bluuebunny/crossref_metadata_2025 huggingface dataset:
The Approved Dose of Ivermectin Alone is not the Ideal Dose for the Treatment of COVID‐19
Authors: Schmith Virginia D. , Zhou Jie (Jessie) , Lohmer Lauren R.L.
Published: May 2020

Caly et al.1 reported that ivermectin inhibited severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) in vitro for up to 48 hours using ivermectin at 5 μM. The concentration resulting in 50% inhibition (IC50; 2 µM) was > 35× higher than the maximum plasma concentration (Cmax) after oral administration of the approved dose of ivermectin when given fasted. Simulations were conducted using an available population pharmacokinetic model to predict total (bound and unbound) and unbound plasma concentration‐time profiles after a single and repeat fasted administration of the approved dose of ivermectin (200 μg/kg), 60 mg, and 120 mg. Plasma total Cmax was determined and then multiplied by the lung:plasma ratio reported in cattle to predict the lung Cmax after administration of each single dose. Plasma ivermectin concentrations of total (bound and unbound) and unbound concentrations do not reach the IC50, even for a dose level 10× higher than the approved dose. Even with the high lung:plasma ratio, ivermectin is unlikely to reach the IC50 in the lungs after single oral administration of the approved dose (predicted lung: 0.0873 µM) or at doses 10× higher that the approved dose administered orally (predicted lung: 0.820 µM). In summary, the likelihood of a successful clinical trial using the approved dose of ivermectin is low. Combination therapy should be evaluated in vitro. Repurposing drugs for use in coronavirus disease 2019 (COVID‐19) treatment is an ideal strategy but is only feasible when product safety has been established and experiments of repurposed drugs are conducted at clinically relevant concentrations.
Modeling the Physicochemical Properties of Natural Deep Eutectic Solvents
Authors: Kovács Attila , Neyts Erik C. , Cornet Iris , Wijnants Marc , Billen Pieter
Published: May 2020

Natural deep eutectic solvents (NADES) are mixtures of naturally derived compounds with a significantly decreased melting point owing to specific interactions among the constituents. NADES have benign properties (low volatility, flammability, toxicity, cost) and tailorable physicochemical properties (by altering the type and molar ratio of constituents); hence, they are often considered to be a green alternative to common organic solvents. Modeling the relation between their composition and properties is crucial though, both for understanding and predicting their behavior. Several efforts have been made to this end. This Review aims at structuring the present knowledge as an outline for future research. First, the key properties of NADES are reviewed and related to their structure on the basis of the available experimental data. Second, available modeling methods applicable to NADES are reviewed. At the molecular level, DFT and molecular dynamics allow density differences and vibrational spectra to be interpreted, and interaction energies to be computed. Additionally, properties at the level of the bulk medium can be explained and predicted by semi‐empirical methods based on ab initio methods (COSMO‐RS) and equation of state models (PC‐SAFT). Finally, methods based on large datasets are discussed: models based on group‐contribution methods and machine learning. A combination of bulk‐medium and dataset modeling allows qualitative prediction and interpretation of phase equilibria properties on the one hand, and quantitative prediction of melting point, density, viscosity, surface tension, and refractive index on the other. Multiscale modeling, combining molecular and macroscale methods, is expected to strongly enhance the predictability of NADES properties and their interaction with solutes, and thus yield truly tailorable solvents to accommodate (bio)chemical reactions.
A deep learning approach with Bayesian optimization and ensemble classifiers for detecting denial of service attacks
Authors: Gormez Yasin , Aydin Zafer , Karademir Ramazan , Gungor Vehbi C.
Published: May 2020

Detecting malicious behavior is important for preventing security threats in a computer network. Denial of Service (DoS) is among the popular cyber attacks targeted at web sites of high‐profile organizations and can potentially have high economic and time costs. In this paper, several machine learning methods including ensemble models and autoencoder‐based deep learning classifiers are compared and tuned using Bayesian optimization. The autoencoder framework enables to extract new features by mapping the original input to a new space. The methods are trained and tested both for binary and multi‐class classification on Digiturk and Labris datasets, which were introduced recently for detecting various types of DDoS attacks. The best performing methods are found to be ensembles though deep learning classifiers achieved comparable level of accuracy.
Future IoT‐enabled threats and vulnerabilities: State of the art, challenges, and future prospects
Authors: Srivastava Astha , Gupta Shashank , Quamara Megha , Chaudhary Pooja , Aski Vidyadhar Jinnappa
Published: May 2020

