bluuebunny/crossref_metadata_2025 huggingface dataset:
Self‐selecting peer groups formed within the laboratory environment have a lasting effect on individual student attainment and working practices
Authors: Lacey Melissa M. , Campbell Susan G. , Shaw Holly , Smith David P.
Published: May 2020

Within the present study, we investigate the lasting effect of laboratory peer group interactions on the end of year attainment of Biosciences and Chemistry students. By asking students to identify who they primarily work with within the laboratory environment and evaluating the interactions through cluster analysis, we identified two main categories of laboratory peer groups: the first long‐lived well‐established pairings of two students, ‘swans’, who work together for all or the majority of the laboratory sessions; and the second dynamic fluid groups, ‘dolphins’, of between three and nine students who work with each other interchangeably. Statistical analysis is presented, which demonstrates that individuals within each laboratory peer group were likely to achieve a similar average mark at the end of the first year of study on the course. We identified the driving factors for the formation of these groups as friendship and perceived work ethic. There is a preference for high‐achieving students to work with other high‐achieving students and lower‐achieving to group around a shared social background. Targeted interventions, in which pairings were selected by the tutor at the onset of the study, altered the ratio from long‐lived pairs to more dynamic groups and increased students’ willingness to work with others outside of their group but did not change the drivers of group formation or resulting pattern of achievement. We conclude with recommendations around group working within the laboratory environment.
Negative Binomial Regression
Authors: Juarez‐Colunga E. , Dean C. B.
Published: May 2020

Count data occur commonly in very many fields. Some examples include seizures, asthma attacks, days of absence from work, annual forest fires in a region, insurance claims in a portfolio, or recurrences of cancer. The basic count model is the Poisson process, a model that forms a foundation upon which several other count models can be linked, as extensions in some manner. These extensions address departures from assumptions underpinning the Poisson model. The negative binomial distribution is a widely used count model that can, to some extent, address some of the violations of assumptions of Poisson models. Because of its flexibility, it is commonly used in statistical applications. In this article, we provide an overview of negative binomial regression and outline both maximum likelihood and robust estimation. We discuss how the negative binomial model is a generalization of the Poisson and provide an example that considers recurrence of bladder cancer tumors.
Limiting treatment plan complexity by applying a novel commercial tool
Authors: Scaggion Alessandro , Fusella Marco , Agnello Giancarmelo , Bettinelli Andrea , Pivato Nicola , Roggio Antonella , Rossato Marco A. , Sepulcri Matteo , Paiusco Marta
Published: May 2020

Purpose

A recently introduced commercial tool is tested to assess whether it is able to reduce the complexity of a treatment plan and improve deliverability without compromising overall quality.

Methods

Ten prostate and ten oropharynx plans of previously treated patients were reoptimized using the aperture shape controller (ASC) tool recently introduced in Eclipse TPS (Varian Medical Systems, Palo Alto, CA). The performance of ASC was assessed in terms of the overall plan quality using a plan quality metric, the reduction in plan complexity through the analysis of 14 of the most common plan complexity metrics, and the change in plan deliverability through 3D dosimetric measurements. Similarly, plans optimized limiting the total number of delivered monitor units was assessed and compared. The two strategies were also combined to assess their potential combination.

Results

The plans optimized by exploiting the ASC generally show a reduced number of total Monitor Units, a more constant gantry rotation and a MLC modulation characterized by larger and less complicated shapes with leaves traveling shorter overall lengths.

Conclusions

This first experience suggests that the ASC is an effective tool to reduce the unnecessary complexity of a plan. This turns into an increased plan deliverability with no loss of plan quality.
Early life metal dysregulation in amyotrophic lateral sclerosis
Authors: Figueroa‐Romero Claudia , Mikhail Kristen A. , Gennings Chris , Curtin Paul , Bello Ghalib A. , Botero Tatiana M. , Goutman Stephen A. , Feldman Eva L. , Arora Manish , Austin Christine
Published: May 2020

Objective

Deficiencies and excess of essential elements and toxic metals are implicated in amyotrophic lateral sclerosis (ALS), but the age when metal dysregulation appears remains unknown. This study aims to determine whether metal uptake is dysregulated during childhood in individuals eventually diagnosed with ALS.

Methods

Laser ablation‐inductively coupled plasma‐mass spectrometry was used to obtain time series data of metal uptake using biomarkers in teeth from autopsies or dental extractions of ALS (n = 36) and control (n = 31) participants. Covariate data included sex, smoking, occupational exposures, and ALS family history. Case–control differences were identified in temporal profiles of metal uptake for individual metals using distributed lag models. Weighted quantile sum (WQS) regression was used for metals mixture analyses. Similar analyses were performed on an ALS mouse model to further verify the relevance of dysregulation of metals in ALS.

Results

Metal levels were higher in cases than in controls: 1.49 times for chromium (1.11–1.82; at 15 years), 1.82 times for manganese (1.34–2.46; at birth), 1.65 times for nickel (1.22–2.01; at 8 years), 2.46 times for tin (1.65–3.30; at 2 years), and 2.46 times for zinc (1.49–3.67; at 6 years). Co‐exposure to 11 elements indicated that childhood metal dysregulation was associated with ALS. The mixture contribution of metals to disease outcome was likewise apparent in tooth biomarkers of an ALS mouse model, and differences in metal distribution were evident in ALS mouse brains compared to brains from littermate controls.

