bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring the impact of pharmacoepidemiologic research using altmetrics: A case study of aCNODESdrug‐safety article
Authors: Gamble J.M. , Traynor Robyn L. , Gruzd Anatoliy , Mai Philip , Dormuth Colin R. , Sketris Ingrid S.
Published: March 2018

Purpose

To provide an overview of altmetrics, including their potential benefits and limitations, how they may be obtained, and their role in assessing pharmacoepidemiologic research impact.

Methods

Our review was informed by compiling relevant literature identified through searching multiple health research databases (PubMed, Embase, and CIHNAHL) and grey literature sources (websites, blogs, and reports). We demonstrate how pharmacoepidemiologists, in particular, may use altmetrics to understand scholarly impact and knowledge translation by providing a case study of a drug‐safety study conducted by the Canadian Network of Observational Drug Effect Studies.

Results

A common approach to measuring research impact is the use of citation‐based metrics, such as an article's citation count or a journal's impact factor. “Alternative” metrics, or altmetrics, are increasingly supported as a complementary measure of research uptake in the age of social media. Altmetrics are nontraditional indicators that capture a diverse set of traceable, online research‐related artifacts including peer‐reviewed publications and other research outputs (software, datasets, blogs, videos, posters, policy documents, presentations, social media posts, wiki entries, etc).

Conclusion

Compared with traditional citation‐based metrics, altmetrics take a more holistic view of research impact, attempting to capture the activity and engagement of both scholarly and nonscholarly communities. Despite the limited theoretical underpinnings, possible commercial influence, potential for gaming and manipulation, and numerous data quality‐related issues, altmetrics are promising as a supplement to more traditional citation‐based metrics because they can ingest and process a larger set of data points related to the flow and reach of scholarly communication from an expanded pool of stakeholders. Unlike citation‐based metrics, altmetrics are not inherently rooted in the research publication process, which includes peer review; it is unclear to what extent they should be used for research evaluation.
Methodology for computing the burden of disease of adverse events following immunization
Authors: McDonald Scott A. , Nijsten Danielle , Bollaerts Kaatje , Bauwens Jorgen , Praet Nicolas , van der Sande Marianne , Bauchau Vincent , de Smedt Tom , Sturkenboom Miriam , Hahné Susan
Published: March 2018

Purpose

Composite disease burden measures such as disability‐adjusted life‐years (DALY) have been widely used to quantify the population‐level health impact of disease or injury, but application has been limited for the estimation of the burden of adverse events following immunization. Our objective was to assess the feasibility of adapting the DALY approach for estimating adverse event burden.

Methods

We developed a practical methodological framework, explicitly describing all steps involved: acquisition of relative or absolute risks and background event incidence rates, selection of disability weights and durations, and computation of the years lived with disability (YLD) measure, with appropriate estimation of uncertainty. We present a worked example, in which YLD is computed for 3 recognized adverse reactions following 3 childhood vaccination types, based on background incidence rates and relative/absolute risks retrieved from the literature.

Results

YLD provided extra insight into the health impact of an adverse event over presentation of incidence rates only, as severity and duration are additionally incorporated. As well as providing guidance for the deployment of DALY methodology in the context of adverse events associated with vaccination, we also identified where data limitations potentially occur.

Conclusions

Burden of disease methodology can be applied to estimate the health burden of adverse events following vaccination in a systematic way. As with all burden of disease studies, interpretation of the estimates must consider the quality and accuracy of the data sources contributing to the DALY computation.
Discontinuation and dose adjustment of metoprolol after metoprolol‐paroxetine/fluoxetine co‐prescription in Dutch elderly
Authors: Bahar Muh. Akbar , Wang Yuanyuan , Bos Jens H.J. , Wilffert Bob , Hak Eelko
Published: March 2018

Purpose

Co‐prescription of paroxetine/fluoxetine (a strong CYP2D6 inhibitor) in metoprolol (a CYP2D6 substrate) users is common, but data on the clinical consequences of this drug‐drug interaction are limited and inconclusive. Therefore, we assessed the effect of paroxetine/fluoxetine initiation on the existing treatment with metoprolol on the discontinuation and dose adjustment of metoprolol among elderly.

Methods

We performed a cohort study using the University of Groningen IADB.nl prescription database (www.IADB.nl). We selected all elderly (≥60 years) who had ever been prescribed metoprolol and had a first co‐prescription of paroxetine/fluoxetine, citalopram (weak CYP2D6 inhibitor), or mirtazapine (negative control) from 1994 to 2015. The exposure group was metoprolol and paroxetine/fluoxetine co‐prescription, and the other groups acted as controls. The outcomes were early discontinuation and dose adjustment of metoprolol. Logistic regression was applied to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI).

Results

Combinations of metoprolol‐paroxetine/fluoxetine, metoprolol‐citalopram, and metoprolol‐mirtazapine were started in 528, 673, and 625 patients, respectively. Compared with metoprolol‐citalopram, metoprolol‐paroxetine/fluoxetine was not significantly associated with the early discontinuation and dose adjustment of metoprolol (OR = 1.07, 95% CI:0.77‐1.48; OR = 0.87, 95% CI:0.57‐1.33, respectively). In comparison with metoprolol‐mirtazapine, metoprolol‐paroxetine/fluoxetine was associated with a significant 43% relative increase in early discontinuation of metoprolol (OR = 1.43, 95% CI:1.01‐2.02) but no difference in the risk of dose adjustment. Stratified analysis by gender showed that women have a significantly high risk of metoprolol early discontinuation (OR = 1.62, 95% CI:1.03‐2.53).