In the recent era, the security issues affecting the future Internet‐of‐Things (IoT) standards has fascinated noteworthy consideration from numerous research communities. In this view, numerous assessments in the form of surveys were proposed highlighting several future IoT‐centric subjects together with threat modeling, intrusion detection systems (IDS), and various emergent technologies. In contrast, in this article, we have focused exclusively on the emerging IoT‐related vulnerabilities. This article is a multi‐fold survey that emphasizes on understanding the crucial causes of novel vulnerabilities in IoT paradigms and issues in existing research. Initially, we have emphasized on different layers of IoT architecture and highlight various emerging security challenges associated with each layer along with the key issues of different IoT systems. Secondly, we discuss the exploitation, detection, and defense methodologies of IoT malware‐enabled distributed denial of service (DDoS), Sybil, and collusion attack capabilities. We have also discussed numerous state‐of‐the‐art strategies for intrusion detection and methods for IDS setup in future IoT systems. Third, we have presented a brief classification of existing IoT authentication protocols and a comparative analysis of such protocols based on different IoT‐enabled cyber attacks. For conducting a real‐time future IoT research, we have presented some emerging blockchain solutions. We have also discussed a comparative examination of some of the recently developed simulation tools and IoT test beds that are characterized based on different layers of IoT infrastructure. We have also outlined some of the open issues and future research directions and also facilitate the readers with broad classification of existing surveys in this domain that addresses several scopes related to the IoT paradigm. This survey article focuses in enabling IoT‐related research activities by comparing and merging scattered surveys in this domain.
Divergent selection on flowering phenology but not on floral morphology between two closely related orchids
Authors: Chapurlat Elodie , Le Roncé Iris , Ågren Jon , Sletvold Nina
Published: May 2020

Closely related species often differ in traits that influence reproductive success, suggesting that divergent selection on such traits contribute to the maintenance of species boundaries. Gymnadenia conopseass. andGymnadenia densifloraare two closely related, perennial orchid species that differ in (a) floral traits important for pollination, including flowering phenology, floral display, and spur length, and (b) dominant pollinators. If plant–pollinator interactions contribute to the maintenance of trait differences between these two taxa, we expect current divergent selection on flowering phenology and floral morphology between the two species. We quantified phenotypic selection via female fitness in one year on flowering start, three floral display traits (plant height, number of flowers, and corolla size) and spur length, in six populations ofG. conopseas.s. and in four populations ofG. densiflora.There was indication of divergent selection on flowering start in the expected direction, with selection for earlier flowering in two populations of the early‐floweringG. conopseas.s. and for later flowering in one population of the late‐floweringG. densiflora. No divergent selection on floral morphology was detected, and there was no significant stabilizing selection on any trait in the two species. The results suggest ongoing adaptive differentiation of flowering phenology, strengthening this premating reproductive barrier between the two species.Synthesis: This study is among the first to test whether divergent selection on floral traits contribute to the maintenance of species differences between closely related plants. Phenological isolation confers a substantial potential for reproductive isolation, and divergent selection on flowering time can thus greatly influence reproductive isolation and adaptive differentiation.
One‐Pot Successive Turbo Grignard Reactions for the Facile Synthesis of α‐Aryl‐α‐Trifluoromethyl Alcohols
Authors: Kani Ryunosuke , Inuzuka Toshiyasu , Kubota Yasuhiro , Funabiki Kazumasa
Published: May 2020

A novel straightforward one‐pot methodology for two successive turbo Grignard reagent (iPrMgCl·LiCl) reactions, was developed for a facile synthesis of α‐aryl‐α‐trifluoromethyl alcohols, motifs of value in pharmaceutical chemistry. The method displayed broad functional group tolerance, including reducible groups. Dual roles of iPrMgCl·LiCl were exploited in the tandem reaction with commercially available iodoarenes or iodoheteroarenes and 2,2,2‐trifluoroethyl trifluoroacetate. The process encompasses three successive reactions in a one‐pot process: the iPrMgCl·LiCl‐mediated iodine/magnesium‐exchange reaction of iodoarenes or iodoheteroarenes; nucleophilic addition of various generated aryl or heteroarylmagnesium reagents to 2,2,2‐trifluoroethyl trifluoroacetate; and the reduction of in‐situ generated aryl trifluoromethyl ketones with iPrMgCl·LiCl, to produce the corresponding α‐aryl or α‐heteroaryl‐α‐trifluoromethyl alcohols bearing various substituents, including reducible functional groups in good to excellent yields.
Evaluation of commercial biochar in South Korea for environmental application and carbon sequestration
Authors: Oh Seok‐Young , Shin Myungsu , Seo Yong‐Deuk , Cha Soo‐Won
Published: May 2020

The performance of commercial wood chip (WC) and biosolid (BS) biochars available in bulk from carbonization processes in South Korea was examined via determination of sorption capacity from batch experiments and evaluation of carbon sequestration using biochar–mortar composites according to construction and environmental properties. Compared with rice straw (RS) biochar synthesized in a laboratory, the sorption capacities of WC and BC biochars are determined by the types of contaminants, the properties of the biochar, and sorption mechanisms. BS and WC biochars are competitive as sorbents for nitro explosives and chlorinated phenols. Characterization of biochar–mortar composites showed that 3–5 wt% biochar inclusion did not significantly change the composites' engineering properties, including flowability, compressive strength, and thermal conductivity. As the biochar content increased in the biochar–mortar composites, the benzene and toluene concentrations in air were accordingly reduced, suggesting that biochar inclusion may be favorable to remove volatile toxic contaminants that cause sick building syndrome. The toxicity characteristics leaching procedure (TCLP) and Micotox® bioassay tests showed that biochar–mortar composites were not toxic. These results suggest that BS and WC biochars in South Korea are competitive as sorbents for some organic contaminants and that biochar–mortar composites may be environmentally friendly carbon‐sequestering construction materials.
Pyrolysis of waste milk packets in a screw‐type continuous reactor: Optimization through response surface methodology and products characterization
Authors: Almas Sadiya , Lal Navneeta , Varma Anil Kumar , Thakur Lokendra Singh , Mondal Prasenjit
Published: May 2020

