bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural basis of AMPA receptor inhibition by trans‐4‐butylcyclohexane carboxylic acid
Authors: Yelshanskaya Maria V. , Singh Appu K. , Narangoda Chamali , Williams Robin S.B. , Kurnikova Maria G. , Sobolevsky Alexander I.
Published: September 2020

Background and Purpose

AMPA receptors, which shape excitatory postsynaptic currents and are directly involved in overactivation of synaptic function during seizures, represent a well‐accepted target for anti‐epileptic drugs. Trans‐4‐butylcyclohexane carboxylic acid (4‐BCCA) has emerged as a new promising anti‐epileptic drug in several in vitro and in vivo seizure models, but the mechanism of its action remained unknown. The purpose of this study is to characterize structure and dynamics of 4‐BCCA interaction with AMPA receptors.

Experimental Approach

We studied the molecular mechanism of AMPA receptor inhibition by 4‐BCCA using a combination of X‐ray crystallography, mutagenesis, electrophysiological assays, and molecular dynamics simulations.

Key Results

We identified 4‐BCCA binding sites in the transmembrane domain (TMD) of AMPA receptor, at the lateral portals formed by transmembrane segments M1–M4. At this binding site, 4‐BCCA is very dynamic, assumes multiple poses, and can enter the ion channel pore.

Conclusion and Implications

4‐BCCA represents a low‐affinity inhibitor of AMPA receptors that acts at the TMD sites distinct from non‐competitive inhibitors, such as the anti‐epileptic drug perampanel and the ion channel blockers. Further studies might examine the possibsility of synergistic use of these inhibitors in treatment of epilepsy and a wide range of neurological disorders and gliomas.

LINKED ARTICLES

This article is part of a themed issue on Structure Guided Pharmacology of Membrane Proteins (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.14/issuetoc
Structural determinants of TRPV4 inhibition and identification of new antagonists with antiviral activity
Authors: Doñate‐Macian Pablo , Duarte Yorley , Rubio‐Moscardo Fanny , Pérez‐Vilaró Gemma , Canan Jonathan , Díez Juana , González‐Nilo Fernando , Valverde Miguel A.
Published: September 2020

Background and Purpose

The transient receptor potential vanilloid 4 (TRPV4) cation channel participates in multiple physiological processes and is also at the core of different diseases, making this channel an interesting pharmacological target with therapeutic potential. However, little is known about the structural elements governing its inhibition.

Experimental Approach

We have now combined in silico drug discovery and molecular dynamics simulation based on Xenopus tropicalis xTRPV4 structure with functional studies measuring cell Ca2+ influx mediated by human TRPV4 channel to characterize the binding site of known TRPV4 inhibitors and to identify novel small molecule channel modulators.

Key Results

We have found that the inhibitor HC067047 binds to a pocket conformed by residues from S2–S3 linker (xTRPV4‐D542), S4 (xTRPV4‐M583 and Y587 and S5 (xTRPV4‐D609 and F613). This pocket was also used for structure‐based virtual screening in the search of novel channel modulators. Forty potential hits were selected based on the lower docking scores (from ~250,000 compounds) and their effect upon TRPV4 functionally tested. Three were further analysed for stability using molecular dynamics simulation and functionally tested on TRPV4 channels carrying mutations in the binding pocket. Compound NSC151066, shown to require residue xTRPV4‐M583 for its inhibitory effect, presented an IC50 of 145 nM and demonstrated to be an effective antiviral against Zika virus with a potency similar to HC067047.

Conclusion and Implications

Together, we propose structural insights into the inhibition of TRPV4 and how this information can be used for the design of novel channel modulators.

LINKED ARTICLES

This article is part of a themed issue on Structure Guided Pharmacology of Membrane Proteins (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.14/issuetoc
Methnaridine is an orally bioavailable, fast‐killing and long‐acting antimalarial agent that cures Plasmodium infections in mice
Authors: Wang Weisi , Yao Junmin , Chen Zhuo , Sun Yiming , Shi Yuqing , Wei Yufen , Zhou Hejun , Yu Yingfang , Li Shizhu , Duan Liping
Published: September 2020

Background and Purpose

Malaria is one of the deadliest diseases in the world. Novel chemotherapeutic agents are urgently required to combat the widespread Plasmodium resistance to frontline drugs. Here, we report the discovery of a novel benzonaphthyridine antimalarial, methnaridine, which was identified using a structural optimization strategy.

Experimental Approach

An integrated pharmacological approach was used to evaluate the antimalarial profile of methnaridine. The pharmacokinetic properties of methnaridine were investigated along with the associated safety profile. Host immune response patterns were also analysed.

Key Results

Methnaridine exhibited potent antimalarial activity against P. falciparum (3D7: IC50 = 0.0066 μM; Dd2: IC50 = 0.0056 μM). In P. berghei‐infected mice, oral administration effectively suppressed parasitemia (ED50 = 0.52 mg·kg−1·day−1) and cured the established infection (CD50 = 10.13 mg·kg−1·day−1). These results are equivalent to or better than those of other antimalarial agents in clinical use. Notably, a four‐dose oral regimen at a dosage of 25 mg·kg−1 achieved a complete cure of P. berghei infection in mice. Methnaridine exhibited a rapid parasiticidal profile (PCT99 = 36.0 h) and showed no cross‐resistance to chloroquine. Pharmacokinetic studies revealed that methnaridine is readily absorbed, long‐lasting and slowly cleared. The safety profile of methnaridine is also satisfactory (maximum tolerated dose = 1,125 mg·kg−1). In addition, following methnaridine treatment, infection‐induced Th1 immune response was almost fully alleviated in mice.

