bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensitive and broadly applicable residual disease detection in acute myeloid leukemia using flow cytometry‐based leukemic cell enrichment followed by mutational profiling
Authors: Daga Shruti , Rosenberger Angelika , Kashofer Karl , Heitzer Ellen , Quehenberger Franz , Halbwedl Iris , Graf Ricarda , Krisper Nina , Prietl Barbara , Höfler Gerald , Reinisch Andreas , Zebisch Armin , Sill Heinz , Wölfler Albert
Published: June 2020

Persistent measurable residual disease (MRD) is an increasingly important prognostic marker in acute myeloid leukemia (AML). Currently, MRD is determined by multi‐parameter flow cytometry (MFC) or PCR‐based methods detecting leukemia‐specific fusion transcripts and mutations. However, while MFC is highly operator‐dependent and difficult to standardize, PCR‐based methods are only available for a minority of AML patients. Here we describe a novel, highly sensitive and broadly applicable method for MRD detection by combining MFC‐based leukemic cell enrichment using an optimized combinatorial antibody panel targeting CLL‐1, TIM‐3, CD123 and CD117, followed by mutational analysis of recurrently mutated genes in AML. In dilution experiments this method showed a sensitivity of 10−4 to 10−5 for residual disease detection. In prospectively collected remission samples this marker combination allowed for a median 67‐fold cell enrichment with sufficient DNA quality for mutational analysis using next generation sequencing (NGS) or digital PCR in 39 out of 41 patients. Twenty‐one samples (53.8%) tested MRD positive, whereas 18 (46.2%) were negative. With a median follow‐up of 559 days, 71.4% of MRD positive (15/21) and 27.8% (5/18) of MRD negative patients relapsed (P = .007). The cumulative incidence of relapse (CIR) was higher for MRD positive patients (5‐year CIR: 90.5% vs 28%, P < .001). In multivariate analysis, MRD positivity was a prominent factor for CIR. Thus, MFC‐based leukemic cell enrichment using antibodies against CLL‐1, TIM‐3, CD123 and CD117 followed by mutational analysis allows high sensitive MRD detection and is informative on relapse risk in the majority of AML patients.
Cryogenic OrbiSIMS Localizes Semi‐Volatile Molecules in Biological Tissues
Authors: Newell Clare L. , Vorng Jean‐Luc , MacRae James I. , Gilmore Ian S. , Gould Alex P.
Published: June 2020

OrbiSIMS is a recently developed instrument for label‐free imaging of chemicals with micron spatial resolution and high mass resolution. We report a cryogenic workflow for OrbiSIMS (Cryo‐OrbiSIMS) that improves chemical detection of lipids and other biomolecules in tissues. Cryo‐OrbiSIMS boosts ionization yield and decreases ion‐beam induced fragmentation, greatly improving the detection of biomolecules such as triacylglycerides. It also increases chemical coverage to include molecules with intermediate or high vapor pressures, such as free fatty acids and semi‐volatile organic compounds (SVOCs). We find that Cryo‐OrbiSIMS reveals the hitherto unknown localization patterns of SVOCs with high spatial and chemical resolution in diverse plant, animal, and human tissues. We also show that Cryo‐OrbiSIMS can be combined with genetic analysis to identify enzymes regulating SVOC metabolism. Cryo‐OrbiSIMS is applicable to high resolution imaging of a wide variety of non‐volatile and semi‐volatile molecules across many areas of biomedicine.
A Yolk–Shell‐Structured FePO4 Cathode for High‐Rate and Long‐Cycling Sodium‐Ion Batteries
Authors: Zhang Zhuangzhuang , Du Yichen , Wang Qin‐Chao , Xu Jingyi , Zhou Yong‐Ning , Bao Jianchun , Shen Jian , Zhou Xiaosi
Published: June 2020

Amorphous iron phosphate (FePO4) has attracted enormous attention as a promising cathode material for sodium‐ion batteries (SIBs) because of its high theoretical specific capacity and superior electrochemical reversibility. Nevertheless, the low rate performance and rapid capacity decline seriously hamper its implementation in SIBs. Herein, we demonstrate a sagacious multi‐step templating approach to skillfully craft amorphous FePO4 yolk–shell nanospheres with mesoporous nanoyolks supported inside the robust porous outer nanoshells. Their unique architecture and large surface area enable these amorphous FePO4 yolk–shell nanospheres to manifest remarkable sodium storage properties with high reversible capacity, outstanding rate performance, and ultralong cycle life.
Lasso Proteins: Modular Design, Cellular Synthesis, and Topological Transformation
Authors: Liu Yajie , Wu Wen‐Hao , Hong Sumin , Fang Jing , Zhang Fan , Liu Geng‐Xin , Seo Jongcheol , Zhang Wen‐Bin
Published: June 2020

Entangled proteins have attracted significant research interest. Herein, we report the first rationally designed lasso proteins, or protein [1]rotaxanes, by using a p53dim‐entwined dimer for intramolecular entanglement and a SpyTag‐SpyCatcher reaction for side‐chain ring closure. The lasso structures were confirmed by proteolytic digestion, mutation, NMR spectrometry, and controlled ligation. Their dynamic properties were probed by experiments such as end‐capping, proteolytic digestion, and heating/cooling. As a versatile topological intermediate, a lasso protein could be converted to a rotaxane, a heterocatenane, and a “slide‐ring” network. Being entirely genetically encoded, this robust and modular lasso‐protein motif is a valuable addition to the topological protein repertoire and a promising candidate for protein‐based biomaterials.
Rheumatoid Arthritis Pathogenesis, Prediction, and Prevention: An Emerging Paradigm Shift
Authors: Deane Kevin D. , Holers V. Michael
Published: June 2020