In this work, the pyrolysis of waste milk packets was conducted in a screw‐type continuous reactor. The waste milk packets were characterized by the proximate, ultimate, and thermal analyses. The central composite rotatable design has been applied with the variation of reaction temperature and residence time to investigate the optimum process conditions. In addition, different input‐output models have been developed for predicting oil, gas, and char yield. The optimum process temperature and residence time were identified to be 477°C and 45 min, respectively. The yield of oil, gas, and char at the optimum conditions achieved were 51.19 wt%, 41.79 wt%, and 7.00 wt%, respectively. Ultimate composition, physical properties, heating value, and chemical composition analysis of oil have been performed. The composition of gaseous products has been analyzed. The physical properties of the oil were comparable to conventional fuels. The carbon range of the oil is C5–C16, which can be used as a transportation fuel.
Optimization of the formula and processing of a sweet potato leaf powder‐based beverage
Authors: Luo Dan , Mu Tai‐Hua , Sun Hongnan , Chen Jingwang
Published: May 2020

For the development of a sweet potato leaf powder (SPLP)‐based beverage, we investigated the effects of blanching methods on SPLP quality (including color, nutritional and functional compositions and antioxidant activity), and the effects of particle size and stabilizers on suspension stability of final product. The total polyphenol and antioxidant activity of SPLP of uncut group were 1.69 and 1.91 times those of cut group, respectively, and the indices of nutritional quality of copper, manganese and vitamin E of uncut group were significantly greater than cut group. The ultrafine SPLP‐produced lowest gravitational sedimentation ratio (49%), indicating it had greatest suspension stability. The optimized formula of SPLP‐based beverage was as follows: ultrafine SPLP of uncut group was mixed with 2.5% (w/w, powder basis) xanthan gum, 1% calcium lactate, 2% ascorbic acid, 12% maltodextrin, 20% xylitol, and 0.9% apple essence. The final product had high nutritional value along with consumer‐acceptable flavor and texture.
Probing regional cortical excitability via input–output properties using transcranial magnetic stimulation and electroencephalography coupling
Authors: Raffin Estelle , Harquel Sylvain , Passera Brice , Chauvin Alan , Bougerol Thierry , David Olivier
Published: May 2020

The modular organization of the cortex refers to subsets of highly interconnected nodes, sharing specific cytoarchitectural and dynamical properties. These properties condition the level of excitability of local pools of neurons. In this study, we described TMS evoked potentials (TEP) input–output properties to provide new insights into regional cortical excitability. We combined robotized TMS with EEG to disentangle region‐specific TEP from threshold to saturation and describe their oscillatory contents. Twenty‐two young healthy participants received robotized TMS pulses over the right primary motor cortex (M1), the right dorsolateral prefrontal cortex (DLPFC) and the right superior occipital lobe (SOL) at five stimulation intensities (40, 60, 80, 100, and 120% resting motor threshold) and one short‐interval intracortical inhibition condition during EEG recordings. Ten additional subjects underwent the same experiment with a realistic sham TMS procedure. The results revealed interregional differences in the TEPs input–output functions as well as in the responses to paired‐pulse conditioning protocols, when considering early local components (<80 ms). Each intensity in the three regions was associated with complex patterns of oscillatory activities. The quality of the regression of TEPs over stimulation intensity was used to derive a new readout for cortical excitability and dynamical properties, revealing lower excitability in the DLPFC, followed by SOL and M1. The realistic sham experiment confirmed that these early local components were not contaminated by multisensory stimulations. This study provides an entirely new analytic framework to characterize input–output relations throughout the cortex, paving the way to a more accurate definition of local cortical excitability.
Circulating Osteocalcin-Positive Cells as a Novel Diagnostic Biomarker for Bone Metastasis in Breast Cancer Patients
Authors: Lee Kyung-Hun , Lee Kyoung Jin , Kim Tae-Yong , Hutomo Febby , Sun Hyun Jin , Cheon Gi Jeong , Park Serk In , Cho Sun Wook , Im Seock-Ah
Published: May 2020

Current diagnosis of bone metastasis (BM) in breast cancer relies on structural changes of bone that occur only in the advanced stage. A sensitive biomarker for detecting early progression of bone metastasis is urgently required. We performed clinical and preclinical studies to investigate diagnostic value of circulating osteocalcin-positive cells (cOC) in breast cancer bone metastasis. Metastatic breast cancer patients (n = 92) with or without bone metastasis (ie, BM+ or BM–) were enrolled, and cOC were measured at enrollment. Patients were followed up for bone metastasis progression for 18 months. BM+ patients (n = 59) were divided into progressive (PD) or stable disease (SD) groups, based on imaging studies at the end of the 18-month study. The PD group had higher baseline cOC compared with the SD group. Furthermore, higher cOC resulted in reduced BM progression-free survival. Three patients in the BM– group (n = 33) developed new BM during the 18-month study, and these patients had a higher level of baseline cOC compared with the remaining BM– patients. In murine preclinical studies, cOC increased at early time points when micro-metastases were evident only by histology but undetectable by bioluminescence imaging. Also, cOC levels predicted the progression of BM and correlated significantly with BM tumor burden. cOC increased in the early phase of breast cancer BM and can predict BM progression, supporting cOC as a potential novel biomarker. © 2020 American Society for Bone and Mineral Research.
Increasing success in college: Examining the impact of a project‐based introductory engineering course
Authors: Nguyen Ha , Wu Lily , Fischer Christian , Washington Gregory , Warschauer Mark
Published: May 2020