Conclusion and Implications

Methnaridine is an orally bioavailable, fast‐acting and long‐lasting agent with excellent antimalarial properties. Our study highlights the potential of methnaridine for clinical development as a promising antimalarial candidate.
Nicotine stimulates ion transport via metabotropic β4 subunit containing nicotinic ACh receptors
Authors: Kumar Praveen , Scholze Petra , Fronius Martin , Krasteva‐Christ Gabriela , Hollenhorst Monika I.
Published: September 2020

Background and Purpose

Mucociliary clearance is an innate immune process of the airways, essential for removal of respiratory pathogens. It depends on ciliary beat and ion and fluid homeostasis of the epithelium. We have shown that nicotinic ACh receptors (nAChRs) activate ion transport in mouse tracheal epithelium. Yet the receptor subtypes and signalling pathways involved remained unknown.

Experimental Approach

Transepithelial short circuit currents (ISC) of freshly isolated mouse tracheae were recorded using the Ussing chamber technique. Changes in [Ca2+]i were studied on freshly dissociated mouse tracheal epithelial cells.

Key Results

Apical application of the nAChR agonist nicotine transiently increased ISC. The nicotine effect was abolished by the nAChR antagonist mecamylamine. α‐Bungarotoxin (α7 antagonist) had no effect. The agonists epibatidine (α3β2, α4β2, α4β4 and α3β4) and A‐85380 (α4β2 and α3β4) increased ISC. The antagonists dihydro‐β‐erythroidine (α4β2, α3β2, α4β4 and α3β4), α‐conotoxin MII (α3β2) and α‐conotoxin PnIA (α3β2) reduced the nicotine effect. Nicotine‐ and epibatidine‐induced currents were unaltered in β2−/−mice, but in β4−/− mice no increase was observed. In the presence of thapsigargin (endoplasmatic reticulum Ca2+‐ATPase inhibitor) or the ryanodine receptor antagonists JTV‐519 and dantrolene there was a reduction in the nicotine‐effect, indicating involvement of Ca2+ release from intracellular stores. Additionally, the PKA inhibitor H‐89 and the TMEM16A (Ca2+‐activated chloride channel) inhibitor T16Ainh‐A01 significantly reduced the nicotine‐effect.

Conclusion and Implications

α3β4 nAChRs are responsible for the nicotine‐induced current changes via Ca2+ release from intracellular stores, PKA and ryanodine receptor activation. These nAChRs might be possible targets to stimulate chloride transport via TMEM16A.
Synthesis and activity of novel indirubin derivatives
Authors: Sun Bin , Wang Jiahao , Liu Luohua , Mao Longfei , Peng Lizeng , Wang Yuwei
Published: September 2020

A series of indirubin derivatives hydrochloride were obtained using a convenient and mild method from indirubin. The newly synthesized compounds and their derivatives were characterized by 1H NMR, 13C NMR, and MS. Furthermore, we tested their IDO1 enzyme inhibitory activity and anti‐proliferative activities in K562 tumor cells. The experimental results revealed that some of the compounds showed potential anti‐enzyme and anti‐tumor activity. Among of them, compound 4b exhibited certain inhibitory activity on IDO1 (IC50: 29.52 μmol/L), and compound 4a displayed activity similar to indirubin in K562 tumor cells (IC50: 24.96 μmol/L). This type of indirubin derivative is expected to have the potential to act as an immunologically active anti‐tumor drug, indicating that further research will be worthwhile.
Measuring and decomposing socioeconomic‐related inequality in the use of oral health services among Chinese adults
Authors: Xu Mengru , Gao Xiaoli , Wu Huijing , Ding Min , Zhang Chunzi , Du Shuo , Wang Xing , Feng Xiping , Tai Baojun , Hu Deyu , Lin Huancai , Wang Bo , Wang Chunxiao , Zheng Shuguo , Liu Xuenan , Rong Wensheng , Wang Weijian , Xu Tao , Si Yan
Published: September 2020

Objectives

This study aimed to measure socioeconomic‐related inequality and horizontal inequity in the use of oral health services and decompose this inequality among adults of different age groups in China.

Methods

In total, 10 973 adults (3669 aged 35‐44 years, 3767 aged 55‐64 years and 3537 aged 65‐74 years) who participated in the 4th National Oral Health Survey (2015‐2016) in China were included. Concentration curves and the Erreygers‐corrected concentration index (EI) were employed to measure socioeconomic‐related inequality in the use of oral health services. Then, inequity in this utilization was measured by the horizontal inequity index (HI). Furthermore, decomposition analyses were conducted for the three groups to explain the contributions of income level, need factors (ie self‐assessed oral health and evaluated oral health status), other factors (ie sex, residential location, educational attainment level and type of basic insurance) and a residual term to overall inequality in oral health service utilization.

Results

The significant positive EI and HI values indicated that pro‐rich inequality and inequity in oral health service utilization exist among Chinese adults. Income and type of basic medical insurance contributed the most to socioeconomic‐related inequality in the use of oral health services among adults aged 55‐64 and 65‐74 years. However, the main driving factors of socioeconomic inequality among adults aged 35‐44 years in dental care use included income, educational achievement, type of basic medical insurance and residential location. The need variables accounted for a very small proportion of overall socioeconomic‐related inequality in oral health service use in all three groups.