Rheumatoid arthritis (RA) is currently diagnosed and treated when an individual presents with signs and symptoms of inflammatory arthritis (IA) as well as other features, such as autoantibodies and/or imaging findings, that provide sufficient confidence that the individual has RA‐like IA (e.g., meeting established classification criteria) that warrants therapeutic intervention. However, it is now known that there is a stage of seropositive RA during which circulating biomarkers and other factors (e.g., joint symptoms) can be used to predict if and when an individual who does not currently have IA may develop future clinically apparent IA and classifiable RA. Indeed, the discovery of the “pre‐RA” stage of seropositive disease has led to the development of several clinical trials in which individuals are studied to identify ways to delay or prevent the onset of clinically apparent IA/RA. This review focuses on several issues pertinent to understanding the prevention of RA. These include discussion of the pathogenesis of pre‐RA development, prediction of the likelihood and timing of future classifiable RA, and a review of completed and ongoing clinical trials in RA prevention. Furthermore, this review discusses challenges and opportunities to be addressed to effect a paradigm shift in RA, where in the near future, proactive risk assessment focused on prevention of RA will become a public health strategy in much the same manner as cardiovascular disease is managed today.
Bioactive Plasma Mitochondrial DNA Is Associated With Disease Progression in Scleroderma‐Associated Interstitial Lung Disease
Authors: Ryu Changwan , Walia Anjali , Ortiz Vivian , Perry Carrighan , Woo Sam , Reeves Benjamin C. , Sun Huanxing , Winkler Julia , Kanyo Jean E. , Wang Weiwei , Vukmirovic Milica , Ristic Nicholas , Stratton Eric A. , Meena Sita Ram , Minasyan Maksym , Kurbanov Daniel , Liu Xinran , Lam TuKiet T. , Farina Giuseppina , Gomez Jose L. , Gulati Mridu , Herzog Erica L.
Published: June 2020

Objective

Systemic sclerosis–associated interstitial lung disease (SSc‐ILD) is characterized by variable clinical outcomes, activation of innate immune pattern‐recognition receptors (PRRs), and accumulation of α‐smooth muscle actin (α‐SMA)–expressing myofibroblasts. The aim of this study was to identify an association between these entities and mitochondrial DNA (mtDNA), an endogenous ligand for the intracellular DNA–sensing PRRs Toll‐like receptor 9 (TLR‐9) and cyclic GMP‐AMP synthase/stimulator of interferon genes (cGAS/STING), which has yet to be determined.

Methods

Human lung fibroblasts (HLFs) from normal donors and SSc‐ILD explants were treated with synthetic CpG DNA and assayed for α‐SMA expression and extracellular mtDNA using quantitative polymerase chain reaction for the human MT‐ATP6 gene. Plasma MT‐ATP6 concentrations were evaluated in 2 independent SSc‐ILD cohorts and demographically matched controls. The ability of SSc‐ILD and control plasma to induce TLR‐9 and cGAS/STING activation was evaluated with commercially available HEK 293 reporter cells. Plasma concentrations of type I interferons (IFNs), interleukin‐6 (IL‐6), and oxidized DNA were measured using electrochemiluminescence and enzyme‐linked immunosorbent assay–based methods. Extracellular vesicles (EVs) precipitated from plasma were evaluated for MT‐ATP6 concentrations and proteomics via liquid chromatography mass spectrometry.

Results

Normal HLFs and SSc‐ILD fibroblasts developed increased α‐SMA expression and MT‐ATP6 release following CpG stimulation. Plasma mtDNA concentrations were increased in the 2 SSc‐ILD cohorts, reflective of ventilatory decline, and were positively associated with both TLR‐9 and cGAS/STING activation as well as type I IFN and IL‐6 expression. Plasma mtDNA was not oxidized and was conveyed by EVs displaying a proteomics profile consistent with a multicellular origin.

Conclusion

These findings demonstrate a previously unrecognized connection between EV‐encapsulated mtDNA, clinical outcomes, and intracellular DNA–sensing PRR activation in SSc‐ILD. Further study of these interactions could catalyze novel mechanistic and therapeutic insights into SSc‐ILD and related disorders.
Chemiluminescence assay for Listeria monocytogenes based on Cu/Co/Ni ternary nanocatalyst coupled with penicillin as generic capturing agent
Authors: Zhang Yue , Cui Gaoxi , Meng Yuchan , Wang Yujing , Hun Xu
Published: June 2020

Bacterial pathogen control is important in seafood production. In this study, a Cu/Co/Ni ternary nanoalloy (Cu/Co/Ni TNA) was synthesized using the oleylamine reducing method. It was found that Cu/Co/Ni TNA greatly enhanced the chemiluminescence (CL) signal of the hydroxylamine‐O‐sulfonic acid (HOSA)–luminol system. The CL properties of Cu/Co/Ni TNA were investigated systemically. The possible CL mechanism also was intensively investigated. Based on the enhanced CL phenomenon of Cu/Co/Ni TNA, a Cu/Co/Ni TNA, penicillin, and anti‐L. monocytogenes (Listeria monocytogenes) antibody‐based sandwich complex assay for detection of L. monocytogenes was established. In this sandwich CL assay, penicillin was employed to capture and enrich pathogenic bacteria with penicillin‐binding proteins (PBPs) while anti‐L. monocytogenes antibody was adopted as the specific recognition molecule to recognize L. monocytogenes. L. monocytogenes was detected sensitively based on this new Cu/Co/Ni TNA–HOSA–luminol CL system. The CL intensity was proportional to the L. monocytogenes concentration ranging from 2.0 × 102 CFU ml−1 to 3.0 × 107 CFU ml−1 and the limit of detection wa 70 CFU ml−1. The reliability and potential applications of our method was verified by comparison with official methods and recovery tests in environment and food samples.
Gelatin grafted poly(D,L‐lactide) as an inhibitor of protein aggregation: An in vitro case study
Authors: Balavigneswaran Chelladurai Karthikeyan , Kumar Gaurav , Vignesh Kumar Chandrasekaran , Sellamuthu Satheeshkumar , Kasiviswanathan Uvanesh , Ray Biswajit , Muthuvijayan Vignesh , Mahto Sanjeev Kumar , Misra Nira
Published: June 2020