Background

Project‐based learning has shown promise in improving learning outcomes for diverse students. However, studies on its impacts have largely focused on the perceptions of students and instructors or students' immediate performance. This study reports the impact of taking a project‐based introductory engineering course on students' subsequent academic success.

Purpose/Hypothesis

This quantitative study examines characteristics related to enrollment in the project‐based introductory engineering course and subsequent academic performance. We hypothesized that participation in the course would be associated with higher academic performance in subsequent engineering courses. In addition, we examined heterogeneity effects for students traditionally underrepresented in engineering education.

Design/Method

This study utilized data on students' demographics, academic preparation, course enrollment, and course performance from 1,318 engineering students from a large public university in Southern California. Logistic regression analysis with robust standard errors examined enrollment patterns. We applied propensity scores as inverse‐probability weights in multiple linear models to calculate the average treatment effect on the treated for participants from the project‐based introductory engineering course in five subsequent engineering courses. This analysis was conducted for all students and for selected student subgroups.

Results

Enrollment in the project‐based introductory engineering course was positively associated with students' performance in some subsequent engineering courses and did not adversely affect students traditionally underrepresented in engineering.

Conclusions

This study provides an example of a project‐based introductory engineering course that can support students' academic success in engineering. The benefits detected for some student populations (e.g., female) are encouraging for broadening engineering pathways.
Antecedents and consequences of empowering leadership: Leader power distance, leader perception of team capability, and team innovation
Authors: Tang Guiyao , Chen Yang , van Knippenberg Daan , Yu Bingjie
Published: May 2020

The evidence that empowering leadership is an effective form of team leadership brings the question on what the antecedents of empowering leadership are into focus. We propose that empowering leadership is driven by considerations of the normative and situational appropriateness of empowering leadership that are associated with leader power distance value and leader perception of team capability. We propose that leader power distance and perceived team capability interact such that the influence of leader power distance on empowering leadership is stronger with higher perceived team capability. We extend our model to show that by affecting empowering leadership, the interaction of leader power distance and perceived team capability indirectly influences team innovation, an important team outcome associated with empowered teamwork. We tested our model in two multisource surveys in China: Study 1 of 84 technical teams and Study 2 of 83 financial service teams. We discuss how our study contributes to empowering leadership theory by providing a theoretical perspective that lends itself well to identifying other trait and situational antecedents of empowering leadership.
Nutrition Support Team Oversight and Appropriateness of Parenteral Nutrition in Hospitalized Adults: A Systematic Review
Authors: Stidham Morgan A. , Douglas Joy W.
Published: May 2020

Inappropriate parenteral nutrition (PN) administration often occurs in hospitalized patients, increasing the risk of complications. Nutrition support teams (NSTs) regulate and approve PN use in some hospitals. This systematic review examined whether appropriateness of PN use in hospitalized adult patients increased under NST oversight. Ten databases were searched systematically to select studies from 2004 to 2020 that analyzed appropriateness of PN use in adult hospitalized patients under NST oversight. Studies were included if appropriateness of PN was examined and NSTs were involved in PN orders or recommendations. Studies were evaluated using the Quality Criteria Checklist from the Academy of Nutrition and Dietetics Evidence Analysis Library. Nine studies were included in the final analysis. One received a positive rating on the quality checklist, whereas 8 received a neutral rating. Inappropriate PN use varied from 4.3% to 18%. Two studies compared PN use between multiple hospitals, both with and without NSTs. Two compared appropriateness before and after NST implementation, whereas another 2 studies compared it before and after NST restructuring. Three studies examined appropriateness of PN with NST oversight at a single facility with no control group. Overall, NSTs were associated with decreased incidence of inappropriate PN use. No studies were randomized, and several did not describe demographics between groups. Although NSTs appear to decrease inappropriate PN use, the results are limited because of study design or reporting. Future studies should monitor and evaluate clinical outcomes, such as mortality, and utilize more rigorous methodologies.
Synthesis and Characterization of Fluorescent Surfactants for Studying the Penetration of Cosmetic Surfactants on the Skin
Authors: Kong Shuai , Shen Chong , Luo Yulu , Meng Qin
Published: May 2020