Interpretation

Overall, our study reveals direct evidence that altered metal uptake during specific early life time windows is associated with adult‐onset ALS.
Psychometric Testing of the Debriefing Assessment for Simulation in Healthcare (DASH) for Trainee‐led, In Situ Simulations in the Pediatric Emergency Department Context
Authors: Zargham Shiva , Hanson Amy , Laniewicz Megan , Sandquist Mary , Kessler David O. , Gilbert Gregory E. , Calhoun Aaron W.
Published: May 2020

Objectives

Effective trainee‐led debriefing after critical events in the pediatric emergency department has potential to improve patient care, but debriefing assessments for this context have not been developed. This study gathers preliminary validity and reliability evidence for the Debriefing Assessment for Simulation in Healthcare (DASH) as an assessment of trainee‐led post–critical event debriefing.

Methods

Eight fellows led teams in three simulated critical events, each followed by a video‐recorded discussion of performance mimicking impromptu debriefings occurring after real clinical events. Three raters assessed the recorded debriefings using the DASH, and their feedback was collated. Data were analyzed using generalizability theory, Gwet’s AC2, intraclass correlation coefficient (ICC), and coefficient alpha. Validity was examined using Messick’s framework.

Results

The DASH instrument had relatively low traditional inter‐rater reliability (Gwet’s AC2 = 0.24, single‐rater ICC range = 0.16‐0.35), with 30% fellow, 19% rater, and 23% rater by fellow variance. DASH generalizability (G) coefficient was 0.72, confirming inadequate reliability for research purposes. Decision (D) study results suggest the DASH can attain a G coefficient of 0.8 with five or more raters. Coefficient alpha was 0.95 for the DASH. A total of 90 and 40% of items from Elements 1 and 4, respectively, were deemed “not applicable” or left blank.

Conclusions

Our results suggest that the DASH does not have sufficient validity and reliability to rigorously assess debriefing in the post–critical event environment but may be amenable to modification. Further development of the tool will be needed for optimal use in this context.
Shedding Light on the Diverse Reactivity of NacNacAl with N‐Heterocycles
Authors: Dmitrienko Anton , Pilkington Melanie , Britten James F. , Gabidullin Bulat M. , van der Est Art , Nikonov Georgii I.
Published: May 2020

The aluminum(I) compound NacNacAl (NacNac=[ArNC(Me)CHC(Me)NAr]−, Ar=2,6‐iPr2C6H3, 1) shows diverse and substrate‐controlled reactivity in reactions with N‐heterocycles. 4‐Dimethylaminopyridine (DMAP), a basic substrate in which the 4‐position is blocked, induces rearrangement of NacNacAl by shifting a hydrogen atom from the methyl group of the NacNac backbone to the aluminum center. In contrast, C−H activation of the methyl group of 4‐picoline takes place to produce a species with a reactive terminal methylene. Reaction of 1 with 3,5‐lutidine results in the first example of an uncatalyzed, room‐temperature cleavage of an sp2 C−H bond (in the 4‐position) by an AlI species. Another reactivity mode was observed for quinoline, which undergoes 2,2′‐coupling. Finally, the reaction of 1 with phthalazine produces the product of N−N bond cleavage.
Recent advances in anticancer ruthenium Schiff base complexes
Authors: Parveen Shazia
Published: May 2020

Nowadays in cancer treatment, both metal complexes and organic molecules are being widely used. Current years have seen a surge of interest in the application of organometallic compounds to treat cancer and other diseases. Undeniably, the unique properties of organometallic compounds, intermediate between those of classical inorganic and organic materials, provide new opportunities in the field of medicinal chemistry. Since the discovery of cisplatin, many transition metal complexes have been synthesized and assayed for anticancer activity. In recent years, ruthenium‐based Schiff base complexes have emerged as promising antitumor and antimetastatic agents with potential uses in treatment of platinum‐resistant tumors or as alternatives to platinum‐based chemotherapy. Advantages of utilizing ruthenium complexes in drug development include reliable methods of synthesizing stable complexes; the ability to tune ligand affinities, electron transfer and substitution rates, and reduction potentials; and an increasing knowledge of the biological effects of such complexes. This great expansion of ruthenium‐based Schiff base complexes is mainly due to the unique ability of the ruthenium core to permit multiple oxidation states, hence versatile electron‐transfer pathways, and because of the ease of preparation with versatile and variable‐denticity Schiff base ligands. This review aims to bring the reader up to date with the more recent Ru(II)/(III)‐based Schiff base complexes that have been synthesized and investigated for their cytotoxicity.
Application of lipase immobilized on a hydrophobic support for the synthesis of aromatic esters
Authors: dos Santos Marta Maria Oliveira , Gama Rafaela Santos , de Carvalho Tavares Iasnaia Maria , Santos Pedro Henrique , Gonçalves Márcia Soares , de Carvalho Marise Silva , de Barros Vilas Boas Eduardo Valério , de Oliveira Julieta Rangel , Mendes Adriano Aguiar , Franco Marcelo
Published: May 2020