Conclusion

Paroxetine/fluoxetine initiation in metoprolol prescriptions, especially for female older patients, is associated with the risk of early discontinuation of metoprolol.
Do Electronic Cigarettes Have a Role in Tobacco Cessation?
Authors: Franks Andrea S. , Sando Karen , McBane Sarah
Published: March 2018

Tobacco use continues to be a major cause of morbidity and mortality. Even with behavioral and pharmacologic treatment, long‐term tobacco cessation rates are low. Electronic nicotine delivery systems, commonly referred to as electronic cigarettes or e‐cigarettes, are increasingly used for tobacco cessation. Because e‐cigarettes are widely used in this setting, health care professionals need to know if they are safe and effective. The purpose of this article is to review literature regarding use of e‐cigarettes as a tool for tobacco cessation in patients who are ready to quit, as well as those who are not ready to quit, along with some selected patient populations. The safety and clinical implications of e‐cigarette use are also reviewed. Small, short‐term studies assessing smokers’ use of e‐cigarettes suggest that e‐cigarettes may be well tolerated and modestly effective in achieving abstinence. High‐quality studies are lacking to support e‐cigarettes use for cessation in patients with mental health issues. One small prospective cohort study concluded that patients with mental health issues reduced cigarette use with e‐cigarette use. Although one study found that patients with cancer reported using e‐cigarettes as a tobacco‐cessation strategy, e‐cigarettes were not effective in supporting abstinence 6 and 12 months later. Additional research is needed to evaluate the use of e‐cigarettes for smoking cessation in patients with pulmonary diseases. No data exist to describe the efficacy of e‐cigarettes for smoking cessation in pregnant women. Although study subjects report minimal adverse effects with e‐cigarettes and the incidence of adverse effects decreases over time, long‐term safety data are lacking. Health care providers should assess e‐cigarette use in their patients as part of the tobacco cessation process.
Effect of annealing time and molecular weight on melt memory of random ethylene 1‐butene copolymers
Authors: Chen Xuejian , Qu Chen , Alamo Rufina G
Published: March 2018

The effects of annealing time and molecular weight on the strong melt memory effect observed in random ethylene 1‐alkene copolymers are analyzed in a series of model ethylene 1‐butene copolymers with 2.2 mol% branches. Melt memory is associated with molten clusters of ethylene sequences from the initial crystals that remain in close proximity and are unable to diffuse quickly to the randomized melt state, thus increasing the recrystallization rate. Melt memory persists even for greater than 1000 min annealing indicating a long‐lived nature of the clusters that only fully dissolve at melt temperatures above a critical value (>160 °C). Below the critical melt temperature, molecular weight and annealing temperature have a strong influence on the slow kinetics of melt memory. For the copolymers analyzed, slow dissolution of clusters is experimentally observed only for Mw < 50 000 g mol−1. More stable clusters that survive higher annealing temperatures display slower dissolution rates than clusters remaining at lower temperatures. The threshold crystallinity level to enable melt memory (Xc,threshold) decreases with increasing molecular weight and decreasing annealing temperature similarly to the variation of the chain diffusivity in the melt. The process leading to melt memory is thermally activated as the variation of Xc,threshold with temperature follows Arrhenius behavior with high activation energy (ca 108 kJ mol−1) that is independent of molecular weight. © 2018 Society of Chemical Industry
Synthesis of imide‐based methacrylic monomers and their copolymerization with methyl methacrylate: monomer reactivity ratios and heat resistance properties
Authors: Ko Kun‐Young , Baek Seung‐Suk , Hwang Seok‐Ho
Published: March 2018

The newly designed methacrylic monomer series 4‐phthalimidocyclohexyl methacrylate (PCMA), 4‐hexahydrophthalimidocyclohexyl methacrylate (HPCMA) and 4‐hexahydro‐3,6‐methanophthalimidocyclohexyl methacrylate (HMPCMA) were synthesized. Their homopolymers and methyl methacrylate (MMA) based copolymer series were polymerized by free‐radical polymerization. The copolymer compositions were characterized using 1H NMR spectra. The monomer reactivity ratios were calculated employing the Fineman−Ross (F‐T) and Kelen−Tüdös (K‐T) methods at low conversion. The values of r1 and r2 obtained by the F‐T and K‐T methods appear to be in close agreement (their average values are r1 = 1.3061 and r2 = 0.7336 for poly(PCMA‐co‐MMA), r1 = 1.5169 and r2 = 0.6840 for poly(HPCMA‐co‐MMA), r1 = 1.7748 and r2 = 0.5664 for poly(HMPCMA‐co‐MMA)) . The thermal stabilities and thermomechanical characteristics of the homopolymer and copolymer series were investigated by differential scanning calorimetry, thermogravimetric analysis and dynamic mechanical thermal analysis. © 2018 Society of Chemical Industry
Demonstration of NC(sp2)‐centered stereofluctuations in a guanidine derivative and its cation
Authors: Knorr Rudolf , Böhrer Petra
Published: March 2018