Amyloids are a group of proteins that are capable of forming aggregated amyloid fibrils, which is responsible for many neurodegenerative diseases including Alzheimer's disease (AD). In our previous study, synthesis and characterization of star‐shaped poly(D,L‐lactide)‐b‐gelatin (ss‐pLG) have been reported. In the present work, we have extended our work to study ss‐pLG against protein aggregation. To the best of our knowledge, this is the first report on the inhibition of amyloid fibrillation by protein grafted poly(D,L‐lactide). Bovine serum albumin (BSA) was chosen as the model protein, which readily forms fibril under high temperature. We found that ss‐pLG efficiently suppressed the fibril formation of BSA compared with gelatin (Gel), which was supported by Thioflavin T assay, circular dichroism (CD) spectroscopy and atomic force microscopy (AFM). In addition, ss‐pLG significantly curtailed amyloid‐induced hemolysis. We also found that incubation of ss‐pLG with neuroblastoma cells (MC65) protected the cells from fibril‐induced toxicity. The rescuing efficiency of ss‐pLG was better than Gel, which could be attributed to the reduced lamella thickness in branched ss‐pLG. These results suggest the significance of gelatin grafting, which probably allows gelatin to interact with the key residues of the amyloidogenic core of BSA effectively.
Quantitative ultrasound radiomics in predicting response to neoadjuvant chemotherapy in patients with locally advanced breast cancer: Results from multi‐institutional study
Authors: DiCenzo Daniel , Quiaoit Karina , Fatima Kashuf , Bhardwaj Divya , Sannachi Lakshmanan , Gangeh Mehrdad , Sadeghi‐Naini Ali , Dasgupta Archya , Kolios Michael C. , Trudeau Maureen , Gandhi Sonal , Eisen Andrea , Wright Frances , Look Hong Nicole , Sahgal Arjun , Stanisz Greg , Brezden Christine , Dinniwell Robert , Tran William T. , Yang Wei , Curpen Belinda , Czarnota Gregory J.
Published: June 2020

Background

This study was conducted in order to develop a model for predicting response to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer (LABC) using pretreatment quantitative ultrasound (QUS) radiomics.

Methods

This was a multicenter study involving four sites across North America, and appropriate approval was obtained from the individual ethics committees. Eighty‐two patients with LABC were included for final analysis. Primary tumors were scanned using a clinical ultrasound system before NAC was started. The tumors were contoured, and radiofrequency data were acquired and processed from whole tumor regions of interest. QUS spectral parameters were derived from the normalized power spectrum, and texture analysis was performed based on six QUS features using a gray level co‐occurrence matrix. Patients were divided into responder or nonresponder classes based on their clinical‐pathological response. Classification analysis was performed using machine learning algorithms, which were trained to optimize classification accuracy. Cross‐validation was performed using a leave‐one‐out cross‐validation method.

Results

Based on the clinical outcomes of NAC treatment, there were 48 responders and 34 nonresponders. A K‐nearest neighbors (K‐NN) approach resulted in the best classifier performance, with a sensitivity of 91%, a specificity of 83%, and an accuracy of 87%.

Conclusion

QUS‐based radiomics can predict response to NAC based on pretreatment features with acceptable accuracy.
Impact of poultry litter application on alfalfa grown in Mississippi
Authors: Rushing J. Brett , Lemus Rocky W. , Maples Joshua G. , Lyles Johnson C.
Published: June 2020

Alfalfa (Medicago sativa L.) production in the Coastal Plain of the southeastern United States requires enhanced soil fertility management to capitalize on increased dry matter yield and nutritive value. Poultry litter (PL) is an abundant fertilizer source that has been recognized as an economical choice for pasture and hay production. A field trial was established in east‐central Mississippi in which PL and inorganic fertilizer sources were compared in three alfalfa cultivars in 2018 and 2019. Fertilizer treatments included (a) 2 ton PL acre−1 (Treatment 1); (b) 4 ton PL acre−1 (Treatment 2); (c) inorganic N, P, and K delivered at similar rates to Treatment 1; and (d) inorganic P, and K (no N) supplied at same rates as Treatment 3. The cultivars were Bulldog 505, Bulldog 805, and AlfaGraze 600RR. Forage mass (FM), plant persistence (PER), nutritive value [crude protein (CP), total digestible nutrients (TDN), and relative forage quality (RFQ)], and economic comparisons were conducted. Repeated measures analysis observed no differences between cultivars or treatments for FM, PER, or CP. Bulldog 505 had superior TDN and RFQ values for 7 out of 11 total harvests. Plots with applied PL (2 or 4 ton acre−1) recorded greater TDN values than inorganic sources in 4 of 11 harvests. In 2018, Bulldog 505 produced the lowest cost per ton ($96.29 ton−1); in 2019, similar costs were observed between Bulldog 505 ($147.57 ton−1) and Bulldog 805 ($147.96 ton−1). Poultry litter sources resulted in the lowest cost per ton for both years of the trial.
The Aggregation Regularity Effect of Multiarylpyrroles on Their Near‐Infrared Aggregation‐Enhanced Emission Property
Authors: Qu Jiamin , Ren Fei , Shi Jianbing , Tong Bin , Cai Zhengxu , Dong Yuping
Published: June 2020