Conclusions

Oral healthcare service utilization was disproportionately concentrated among better‐off Chinese adults. The primary determinants of inequality in dental care use in different age groups provide information for policymakers to create more targeted policies to achieve equity in the oral healthcare system in China.
Bidirectional association between alopecia areata and atopic dermatitis: A population‐based cohort study in Taiwan
Authors: Wei Yu‐Hsun , Tai Ying‐Hsuan , Dai Ying‐Xiu , Chang Yun‐Ting , Chen Tzeng‐Ji , Chen Mu‐Hong
Published: September 2020

Background

An association between alopecia areata (AA) and atopic dermatitis (AD) has been reported in previous studies. However, the temporality of this relationship remains unclear based on prior cross‐sectional and case‐control studies.

Objective

This study aimed to investigate the bidirectional association between AA and AD.

Methods

Participants were recruited from the National Health Insurance Research Database of Taiwan. In analysis 1, we included 12 022 AA patients and 48 088 matched controls to assess the association between AA and AD risks. In analysis 2, 40 307 AD patients and 161 228 matched controls were included to assess the association between AD and AA risks. A Cox regression model was used to calculate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs).

Results

Compared with controls, AA patients had a significantly increased risk of developing AD (aHR: 5.47; 95% CI: 4.76‐6.28) after adjustment for potential confounders. Likewise, AD patients had a significantly increased risk of developing AA (aHR: 6.00; 95% CI: 5.04‐7.14).

Conclusions

Our study demonstrated a bidirectional association between AA and AD, suggesting that these two diseases may share common pathogenic mechanisms. This finding has implications for follow‐up and screening of AA patients for AD and vice versa.
Relationship between natural and infection-induced antibodies in systemic autoimmune diseases (SAD): SLE, SSc and RA
Authors: Böröcz K , Simon D , Erdő-Bonyár S , Kovács K T , Tuba É , Czirják L , Németh P , Berki T
Published: September 2020

Infection or vaccine-induced T cell-dependent immune response and the subsequent high-affinity neutralizing antibody production have been extensively studied, while the connection between natural autoantibodies (nAAbs) and disease-specific antibodies has not been thoroughly investigated. Our goal was to find the relationship between immunoglobulin (Ig)M and IgG isotype nAAbs and infection or vaccine-induced and disease-related autoantibody levels in systemic autoimmune diseases (SAD). A previously described indirect enzyme-linked immunosorbent assay (ELISA) test was used for detection of IgM/IgG nAAbs against citrate synthase (anti-CS) and F4 fragment (anti-F4) of DNA topoisomerase I in 374 SAD samples, with a special focus on systemic lupus erythematosus (SLE) (n = 92), rheumatoid arthritis (n = 73) and systemic sclerosis (n = 157) disease groups. Anti-measles IgG and anti-dsDNA IgG/IgM autoantibodies were measured using commercial and in-house indirect ELISA tests. In all SAD groups the anti-measles IgG-seropositive cases showed significantly higher anti-CS IgG titers (P = 0·011). In anti-dsDNA IgG-positive SLE patients, we detected significantly higher levels of anti-CS and anti-F4 IgG nAAbs (P = 0·001 and < 0·001, respectively). Additionally, we found increased levels of IgM isotypes of anti-CS and anti-F4 nAAbs in anti-dsDNA IgM-positive SLE patients (P = 0·002 and 0·016, respectively). The association between IgG isotypes of pathogen- or autoimmune disease-related antibodies and the IgG nAAbs may underscore the immune response-inducible nature of the diseases investigated. The relationship between protective anti-dsDNA IgM and the IgM isotype of anti-F4 and anti-CS may provide immunoserological evidence for the beneficial roles of nAAbs in SLE patients.
Changes in mucogingival junction after an apically positioned flap with collagen matrix at sites with or without previous guided bone regeneration: A prospective comparative cohort study
Authors: Ko Kyung‐A , Lee Jung‐Seok , Kim Jang‐Hyun , Park Ji‐Man , Gruber Reinhard , Thoma Daniel S.
Published: September 2020

Aim

To assess changes in the position of the mucogingival junction (MGJ) after an apically positioned flap (APF) with collagen matrix performed at sites with or without previous guided bone regeneration (GBR).

Materials and Methods

Dental implants were placed with or without GBR (group GBR or non‐GBR) depending on the available ridge width in 30 patients with a limited width of keratinized mucosa (MGJ placed more coronally than the expected prosthetic margin). An apically positioned flap with collagen matrix was performed in both groups. Changes in the position of the MGJ from the day of an apically positioned flap up to 1, 3, and 12 months thereafter were assessed on digital scans (primary endpoint). Secondary endpoints were the width and thickness of the keratinized mucosa, and the position of the mucosal margin.

Results

The position of the MGJ changed significantly from baseline to the first month, by 5.25 ± 2.10 and 4.40 ± 1.41 mm in groups GBR and non‐GBR, respectively. Thereafter, the position remained stable in both groups up to 1 year (changes from baseline of 5.46 ± 2.28 and 4.58 ± 1.92 mm, respectively; p = .34). The position of the mucosal margin did not differ between groups GBR and non‐GBR (–1.57 ± 2.04 and –1.75 ± 2.08 mm, respectively; p = .84), nor did the width of the keratinized mucosa (1.20 ± 1.03 and 0.99 ± 0.66 mm, p = .91) or its thickness (1.28 ± 0.44 and 1.40 ± 0.78 mm, p = .87).