Surfactants are one of the important ingredients of cosmetics. However, their penetration and penetration‐promoting behavior in the skin has not been well understood. Aiming to explore the surfactant penetration in skin, a novel fluorescent surfactant F‐C16, based on sodium fluorescein, was synthesized in this paper. F‐C16 has a fluorescence maxima (λem) of around 530 nm, and its fluorescence increased with the polarity of solvent. It possesses good emulsifying properties and low cytotoxicity. Hence, it can be used as a quickly detected indicator for surfactants in cosmetics. As demonstrated by this fluorescent surfactant, it was found that the surfactants can penetrate well into skin and cells. It seems that surfactants in cosmetics can enter the cells and reach the dermal layer of skin.
Electrospun potato starch nanofibers for thyme essential oil encapsulation: antioxidant activity and thermal resistance
Authors: Fonseca Laura M , Radünz Marjana , dos Santos Hackbart Helen C , da Silva Francine T , Camargo Taiane M , Bruni Graziella P , Monks Jander LF , da Rosa Zavareze Elessandra , Dias Alvaro RG
Published: May 2020

BACKGROUND

Thyme essential oil (TEO) is an excellent natural substitute for synthetic compounds to maintain the quality and safety of food products. It acts as an antioxidant agent. We aimed to nanoencapsulate TEO at concentrations of 1%, 3%, and 5% (v/w, dry basis) in electrospun nanofibers made of starch (50% w/v) and formic acid (75% v/v). The rheological parameters of the fiber‐forming solutions were measured, and various physical and chemical properties of the nanofibers were analyzed.

RESULTS

The starch/TEO nanofibers presented homogeneous morphology. The starch nanofibers showed high encapsulation efficiency (EE, 99.1% to 99.8%), which, along with the Fourier transform infra‐red (FTIR) spectrum and thermogravimetric analysis (TGA) analysis, indicate strong protection of the phenolic compounds of TEO. Nanofibers with 5% TEO retained up to 50% of the phenolic compounds after exposure to thermal treatment. The antioxidant activity against 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) radicals of the starch/TEO nanofibers varied from 11.1% to 14.2% and the inhibition values (29.8%, P ≤ 0.05) against hydroxyl radicals were the same for free TEO and the nanofibers.

CONCLUSION

Owing to these properties, electrospun starch/TEO nanofibers can be applied in food products or food packaging.
Characterization of Early Hepatocellular Carcinoma and High‐Grade Dysplastic Nodules on Contrast‐Enhanced Ultrasound
Authors: Fan Pei‐li , Xia Han‐sheng , Ding Hong , Dong Yi , Chen Ling‐li , Wang Wen‐ping
Published: May 2020

Objectives

To explore the enhancement features of early hepatocellular carcinoma (HCC, including well‐differentiated HCC and high‐grade dysplastic nodules with a focus of HCC) and high‐grade dysplastic nodules (HGDNs) on contrast‐enhanced ultrasound (CEUS), correlated with the histopathologic findings.

Methods

This retrospective study enrolled 81 patients with 85 pathologically confirmed hepatic lesions (69 early HCCs and 16 HGDNs). All of the hepatic lesions were examined by CEUS with SonoVue (Bracco SpA, Milan, Italy) before surgery or biopsy. The enhancement features of early HCCs and HGDNs were evaluated and compared with histopathologic findings.

Results

Thirty‐eight (55.1%) early HCCs showed arterial‐phase hyperenhancement (APHE). The major enhancement pattern of early HCCs was APHE without portal venous/late‐phase wash‐out (20 of 69 [29.0%]). Eight (11.6%) early HCCs manifested APHE. Wash‐out was observed in 30 (43.5%) early HCCs. Sixteen (23.2%) early HCCs showed very‐late wash‐out (>120 seconds). Wash‐out was not observed in all HGDNs. Of the 16 HGDNs, arterial‐phase isoenhancement without portal venous/late‐phase wash‐out was the major enhancement pattern (n = 7 [43.8%]). The degree of CD34 expression of sinusoidal endothelial cells was more diffuse in early HCCs than in HGDNs (56.5% versus 12.5%; P = .001). Arterial‐phase enhancement patterns of early HCCs on CEUS were correlated with the degree of CD34 expression (P = .039).

Conclusions

Enhancement patterns were significantly different between early HCCs and HGDNs on CEUS. Diffuse CD34 expression of sinusoidal endothelial cells in early HCC was correlated with APHE on CEUS.
Patient‐Reported Quality of Life After Resection With Primary Closure for Oral Tongue Carcinoma
Authors: Ochoa Edgar , Larson Andrew R. , Han Mary , Webb Katherine L. , Stanford‐Moore Gaelen B. , El‐Sayed Ivan H. , George Jonathan R. , Ha Patrick K. , Heaton Chase M. , Ryan William R.
Published: May 2020

Objectives/Hypothesis

For early‐stage oral tongue carcinoma and carcinoma in situ (ESOTCCIS), we evaluated patient‐reported quality‐of‐life (QOL) outcomes following resection with primary closure (R‐PC).

Study Design

Retrospective review at an academic cancer center.

Methods

Thirty‐nine ESOTCCIS patients (Tis, T1, T2) who underwent R‐PC without radiation completed the University of Washington Quality of Life Questionnaire Version 4 (UW‐QOL) at least 6 months since R‐PC (mean = 2.39 years; range = 0.5–6.7 years). We compared UW‐QOL scores for pain, swallowing, chewing, speech, and taste to established normative population scores. Multivariable regression analysis evaluated factors associated with QOL impairment.