NMR line shapes and coalescences of pairs of diastereotopic reporter nuclei (1H and 13C) at suitable molecular positions were used to measure the stereofluctuation rate constants of an N‐aryl cycloguanidine model compound of the type aryl—N═C[N(CH3)CH2]2 (7 in Scheme ) in toluene and in CDCl3 as the solvents. The key criterion is coincidence or noncoincidence of the rate constants, which revealed that both free N═C double‐bond rotation and free N—aryl single‐bond rotation occur much more slowly than in‐plane, lone‐electron pair inversion at nitrogen, which is fast even at −99°C. The related cycloguanidinium model compound (6 in Scheme ) cannot perform such an N‐inversion but simulates it at roughly 35°C in CDCl3 and in Cl2CD—CDCl2 through a less rapid N═C half‐rotation that is coupled with a correlated, counter‐sense N—aryl half‐rotation, whereas both free N═C double‐bond rotation and free N—aryl rotation are again significantly slower.
Cu(II)‐catalyzed hydrolysis of tris‐2‐pyridyl phosphate assisted by sodium dodecyl sulfate micelles
Authors: Wanderlind Eduardo H. , Bittencourt Catiunaiara R. , Manfredi Alex M. , Gerola Adriana P. , Souza Bruno S. , Fiedler Haidi D. , Nome Faruk
Published: March 2018

Hydrolysis of the phosphate triester tris‐2‐pyridyl phosphate is catalyzed upon complexation with Cu2+, with enhancements of the order of 107‐fold in comparison to the spontaneous hydrolysis of the substrate. Experimental and theoretical results suggest that Cu2+ most probably coordinates to the nitrogen atoms of two of the pyridyl substituents disposing a metallo‐bound water or hydroxo ligand at appropriate distance for intramolecular attack on phosphorus. Micelles of the anionic sodium dodecyl sulfate remarkably accelerate the reactions, acting as nanoreactors that concentrate in the micellar microenvironment both the hydrophobic substrate and the positively charged metal ion, favoring complexation between tris‐2‐pyridyl phosphate and Cu2+.
Salicylaldimine‐functionalized poly(m‐phenyleneethynylene) as turn‐on chemosensor for ferric ion
Authors: Thavornsin Nopparat , Rashatasakhon Paitoon , Sukwattanasinitt Mongkol , Wacharasindhu Sumrit
Published: March 2018

A new turn on fluorescent probe for ferric ion based on poly(m‐phenyleneethynylene salicylaldimine) (PPE‐IM) has been developed. The preparation ofPPE‐IMinvolves post‐polymerization functionalization of the corresponding polymeric amine,PPE‐AM, via the condensation with salicylaldehyde. The degree of polymerization of bothPPE‐IMandPPE‐IMis 17 with polydispersity index of 1.5. In aqueous solution, the polymericPPE‐IMis highly stable unlike its small molecule analog which is gradually hydrolyzed. The weak fluorescence of initialPPE‐IM(λem = 470) is greatly enhanced by 300 folds upon the addition of Fe3+. The1H NMR reveals that the fluorescence enhancement is caused by Fe3+‐induced hydrolysis of the imine group. The sensing system shows a detection limit of 0.14 μM of Fe3+. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem.2018,56, 1155–1161
Resistance to discontinuing breast cancer screening in older women: A qualitative study
Authors: Housten Ashley J. , Pappadis Monique R. , Krishnan Shilpa , Weller Susan C. , Giordano Sharon H. , Bevers Therese B. , Volk Robert J. , Hoover Diana S.
Published: March 2018

Objective

Screening mammography is associated with reduced breast cancer‐specific mortality; however, among older women, evidence suggests that the potential harms of screening may outweigh the benefits. We used a qualitative approach to examine the willingness of older women from different racial/ethnic groups to discontinue breast cancer screening.

Methods

Women ≥70 years of age who reported having a screening mammogram in the past 3 years and/or reported that they intended to continue screening in the future were recruited for in‐depth interviews. Participants who intended to continue screening were asked to describe how the following hypothetical scenarios would impact a decision to discontinue screening: health concerns or limited life expectancy, a physician's recommendation to discontinue, reluctance to undergo treatment, and recommendations from experts or governmental panels to stop screening. Semi‐structured, face‐to‐face interviews were audio‐recorded. Data coding and analysis followed inductive and deductive approaches.

Results

Regardless of the scenario, participants (n = 29) expressed a strong intention to continue screening. Based on the hypothetical physician recommendations, intentions to continue screening appeared to remain strong. They did not envision a change in their health status that would lead them to discontinue screening and were skeptical of expert/government recommendations. There were no differences observed according to age, race/ethnicity, or education.

Conclusions

Among older women who planned to continue screening, intentions to continue breast cancer screening appear to be highly resilient and resistant to recommendations from physicians or expert/government panels.
The ecology of patient and caregiver participation in consultations involving advanced cancer
Authors: Freytag Jennifer , Street Jr Richard L. , Xing Guibo , Duberstein Paul R. , Fiscella Kevin , Tancredi Daniel J. , Fenton Joshua J. , Kravitz Richard L. , Epstein Ronald M.
Published: March 2018

Objective

To identify predictors of participation of patients with advanced cancer in clinical encounters with oncologists and to assess the impact of patient and caregiver participation on perceptions of physician support.

Methods

This is a secondary data analysis from the Values and Options in Cancer Care study, a cluster randomized clinical trial of a patient‐centered communication intervention. Patients and caregivers completed pre‐visit and post‐visit health and communication measures. Audio recorded patient‐caregiver (when present)‐physician encounters were coded for active patient/caregiver participation behaviors (eg, question asking, expressing concern) and for physicians' facilitative communication (eg, partnership‐building, support). Mixed linear regression models were used to identify patient, physician, and situational factors predicting patient and patient plus caregiver communication behaviors and post‐visit outcomes.