The present study aimed at preparing three biocatalysts via physical adsorption of lipases from Candida rugosa (CRL), Mucor javanicus, and Candida sp. on a hydrophobic and mesoporous support (Diaion HP‐20). These biocatalysts were later applied to the synthesis of aromatic esters of apple peel and citrus (hexyl butyrate), apple and rose (geranyl butyrate), and apricot and pineapple (propyl butyrate). Scanning electron microscopy and gel electrophoresis confirmed a selective adsorption of lipases on Diaion, thus endorsing simultaneous immobilization and purification. Gibbs free energy (∆G) evinced the spontaneity of the process (–17.9 kJ/mol ≤ ∆G ≤ –5.1 kJ/mol). Maximum immobilized protein concentration of 30 mg/g support by CRL. This biocatalyst was the most active in olive oil hydrolysis (hydrolytic activity of 126.0 ± 2.0 U/g) and in the synthesis of aromatic esters. Maximum conversion yield of 89.1% was attained after 150 Min for the synthesis of hexyl butyrate, followed by the synthesis of geranyl butyrate (87.3% after 240 Min) and propyl butyrate (80.0% after 150 Min). CRL immobilized on Diaion retained around 93% of its original activity after six consecutive cycles of 150 Min for the synthesis of hexyl butyrate.
Applicability of ninhydrin as a fluorescent reagent for estimation of teicoplanin in human plasma using salting‐out assisted liquid–liquid extraction technique
Authors: Ali Marwa F. B. , Salman Baher I. , Hussein Samiha A. , Marzouq Mostafa A.
Published: May 2020

The applicability of ninhydrin, a widely used derivatizing reagent, for determination of teicoplanin (TEIC) in its pure form, pharmaceutical vials, and in human plasma was investigated. The presented spectrofluorimetric method was based on a condensation reaction between ninhydrin and the primary amine group existing in TEIC (in the presence of phenylacetaldehyde) to produce a highly fluorescent product detected at 460 nm (λex,390 nm). Calibration plots were constructed in the concentration range 60–600 ng mL–1 with a good correlation coefficient of 0.9998 and a low detection limit of 10.84 ng mL–1. The method was subjected to a bioanalytical validation study according to US‐FDA recommendations. The proposed method was applied for analysis of TEIC in commercial vials with high recovery result 101.88 ± 1.11%. In addition, the method was utilized efficiently for detection of TEIC in human plasma using salting‐out assisted liquid–liquid extraction technique (SALLE) with a recovery range from 96.71 ± 1.08% to 97.71 ± 0.86%. SALLE is an effective approach used for extraction of TEIC from human plasma without interferences using ammonium sulphate. The proposed method is highly recommended to monitor TEIC in clinical laboratory samples and therapeutic drug monitoring systems.
Hybrid‐EKF: Hybrid model coupled with extended Kalman filter for real‐time monitoring and control of mammalian cell culture
Authors: Narayanan Harini , Behle Lars , Luna Martin F. , Sokolov Michael , Guillén‐Gosálbez Gonzalo , Morbidelli Massimo , Butté Alessandro
Published: May 2020

In a decade when Industry 4.0 and quality by design are major technology drivers of biopharma, automated and adaptive process monitoring and control are inevitable requirements and model‐based solutions are key enablers in fulfilling these goals. Despite strong advancement in process digitalization, in most cases, the generated datasets are not sufficient for relying on purely data‐driven methods, whereas the underlying complex bioprocesses are still not completely understood. In this regard, hybrid models are emerging as a timely pragmatic solution to synergistically combine available process data and mechanistic understanding. In this study, we show a novel application of the hybrid‐EKF framework, that is, hybrid models coupled with an extended Kalman filter for real‐time monitoring, control, and automated decision‐making in mammalian cell culture processing. We show that, in the considered application, the predictive monitoring accuracy of such a framework improves by at least 35% when developed with hybrid models with respect to industrial benchmark tools based on PLS models. In addition, we also highlight the advantages of this approach in industrial applications related to conditional process feeding and process monitoring. With regard to the latter, for an industrial use case, we demonstrate that the application of hybrid‐EKF as a soft sensor for titer shows a 50% improvement in prediction accuracy compared with state‐of‐the‐art soft sensor tools.
Incidence and survival of rare cancers in the US and Europe
Authors: Botta Laura , Gatta Gemma , Trama Annalisa , Bernasconi Alice , Sharon Elad , Capocaccia Riccardo , Mariotto Angela B. ,   the RARECAREnet working group
Published: May 2020

Geographical variability of cancer burden was almost exclusively estimated for common cancers. Since rare cancers (RC) have become an area of priority for basic and clinical research and public health organizations, this paper provides, using a common methodology, a detailed comparison of incidence and survival for RC in the US and Europe. We estimated incidence and net survival of 199 malignant RC from data of 2 580 000 patients collected by 18 US‐SEER and 94 European registries, diagnosed within the most recent common period 2000‐2007. RC were defined according to the criterion of crude annual incidence rates <6/100 000. In total, 196 RC were classified as rare in both populations. Of these, 43 had incidence rates significantly different by at least 0.2 per 100 000:34 higher in the US and 9 higher in Europe. Five‐year net survival for all RC combined significantly differed: 54% in the US and 48% in Europe. Survival for 62 RC was significantly higher in the US vs 6 higher in Europe. Differences were not concentrated in a particular cancer family, and were mostly relevant for cases diagnosed >65+ years of age. Use of standardized methods evidenced that incidence and survival rate of majority of RC were higher in the United States compared to Europe. Possible reasons for such differences, requiring further studies, include distribution of risk factors, ability to diagnose RC, different registration practices, and use of updated International Classification of Diseases for Oncology.
Fibronectin promotes tumor cells growth and drugs resistance through a CDC42‐YAP‐dependent signaling pathway in colorectal cancer
Authors: Ye Yu , Zhang Ruifeng , Feng Haiyang
Published: May 2020