Results

ESOTCCIS patients who underwent R‐PC in comparison to the normative population reported significantly worse mean speech (87.7 vs. 98, P < .001) and taste (85.6 vs. 95, P = .002) scores and no significant differences in mean pain (91.7 vs. 86, P = .96), swallowing (100 vs. 98, P = .98), chewing (97.4 vs. 94, P = .98) scores. For speech and taste, 59% (23/39) reported no postoperative change from baseline, whereas 41% (16/39) and 35.9% (14/39) reported mild impairment, respectively. Overall, postoperative QOL was reported as good, very good, or outstanding by 87.2% (34/39). Higher American Society of Anesthesiologists class, cT1 compared to CIS, and ventral tongue involvement were independently associated with worse speech. Age < 60 years was independently associated with worse taste.

Conclusions

ESOTCCIS patients who undergo R‐PC without radiation can expect long‐term swallowing, chewing, and pain to be in the normative range. Although a majority of patients can expect to achieve normative speech and taste outcomes, R‐PC carries the risks of mild speech and/or taste impairments.

Level of Evidence

4 Laryngoscope, 131:312–318, 2021
Plasma Metabolomics Profiles are Associated with the Amount and Source of Protein Intake: A Metabolomics Approach within the PREDIMED Study
Authors: Hernández‐Alonso Pablo , Becerra‐Tomás Nerea , Papandreou Christopher , Bulló Mònica , Guasch‐Ferré Marta , Toledo Estefanía , Ruiz‐Canela Miguel , Clish Clary B. , Corella Dolores , Dennis Courtney , Deik Amy , Wang Dong D. , Razquin Cristina , Drouin‐Chartier Jean‐Philippe , Estruch Ramon , Ros Emilio , Fitó Montserrat , Arós Fernando , Fiol Miquel , Serra‐Majem Lluís , Liang Liming , Martínez‐González Miguel A , Hu Frank B , Salas‐Salvadó Jordi
Published: May 2020

Scope

The plasma metabolomics profiles of protein intake have been rarely investigated. The aim is to identify the distinct plasma metabolomics profiles associated with overall intakes of protein as well as with intakes from animal and plant protein sources.

Methods and results

A cross‐sectional analysis using data from 1833 participants at high risk of cardiovascular disease is conducted. Associations between 385 identified metabolites and the intake of total, animal protein (AP), and plant protein (PP), and plant‐to‐animal ratio (PR) are assessed using elastic net continuous regression analyses. A double 10‐cross‐validation (CV) procedure is used and Pearson correlations coefficients between multi‐metabolite weighted models and reported protein intake in each pair of training‐validation datasets are calculated. A wide set of metabolites is consistently associated with each protein source evaluated. These metabolites mainly consisted of amino acids and their derivatives, acylcarnitines, different organic acids, and lipid species. Few metabolites overlapped among protein sources (i.e., C14:0 SM, C20:4 carnitine, GABA, and allantoin) but none of them toward the same direction. Regarding AP and PP approaches, C20:4 carnitine and dimethylglycine are positively associated with PP but negatively associated with AP. However, allantoin, C14:0 SM, C38:7 PE plasmalogen, GABA, metronidazole, and trigonelline (N‐methylnicotinate) behave contrarily. Ten‐CV Pearson correlation coefficients between self‐reported protein intake and plasma metabolomics profiles range from 0.21 for PR to 0.32 for total protein.

Conclusions

Different sets of metabolites are associated with total, animal, and plant protein intake. Further studies are needed to assess the contribution of these metabolites in protein biomarkers’ discovery and prediction of cardiometabolic alterations.
Estimation of pharmacokinetic parameters from DCE‐MRI by extracting long and short time‐dependent features using an LSTM network
Authors: Zou Jiaren , Balter James M. , Cao Yue
Published: May 2020

Purpose

T1‐weighted dynamic contrast‐enhanced Magnetic Resonance Imaging (DCE‐MRI) is typically quantified by least squares (LS) fitting to a pharmacokinetic (PK) model to yield parameters of microvasculature and perfusion in normal and disease tissues. Such fitting is both time‐consuming as well as subject to inaccuracy and instability in parameter estimates. Here, we propose a novel neural network approach to estimate the PK parameters by extracting long and short time‐dependent features in DCE‐MRI.

Methods

A Long Short‐Term Memory (LSTM) network, widely used for processing sequence data, was employed to map DCE‐MRI time‐series accompanied with an arterial input function to parameters of the extended Tofts model. Head and neck DCE‐MRI from 103 patients were used for training and testing the LSTM model. Arterial input functions (AIFs) from 78 patients were used to generate synthetic DCE‐MRI time‐series for training, during which data augmentation was used to overcome the limited size of in vivo data. The model was tested on independent synthesized DCE data using AIFs from 25 patients. The LSTM performance was optimized for the numbers of layers and hidden state features. The performance of the LSTM was tested for different temporal resolution, total acquisition time, and contrast‐to‐noise ratio (CNR), and compared to the conventional LS fitting and a CNN‐based method.