Conclusion

Apically positioned flap combined with a collagen matrix results in a more apical position of the MGJ at sites with or without GBR. Following a coronal shift during the first month after the apical positioning of the flap, the level of the MGJ remained stable.
Applying the CRISP‐DM Framework for Teaching Business Analytics
Authors: Jaggia Sanjiv , Kelly Alison , Lertwachara Kevin , Chen Leida
Published: September 2020

Experiential learning opportunities have been proven effective in teaching applied and complex subjects such as business analytics. Current business analytics pedagogy tends to focus heavily on the modeling phase with students often lacking a comprehensive understanding of the entire analytics process including dealing with real‐life data that are not necessarily "clean" and/or small. Similarly, the emphasis on analytical rigor often comes at the expense of storytelling, which is among the most important aspects of business analytics. In this article, we demonstrate how the philosophy of the Cross Industry Standard Process for Data Mining (CRISP‐DM) framework can be infused into the teaching of business analytics through a term‐long project that simulates the real‐world analytics process. The project focuses on problem formulation, data wrangling, modeling, performance evaluation, and storytelling, using real data and the programming language R for illustration. We also discuss the pedagogical theories and techniques involved in the application of the CRISP‐DM framework. Finally, we document how the CRISP‐DM framework has proved to be effective in helping students navigate through complex analytics issues by offering a structured approach to solving real‐world problems.
Endoscopic endoclip papilloplasty preserves sphincter of oddi function
Authors: Wang Yingchun , Chang Hong , Zhang Yaopeng , Wang Kun , Zhang Hejun , Yan Xiue , Meng Lingyu , Yao Wei , Li Ke , Huang Yonghui
Published: September 2020

Background

Endoscopic sphincterotomy (EST) can destroy sphincter of Oddi (SO) structure and function. The purpose of this study was to assess the feasibility of endoscopic endoclip papilloplasty (EEPP) in restoring SO function after EST.

Methods

Seven 26‐week‐old domestic pigs were divided into control and EEPP groups. Necropsy and haematoxylin‐eosin staining plus anti‐α‐smooth muscle actin (α‐SMA) staining of papilla and sphincter of Oddi manometry (SOM) were conducted in animals at three independent time points.

Results

EST and EEPP were safely performed in all 7 pigs without serious adverse events. For primary outcome, compared to the controls, EEPP generated smaller dilation and less inflammation. Fibrous repair of the papilla was observed at 24 weeks after EEPP. For secondary outcome, in the control group, SO basal pressure (17.25 ± 18.14 to 5.50 ± 0.71 mmHg), SO contraction amplitude (46.00 ± 19.20 to 34.50 ± 48.79 mmHg), peak (4.50 ± 4.04 to 1.50 ± 2.12) and frequency (3.05 ± 3.29 to 1.41 ± 2.19/min) were reduced after EST. Further reductions to almost 0 of these SOM parameters were observed 3 weeks later, including common bile duct pressure and SO contraction period. In contrast, in the EEPP group, these manometric data were recovered to pre‐EST levels, including CBD pressure (11.5 ± 7.31 vs 11 ± 2.16 mmHg), SO pressure (17.50 ± 17.75 vs 18.20 ± 21.39 mmHg) and SO contraction amplitude (53.67 ± 21.54 vs 60.00 ± 36.08 mmHg). However, no significant differences were observed between control and EEPP groups by Student t test.

Conclusions

In this porcine study, EEPP accelerated and improved papillary healing after EST, further preserved SO function.
INVESTMENT CHOICE ARCHITECTURE IN TRUST GAMES: WHEN “ALL‐IN” IS NOT ENOUGH
Authors: Gómez‐Miñambres Joaquín , Schniter Eric , Shields Timothy W.
Published: September 2020

While many economic interactions feature “All‐or‐Nothing” options nudging investors towards going “all‐in,” such designs may unintentionally affect reciprocity. We manipulate the investor's action space in two versions of the “trust game.” In one version investors can invest either “all” their endowment or “nothing.” In the other version, they can invest any amount of the endowment. Consistent with our intentions‐based model, we show that “all‐or‐nothing” designs coax more investment but limit investors' demonstrability of intended trust. As a result, “all‐in” investors are less generously reciprocated than when they can invest any amount, where full investments are a clearer signal of trustworthiness.(JELC72, C90, C91, D63, D64, L51)
A walk in the park? Characterizing gait‐related artifacts in mobile EEG recordings
Authors: Jacobsen Nadine Svenja Josée , Blum Sarah , Witt Karsten , Debener Stefan
Published: September 2020

Brain activity during natural walking outdoors can be captured using mobile electroencephalography (EEG). However, EEG recorded during gait is confounded with artifacts from various sources, possibly obstructing the interpretation of brain activity patterns. Currently, there is no consensus on how the amount of artifact present in these recordings should be quantified, or is there a systematic description of gait artifact properties. In the current study, we expand several features into a seven‐dimensional footprint of gait‐related artifacts, combining features of time, time‐frequency, spatial, and source domains. EEG ofN = 26 participants was recorded while standing and walking outdoors. Footprints of gait‐related artifacts before and after two different artifact attenuation strategies (after artifact subspace reconstruction (ASR) and after subsequent independent component analysis [ICA]) were systematically different. We also evaluated topographies, morphologies, and signal‐to‐noise ratios (SNR) of button‐press event‐related potentials (ERP) before and after artifact handling, to confirm gait‐artifact reduction specificity. Morphologies and SNR remained unchanged after artifact attenuation, whereas topographies improved in quality. Our results show that the footprint can provide a detailed assessment of gait‐related artifacts and can be used to estimate the sensitivity of different artifact reduction strategies. Moreover, the analysis of button‐press ERPs demonstrated its specificity, as processing did not only reduce gait‐related artifacts but ERPs of interest remained largely unchanged. We conclude that the proposed footprint is well suited to characterize individual differences in gait‐related artifact extent. In the future, it could be used to compare and optimize recording setups and processing pipelines comprehensively.
The burden of decisional uncertainty in the treatment of status epilepticus
Authors: Sánchez Fernández Iván , Gaínza‐Lein Marina , Barcia Aguilar Cristina , Amengual‐Gual Marta , Loddenkemper Tobias
Published: September 2020