Fibronectin (FN) is a high‐molecular‐weight glycoprotein of the extracellular matrix (ECM) that binds to membrane‐spanning receptor proteins or other elements in ECM. The expression of FN could be involved in the cancer cells proliferation or migration, and the molecular mechanisms responsible for FN induced protumor signals begin to be elucidated. Here, we report that the elevated expression of FN was observed in those chemoresistant tumor tissues from patients with colorectal cancer. Consistently, FN culture significantly strengthened the proliferation of colorectal cancer cells, induced the colorectal tumor sustained growth and drug resistance in vitro and in vivo. In mechanism, FN could bind to integrin αvβ1, resulting the downstream cell division cycle 42/yes‐associated protein 1 (CDC42/YAP‐1) signaling pathway activation. The activation of CDC42/YAP‐1 signal induces the upregulation of transcription factor SOX2, causing the sustained growth and drugs resistance in colorectal cancer. Blockade of integrin αvβ1 significantly suppressed the colorectal cancer growth and drugs resistance development in vitro and in vivo, which provides a new target for clinical colorectal cancer treatment.
Folium Sennae and emodin reverse airway smooth muscle contraction
Authors: Qiu Jun‐Ying , Ma Li‐Qun , Liu Bei‐Bei , Zhang Wen‐Jing , Liu Meng‐Su , Wang Ge‐Ge , Zhao Xiao‐Xue , Luo Xi , Wang Qian , Xu Hao , Zang Dun‐An , Shen Jinhua , Peng Yong‐Bo , Zhao Ping , Xue Lu , Yu Meng‐Fei , Chen Weiwei , Dai Jiapei , Liu Qing‐Hua
Published: May 2020

The objective of this project was to find a bronchodilatory compound from herbs and clarify the mechanism. We found that the ethanol extract of Folium Sennae (EEFS) can relax airway smooth muscle (ASM). EEFS inhibited ASM contraction, induced by acetylcholine, in mouse tracheal rings and lung slices. High‐performance liquid chromatography assay showed that EEFS contained emodin. Emodin had a similar reversal action. Acetylcholine‐evoked contraction was also partially reduced by nifedipine (a selective inhibitor of L‐type voltage‐dependent Ca2+ channels, LVDCCs), YM‐58483 (a selective inhibitor of store‐operated Ca2+ entry, SOCE), as well as Y‐27632 (an inhibitor of Rho‐associated protein kinase). In addition, LVDCC‐ and SOCE‐mediated currents and cytosolic Ca2+ elevations were inhibited by emodin. Emodin reversed acetylcholine‐caused increases in phosphorylation of myosin phosphatase target subunit 1. Furthermore, emodin, in vivo, inhibited acetylcholine‐induced respiratory system resistance in mice. These results indicate that EEFS‐induced relaxation results from emodin inhibiting LVDCC, SOCE, and Ca2+ sensitization. These findings suggest that Folium Sennae and emodin may be new sources of bronchodilators.
Transcatheter edge‐to‐edge mitral valve repair for annuloplasty ring dehiscence: The peri‐ring approach
Authors: Otero Diana , Raza Munis , Kahlon Tanvir , Singh Vikas
Published: May 2020

Recurrent severe primary mitral regurgitation from annuloplasty ring dehiscence is very rare and is associated with adverse outcomes. We present a case where transcatheter edge‐to‐edge mitral repair with MitraClip was used in high surgical risk patient using a peri‐ring approach due to unfavorable anatomy for a conventional intra‐ring approach.
The snared wire technique for Sapien valve implantation in the pulmonary position
Authors: Maschietto Nicola , Sperotto Francesca , Esch Jesse E. , Porras Diego , Callahan Ryan
Published: May 2020

Objectives

Description of the snared wire technique (SWT) to facilitate the delivery of the Sapien valve in pulmonary position, and comparison with standard delivery technique.

Background

Transcatheter pulmonary valve replacement (TPVR) with the Sapien delivery system has proven to be challenging. Therefore, alternative strategies for facilitating its delivery in this position are needed.

Methods

Retrospective analysis of patients who underwent TPVR with or without the new SWT. The SWT was chosen as an elective strategy when the anatomy was judged to be challenging for TPVR (planned SWT) or as a rescue strategy when a standard delivery failed (rescue SWT).

Results

From February 2018 to January 2020, 84 patients underwent TPVR with a Sapien S3 valve using either a standard delivery (n = 63, 75%) or a SWT (n = 21, 25%). Fifteen patients underwent a planned SWT, six patients underwent a rescue SWT after failure of a standard delivery. All planned SWT cases were successful and, compared to the standard delivery group, no significant differences were found in terms of time to valve‐deployment, fluoroscopy time, procedure time, or frequency of complications. Rescue SWT cases had longer fluoroscopy time (p = .05), longer time to valve‐deployment (p = .0001), and higher frequency of complications (p = .002) including tricuspid valve injury (p = .0004), but allowed the operator to successfully implant the valve into the desired location.

