging applications. Although the thermal and mechanical properties have been widely studied in the literature, the effect of the plasticizer on free volume and transport properties has not been deeply analysed. The free volume was characterized using positron annihilation lifetime spectroscopy observing its linear increase with TbC content. The permeability to water vapour, oxygen and carbon dioxide was determined and the obtained results were related to the changes in glass transition temperature, level of crystallinity of the samples and free volume. This work would allow a better understanding of the effect of the plasticizer on the barrier and mechanical properties of polymers allowing the development of competitive materials for packaging applications. © 2018 Society of Chemical Industry
Front Cover: Cover Image, Volume 74, Issue 10
Authors: Busi Roberto , Goggin Danica E , Heap Ian M , Horak Michael J , Jugulam Mithila , Masters Robert A , Napier Richard M , Riar Dilpreet S , Satchivi Norbert M , Torra Joel , Westra Phillip , Wright Terry R
Published: September 2018

The front cover image of the herbicide, 2,4‐D, inside the deep binding pocket of the auxin receptor protein known as TIR1, by Roberto Busi et al., is based on the Review Weed resistance to synthetic auxin herbicides, DOI: 10.1002/ps.4823.

image
Standardizing interestingness measures for association rules
Authors: Shaikh Mateen R. , McNicholas Paul D. , Antonie M. Luiza , Murphy Thomas Brendan
Published: September 2018

Interestingness measures provide information about association rules. The value of an interestingness measure is often interpreted relative to the overall range of the interestingness measure. However, properties of individual association rules can further restrict what value an interestingness measure can achieve. These additional constraints are not typically taken into account in analysis, potentially misleading the investigator. Considering the value of an interestingness measure relative to this further constrained range provides greater insight than the original range alone and can even alter researchers' impressions of the data. Standardizing interestingness measures takes these additional restrictions into account, resulting in values that provide a relative measure of the attainable values. We explore the impacts of standardizing interestingness measures on real and simulated data.
Is the low‐carbon economy efficient in terms of sustainable development? A global perspective
Authors: Zhang Yu , Shen Liyin , Shuai Chenyang , Tan Yongtao , Ren Yitian , Wu Ya
Published: September 2018

Despite great efforts being devoted to, and substantial resources being consumed by low‐carbon economy (LCE) development globally, it appears that little is known about whether LCE development is efficient. This paper measures low‐carbon economy efficiency (LCEE) performance from a global perspective. The Super‐slack‐based measure model is adopted to analyse the LCEE performance of 115 sample countries during 1999–2013. The Malmquist Productivity Index is used to evaluate the dynamic change of LCEE between sample countries. The results indicate that overall worldwide LCEE performance is at low levels, and the differences in LCEE performance among the 115 sample countries are significant. It also indicates that LCEE performance is generally better in developed countries. From the dynamic perspective, a significant improvement in LCEE performance was achieved globally during the survey period, with an overall annual increase of 0.75%. These results provide a valuable reference to policy‐makers and practitioners for adopting measures to promote LCE development effectively at a global level.
Potential benefits of model use in group model building: insights from an experimental investigation
Authors: McCardle‐Keurentjes Marleen H. F. , Rouwette Etiënne A. J. A. , Vennix Jac A. M. , Jacobs Eric
Published: September 2018

How do individuals discover the feedback structure of a situation? Does such knowledge help people design and select better decisions? Do decision aids such as causal loop diagrams help? These questions have so far received limited research attention in controlled studies in system dynamics. Here we test the effectiveness of different methods commonly used in group decision settings such as group model building workshops. We employed a hidden profile experimental design in which each individual in a group possessed private information that must be shared to arrive at a good solution—in this case, policies to improve performance. The task placed participants in the role of a manager in a department at the Saturday Evening Post. Processing of department‐specific information will be needed to discover the full feedback structure.

We compare decision quality and structural understanding across four conditions: (i) a control setting in which participants only receive minutes of a meeting; (ii) a setting in which participants are actively engaged in qualitative modeling (developing a causal loop diagram); (iii) a setting in which participants receive a causal loop diagram as a decision aid; and (iv) setting (iii) but with all participants given full information. Model use had no effect on the importance participants attached to critical information, understanding of model structure, or confidence in their decisions. However, for participants actively engaged in modeling, we found a substantial correlation between importance attached to critical information, understanding, and confidence. The results have implications for group model building research and practice.

© 2018 System Dynamics Society