Increasing the quantum yield of near‐infrared (NIR) emissive dyes is critical for biological applications because these fluorescent dyes generally show decreased emission efficiency under aqueous conditions. In this work, we designed and synthesized several multiarylpyrrole (MAP) derivatives, in which a furanylidene (FE) group at the 3‐position of the pyrrole forms donor‐π‐acceptor molecules, MAP‐FE, with a NIR emissive wavelength and aggregation‐enhanced emission (AEE) features. Different alkyl chains of MAP‐FEs linked to phenyl groups at the 2,5‐position of the pyrrole ring resulted in different emissive wavelengths and quantum yields in aggregated states, such as powders or single crystals. Powder XRD data and single crystal analysis elucidated that the different lengths of alkyl chains had a significant impact on the regularity of MAP‐FEs when they were forced to aggregate or precipitate, which affected the intermolecular interaction and the restriction degree of the rotating parts, which are essential components. Therefore, an increasing number of NIR dyes could be developed by this design strategy to produce efficient NIR dyes with AEE. Moreover, this method can provide general guidance for other related fields, such as organic solar cells and organic light‐emitting materials, because they are all applied in the aggregated state.
Measuring financial toxicity incurred after treatment of head and neck cancer: Development and validation of the Financial Index of Toxicity questionnaire
Authors: Hueniken Katrina , Douglas Catriona M. , Jethwa Ashok R. , Mirshams Maryam , Eng Lawson , Hope Andrew , Chepeha Douglas B. , Goldstein David P. , Ringash Jolie , Hansen Aaron , Martino Rosemary , Li Madeline , Liu Geoffrey , Xu Wei , de Almeida John R.
Published: June 2020

Background

The treatment of head and neck cancer (HNC) may cause significant financial toxicity to patients. Herein, the authors have presented the development and validation of the Financial Index of Toxicity (FIT) instrument.

Methods

Items were generated using literature review and were based on expert opinion. In item reduction, items with factor loadings of a magnitude <0.3 in exploratory factor analysis and inverse correlations (r < 0) in test‐retest analysis were eliminated. Retained items constituted the FIT. Reliability tests included internal consistency (Cronbach α) and test‐retest reliability (intraclass correlation). Validity was tested using the Spearman rho by comparing FIT scores with baseline income, posttreatment lost income, and the Financial Concerns subscale of the Social Difficulties Inventory. Responsiveness analysis compared change in income and change in FIT between 12 and 24 months.

Results

A total of 14 items were generated and subsequently reduced to 9 items comprising 3 domains identified on exploratory factor analysis: financial stress, financial strain, and lost productivity. The FIT was administered to 430 patients with HNC at 12 to 24 months after treatment. Internal consistency was good (α = .77). Test‐retest reliability was satisfactory (intraclass correlation, 0.70). Concurrent validation demonstrated mild to strong correlations between the FIT and Social Difficulties Inventory Money Matters subscale (Spearman rho, 0.26‐0.61; P < .05). FIT scores were found to be inversely correlated with baseline household income (Spearman rho, −0.34; P < .001) and positively correlated with lost income (Spearman rho, 0.24; P < .001). Change in income was negatively correlated with change in FIT over time (Spearman rho, −0.25; P = .04).

Conclusions

The 9‐item FIT demonstrated internal and test‐retest reliability as well as concurrent and construct validity. Prospective testing in patients with HNC who were treated at other facilities is needed to further establish its responsiveness and generalizability.
Hand gesture recognition based on attentive feature fusion
Authors: Yu Bin , Luo Zhiming , Wu Huangbin , Li Shaozi
Published: June 2020

Video‐based hand gesture recognition plays an important role in human‐computer interaction (HCI). Recent advanced methods usually add 3D convolutional neural networks to capture the information from both spatial and temporal dimensions. However, these methods suffer the issue of requiring large‐scale training data and high computational complexity. To address this issue, we proposed an attentive feature fusion framework for efficient hand‐gesture recognition. In our proposed model, we utilize a shallow two‐stream CNNs to capture the low‐level features from the original video frame and its corresponding optical flow. Following, we designed an attentive feature fusion module to selectively combine useful information from the previous two streams based on the attention mechanism. Finally, we obtain a compact embedding of a video by concatenating features from several short segments. To evaluate the effectiveness of our proposed framework, we train and test our method on a large‐scale video‐based hand gesture recognition dataset, Jester. Experimental results demonstrate that our approach obtains very competitive performance on the Jester dataset with a classification accuracy of 95.77%.
Effect of Remote Substituents on the Torquoselectivity of 3‐Silyl Cyclobutene‐Derivatives Ring‐Opening Reactions
Authors: Larrañaga Olatz , de Cózar Abel
Published: June 2020

We have quantum chemically studied the structure and nature of 1‐substituted 3‐trimethylsilyl cyclobutenes and 2,2‐disubstituted‐7‐trimethylsilyl bycyclo[4.2.0]octa‐1(6),3‐dienes comparing their reactivity to archetypal 3‐substituted cyclobutene systems using density functional theory at M06‐2X(PCM)/TZ2P level. We wish to understand how the ring opening reaction is affected by a substituent not directly connected to the σ Carbon‐Carbon breaking bond. To this end, we have analyzed the reaction profiles considering second order perturbation energies and natural steric analysis within NBO framework.
PLiMAP: Proximity‐Based Labeling of Membrane‐Associated Proteins
Authors: Jose Gregor P. , Pucadyil Thomas J.
Published: June 2020

Peripheral membrane proteins participate in numerous biological pathways. Thus, methods to analyze their membrane‐binding characteristics have become important. In this report, we detail protocols for the synthesis and utilization of a photoactivable fluorescent lipid as a reporter to monitor membrane binding of proteins. The assay, referred to as proximity‐based labeling of membrane‐associated proteins (PLiMAP), is based on UV activation of a fluorescent lipid reporter, which in turn crosslinks with proteins bound to membranes and renders them fluorescent. © 2020 Wiley Periodicals LLC.