Results

Physician partnership building predicted greater expressions of concern and more assertive responses from patients and patient‐caregiver pairs. Patients' perceptions of greater connectedness with their physician predicted fewer patient expressions of concern. Patient perceptions of physician respect for their autonomy were lower among patients accompanied by caregivers. Caregiver perceptions of physician respect for patient autonomy decreased with increasing patient age and varied by site.

Conclusions

In advanced cancer care, patient and caregiver communication is affected by ecological factors within their consultations. Physicians can support greater patient participation in clinical encounters through facilitative communication such as partnership‐building and supportive talk. The presence of a caregiver complicates this environment, but partnership building techniques may help promote patient and caregiver participation during these visits.
Moisture barrier films containing plasma polymer fluorocarbon/inorganic multilayers fabricated via continuous roll‐to‐roll sputtering
Authors: Kim Sung Hyun , Kim Mac , Lee Jae Heung , Lee Sang‐Jin
Published: March 2018

We propose a novel fabrication method for the moisture barrier films composed of plasma polymer fluorocarbon (PPFC) and inorganic (SiNx or SiO2) multilayers using a continuous roll‐to‐roll sputtering process. PPFC thin films are produced via the mid‐range frequency sputtering of a carbon nanotube‐polytetrafluoroethylene composite target. After depositing a PPFC layer on the surface of the multilayer structure, it exhibited a high degree of water repellency and enhanced transmittance in the visible light region. The produced 2‐dyad structure containing a SiNx inorganic layer deposited on a polyethylene terephthalate substrate demonstrates good barrier properties characterized by a water vapor transmittance rate (WVTR) of 1.8 × 10−2 g/m2/day. By replacing the inorganic layer with a SiO2 thin film, a better barrier film with a WVTR value of 1.1 × 10−2 g/m2/day is obtained.
Airway cells from protracted bacterial bronchitis and bronchiectasis share similar gene expression profiles
Authors: Chen Alice C.‐H. , Pena Olga M. , Nel Hendrik J. , Yerkovich Stephanie T. , Chang Anne B. , Baines Katherine J. , Gibson Peter G. , Petsky Helen L. , Pizzutto Susan J. , Hodge Sandra , Masters Ian B. , Buntain Helen L. , Upham John W.
Published: March 2018

Aim

Protracted bacterial bronchitis (PBB) is a common cause of prolonged cough in young children, and may be a precursor of bronchiectasis. Bacteria are often present in the lower airways in both PBB and bronchiectasis and may cause persistent infections. However, there is a paucity of information available on the pathogenesis of PBB and the factors associated with persistent bacterial infection and progression to bronchiectasis. This study hypothesised that lung immune cells in recurrent PBB and bronchiectasis differentially express genes related to immune cell dysfunction compared to lung immune cells from control subjects.

Method

Cells isolated from bronchoalveolar lavage (adult‐control and PBB BAL cells) were stimulated with nontypeable Haemophilus influenzae (NTHi), and expression of genes involved in various inflammatory pathways was assessed.

Result

NTHi induced production of large amounts of IL‐1β, IL‐6, and IL‐8 in adult‐control BAL cells, however BAL cells from PBB airways appeared refractory to NTHi stimulation. BAL cells from PBB and bronchiectasis showed differential expression of several genes relative to control cells, including CCL20, MARCO, CCL24, IL‐10, PPAR‐γ, CD200R, TREM2, RelB. Expression of genes involved in resolution of inflammation and anti‐inflammation response, such as CD200R and IL‐10, was associated with the number of pathogenic bacteria found in the airways.

Conclusion

In summary, we have shown that the expression of genes related to macrophage function and resolution of inflammation are similar in PBB and bronchiectasis. Lung immune cell dysfunction in PBB and bronchiectasis may contribute to poor bacterial clearance and prolonged resolution of inflammation.
A graphical method for comparing nocturnal oxygen saturation profiles in individuals and populations: Application to healthy infants and preterm neonates
Authors: Terrill Philip I. , Dakin Carolyn , Edwards Bradley A. , Wilson Stephen J. , MacLean Joanna E.
Published: March 2018

Study Objectives

Pulse‐oximetry (SpO2) allows the identification of important clinical physiology. However, summary statistics such as mean values and desaturation incidence do not capture the complexity of the information contained within continuous recordings. The aim of this study was to develop an objective method to quantify important SpO2 characteristics; and assess its utility in healthy infant and preterm neonate cohorts.

Methods

An algorithm was developed to calculate the desaturation incidence, depth, and duration. These variables are presented using three plots: SpO2 cumulative‐frequency relationship; desaturation‐depth versus incidence; desaturation‐duration versus incidence. This method was applied to two populations who underwent nocturnal pulse‐oximetry: (1) thirty‐four healthy term infants studied at 2‐weeks, 3, 6, 12, and 24‐months of age and (2) thirty‐seven neonates born <26 weeks and studied at discharge from NICU (37‐44 weeks post‐conceptual age).

Results

The maturation in healthy infants was characterized by reduced desaturation index (27.2/h vs 3.3/h at 2‐weeks and 24‐months, P < 0.01), and increased percentage of desaturation events ≥6‐s in duration (27.8% vs 43.2% at 2‐weeks and 3‐months, P < 0.01). Compared with term‐infants, preterm infants had a greater desaturation incidence (54.8/h vs 27.2/h, P < 0.01), and these desaturations were deeper (52.9% vs 37.6% were ≥6% below baseline, P < 0.01). The incidence of longer desaturations (≥14‐s) in preterm infants was correlated with healthcare utilization over the first 24‐months (r = 0.63, P < 0.01).