Results

Compared to LS fitting, the LSTM model had comparable accuracy in PK parameter estimations from fully temporal‐sampled DCE‐MRI data (~3 s per frame), but much better accuracy for the data with temporally subsampling (4s or greater per frame), total acquisition time truncation by 48%‐16%, or low CNR (5 and 10). The LSTM reduced normalized root mean squared error by 40.4%, 46.9%, and 53.0% for sampling intervals of 4s, 5s, and 6s, respectively, compared to LS fitting. Compared to the CNN model, the LSTM model reduced the error in the parameter estimates up to 55.2%. Also, the LSTM improved the inference time by ~ 14 times on CPU compared to LS fitting.

Conclusion

Our study suggests that the LSTM model could achieve improved robustness and computation speed for PK parameter estimation compared to LS fitting and the CNN based network, particularly for suboptimal data.
In vivo comparison of MRI‐based and MRS‐based quantification of adipose tissue fatty acid composition against gas chromatography
Authors: Trinh Lena , Peterson Pernilla , Leander Peter , Brorson Håkan , Månsson Sven
Published: May 2020

Purpose

To compare MR‐based fatty acid composition (FAC) quantification methods against the gold standard technique, gas chromatography (GC), with comparison of a free and a constrained signal model. The FAC was measured in the healthy and edematous legs of lymphedema patients.

Methods

In vivo MRS and MRI data were acquired from 19 patients at 3 T. Biopsies were collected from subcutaneous adipose tissue of both thighs during liposuction. The saturated, monounsaturated, and polyunsaturated fatty acid fractions (fSFA, fMUFA and fPUFA, respectively) were estimated with the MR‐based methods using two signal models: free and constrained (number of methylene‐interrupted double bonds expressed in number of double bonds, based on GC data). Linear regression, Bland–Altman plots, and correlation coefficients were used to evaluate the MR methods against the GC of the biopsies. Paired t‐test was used to compare the FAC difference between edematous and healthy legs.

Results

The estimated parameters correlated well with the GC data (rSFA, rMUFA, and rPUFA = 0.82, 0.81 and 0.89, respectively) using the free model MRI‐based approach. In comparison, the MRS‐based method resulted in weaker correlations and larger biases compared with MRI. In both cases, correct estimation of fMUFA and fPUFA fractions were not possible using the constrained model. The difference in FAC of healthy and edematous legs were estimated to 0.008 (P = .01), −0.009 (P = .005), and 0.002 (P = .03) for fSFA, fMUFA, and fPUFA.

Conclusion

In this study, MRI‐based FAC quantification was highly correlated, although slightly biased, compared with GC, whereas the MRS‐based approach resulted in weaker correlations. Small but significant differences could be found between the healthy and edematous legs of lymphedema patients using GC analysis.
Trajectories of BMI Before Diagnosis of Type 2 Diabetes: The Rotterdam Study
Authors: Nano Jana , Dhana Klodian , Asllanaj Eralda , Sijbrands Eric , Ikram M. Arfan , Dehghan Abbas , Muka Taulant , Franco Oscar H.
Published: May 2020

Objective

People with diabetes show great variability in weight

gain and duration of obesity at the time of diagnosis. BMI trajectories and other cardiometabolic risk factors prior to type 2 diabetes

were investigated.

Methods

A total of 6,223 participants

from the Rotterdam Study cohort were included. BMI patterns before diagnosis of diabetes were identified through latent class

trajectories.

Results

During a mean follow‐up of

13.7 years, 565 participants developed type 2 diabetes. Three distinct trajectories of BMI were identified, including the

“progressive overweight” group (n = 481, 85.1%), “progressive weight loss” group

(n = 59, 10.4%), and “persistently high BMI” group (n = 25, 4.4%). The

majority, the progressive overweight group, was characterized by a steady increase of BMI in the overweight range 10 years before

diabetes diagnosis. The progressive weight loss group had fluctuations of glucose and marked beta cell function loss. The

persistently high BMI group was characterized by a slight increase in insulin levels and sharp increase of insulin resistance

accompanied by a rapid decrease of beta cell function.

Conclusions

Heterogeneity of BMI changes prior to type 2 diabetes was found in a middle‐aged and elderly white population.

Prevention strategies should be tailored rather than focusing only on high‐risk individuals.
Biological Ion Exchange Provides DOC Removal in Small Communities
Authors: Zimmermann Karl , Barbeau Benoit , Dezfoolian Maryam , Cook Candace , Mohseni Madjid
Published: May 2020

A small community in British Columbia, Canada, needed a water treatment process that required minimal maintenance but could handle the community's unique challenges. In the end, a university collaboration led to an effective biological ion exchange system.
Fabrication of very effective ferroferric oxide and multiwalled carbon nanotubes@polyetherimide/poly(ether ether ketone) electromagnetic interference shielding composites
Authors: Jiang Botao , Luan Jiashuang , Qin Shi , Wu Tonghua , Wang Guibin , Zhang Shuling
Published: May 2020