Basic Protocol 1: Synthesis of BODIPY‐diazirine phosphatidylethanolamine (BDPE)

Basic Protocol 2: Preparation of BDPE‐containing liposomes

Basic Protocol 3: Performing PLiMAP with a candidate protein

Basic Protocol 4: Quantitation of liposome‐binding properties of the candidate protein from analyzing in‐gel fluorescence

Support Protocol: Purification of GST‐2×P4M domain of SidM protein
Genetic Variant in CHRNA5 and Response to Varenicline and Combination Nicotine Replacement in a Randomized Placebo‐Controlled Trial
Authors: Chen Li‐Shiun , Baker Timothy B. , Miller J. Philip , Bray Michael , Smock Nina , Chen Jingling , Stoneking Faith , Culverhouse Robert C. , Saccone Nancy L. , Amos Christopher I. , Carney Robert M. , Jorenby Douglas E. , Bierut Laura J.
Published: June 2020

It is unclear if genetic variants affect smoking cessation treatment response. This study tested whether variants in the cholinergic receptor nicotinic alpha 5 subunit (CHRNA5) predict response to smoking cessation medication by directly comparing the two most effective smoking cessation pharmacotherapies. In this genotype‐stratified randomized, double‐blind, placebo‐controlled clinical trial (May 2015–August 2019 in St Louis, Missouri), smokers were randomized by genotype in blocks of six (1:1:1 ratio) to three conditions: 12 weeks of placebo (n = 273), combination nicotine patch and lozenge (combination nicotine replacement therapy, cNRT, n = 275), or varenicline (n = 274). All participants received counseling and were followed for 12 months. The primary end point was biochemically verified 7‐day point prevalence abstinence at the end of treatment (EOT, week 12). Trial registration and eligibility criteria are on clinicaltrials.gov (https://clinicaltrials.gov/) (NCT02351167). We conducted the genetic analyses separately for 516 European ancestry (EA) smokers and 306 non‐EA smokers (including 270 African American smokers). In African American smokers, there was a genotype‐by‐treatment interaction for EOT abstinence (χ2 = 10.7, degrees of freedom = 2. P = 0.0049): specifically, cNRT was more effective in smokers with rs16969968 GG genotype than was placebo, while varenicline was more effective in smokers of GA/AA genotypes. In EA ancestry smokers, there was no significant genotype‐by‐treatment interaction. In the whole sample, although both were effective at EOT, only varenicline, and not cNRT, was significantly effective relative to placebo at 6‐month follow‐up. Importantly, this study suggests that genetic information can further enhance smoking cessation treatment effectiveness.
Latitude and protection affect decadal trends in reef trophic structure over a continental scale
Authors: Madin Elizabeth M. P. , Madin Joshua S. , Harmer Aaron M. T. , Barrett Neville S. , Booth David J. , Caley M. Julian , Cheal Alistair J. , Edgar Graham J. , Emslie Michael J. , Gaines Steven D. , Sweatman Hugh P. A.
Published: June 2020

The relative roles of top‐down (consumer‐driven) and bottom‐up (resource‐driven) forcing in exploited marine ecosystems have been much debated. Examples from a variety of marine systems of exploitation‐induced, top‐down trophic forcing have led to a general view that human‐induced predator perturbations can disrupt entire marine food webs, yet other studies that have found no such evidence provide a counterpoint. Though evidence continues to emerge, an unresolved debate exists regarding both the relative roles of top‐down versus bottom‐up forcing and the capacity of human exploitation to instigate top‐down, community‐level effects. Using time‐series data for 104 reef communities spanning tropical to temperate Australia from 1992 to 2013, we aimed to quantify relationships among long‐term trophic group population density trends, latitude, and exploitation status over a continental‐scale biogeographic range. Specifically, we amalgamated two long‐term monitoring databases of marine community dynamics to test for significant positive or negative trends in density of each of three key trophic levels (predators, herbivores, and algae) across the entire time series at each of the 104 locations. We found that trophic control tended toward bottom‐up driven in tropical systems and top‐down driven in temperate systems. Further, alternating long‐term population trends across multiple trophic levels (a method of identifying trophic cascades), presumably due to top‐down trophic forcing, occurred in roughly fifteen percent of locations where the prerequisite significant predator trends occurred. Such alternating trophic trends were significantly more likely to occur at locations with increasing predator densities over time. Within these locations, we found a marked latitudinal gradient in the prevalence of long‐term, alternating trophic group trends, from rare in the tropics (<5% of cases) to relatively common in temperate areas (~45%). Lastly, the strongest trends in predator and algal density occurred in older no‐take marine reserves; however, exploitation status did not affect the likelihood of alternating long‐term trophic group trends occurring. Our data suggest that the type and degree of trophic forcing in this system are likely related to one or more covariates of latitude, and that ecosystem resiliency to top‐down control does not universally vary in this system based on exploitation level.
Hyperkalaemia and hypokalaemia outpatient management: a survey of 500 French general practitioners
Authors: Abensur Vuillaume Laure , Rossignol Patrick , Lamiral Zohra , Girerd Nicolas , Boivin Jean‐Marc
Published: June 2020

Aims

How general practitioners (GPs) manage dyskalaemia is currently unknown. This study aimed at describing GP practices regarding hypokalaemia or hyperkalaemia diagnosis and management in their outpatients.