Conclusions

This tool allows the objective comparison of extended oximetry recordings between groups and for individuals; and serves as a basis for the development of reference ranges for populations.
Non‐invasive ventilation practices in children across Europe
Authors: Mayordomo‐Colunga Juan , Pons‐Òdena Martí , Medina Alberto , Rey Corsino , Milesi Christophe , Kallio Merja , Wolfler Andrea , García‐Cuscó Mireia , Demirkol Demet , García‐López Milagros , Rimensberger Peter
Published: March 2018

Objectives

To describe the diversity in practice in non‐invasive ventilation (NIV) in European pediatric intensive care units (PICUs).

Working hypothesis

No information about the use of NIV in Pediatrics across Europe is currently available, and there might be a wide variability regarding the approach.

Study design

Cross‐sectional electronic survey.

Methodology

The survey was distributed to the ESPNIC mailing list and to researchers in different European centers.

Results

One hundred one units from 23 countries participated. All respondent units used NIV. Almost all PICUs considered NIV as initial respiratory support (99.1%), after extubation (95.5% prophylactically, 99.1% therapeutically), and 77.5% as part of palliative care. Overall NIV use outside the PICUs was 15.5% on the ward, 20% in the emergency department, and 36.4% during transport. Regarding respiratory failure cause, NIV was delivered in pneumonia (97.3%), bronchiolitis (94.6%), bronchospasm (75.2%), acute pulmonary edema (84.1%), upper airway obstruction (76.1%), and in acute respiratory distress syndrome (91% if mild, 53.1% if moderate, and 5.3% if severe). NIV use in asthma was less frequent in Northern European units in comparison to Central and Southern European PICUs (P = 0.007). Only 47.7% of the participants had a written protocol about NIV use. Bilevel NIV was applied mostly through an oronasal mask (44.4%), and continuous positive airway pressure through nasal cannulae (39.8%). If bilevel NIV was required, 62.3% reported choosing pressure support (vs assisted pressure‐controlled ventilation) in infants; and 74.5% in older children.

Conclusions

The present study shows that NIV is a widespread technique in European PICUs. Practice across Europe is variable.
ProtaBank: A repository for protein design and engineering data
Authors: Wang Connie Y. , Chang Paul M. , Ary Marie L. , Allen Benjamin D. , Chica Roberto A. , Mayo Stephen L. , Olafson Barry D.
Published: March 2018

We present ProtaBank, a repository for storing, querying, analyzing, and sharing protein design and engineering data in an actively maintained and updated database. ProtaBank provides a format to describe and compare all types of protein mutational data, spanning a wide range of properties and techniques. It features a user‐friendly web interface and programming layer that streamlines data deposition and allows for batch input and queries. The database schema design incorporates a standard format for reporting protein sequences and experimental data that facilitates comparison of results across different data sets. A suite of analysis and visualization tools are provided to facilitate discovery, to guide future designs, and to benchmark and train new predictive tools and algorithms. ProtaBank will provide a valuable resource to the protein engineering community by storing and safeguarding newly generated data, allowing for fast searching and identification of relevant data from the existing literature, and exploring correlations between disparate data sets. ProtaBank invites researchers to contribute data to the database to make it accessible for search and analysis. ProtaBank is available at https://protabank.org.
Structural basis for tumor necrosis factor blockade with the therapeutic antibody golimumab
Authors: Ono Masatsugu , Horita Shoichiro , Sato Yumi , Nomura Yayoi , Iwata So , Nomura Norimichi
Published: March 2018

Tumor necrosis factor α (TNFα) is a proinflammatory cytokine, and elevated levels of TNFα in serum are associated with various autoimmune diseases, including rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn's disease (CD), psoriasis, and systemic lupus erythaematosus. TNFα performs its pleiotropic functions by binding to two structurally distinct transmembrane receptors, TNF receptor (TNFR) 1 and TNFR2. Antibody‐based therapeutic strategies that block excessive TNFα signaling have been shown to be effective in suppressing such harmful inflammatory conditions. Golimumab (Simponi®) is an FDA‐approved fully human monoclonal antibody targeting TNFα that has been widely used for the treatment of RA, AS, and CD. However, the structural basis underlying the inhibitory action of golimumab remains unclear. Here, we report the crystal structure of the Fv fragment of golimumab in complex with TNFα at a resolution of 2.73 Å. The resolved structure reveals that golimumab binds to a distinct epitope on TNFα that does not overlap with the binding residues of TNFR2. Golimumab exerts its inhibitory effect by preventing binding of TNFR1 and TNFR2 to TNFα by steric hindrance. Golimumab does not induce conformational changes in TNFα that could affect receptor binding. This mode of action is specific to golimumab among the four anti‐TNFα therapeutic antibodies currently approved for clinical use.
The what, when, and why of human prostate cancer xenografts
Authors: Brennen W. Nathaniel , Isaacs John T.
Published: March 2018

Background

Presently, ∼85 serially transplantable human prostate cancer xenografts spanning the phenotypic, epigenetic, and genetic heterogeneity seen clinically are available in a variety of laboratories throughout the world. If distributed to the prostate cancer research community, these can provide an experimental platform for resolving the specificity versus generalizability of basic cancer biology principles (eg, credentialing of therapeutic molecular targets) and for validating translational approaches for prevention, diagnosis, and therapy. Thus, there is an urgent need to distribute the already established serially transplantable human prostate cancer xenografts and to develop robust methods for establishing new ones.