Objective

Treatments for convulsive status epilepticus (SE) have a wide range of effectiveness. The estimated effectiveness of non‐intravenous benzodiazepines (non‐IV BZDs) ranges from approximately 70% to 90% and the estimated effectiveness of non‐benzodiazepine antiseizure medications (non‐BZD ASMs) ranges from approximately 50% to 80%. This study aimed to quantify the clinical and economic burden of decisional uncertainty in the treatment of SE.

Methods

We performed a decision analysis that evaluates how decisional uncertainty on treatment choices for SE impacts hospital admissions, intensive care unit (ICU) admissions, and costs in the United States. We evaluated treatment effectiveness based on the available literature.

Results

Use of a non‐IV BZD with high estimated effectiveness, like intranasal midazolam, rather than one with low estimated effectiveness, like rectal diazepam, would result in a median (p25‐p75) reduction in hospital admissions from 6 (3.9‐8.8) to 1.1 (0.7‐1.8) per 100 cases and associated cost reductions of $638 ($289‐$1064) per pediatric patient and $1107 ($972‐$1281) per adult patient. For BZD‐resistant SE, use of a non‐BZD ASM with high estimated effectiveness, like phenobarbital, rather than one with low estimated effectiveness, like phenytoin/fosphenytoin, would result in a reduction in ICU admissions from 9.1 (7.3‐11.2) to 3.9 (2.6‐5.5) per 100 cases and associated cost reduction of $1261 ($445‐$2223) per pediatric patient and $319 ($‐93‐$806) per adult patient. Sensitivity analyses showed that relatively minor improvements in effectiveness may lead to substantial reductions in downstream hospital admissions, ICU admissions, and costs.

Significance

Decreasing decisional uncertainty and using the most effective treatments for SE may substantially decrease hospital admissions, ICU admissions, and costs.
Experimental and computational study on thermo‐mechanical fatigue life of aluminium alloy piston
Authors: Li Ziliang , Li Jianxing , Chen Zhengke , Guo Jinbao , Zhu Ye , Luo Yu
Published: September 2020

To assess the life of a new diesel aluminium alloy piston under thermal shock loads, thermo‐mechanical fatigue (TMF) testing was conducted to characterise the TMF properties of the piston alloy, and an empirical model based on the constraint ratio concept was proposed to predict the TMF life of the piston. Considering that the empirical model required expensive experimental support, a platform with high‐frequency induction heating was established to simulate the force on the piston under thermal shock loads to calculate the piston life using the thermal shock test. Additionally, a finite element method was developed to compute the distributions of temperature, strain, and stress during this process. The characteristics of crack initiation and propagation in TMF test rods and piston mock‐ups were also investigated. The results showed that the TMF test rod suffered brittle fracture with brittle quasi‐cleavage features. The microcracks mainly occurred in primary Si particles due to stress concentration around the primary Si particles induced by the difference between the thermal expansion coefficients of Si and Al. From a macro perspective, the piston initially cracked at the rim above the pinhole, where the stress is larger than that along other directions. From a micro perspective, the protrusions of various sizes on the piston rim were induced by the compression stresses at high temperature. The piston cracks usually initiate around primary Si particles, propagate along the edge of primary Si in a straight line, bifurcate and then stop at a certain depth. If the piston was only heated, cracks or plastic deformations were not produced. The piston life can be assessed using the proposed empirical model based on the constraint ratio concept or thermal shock testing based on the developed platform. The difference between the predicted and experimental life was not greater than 7%.
Identifying invasive fish species threats to RAMSAR wetland sites in the Caspian Sea region—A case study of the Anzali Wetland Complex (Iran)
Authors: Moghaddas Seyed Daryoush , Abdoli Asghar , Kiabi Bahram H. , Rahmani Hossein , Vilizzi Lorenzo , Copp Gordon H.
Published: September 2020

Risk screening tools play a crucial role in identifying potential high‐risk non‐native (NN) fish species. In this study, potentially invasive NN fish species in the Anzali Wetland Complex (AWC), which is located on the south coast of the Caspian Sea (Iran), were identified using the Aquatic Species Invasiveness Screening Kit (AS‐ISK). Twenty‐nine freshwater fish species were screened of which 13 exist in the AWC and 16 in close proximity to it (“horizon” species). Receiver operating characteristic curve analysis showed that AS‐ISK could discriminate reliably between non‐invasive and invasive fish species for the AWC. Mean threshold scores were 3.25 for the Basic Risk Assessment (BRA) and 11.75 for the BRA + CCA (BRA + Climate Change Assessment), and these, respectively, classified 89.7% and 86.2% of the species as high risk. The CCA resulted in an increase in the BRA scores for 86.2% of the species, suggesting the need to account in future NN species management for a likely increased invasiveness of those species under future climate conditions. These results suggest that AS‐ISK could prove an effective tool for identifying potentially invasive NN freshwater fishes in other wetlands of the Caspian Sea basin.
Development of cordierite/mullite composites using industrial wastes
Authors: de Brito Igor Pinheiro , de Almeida Ester Pires , de Araújo Neves Gelmires , de Lucena Lira Hélio , Menezes Romualdo Rodrigues , da Silva Valmir José , de Lima Santana Lisiane Navarro
Published: September 2020