Methods and results

A telephone survey was conducted among French GPs with a 20‐item questionnaire (16 closed‐ended questions and 12 open‐ended questions) regarding their usual management of hypokalaemia or hyperkalaemia patients, both broadly and more specifically in patients with heart failure and/or chronic kidney disease and/or in patients treated with angiotensin‐converting enzyme/angiotensin receptor blockers or mineralocorticoid receptor antagonists. We aimed to interview 500 GPs spread geographically throughout France. This descriptive survey results are presented as mean ± standard deviation (if normally distributed or as median and inter‐quartile range if the distribution was skewed). Categorical variables are expressed as frequencies and proportions (%). A total of 500 GPs participated in the study. Dyskalaemia thresholds (for diagnosis and intervention) and management patterns were highly heterogeneous. The mean ± SD (range) potassium level leading to ‘intervene’ was 5.32 ± 0.34 mmol/L (4.5–6.5) for hyperkalaemia and 3.23 ± 0.34 mmol/L (2.0–6.5) for hypokalaemia. Potassium levels leading to refer the patient to the emergency department (ED) were 6.14 ± 0.55 (4.5–10) and 2.69 ± 0.42 mmol/L (1–4), respectively. Potassium binders (51–65%) or potassium supplements (67–74%) were frequently used to manage hyperkalaemia or hypokalaemia. GPs uncommonly referred their dyskalaemic patients to cardiologists or nephrologists (or to the emergency department, if the latter was deemed necessary owing to the severity of the dyskalaemia). We identified an association between the close vicinity of GP office from an ED and ‘referring a heart failure patient’ (19.2% with ED vs. 8.6% without ED) and referring a heart failure and chronic kidney disease patient on mineralocorticoid receptor antagonist (16.7% with ED vs. 9.3% without ED). Although the majority (67%) of GPs had an electrocardiogram on hand, it was rarely used (14%) in dyskalaemic patients. Subgroup analyses considering gender, age of the participating GPs, and high‐income/low‐income regions did not identify specific patterns regarding the multidimensional aspect of dyskalaemia management.

Conclusions

Owing to the considerable heterogeneity of French GP practices toward dyskalaemia diagnosis and management approaches, there is a likely need to standardize (potentially enabled by therapeutic algorithms) practices.
New renal haemodynamic indices can predict worsening of renal function in acute decompensated heart failure
Authors: Mostafa Amir , Said Karim , Ammar Walid , Eltawil Ahmed Elsayed , Abdelhamid Magdy
Published: June 2020

Aims

Worsening of renal function (WRF) is a common complication in patients with acute decompensated heart failure (ADHF). We aimed to evaluate the role of intrarenal Doppler ultrasound (IRD) in the early prediction of WRF in this patient group.

Methods and results

Among 90 patients (age: 57.5 ± 11.1 years; 62% male) hospitalized with ADHF, resistivity index (RI), acceleration time (AT), and pulsatility index (PI) were measured on admission and at 24 and 72 h. WRF was defined as increased serum creatinine ≥0.3 mg/dL from baseline. Adverse clinical outcomes were defined as the composite of death, use of vasopressors, and need for ultrafiltration for refractory oedema. WRF developed in 40% of patients. Mean values of renal AT, RI, and PI on admission were 59.7 ± 15, 0.717 ± 0.08, and 1.5 ± 0.48 ms, respectively. At 24 h, there was significant decrease in AT (to 56.7 ± 10 ms, P = 0.02) and renal RI (to 0.732 ± 0.07; P < 0.001); these changes were maintained up to 72 h. Renal PI showed no significant changes. Independent predictors of WRF were renal AT at 24 h and admission values of renal RI, left ventricular ejection fraction, and plasma cystatin C. Renal AT at 24 h ≥ 57.8 ms had 89% sensitivity and 70% specificity for the prediction of WRF. Independent predictors for adverse clinical outcomes were left ventricular end systolic dimension and WRF.

Conclusions

Among ADHF patients receiving diuretic therapy, measurement of renal AT and RI by IRD can help identify patients at increased risk for WRF.
Functional estimation of diversity profiles
Authors: Fortuna Francesca , Gattone Stefano Antonio , Di Battista Tonio
Published: June 2020

It is well known that the diversity profile provides a complete picture about the evenness of the relative abundance distribution of an ecological population. This complexity measure is a continuous function evaluated on a suitable grid of values x ≥ 0 that determine the measure's sensitivity to the most dominant species. In this paper, a functional design‐based estimation of diversity profiles is developed by applying a framework based on functional data analysis (FDA). These curves, which are positive, decreasing, and convex, can be viewed as constrained functional data. Therefore, a naive direct application of the FDA methodology can be misleading, both theoretically and practically. To tackle this problem, the diversity profile is defined in terms of a differential equation, in such a manner that the function to be estimated is unconstrained. An approximation of the bias and the variance of the estimator is derived using the delta method. The accuracy of the proposed functional constrained estimator is evaluated through a simulation study. The procedure is also applied on a real dataset concerning tree stem diameter diversity.
An improved opportunistic group replacement maintenance strategy for wind turbines
Authors: Ma Zhiyong , Wang Dameng , Wu Shiming , Teng Wei , Liu Yibing
Published: June 2020