Methods

To accelerate the development of such additional xenografts, particularly from patients treated with the newer standard of care agents (ie, abiraterone, enzalutamide, cabazitaxel, alpharadin, etc), a historic review of the field will be presented.

Results

Over the last 50 years, multiple groups throughout the world have developed methods for the successful establishment of serially transplantable human prostate cancer xenografts using a variety of immune deficient mice. These are summarized chronologically.

Conclusions and Future

With the ever growing appreciation of the value of personalized medicine (aka precision medicine), methods need to be developed that allow efficient and timely growth of primary patient derived prostate cancer xenografts (PDXs), which can be used as “avatars” for defining optimal therapy for that specific patient. Such development should be based upon the leads obtained from the successful establishment of serially transplantable prostate cancer xenografts described in this review.
Complex formation dynamics of native and mutated pyrin's B30.2 domain with caspase‐1
Authors: Arakelov Grigor , Arakelov Vahram , Nazaryan Karen
Published: March 2018

Pyrin protein is the product of the MEFV gene, mutations in which cause manifestation of familial Mediterranean fever (FMF). Functions of pyrin are not completely clear. The secondary structure of the pyrin is represented with four domains and two motifs. Mutations p.M680I, p.M694V, p.M694I, p.K695R, p.V726A, and p.A744S, which are located in the B30.2 domain of pyrin protein, are responsible for manifestation of the most common and severe forms of FMF. All the domains and the motifs of pyrin, are directly or indirectly, involved in the protein–protein interaction with proteins of apoptosis and regulate the cascade of inflammatory reactions, which is impaired due to pyrin mutations. It is well known, that malfunction of the pyrin‐caspase‐1 complex is the main reason of inflammation during FMF. Complete tertiary structure of pyrin and the effects of mutations in it are experimentally not studied yet. The aim of this study was to identify possible effects of the abovementioned mutations in the B30.2 domain tertiary structure and to determine their potential consequences in formation of the B30.2‐caspase‐1 complex. Using in silico methods, it was found, that these mutations led to structural rearrangements in B30.2 domain tertiary structure, causing shifts of binding sites and altering the interaction energy between B30.2 and caspase‐1.
Consequence assessment of anhydrous ammonia release using CFD‐probit analysis
Authors: Namboothiri Nandu V. , Soman AR
Published: March 2018

An accidental release of hazardous chemical can happen in industries during its production, storage, and transportation. The consequence assessment is a method of analyzing the impact of hazardous chemical release into the environment. It includes the identification of threat zone and its impact on people. Consequence assessment is a primary part of risk assessment which is essential for the development of mitigation strategy. In this study, a consequence assessment of anhydrous ammonia release from a storage facility was conducted and the mitigation strategy was developed. A hypothetical accidental release of ammonia from a storage facility in a chemical process industry was assumed. The evaporation of ammonia pool formed by the release was estimated using CFD analysis and the dispersion of the ammonia was found out using ALOHA. Three different wind speed was taken for analyzing the consequences. Probability of death of people living in the threat zone was estimated by probit analysis. A mitigation strategy was developed based on adsorption principle using modified carbon nanoparticles. © 2018 American Institute of Chemical Engineers Process Saf Prog 37: 525–534, 2018
Potential global distribution of Diabrotica species and the risks for agricultural production
Authors: Marchioro Cesar A , Krechemer Flavia S
Published: March 2018

BACKGROUND

Despite efforts in the last few decades to prevent biological invasions, agricultural pests continue to spread as a result of globalization and international trade. This study was conducted to identify suitable areas for the occurrence of four Diabrotica species and to assess the potential impact of these species in a scenario of invasion followed by spread throughout the estimated suitable regions.

RESULTS

Our findings reveal that a large proportion of the suitable areas for Diabrotica species overlap with cultivated areas. Niche analyses also demonstrated that these species occupy a small proportion of the suitable habitats available to them, indicating that, if new areas are invaded, there is a risk of spread throughout adjacent regions.

CONCLUSION

Most of the suitable areas for Diabrotica species overlap with highly productive agricultural areas, suggesting that a potential spread of these species may cause economic loss. Our study provides a valuable contribution to the development of tools aiming to predict the potential spread of these species throughout the world. © 2018 Society of Chemical Industry
Frequency and intensity of pyrethroid resistance through the CDC bottle bioassay and their association with the frequency of kdr mutations in Aedes aegypti (Diptera: Culicidae) from Mexico
Authors: Lopez‐Monroy Beatriz , Gutierrez‐Rodriguez Selene M , Villanueva‐Segura Olga Karina , Ponce‐Garcia Gustavo , Morales‐Forcada Franco , Alvarez Leslie C , Flores Adriana E
Published: March 2018

BACKGROUND

The control of Aedes aegypti (L.), the main urban vector that causes arboviral diseases such as dengue, Chikungunya and Zika, has proved to be a challenge because of a rapid increase in insecticide resistance. Therefore, adequate monitoring of insecticide resistance is an essential element in the control of Ae. aegypti and the diseases it transmits. We estimated the frequency and intensity (Resistance Frequency Rapid Diagnostic Test [F‐RDT] and Resistance Intensity Rapid Diagnostic Test [I‐RDT]) of pyrethroid resistance in populations of Ae. aegypti from Mexico using the bottle bioassay and results were related to the frequencies of knockdown resistance (kdr) mutations V1016I and F1534C.