Conclusions

Even in the most challenging anatomies, the SWT represents a feasible and effective alternative strategy for TPVR with the Sapien valve that should be considered when other techniques have failed.
New combined surgery for cervical cancer complicated by pelvic organ prolapse using autologous fascia lata: A case report
Authors: Ota Yukihide , Suzuki Yukio , Matsunaga Tatsuya , Ninomiya Ryunosuke , Kagimoto Shintaro , Miyagi Etsuko
Published: May 2020

Radical hysterectomy and immediate sacral colpopexy using autologous fascia lata could be considered a treatment option for cervical cancer complicated by severe and symptomatic pelvic organ prolapse.
Unveiling VIVO2+ Binding Modes to Human Serum Albumins by an Integrated Spectroscopic–Computational Approach
Authors: Sciortino Giuseppe , Sanna Daniele , Lubinu Giuseppe , Maréchal Jean‐Didier , Garribba Eugenio
Published: May 2020

Human serum albumin (HSA) is involved in the transport of metal ions and potential metallodrugs. Depending on the metal, several sites are available, among which are N‐terminal (NTS) and multi‐metal binding sites (MBS). Despite the large number of X‐ray determinations for albumins, only one structure with Zn2+ is available. In this work, the binding to HSA of the VIVO2+ ion was studied by an integrated approach based on spectroscopic and computational methods, which allowed the systems to be characterized even in the absence of X‐ray analysis. The behavior depends on the type of albumin, defatted (HSAd) or fatted (HSAf). With HSAd ‘primary’ and ‘secondary’ sites were revealed, NTS with (His3, His9, Asp13, Asp255) and MBS with (His67, His247, Asp249, Asn99 or H2O); with increasing the ratio VIVO2+/HSAd, ‘tertiary’ sites, with one His‐N and other donors (Asp/Glu‐O or carbonyl‐O) are populated. With HSAf, fatty acids (FAs) cause a rotation of the subdomains IA and IIA, which results in the formation of a dinuclear ferromagnetic adduct (VIVO)2D(HSAf) with a μ1,1‐Asp249 and the binding of His247, Glu100, Glu252, and His67 or Asn99. FAs hinder also the binding of VIVO2+ to the MBS.
Patterns and predictors of cancer‐related fatigue in ovarian and endometrial cancers: 1‐year longitudinal study
Authors: Poort Hanneke , de Rooij Belle H. , Uno Hajime , Weng Shicheng , Ezendam Nicole P. M. , van de Poll‐Franse Lonneke , Wright Alexi A.
Published: May 2020

Background

Fatigue is a common and distressing symptom for patients with gynecologic cancers. Few studies have empirically examined whether it spontaneously resolves. This study was aimed at identifying longitudinal patterns of fatigue and predictors of clinically significant fatigue 1 year after treatment completion.

Methods

This was a prospective cohort study of women with newly diagnosed ovarian (n = 81) or endometrial cancer (n = 181) that did not progress or recur within 1 year of treatment completion. Symptoms of fatigue, depression, and anxiety were assessed after surgery and 6 and 12 months after treatment completion with the Fatigue Assessment Scale and the Hospital Anxiety and Depression Scale. Patients' fatigue scores over time were classified (scores of 22‐50, clinically significant; scores of 10‐21, not clinically significant). Logistic regression models were fit to examine associations between fatigue and patient characteristics.

Results

Among 262 participants, 48% reported clinically significant fatigue after surgery. One year later, 39% reported fatigue. There were 6 patterns over time: always low (37%), always high (25%), high then resolves (18%), new onset (10%), fluctuating (6%), and incidental (5%). Patients with fatigue after surgery were more likely to report fatigue at 12 months in comparison with others (odds ratio [OR], 6.08; 95% confidence interval [CI], 2.82‐13.11;P < .001). Patients with depressive symptoms also had higher odds of fatigue (OR, 3.36; 95% CI, 1.08‐10.65;P = .039), although only one‐third of fatigued patients reported depressive symptoms.

Conclusion

Nearly half of women with gynecologic cancers had clinically significant fatigue after surgery, whereas 44% and 39% had fatigue 6 months and 1 year later; this suggests that spontaneous regression of symptoms is relatively rare. Women who reported fatigue, depressive symptoms, or 2 or more medical comorbidities had higher odds of reporting fatigue 1 year later. Future studies should test scalable interventions to improve fatigue in women with gynecologic cancers.
Predicate logic reasoning for exploration coordination of multi‐robot systems in structured environments
Authors: Dai Xuefeng , Wang Jiazhi , Zhao Jianqi , Li Dahui , Yao Zhifeng
Published: May 2020

To improve time efficiency for structured environment exploration of multi‐robot systems, a novel coordinated strategy based on predicate logic reasoning is proposed in this paper. The strategy assigns the room with maximal utility to the robot with the optimal exploring property, and realizes cooperative exploration by considering the room capacity. A set of predicate logic reasoning formulas is established to implement the coordination. The coordination takes into account robot performance and environment property and is conducted in a distributed manner. In addition, to save computing and storage resources, a triple set named as task information was proposed instead of traditional unfinished job list for environment information sharing among robots. The results are validated by computer simulations for two simulated office like environments.
Prioritization of Anti‐SARS‐Cov‐2 Drug Repurposing Opportunities Based on Plasma and Target Site Concentrations Derived from their Established Human Pharmacokinetics
Authors: Arshad Usman , Pertinez Henry , Box Helen , Tatham Lee , Rajoli Rajith K. R. , Curley Paul , Neary Megan , Sharp Joanne , Liptrott Neill J. , Valentijn Anthony , David Christopher , Rannard Steve P. , O’Neill Paul M. , Aljayyoussi Ghaith , Pennington Shaun H. , Ward Stephen A. , Hill Andrew , Back David J. , Khoo Saye H. , Bray Patrick G. , Biagini Giancarlo A. , Owen Andrew
Published: May 2020