Ceramics containing cordierite and mullite as their principal phases are promising for many applications, due to properties such as a low coefficient of thermal expansion, high durability, low dielectric constant, resistance to thermal shock, and refractoriness. The objective of this study was to produce ceramic composites suitable for use as refractory materials. The raw materials were subjected to chemical characterization and the formulations to physical, chemical, and mineralogical characterization. The specimens were formed by pressing, dried at 110°C, and sintered from 1150°C to 1300°C for 2 hours. The following properties were then determined: linear shrinkage, water absorption, apparent porosity, and flexural modulus of rupture. The phases formed, crystal morphology, and coefficient of thermal expansion were evaluated. The cordierite and mullite phases were observed in all formulations at 1250°C and 1300°C. The results obtained from the formulations with a higher content of fine kaolin residue suggest that these formulations have the potential to be used for the manufacture of refractory materials such as furnace rollers and supports.
Study on the effect of Ti, Al, Cu, and Ag doping on the bonding properties of soldered β‐Sn(100)/ZrO2(111) interface
Authors: Guo Weibing , She Zongyu , Xue Haitao , Zhang Xiaoming
Published: September 2020

Selecting active elements for filler metal is very important in soldering of ZrO2 ceramics. In this paper, the effects of Ti, Al, Cu, and Ag active elements on the bonding strength and electronic structures of soldered β‐Sn(100)/ZrO2(111) interface were studied via the method of first principle calculation. The work of adhesion (Wad) results show that the O2‐terminated interface is more stable than other kinds of interfaces. Then, the atoms of Ti, Al, Cu, and Ag were doped into the interface by replacing the Sn atom in situ. It is found that additions of Ti, Al, and Cu atoms can increase the Wad, and Ag atom has the opposite effect. From the results of heat of segregation, doping Ti and Al into the interface is stable in thermodynamics and doping Cu and Ag is not stable. The forming of strong ionic‐covalent Ti‐O and Al‐O bonding contributes to the increase of the interfacial adhesion strength. The calculation results indicate that Ti and Al can act as active elements in Sn to solder ZrO2. The Ti‐O and Al‐O compounds formed at interface can improve the wetting and bonding between Sn‐based solder and ZrO2 ceramics.
Strategies to reduce attrition in managing paediatric obesity: A systematic review
Authors: Ball Geoff D. C. , Sebastianski Meghan , Wijesundera Jessica , Keto‐Lambert Diana , Ho Josephine , Zenlea Ian , Perez Arnaldo , Nobles James , Skelton Joseph A.
Published: September 2020

Objective

To conduct a systematic review of the literature for strategies designed to reduce attrition in managing paediatric obesity.

Methods

We searched Ovid Medline (1946 to May 6, 2020), Ovid Embase (1974 to May 6, 2020), EBSCO CINAHL (inception to May 6, 2020), Elsevier Scopus (inception to April 14, 2020), and ProQuest Dissertations & Theses (inception to April 14, 2020). Reports were eligible if they included any obesity management intervention, included 2 to 18 year olds with overweight or obesity (or if the mean age of participants fell within this age range), were in English, included experimental study designs, and had attrition reduction as a main outcome. Two team members screened studies, abstracted data, and appraised study quality.

Results

Our search yielded 5,415 original reports; six met inclusion criteria. In three studies, orientation sessions (n = 2) and motivational interviewing (MI) (n = 1) were used as attrition‐reduction strategies before treatment enrollment; in three others, text messaging (n = 2) and MI (n = 1) supplemented existing obesity management interventions. Attrition‐reduction strategies led to decreased attrition in two studies, increased in one, and no difference in three. For the two strategies that reduced attrition, (a) pre‐treatment orientation and (b) text messaging between children and intervention providers were beneficial. The quality of the six included studies varied (good [n = 4]; poor [n = 2]).

Conclusion

Some evidence suggests that attrition can be reduced. The heterogeneity of approaches applied and small number of studies included highlight the need for well‐designed, experimental research to test the efficacy and effectiveness of strategies to reduce attrition in managing paediatric obesity.
The Presuicidal Syndrome
Authors: Ringel Erwin
Published: September 2020

ABSTRACT: The Presuicidal Syndrome, first described in 1958, relates to that specific psychic state of mind that leads to suicidal acts. It is an alarm signal indicating a tendency to suicide. The Presuicidal Syndrome has three principal components: constriction; inhibited aggression turned toward the self; and suicidal fantasies. The clinical details of these components are explicated. It is proposed that the Presuicidal Syndrome provides a basis for better judgment of the danger of suicide, makes more focused suicide prevention possible, and is an aid in the disclosure of those factors in society that often lead to suicide.
Effect of initial density on thermal conductivity of new micro‐pipeline heat conduction C/SiC composites
Authors: Zhang Yunhai , Liu Yongsheng , Cao Yejie , Cao Liyang , Wang Jing , Pan Yu , Wang Ning
Published: September 2020