RESULTS

All populations under study were resistant to the pyrethroids: bifenthrin (99%), d‐(cis–trans)‐phenothrin (6.3% cis, 91.7% trans) and permethrin (99.5%) according to F‐RDT, and showed moderate to high‐intensity resistance at 10× the diagnostic dose (DD) in I‐RDT. Frequencies of the kdr mutation V1016I in Ae. aegypti populations were correlated with moderate permethrin resistance at 10× DD, whereas F1534C mutation frequencies were correlated with high bifenthrin resistance at 5× DD. Both I1016 and C1535 were highly correlated with high‐intensity phenothrin resistance at 1× to 10× DD.

CONCLUSIONS

This study showed that high frequencies of kdr mutations V1016I and F1534C are reflected in the results of F‐RDT and I‐RDT tests. Bioassays in conjunction with the characterization of genetic resistance mechanisms are indispensable in the strategic and rational management of resistance in mosquitoes. © 2018 Society of Chemical Industry
Novel side reaction accompanying cyclization of Glu(R1)‐Glu(R2) dipeptides via lactamization of the Glu(R1) residue
Authors: Deigin Vladislav , Ksenofontova Olga , Yatskin Oleg , Kublitsky Vadim , Shmygarev Vladimir , Abramovich Rimma , Dubinnyi Maxim , Ivanov Vadim
Published: March 2018

A series of linear peptides with the general formula H‐Glu(R1)‐Glu(R2)‐OH was subjected to cyclization under standard conditions. Formation of respective 2,5‐diketopiperazines was accompanied by transformation of the N‐terminal Glu(R1) to pyroglutamic acid residue. Even in the case R1 is an amino acid residue attached to the N‐terminal γ‐carboxyl group, lactamization leads to its elimination. The observed reaction has not been reported so far in the literature. Correspondingly, an alternative route to Glu(R1)‐Glu(R2)‐containing 2,5‐diketopiperazines was applied to improve the overall yields.
The New Urbanisation Plan and permanent urban settlement of migrants in Chongqing, China
Authors: Zhou Jing
Published: March 2018

For over 30 years, urbanisation in China went along with policies that discouraged migrants from permanently settling in cities. Since 2014, however, policies have shifted towards the encouragement of the urban settlement of migrants. This change has triggered new academic research aimed at re‐understanding the urban integration. Findings of this paper are based on a survey conducted in Chongqing, the first municipality to implement elements of China's New Urbanisation Plan. The focus was on the preference for permanently settling in the city among migrants. Situations before and after the policy transition have been compared, while special attention was given to the impact of 2 key institutional factors—hukou reform and access to public rental housing. The other key to the investigation was whether migrants who have accessed public rental housing seek to buy such housing in order to eventually achieve permanent urban settlement. Results show that the policy transition has had positive effects on the preference of migrants for permanent urban settlement. However, the influence of public rental housing occupancy was quantitatively limited and the impact of the hukou reform has not yet fully crystalized. The policy transition has brought certain equity to disadvantaged and intra‐provincial rural–urban migrants, but this in turn has had negative effects on more advantaged and inter‐provincial migrants. The latter categories appeared to have fewer incentives to approach permanent urban settlement via accessing public rental housing.
Complex Bayesian Modeling Workflows Encoding and Execution Made Easy With a Novel WinBUGS Plugin of the Drug Disease Model Resources Interoperability Framework
Authors: Larizza Cristiana , Borella Elisa , Pasotti Lorenzo , Tartaglione Palma , Smith Mike , Moodie Stuart , Magni Paolo
Published: March 2018

The Drug Disease Model Resources (DDMoRe) Interoperability Framework (IOF) enables pharmacometric model encoding and execution via Model Description Language (MDL) and R language, through the ddmore package. Through its components and converter plugins, the IOF can execute pharmacometric tasks using different target tools, starting from a single MDL‐encoded model. In this article, we present the WinBUGS plugin and show how its integration in the IOF enables an easy implementation of complex Bayesian workflows. We selected a published diabetes‐linked study as a real‐world example, in which two inter‐related models are used to estimate insulin secretion rate in response to a glucose stimulus from intravenous glucose tolerance test (IVGTT) data. This model was implemented following different approaches to propagate uncertainty, via diverse IOF target tools (NONMEM, WinBUGS, PsN, and Xpose). The developed software supports a plethora of pharmacokinetic/pharmacodynamic (PK/PD) modeling features. It provides solutions to reproducibility and interoperability issues in Bayesian modeling, and facilitates the difficult encoding of complex PK/PD models in WinBUGS.
Comparison of Power, Prognosis, and Extrapolation Properties of Four Population Pharmacodynamic Models of HbA1c for Type 2 Diabetes
Authors: Wellhagen Gustaf J. , Karlsson Mats O. , Kjellsson Maria C.
Published: March 2018