There is a rapidly expanding literature on thein vitroantiviral activity of drugs that may be repurposed for therapy or chemoprophylaxis against severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). However, this has not been accompanied by a comprehensive evaluation of the target plasma and lung concentrations of these drugs following approved dosing in humans. Accordingly, concentration 90% (EC90) values recalculated fromin vitroanti‐SARS‐CoV‐2 activity data was expressed as a ratio to the achievable maximum plasma concentration (Cmax) at an approved dose in humans (Cmax/EC90ratio). Only 14 of the 56 analyzed drugs achieved a Cmax/EC90ratio above 1. A more in‐depth assessment demonstrated that only nitazoxanide, nelfinavir, tipranavir (ritonavir‐boosted), and sulfadoxine achieved plasma concentrations above their reported anti‐SARS‐CoV‐2 activity across their entire approved dosing interval. An unbound lung to plasma tissue partition coefficient (KpUlung) was also simulated to derive a lung Cmax/half‐maximal effective concentration (EC50) as a better indicator of potential human efficacy. Hydroxychloroquine, chloroquine, mefloquine, atazanavir (ritonavir‐boosted), tipranavir (ritonavir‐boosted), ivermectin, azithromycin, and lopinavir (ritonavir‐boosted) were all predicted to achieve lung concentrations over 10‐fold higher than their reported EC50. Nitazoxanide and sulfadoxine also exceeded their reported EC50by 7.8‐fold and 1.5‐fold in lung, respectively. This analysis may be used to select potential candidates for further clinical testing, while deprioritizing compounds unlikely to attain target concentrations for antiviral activity. Future studies should focus on EC90values and discuss findings in the context of achievable exposures in humans, especially within target compartments, such as the lungs, in order to maximize the potential for success of proposed human clinical trials.
Analysis of Immunosuppressant Drugs in Whole Blood by Liquid Chromatography–Tandem Mass Spectrometry (LC‐MS/MS)
Authors: Pablo Abed H. , Breaud Autumn R. , Clarke William
Published: May 2020

Immunosuppressant medications help suppress the immune system response through inhibition of various checkpoints in the regulatory biochemical pathway. This is useful in prevention of organ rejection in transplantation or in the treatment of autoimmune diseases such as lupus or rheumatoid arthritis. Quantification of immunosuppressive drugs in blood is needed clinically for optimization of treatment and to avoid toxicity or unwanted side effects. Here, we describe a quantitative method to determine the concentration of cyclosprine A, tacrolimus, sirolimus, and everolimus in whole blood. This method has been used for many years clinically to support patient care. © 2020 by John Wiley & Sons, Inc.
Quantitative analysis of paracetamol, metacetamol, and orthocetamol in equine urine from racehorses in Japan using liquid chromatography–electrospray ionization–tandem mass spectrometry
Authors: Ishii Hideaki , Obara Taku , Kusano Kanichi , Kijima‐Suda Isao
Published: May 2020

Paracetamol is commonly used as an over‐the‐counter analgesic and antipyretic medication for humans, but not sold as a legitimate therapeutic medication for horses in Japan. However, paracetamol is commonly found in horses together with its two isomers, metacetamol and orthocetamol. We previously reported that paracetamol and orthocetamol were both present in selected feed consumed by Japanese racehorses. For the purpose of the doping control of paracetamol in local Japanese horses, we proposed establishing residue limits (Japanese residue limits, JRLs) to minimize the risk of reporting paracetamol from environmental contributions and to differentiate its presence from active administration. Recently, we proposed a preliminary JRL for paracetamol in equine plasma based on a population study of more than 300 Japanese racehorses. In this paper, we will present our studies on the urinary concentrations of paracetamol, metacetamol, and orthocetamol in postrace samples collected from 403 Japanese racehorses over a 1 year period, detected using liquid chromatography–electrospray ionization–tandem mass spectrometry. Our results revealed that the hydrolyzed urinary concentrations of paracetamol, metacetamol, and orthocetamol were in the range 15.7–2,360 ng/mL (median 363 ng/mL), 8.07–382 ng/mL (84.5 ng/mL), and 919–74,418 ng/mL (13,475 ng/mL), respectively. Based on our statistical model, the preliminary JRL of hydrolyzed paracetamol in equine urine was determined to be 7,400 ng/mL, at a risk factor of 1 in 10,000. Further investigations will be required to demonstrate the applicability and validity of our preliminary plasma and urine JRLs to local Japanese racehorses.
A proposal of a procedure to estimate a standard line for contactless estimation of a solar cell voltage in a module using modulated light
Authors: Kobayashi Yasuyuki , Kisu Shunsuke
Published: May 2020

It is important to measure the operating voltage of a cell sealed in a photovoltaic module as well as well‐known faults such as abnormal hot spots observed by thermography or a dark part in electroluminescence distribution on the module for detecting a fault module. This paper proposes a method that radiating modulated light toward a cell and extracting the synchronized signal from the module output by phase detector can estimate the operating voltage quantitatively by using a standard line predicted by shading the module partially.
Methanol production by high‐temperature thermochemical cycle
Authors: Khalid Farrukh , Bicer Yusuf
Published: May 2020