C/SiC composites prepared by chemical vapor infiltration technique (CVI) have been regarded as thermal structural materials widely. However, these composites still suffer from poor functional properties like low thermal conductivity, especially in thickness direction of the composites, limiting their large‐scale applications. Herein, mesophase pitch based carbon fiber (MPCF) and continuous wave laser machining were utilized to construct highly effective heat conductive micro‐pipelines within CVI C/SiC composite. The effect of initial density on the final density and thermal conductivity of the as‐obtained MPCF‐C/SiC composites were investigated. The results revealed that higher initial density would directly enhance the thermal conductivity and reduce the negative impact of the bottle‐neck effect. At temperatures between 100°C and 500°C, MPCF‐C/SiC composites preserved more than threefold of the thermal conductivity (340%) when compared to reference C/SiC composites. This work provides a highly effective route for enhancing the thermal conductivity of C/SiC, which would broaden their future applications.
Constitutive model and failure criterion for orthotropic ceramic matrix composites under macroscopic plane stress
Authors: Yang Chengpeng , Jia Fei , Wang Bo , Huang Tao , Jiao Guiqiong
Published: September 2020

To predict the nonlinear stress‐strain behavior and the rupture strength of orthotropic ceramic matrix composites (CMCs) under macroscopic plane stress, a concise damage‐based mechanical theory including a new constitutive model and two kinds of failure criteria was developed in the framework of continuum damage mechanics (CDM). The damage constitutive model was established using strain partitioning and damage decoupling methods. Meanwhile, the failure criteria were formulated in terms of damage energy release rate (DERR) in order to correlate the failure property of CMCs with damage driving forces, and the maximum DERR criterion and the interactive DERR criterion were suggested simultaneously. For the sake of model evaluation, the theory was applied to a typical CMC with damageable and nonlinear behavior, that is, 2D‐C/SiC. The damage evolution law, strain response and rupture strength under incremental cyclic tension along both on‐axis and off‐axis directions were completely investigated. Comparison between theoretical predictions and experimental data illustrates that the newly developed mechanical theory is potential to give reasonable and accurate results of both stress‐strain response and failure property for orthotropic CMCs.
Robot‐mediated therapy to reduce worrying in persons with visual and intellectual disabilities
Authors: van Wingerden Evelien , Barakova Emilia , Lourens Tino , Sterkenburg Paula S.
Published: September 2020

Background

The study explored the use of a robot‐mediated therapeutic intervention in persons with visual and intellectual disabilities.

Method

Three robot‐mediated intervention sessions were developed to teach three coping skills for worrying. Effectiveness was examined using a multiple‐baseline case study design (N = 7). Baseline, pre‐intervention and post‐intervention assessments included social validity, severity of worrying (PSWQ‐C‐NL), and observations by caregivers (SDQ). Short checklists on worrying were repeated throughout baseline and intervention stages. Transcripts of the sessions were analysed for participants’ emotional openness.

Results

Social validity was equally high before and after the intervention. The intervention did not impact the severity of worrying, although mentor caregivers reported a lower impact of personal difficulties for participants. We found no change in self‐disclosure towards the robot over sessions.

Conclusions

The participants’ positive responses warrant further exploration of using robot‐mediated therapy for persons with visual and intellectual disabilities. Recommendations for additional adaptations are discussed.
Do gender differences in academic attainment correspond with scholastic attitudes? An exploratory study in a UK secondary school
Authors: Pennington Charlotte R. , Kaye Linda K. , Qureshi Adam W. , Heim Derek
Published: September 2020

Research has examined how standardized tests give rise to gender differences in English and STEM attainment, but little research has explored gender differences in classroom‐based attainment and the degree to which these correspond to differences in school‐related attitudes. To explore the extent to which gender‐achievement gaps in classroom‐based performance parallel differences in self‐perceptions and scholastic attitudes. An independent sample of first (n = 187, age 11–12, Study 1) and second‐year students (n = 113, age 12–13, Study 2) from a UK comprehensive secondary school completed a questionnaire measuring academic mindset, self‐efficacy, self‐concept, competence beliefs, personal and social self‐esteem, and endorsement of gender‐subject and career stereotypes. Responses were then matched to their respective classroom grades in English, mathematics, science, and computing. Girls outperformed boys in English in their first year but reported lower global self‐esteem and greater endorsement of science‐career stereotypes. Conversely, girls outperformed boys in mathematics in their second year, but paradoxically reported lower self‐concept and competence beliefs in mathematics and science, and higher competence beliefs in English. Across both studies, mindset, self‐efficacy, competence beliefs, and social self‐esteem were positively related to English attainment; academic self‐efficacy was positively related to mathematics attainment; and mindset, self‐efficacy, self‐concept, and competence beliefs were positively related to science attainment. Gender‐achievement gaps in classroom‐based academic attainment are complex and highly nuanced; they appear to vary between school subjects across years and may not correspond with similar differences in self‐perceptions and scholastic attitudes.
Artificial liver support systems
Authors: Tandon Radhika , Froghi Saied
Published: September 2020

Artificial liver systems are used to bridge between transplantation or to allow a patient's liver to recover. They are used in patients with acute liver failure (ALF) and acute‐on‐chronic liver failure. There are five artificial systems currently in use: molecular adsorbent recirculating system (MARS), single‐pass albumin dialysis (SPAD), Prometheus, selective plasma filtration therapy, and hemodiafiltration. The aim is to compare existing data on the efficiency of these devices. A literature search was conducted using online libraries. Inclusion criteria included randomized control trials or comparative human studies published after the year 2000. A systematic review was conducted for the five individual devices with a more detailed comparison of the biochemistry for the SPAD and MARS systems. Eighty‐nine patients were involved in the review comparing SPAD and MARS. Results showed that there was an average reduction in bilirubin (−53 μmol/L in MARS and −50 μmol/L in SPAD), creatinine (−19.5 μmol/L in MARS and −7.5 μmol/L in SPAD), urea (−0.9 mmol/L in MARS and −0.75 mmol/L in SPAD), and gamma‐glutamyl transferase (−0.215 μmol/L·s in MARS and −0.295 μmol/L·s in SPAD) in both SPAD and MARS. However, there was no significant difference between the changes in the two systems. This review demonstrated that both MARS and SPAD aid recovery of ALF. There is no difference between the efficiency of MARS and SPAD. Because of the limited data, there is a need for more randomized control trials. Evaluating cost and patient preference would aid in differentiating the systems.
Home‐Based Primary and Palliative Care in the Medicaid Program: Systematic Review of the Literature
Authors: Zimbroff Robert M. , Ritchie Christine S. , Leff Bruce , Sheehan Orla C.
Published: September 2020