In traditional opportunistic group replacement maintenance (OGRM) strategy for wind turbines, the reliability thresholds of different subassemblies are set the same and its two‐step optimization for maintenance cost is diseconomy. In this paper, an improved OGRM strategy for wind turbines is proposed. A uniform formulation on maintenance cost concerning different maintenance activities is presented. On the basis of this, an integrated objective function minimizing the maintenance cost is established, and the reliability thresholds of each subassembly of wind turbines are individually severed as the optimization variables of the objective function. The coordinate rotation method is utilized for solving this optimization problem. A maintenance case based on the proposed strategy from a wind farm in North China is implemented, which verifies its superior performance than the traditional opportunistic group maintenance strategy.
Regional debris‐flow and debris‐flood frequency–magnitude relationships
Authors: Jakob Matthias , Mark Emily , McDougall Scott , Friele Pierre , Lau Carie‐Ann , Bale Stephanie
Published: June 2020

Construction of frequency–magnitude (F–M) relationships of debris floods and debris flows is challenging because of few direct observations, discontinuous event occurrence, loss of field evidence, the difficulty of accessing the sediment archive and the challenge of finding suitable statistical methods to analyse the dataset. Consultants often face budget limitations that prohibit application of the full gamut of absolute dating methods, stratigraphic analysis and analytical tools necessary to fully resolve the F–M legacy. In some cases, F–M curves are needed for watersheds without local information, or where obtaining this information is prohibitively expensive. For such watersheds, the F–M relationship may be estimated where several F–M curves have already been assembled in a specific region. Individual F–M curves are normalized by fan area or fan volume, then stratified by process type and geomorphic activity level. This paper describes the development of regional F–M curves for debris flows in southwestern British Columbia and debris flows and debris floods in the Bow River valley near Canmore, Alberta. We apply the regional relationships to other cases in Canada and the United States and demonstrate that the method can be globalized. The regional approach is compared to cases where detailed F–M relationships have been established by other means. Strong negative deviations from the regional debris‐flow or debris‐flood magnitude trends could signal inherent watershed stability, while strong positive deviations could signal extraordinary landslide processes, or suggest that the fan may be largely of paraglacial origin. We highlight some of these outlying cases and develop a method whereby the regional curves can be meaningfully adjusted, or reliance can be placed on lower or upper confidence bounds of the F–M curves. We caution against the indiscriminate use of the regionally based F–M curves, especially in watersheds where multiple geomorphic processes are active. © 2020 John Wiley & Sons, Ltd.
Assessment of various energy storage methods for implementation in hot and arid climates
Authors: AlShafi Manal , Bicer Yusuf
Published: June 2020

Global warming plays an increasing role in our world, as the share of renewable energy sources in the overall production of electricity has witnessed exponential growth over the past years. Consumer demands are required to be met at any moment at a feasible price. However, storing energy in hot and arid climate regions is a sensitive matter as it is critical to consider appropriate technologies to implement for avoiding unnecessary causalities caused by extreme temperatures. This study compares 13 different energy storage methods, namely; pumped hydro, compressed air, flywheels, hot water storage, molten salt, hydrogen, ammonia, lithium‐ion battery, Zn‐air battery, redox flow battery, fuel cells, supercapacitors, and superconducting magnetic storage to be implemented in hot arid regions in terms of water usage, energy density, location dependency, and temperature degradation. A survey was conducted based on prior criteria to compare all 13 energy storage methods. The study concluded that the highest rankings for energy storage techniques are obtained for; Zn‐air battery, superconductors, and flywheels with overall rankings of 7.18, 6.73, and 6.61, respectively. In contrast, some of the rankings are very close to each other implying the potential application of several methods in hot climates.
Effect of steam explosion on nutritional composition and antioxidative activities of okra seed and its application in gluten‐free cookies
Authors: Hu Lei , Guo Jiamin , Zhu Xiwei , Liu Rui , Wu Tao , Sui Wenjie , Zhang Min
Published: June 2020

Health‐conscious consumers are increasingly interested in gluten‐free (GF) foods. Raw okra seed (ROS) flour and steam‐exploded okra seed (SEOS) flour were explored for developing GF cookies with high nutritional values and in vitro enzymatic digestion. Results indicated that the steam explosion exhibited significant effects on enhancing the release of dietary fibers and lipids in okra seed flour at moderate explosion pressure. Although steam explosion caused the loss of flavonoid compounds, moderate high explosion pressure enhanced the release of total phenolics ranged from 294.57 to 619.07 mg GAE/100 g DM with significantly improved DPPH• radical scavenging activity (from 18.78% to 67.34%) and ferric reducing antioxidant power (from 13.37% to 149.04%). The rapidly digestible starch (RDS) content in GF cookies decreased with increasing steam explosion severity, whereas slowly digestible starch (SDS) and resistant starch (RS) contents significantly increased from 36.91% to 40.92% and from 2.50% to 9.06%, respectively. Steam explosion is an effective technique for enhancing the release of nutrients like dietary fiber and total phenolics, and okra seed flour, especially SEOS flour, can be alternative choices to provide food functional materials for developing various GF food products.
Evaluating the effects of the COVID‐19 pandemic on the physical and mental well‐being of obstetricians and gynecologists in Turkey
Authors: Yalçın Bahat Pınar , Aldıkaçtıoğlu Talmaç Merve , Bestel Ayşegül , Topbas Selcuki Nura F. , Karadeniz Ozan , Polat Ibrahim
Published: June 2020

Objective

To apply online surveying to assess the general physical and mental well‐being of obstetricians/gynecologists (OB/GYNs) working in COVID‐19 designated hospitals in Turkey.