Reusing published models saves time; time to be used for informing decisions in drug development. In antihyperglycemic drug development, several published HbA1c models are available but selecting the appropriate model for a particular purpose is challenging. This study aims at helping selection by investigating four HbA1c models, specifically the ability to identify drug effects (shape, site of action, and power) and simulation properties. All models could identify glucose effect nonlinearities, although for detecting the site of action, a mechanistic glucose model was needed. Power was highest for models using mean plasma glucose to drive HbA1c formation. Insulin contribution to power varied greatly depending on the drug target; it was beneficial only if the drug target was insulin secretion. All investigated models showed good simulation properties. However, extrapolation with the mechanistic model beyond 12 weeks resulted in drug effect overprediction. This investigation aids drug development in decisions regarding model choice if reusing published HbA1c models.
Tunable Ultraviolet Photorefractive Effect in LiNbO3/TiO2‐X (X = Pd or N): Theoretically Prediction and Experimental Validation
Authors: Li Ji , Yang Bill
Published: March 2018

In this study, the introduction of unoccupied or partially occupied surface states energy levels into TiO2 upon Pd or N modification, respectively are theoretically predicted, suggesting a tunable carriers behavior in LiNbO3/TiO2‐X (X = Pd or N) composites. Inspired by the theoretical simulation, a new low‐cost method of compositing LiNbO3 with TiO2‐X (X = Pd or N) to mediate the ultraviolet photorefraction of LiNbO3 is proposed. The experimental results indicate that LiNbO3/TiO2 and LiNbO3/TiO2‐Pd show enhanced photorefraction due to reduced recombination of photoinduced carriers or increased free holes in LiNbO3. While LiNbO3/TiO2‐N exhibits photorefraction resistance since the photoinduced holes in LiNbO3 would get trapped by NOX species at the interface. This study will not only provide a simple way to fabricate tailored photorefractive material, but also offer new insights into the mechanism of photorefraction and photorefractive material design method.
Properties of In2S3‐Based pin‐Heterojunctions
Authors: Jawinski Tanja , Wägele Leonard A. , Scheer Roland , Grundmann Marius , von Wenckstern Holger
Published: March 2018

Undoped and vanadium‐doped In2S3 is used to fabricate pin‐diodes. As p‐type semiconductor two materials are compared: nano crystalline NiO and amorphous zinc‐cobalt‐oxid (ZCO). n‐ZnO:Al (AZO) is used as electrode to In2S3. In2S3‐films are grown by co‐evaporation, NiO‐ and ZCO‐films by pulsed laser deposition (PLD) and ZnO:Al‐films by RF sputtering. The diodes exhibit high current rectification of up to 3 and 6 orders of magnitude at ±2 V for diodes with p‐NiO and p‐ZCO, respectively. Diodes with p‐type ZCO are used for solar cell analysis. Upon illumination both solar cell types with undoped and V‐doped In2S3 as absorber material show photovoltaic activity. We find open‐circuit voltages of up to 300 mV and short‐circuit current densities of up to 0.29 mA cm−2.
Herbal medicines in the treatment of psychiatric disorders: 10‐year updated review
Authors: Sarris Jerome
Published: March 2018

This paper provides a 10‐year update of the 2007 systematic review of herbal medicines studied in a broad range of psychiatric disorders, including depression, anxiety, obsessive–compulsive, seasonal affective, bipolar, psychotic, phobic, somatoform, and attention‐deficit hyperactivity disorders. Ovid Medline, PubMed, and the Cochrane Library were searched for herbal medicines with both pharmacological and clinical evidence of psychotropic activity. This updated review now covers clinical trial evidence for 24 herbal medicines in 11 psychiatric disorders. High‐quality evidence was found to exist for the use of Piper methysticum (Kava), Passiflora spp. (passionflower) and Galphimia glauca (galphimia) for anxiety disorders; and Hypericum perforatum (St John's wort) and Crocus sativus (saffron) for major depressive disorder. Other encouraging herbal medicines with preliminary evidence include Curcuma longa (turmeric) in depression, Withania somnifera (ashwagandha) in affective disorders, and Ginkgo biloba (ginkgo) as an adjunctive treatment in Schizophrenia. Although depression and anxiety are commonly researched, many other mental disorders still require further prospective investigation. Although the previous review suggested increasing the adjunctive study of select herbal medicines with pharmaceuticals, this was still only found to sparingly occur in research designs. Aside from this, future focus should involve the incorporation of more biomarker analysis, in particular pharmacogenomics, to determine genetic factors moderating response to herbal medicines.
Toxicological effects of Camellia sinensis (green tea): A review
Authors: Bedrood Zeinab , Rameshrad Maryam , Hosseinzadeh Hossein
Published: March 2018

Many scientific articles proved that green tea (GT), Camellia sinensis, has a great potential to manage central nervous system, cardiovascular, and metabolic diseases and treat cancer and inflammatory disorders. However, it is important to consider that “natural” is not always “safe.” Some relevant articles reported side effects of GT, detrimental effects on health. The aim of this study is to provide a classified report about the toxicity of GT and its main constituents in acute, subacute, subchronic, and chronic states. Furthermore, it discusses on the cytotoxicity, genotoxicity, mutagenicity, carcinogenicity, and developmental toxicity of GT and its main constituents. The most important side effects have been reported hepatotoxicity and gastrointestinal disorders specially while consumed on an empty stomach. GT and its main components are not major teratogen, mutagen, or carcinogen substances. However, there is limited data in using them during pregnancy, and they should be used with caution in pregnancy, breast‐feeding, and susceptible people. Because GT and its main components have a wide variety of drug interactions, consideration should be taken in coadministration of them with narrow therapeutic indexed drugs. Furthermore, they evoke selective cytotoxicity on cancerous cells that could engage them as an adjuvant substance in cancer therapy.