BACKGROUND/OBJECTIVES

To describe the use of home‐based medical care (HBMC) among Medicaid beneficiaries.

DESIGN

A systematic review of the peer‐reviewed and gray literature of home‐based primary care and palliative care programs among Medicaid beneficiaries including dual eligibles.

SETTING

HBMC including home‐based primary care and palliative care programs.

PARTICIPANTS

Studies describing Medicaid beneficiaries receiving HBMC.

MEASUREMENTS

Three groups of studies were included: those focused on HBMC specifically for Medicaid beneficiaries, studies that described the proportion of Medicaid patients receiving HBMC, and those that used Medicaid status as a dependent variable in studying HBMC.

RESULTS

The peer‐reviewed and gray literature searches revealed 574 unique studies of which only 16 met inclusion criteria. Few publications described HBMC as an integral care delivery model for Medicaid programs. Data from the programs described suggest the use of HBMC for Medicaid beneficiaries can reduce healthcare costs. The addition of social supports to HBMC appears to convey additional savings and benefits.

CONCLUSION

This systematic literature review highlights the relative dearth of literature regarding the use and impact of HBMC in the Medicaid population. HBMC has great potential to reduce Medicaid costs, and innovative programs combining HBMC with social support systems need to be tested.
Self‐Reported Cultural Competence of Nurses Providing Nursing Care in Slovakia
Authors: Červený Martin , Dimunová Lucia , Della Pelle Carlo , Papp Katalin , Siaki LTC Leilani A. , Kilíková Mária , Nagórska Małgorzata
Published: September 2020

Purpose

The goals of this study were to determine and evaluate the perception of cultural competence of nurses in the Slovak healthcare system, identify factors that influence their perception, and ascertain opportunities to improve nurses’ cultural competence.

Design

Cross‐sectional nonexperimental study.

Methods

Nurses from Slovakia were surveyed in this cross‐sectional study using the standardized Cultural Competency Assessment (CCA) questionnaire. Statistical analysis was conducted using SPSS version 22 (IBM Corp., Armonk, NY, USA).

Results

In total, 267 nurses responded. Only 28% perceived themselves as very culturally competent to care for people from other cultures. Over 68% received no diversity training. Age (p < .011) and prior diversity training (p < .006) were significantly associated with culturally competent behavior (CCB). A significant relationship (r = 0.17; p < .015) was also confirmed between the self‐reported CCA and CCB.

Conclusions

Culturally competent care is a professional imperative. The ability to deliver high‐quality, culturally congruent care may be enhanced by cultural diversity education and training. Further research is needed to identify other influences on cultural competency and the impact on patient care and outcomes.

Clinical Relevance

There is a need for nurses to enhance their knowledge and skills related to cultural competency, awareness, sensitivity, and behaviors. Education and training contribute to nurses’ ability to provide high‐quality, culturally competent nursing care to patients from different cultures, and may possibly contribute to decreased health disparities.
Clinical characteristics and predictors of the duration of SARS‐CoV‐2 viral shedding in 140 healthcare workers
Authors: Liu W. , Liu Y. , Xu Z. , Jiang T. , Kang Y. , Zhu G. , Chen Z.
Published: September 2020

Background

Epidemiological and clinical features of patients with COVID‐19 have been reported, but none of them focused on medical staff, and few predictors of the duration of viral shedding have been reported. It is urgent to help healthcare workers prevent and recover quickly from the coronavirus disease 2019 (COVID‐19).

Methods

We enrolled 140 medical workers with COVID‐19 in Wuhan. Epidemiological, demographic, clinical, laboratory, radiological treatment and clinical outcome data were collected, and predictors of the duration of viral shedding were explored through multivariable linear regression analysis.

Results

The medical staff with COVID‐19 presented mild clinical symptoms and showed a low frequency of abnormal laboratory indicators. All the medical staff were cured and discharged, of whom 96 (68.6%) were female, 39 (27.9%) had underlying diseases, the median age was 36.0 years, and 104 (74.3%) were infected whilst working in hospital. The median duration of viral shedding was 25.0 days (IQR:20.0–30.0). Multivariable linear regression analysis showed reducing viral shedding duration was associated with receiving recombinant human interferon alpha (rIFN‐α) treatment, whilst the prolonged duration of viral shedding correlated with the use of glucocorticoid treatment, the durations from the first symptom to hospital admission and the improvement in chest computed tomography (CT) evidence. Moreover, infected healthcare workers with lymphocytes less than 1.1 × 109/L on admission had prolonged viral shedding.

Conclusion

Medical staff with timely medical interventions show milder clinical features. Glucocorticoid treatment and lymphocytes less than 1.1 × 109/L are associated with prolonged viral shedding. Early admission and rIFN‐α treatment help shorten the duration of viral shedding.