This paper explores an alternative method of ethanol production using a high‐temperature two‐step electrolytic cycle using carbon dioxide (CO2). The cycle comprises two steps namely; absorption step and electrolytic step. The proposed cycle uses CO2 and water as the feed stocks and produces methanol using electricity. The other chemicals in the cycles are recycled, which are used in the subsequent steps. To assess the performance, evaluation of the exergy and energy efficiencies of the complete cycle is done. Furthermore, the comparison with the traditional/conventional method of methanol production is also made by comparing various efficiencies. The simulation findings reveal the potential utilization of the proposed electrolytic methanol cycle, the exergy efficiency of 94.4% and the energy efficiency of 37.0% can be achieved. Furthermore, it is found that to produce 1 mole of methanol, ideally, 1.4 V of voltage is required by using the proposed cycle. In addition, a detailed parametric study is also conducted to observe the effects of significant parameters such as cycle temperature, supplied electricity, etc. on the cycle performance.
Anglers’ Views on Using Signs to Communicate Fish Consumption Advisories
Authors: Gray Kathleen M , LePrevost Catherine E , Cope W Gregory
Published: May 2020

The purpose of this case study was to examine signs as a means of communicating fish consumption advisory information to English- and Spanish-speaking anglers in North Carolina. This study involved a group of stakeholders, including representatives from local and state agencies, non-governmental organizations, and academia, as well as 38 anglers in focus group discussions to learn about their knowledge and beliefs in the context of fishing in polluted waterways, including what they knew about fish consumption advisories and their perceptions of prototype signs. Across groups, participants identified two confusing elements of signs: the allowable number of servings of fish under advisory and distinct consumption recommendations for different subgroups. They recommended streamlined messaging and the use of visuals, lay terms, and locally relevant languages as ways to improve prototype signs. Additionally, participants identified the state wildlife agency as a common source of information about fish safety, more so than signs. These results suggest opportunities for improved communication of advisories, especially to the most at-risk populations.
Effectiveness of current hygiene practices on minimization of Listeria monocytogenes in different mushroom production‐related environments
Authors: Pennone Vincenzo , Dygico Kenneth Lyonel , Coffey Aidan , Gahan Cormac G.M. , Grogan Helen , McAuliffe Olivia , Burgess Catherine M. , Jordan Kieran
Published: May 2020

Background

The commercial production of Agaricus bisporus is a three stage process: 1) production of compost, also called “substrate”; 2) production of casing soil; and 3) production of the mushrooms. Hygiene practices are undertaken at each stage: pasteurization of the substrate, hygiene practices applied during the production of casing soil, postharvest steam cookout, and disinfection at the mushroom production facilities. However, despite these measures, foodborne pathogens, including Listeria monocytogenes, are reported in the mushroom production environment. In this work, the presence of L. monocytogenes was evaluated before and after the application of hygiene practices at each stage of mushroom production with swabs, samples of substrate, casing, and spent mushroom growing substrates.

Results

L. monocytogenes was not detected in any casing or substrate sample by enumeration according to BS EN ISO 11290‐2:1998. Analysis of the substrate showed that L. monocytogenes was absent in 10 Phase II samples following pasteurization, but was then present in 40% of 10 Phase III samples. At the casing production facility, 31% of 59 samples were positive. Hygiene improvements were applied, and after four sampling occasions, 22% of 37 samples were positive, but no statistically significant difference was observed (p > .05). At mushroom production facilities, the steam cookout process inactivated L. monocytogenes in the spent growth substrate, but 13% of 15 floor swabs at Company 1 and 19% of 16 floor swabs at Company 2, taken after disinfection, were positive.

Conclusion

These results showed the possibility of L. monocytogenes recontamination of Phase III substrate, cross‐contamination at the casing production stage and possible survival after postharvest hygiene practices at the mushroom growing facilities. This information will support the development of targeted measures to minimize L. monocytogenes in the mushroom industry.
Mental stress and physical activity interact with the genetic risk scores of the genetic variants related to sweetness preference in high sucrose‐containing food and glucose tolerance
Authors: Park Sunmin , Liu Meiling , Song Mi Young
Published: May 2020

We hypothesized that subjects with genetic variants that increase sweet taste preference would consume more sucrose‐containing foods and have altered energy and glucose metabolisms, which would have interactions with lifestyles. Korean genome and epidemiology study (KoGES) was conducted to determine genetic variants and lifestyles including nutrient intakes by the Korean Center for Disease and Control during 2004–2013. Subjects were 8,842 adults aged 40–69 years in Ansan/Ansung cohorts in Korea. The associations between genetic risk scores(GRS) selected for influencing higher sweet preference and energy and glucose metabolism were examined using logistic regression after adjusting for covariates. GRS included 8 SNPs, TAS1R2_rs61761364, SLC2A5_rs11121306, SLC2A7_ rs769902, SLC2A5_rs765618, TRPM5_rs1965606, TRPV1_rs224495, TRPV1_ rs8065080, and TRPV1_rs8078502. Sweet taste preference was higher by 1.30‐folds in high GRS than in low GRS (p < .0001). Consistent with sweet taste preference, carriers with high GRS had a higher intake of sucrose‐containing foods by 1.25 (1.08–1.46)‐fold than those with low GRS after adjusting age, gender, BMI, and energy intake. However, glucose intolerance risk was rather lower by 0.861 (0.76–0.98)‐fold in high GRS than low GRS (p < .05). GRS tended to interact with mental stress to affect sucrose intake (p = .048). Only in low mental stress levels, sucrose‐containing food intake was higher in high GRS than low GRS. There was an interaction of GRS with physical activity to influence glucose intolerance. Serum glucose concentrations were lower by 0.808‐folds in high GRS than low GRS only in a high physical activity state. In conclusion, adults with genetically high sweet taste preference had a positive association with high sucrose‐containing food intakes and improved glucose tolerance. The genetic impact on sweetness preference was associated with offset by high mental stress and lack of physical activity.
Effects of a low‐energy diet with and without oat bran and olive oil supplements on body mass index, blood pressure, and serum lipids in diabetic women: A randomized controlled trial
Authors: AlFaris Nora A. , Ba‐Jaber Adnan S.
Published: May 2020