Methods

A prospective survey‐based study using an online survey platform. Three hundred participants working at COVID‐19 designated hospitals in Turkey identified from a hospital database were sent a link to the survey by email between April 29 and May 20, 2020.

Results

A total of 253 OB/GYNs (31 consultants and 222 residents) completed the survey, for a response rate of 84.3%. Of respondents, 191 (76.4%) were anxious about coming into contact with pregnant women infected with COVID‐19. 74.4% stated that they were afraid of getting sick. 64.8% reported that they had fallen into despair at times because of the pandemic. 66.5% stated that their family lives were affected. 72.4% started living separately from their families because of the pandemic.

Conclusion

Despite the difficulties in patient care during the pandemic, OB/GYNs continued providing for their patients, which reflected positively on their perceptions of the profession. The importance of trust in the national healthcare system, presence of adequate PPE, finding a suitable coping mechanism, and family support were essential for Turkish OB/GYNs during the COVID‐19 pandemic.

ClinicalTrials.gov identifier: NCT04327531.

Turkish obstetricians/gynecologists reported anxiety and stress caused by the current situation and future implications of the COVID‐19 pandemic.
The “EA brief”: A single session of parent feedback and coaching to improve emotional attachment and emotional availability (EA)
Authors: McConnell Maren , Closson Lia , Morse Bradley , Wurster Hannah , Flykt Marjo , Sarche Michelle , Biringen Zeynep
Published: June 2020

The goal of this study was to determine the extent to which a brief parenting intervention provided the context for helping families to support positive mother–child interactions as well as more optimal mother and child outcomes. Participants in this study were middle income mothers and their children were between 0–3 years of age (N = 25 dyads). Participants were filmed via Skype during a 20‐minute mother–child free play and completed questionnaires (Time 1) before attending the brief intervention (involving: a single session of one‐on‐one parent feedback and coaching, and information via group meeting, texts, and reading) followed by a repeat of the 20‐minute Skype interaction and the completion of the same questionnaires (Time 2). Paired samples t‐tests were performed, revealing that mothers reported improvements in their personal well‐being (using the Flourishing Scale), reports about the mother‐child relationship (using the Emotional Availability Self Report), and observed interactions, particularly the child's side of the relationship (using the Emotional Availability System), from pretest to posttest. Results are discussed in terms of a single session of parent feedback and coaching (in conjunction with an informational group session and texts) potentially having a role in “planting a seed” for observed and self‐reported parenting enhancement and child development.
Raman microspectroscopic study for the detection of oral field cancerisation using brush biopsy samples
Authors: Behl Isha , Calado Genecy , Vishwakarma Anika , Flint Stephen , Galvin Sheila , Healy Claire M. , Leite Pimentel Marina , Malkin Alison , Byrne Hugh J. , Lyng Fiona M.
Published: June 2020

Field cancerisation (FC) is potentially an underlying cause of poor treatment outcomes of oral squamous cell carcinoma (OSCC). To explore the phenomenon using Raman microspectroscopy, brush biopsies from the buccal mucosa, tongue, gingiva and alveolus of healthy donors (n = 40) and from potentially malignant lesions (PML) of Dysplasia Clinic patients (n = 40) were examined. Contralateral normal samples (n = 38) were also collected from the patients. Raman spectra were acquired from the nucleus and cytoplasm of each cell, and subjected to partial least squares‐discriminant analysis (PLS‐DA). High discriminatory accuracy for donor and PML samples was achieved for both cytopalmic and nuclear data sets. Notably, contralateral normal (patient) samples were also accurately discriminated from donor samples and contralateral normal samples from patients with multiple lesions showed a similar spectral profile to PML samples, strongly indicating a FC effect. These findings support the potential of Raman microspectroscopy as a screening tool for PML using oral exfoliated cells.
Interdisciplinary engineering education: A review of vision, teaching, and support
Authors: Van den Beemt Antoine , MacLeod Miles , Van der Veen Jan , Van de Ven Anne , van Baalen Sophie , Klaassen Renate , Boon Mieke
Published: June 2020

Background

Societal challenges that call for a new type of engineer suggest the need for the implementation of interdisciplinary engineering education (IEE). The aim of IEE is to train engineering students to bring together expertise from different disciplines in a single context. This review synthesizes IEE research with a focus on characterizing vision, teaching practices, and support.

Purpose

We aim to show how IEE is conceptualized, implemented, and facilitated in higher engineering education at the levels of curricula and courses. This aim leads to two research questions:

What aspects of vision, teaching, and support have emerged as topics of interest in empirical studies of IEE?

What points of attention regarding vision, teaching, and support can be identified in empirical studies of IEE as supporting or challenging IEE?

Scope/Method

Ninety‐nine studies published between 2005 and 2016 were included in a qualitative analysis across studies. The procedure included formulation of research questions, searching and screening of studies according to inclusion/exclusion criteria, description of study characteristics, appraisal, and synthesis of results.

Conclusions

Challenges exist for identifying clear learning goals and assessments for interdisciplinary education in engineering (vision). Most pedagogy for interdisciplinary learning is designed to promote collaborative teamwork requiring organization and team management. Our review suggests that developing interdisciplinary skills, knowledge, and values needs sound pedagogy and teaming experiences that provide students with authentic ways of engaging in interdisciplinary practice (teaching). Furthermore, there is a limited understanding of what resources hinder the development of engineering programs designed to support interdisciplinarity (support).