Type 2 diabetes is an epidemic public health issue worldwide. It is common among adults and is more severe among overweight and obese subjects. This study was conducted to evaluate the effects of a low‐energy diet with and without oat bran and olive oil supplements on body mass index, blood pressure, and serum lipids in women with diabetes. It was conducted for three months among 78 participants after dividing them into six groups. Groups 2 to 6 were received low‐energy diet (1,600 kcal/day), with or without oat bran (10 g/day) and olive oil (5 g/day) supplements. Weight, height, blood pressure, and serum lipids were measured. A low‐energy diet with and without oat bran and olive oil supplements lowers body mass index in subjects by 0.9%–6.0% on average. It also lowers systolic and diastolic blood pressure by 1.0%–9.0% and 4.8%–12.6%, respectively. Serum triglycerides were declined in groups 2, 3, and 4 by 27.2%, 17.3%, and 1.7%, respectively, but not significantly. Total cholesterol was dropped significantly by 8.3% only when the low‐energy diet was used with oat bran supplement among obese subjects, while LDL cholesterol was dropped significantly by 20.0% only when it was used with oat bran and olive oil supplements among subjects with high serum triglycerides. Proper control of type 2 diabetes among overweight and obese adults is needed to control cardiovascular complications. This could be accomplished by following a low‐energy diet and incorporating healthy foods such as oat and olive oil into the usual diet.
Subsidiary upgrading and global value chain governance in the multinational enterprise
Authors: Ryan Paul , Buciuni Giulio , Giblin Majella , Andersson Ulf
Published: May 2020

Research Summary

Upgrading and governance in global value chains (GVCs) have been understood mainly through studying the buyer–supplier transaction, where the supplier is typically an independent contractor from a developing economy. Little is known about how subsidiaries of multinational enterprises (MNEs) can upgrade in a GVC, whose core activities are coordinated through the “hierarchy” governance model. Using an in‐depth longitudinal single case study in the medical devices industry, we explain how a subsidiary can accomplish upgrading in an intra‐MNE GVC and, over time, increase its control of this GVC reaching a joint coordinator role for its governance. Our findings show that partaking in innovation may not be the final stage of a subsidiary's upgrading but can represent the start of a new phase that culminates with joint coordination of the GVC.

Managerial Summary

The competitiveness of a global subsidiary is determined by its capacity to upgrade in a GVC and engage in higher value‐adding activities. Moving from production to innovation is generally viewed as the pinnacle for subsidiaries in the accomplishment of upgrading within a GVC, thereby ensuring long‐term survival. We show however that specializing in innovation is not the highest peak a subsidiary can reach. Innovation is in fact a necessary condition for a strategic role for the coordination of a GVC. A subsidiary's management team can deliberately strategize to ascend to such a position in the multi‐business MNE as a GVC joint coordinator for a product category. It can achieve this prominent position by leveraging its innovation capabilities to assume a greater proportion of control over the business's GVC governance. This position of greater prominence for the subsidiary within the MNE advances its internal advantage and strengthens its survival prospects.
Disordered directional brain network interactions during learning dynamics in schizophrenia revealed by multivariate autoregressive models
Authors: Baajour Shahira J. , Chowdury Asadur , Thomas Patricia , Rajan Usha , Khatib Dalal , Zajac‐Benitez Caroline , Falco Dimitri , Haddad Luay , Amirsadri Alireza , Bressler Steven , Stanley Jeffery A. , Diwadkar Vaibhav A.
Published: May 2020

Directional network interactions underpin normative brain function in key domains including associative learning. Schizophrenia (SCZ) is characterized by altered learning dynamics, yet dysfunctional directional functional connectivity (dFC) evoked during learning is rarely assessed. Here, nonlinear learning dynamics were induced using a paradigm alternating between conditions (Encoding and Retrieval). Evoked fMRI time series data were modeled using multivariate autoregressive (MVAR) models, to discover dysfunctional direction interactions between brain network constituents during learning stages (Early vs. Late), and conditions. A functionally derived subnetwork of coactivated (healthy controls [HC]∩SCZ] nodes was identified. MVAR models quantified directional interactions between pairs of nodes, and coefficients were evaluated for intergroup differences (HC ≠ SCZ). In exploratory analyses, we quantified statistical effects of neuroleptic dosage on performance and MVAR measures. During Early Encoding, SCZ showed reduced dFC within a frontal–hippocampal–fusiform network, though during Late Encoding reduced dFC was associated with pathwaystowardthe dorsolateral prefrontal cortex (dlPFC). During Early Retrieval, SCZ showed increased dFC in pathways to and from the dorsal anterior cingulate cortex, though during Late Retrieval, patients showed increased dFC in pathwaystowardthe dlPFC, but decreased dFC in pathwaysfromthe dlPFC. These discoveries constitute novel extensions of our understanding of task‐evoked dysconnection in schizophrenia and motivate understanding of thedirectionalaspect of the dysconnection in schizophrenia. Disordered directionality should be investigated using computational psychiatric approaches that complement the MVAR method used in our work.