This article reports fabrication of very efficient electromagnetic interference (EMI) shielding composites prepared by melt blending of polyether‐ether ketone (PEEK), multiwalled carbon nanotubes (MWCNTs) covered with polyetherimide (PEI), and ferroferric oxide (Fe3O4) nanoparticles as a matrix, dielectric and magnetic loss fillers, respectively. The surface of MWCNTs was modified with PEI to improve their dispersion in the PEEK matrix as well as interfacial adhesion. Fe3O4 nanoparticles were then deposited onto the surface of MWCNTs coated with PEI (MWCNTs@PEI). In this case, MWCNTs@PEI filler served as a carrier for Fe3O4 nanoparticles for their even dispersion in PEEK. Additionally, combination of Fe3O4 nanoparticles and MWCNTs@PEI (Fe3O4 and MWCNTs@PEI) provided the resulting EMI materials with the enhanced electromagnetic absorption ability. This property was then utilized to fabricate PEEK‐based (Fe3O4 and MWCNTs@PEI/PEEK) EMI shielding composites. Specific shielding effectiveness (SSE) of this composite was ~54.4 dB mm−1 in the X band (8.2‐12.4 GHz). Tensile strength and the temperature at 5% weight loss of this novel EMI shielding materials were 117 MPa and 600°C, respectively.
Safety of clozapine use during pregnancy: Analysis of international pharmacovigilance data
Authors: Beex‐Oosterhuis Marieke M. , Samb Amadou , Heerdink Eibert R. , Souverein Patrick C. , Van Gool Arthur R. , Meyboom Ronald H. B. , van Marum Rob J.
Published: May 2020

Purpose

Safety data on clozapine use during pregnancy are limited. The aim of this study was to determine disproportionality in case safety reports on adverse pregnancy outcomes between clozapine and other antipsychotics (OAP) used during pregnancy.

Methods

We included all reports of suspected adverse drug reactions (ADRs) to antipsychotics registered in the World Health Organization global individual case safety report (ICSR) database (VigiBase) in children younger than 2 years and women aged 12‐45 years. A case/non‐case approach was used to evaluate the association between several pregnancy‐related ADRs and clozapine exposure during pregnancy, using 2×2 contingency tables to investigate disproportionality and Standard MedDRA Queries to select cases. Clozapine exposure was defined as all ICSR‐ADR combinations with clozapine as (one of) the suspected drug(s). Non‐exposure was defined as all ICSR‐ADR combinations with OAP as (one of) the suspected drug(s).

Results

We identified 42 236 unique ICSR‐ADR combinations related with clozapine exposure and 170 710 with OAP exposure. Of these, 494 and 4645 ICSR‐ADR combinations involved adverse pregnancy outcomes related with clozapine exposure and OAP exposure respectively. Overall, no signal of disproportionate reporting associating clozapine with the studied adverse pregnancy outcomes was found compared with OAP exposure.

Conclusion

Based on global pharmacovigilance data, we did not find any evidence that clozapine is less safe during pregnancy than OAP. Although this is not automatically equivalent to the relative safety of clozapine during pregnancy, these findings add to the convergence of proofs to allow final conclusions and decisions regarding the treatment of pregnant women with clozapine.
Effect of mixed solvents on phase inversion of polymeric membranes
Authors: Kurada Krishnasri V , Agarwal Amit , De Sirshendu
Published: May 2020

The thermodynamics of phase inversion of polyvinylidene fluoride membrane with mixed solvents (N,N‐dimethyl formamide (DMF) and acetone) were modeled using Flory–Huggins theory. The kinetics of phase inversion were studied by measuring solvent concentration in the precipitation bath. A model was proposed to predict the time‐dependent solvent concentration profile in the precipitation bath. Depending on solvent volatility, the duration of the kinetics‐dominated regime and the evaporation‐dominated regime varies. A comparative analysis of thermodynamic and kinetic factors was used to predict membrane morphology and it was observed that the system under consideration was thermodynamics dominated. The membrane porosity exhibited decreasing porosity up to the Ac60 membrane (acetone to DMF ratio 60) and thereafter the membrane sublayer showed small pores. Addition of acetone resulted in increased crystallinity and surface hydrophilicity. The mean flow pore diameter measured using a liquid–liquid porometer decreased from 105 nm for an Ac0 membrane (acetone to DMF ratio 0) to 17 nm for an Ac60 membrane. Correspondingly, the molecular weight cut‐off of the membranes decreased from 135 kDa (for the Ac0 membrane) to 104 kDa (for the Ac60 membrane). The model proposed in this work can be used as a tool to predict the properties of intermediate compositions and prepare tailor‐made membranes with desired properties. © 2020 Society of Chemical Industry
High‐dimensional single‐index models with censored responses
Authors: Huang Hailin , Shangguan Jizi , Li Xinmin , Liang Hua
Published: May 2020

In this article, we study the estimation of high‐dimensional single index models when the response variable is censored. We hybrid the estimation methods for high‐dimensional single‐index models (but without censorship) and univariate nonparametric models with randomly censored responses to estimate the index parameters and the link function and apply the proposed methods to analyze a genomic dataset from a study of diffuse large B‐cell lymphoma. We evaluate the finite sample performance of the proposed procedures via simulation studies and establish large sample theories for the proposed estimators of the index parameter and the nonparametric link function under certain regularity conditions.
Smart Colorimetric Chemosensors for Multi‐Analyte Signaling: Recognition of Heavy Metal Ions in an Aqueous Medium and DFT Studies
Authors: Tekuri Venkatadri , Mohan Makesh , Trivedi Darshak R.
Published: May 2020

A Schiff's base colorimetric chemosensors R1–R3 consist of carbohydrazide, and heterocyclic aldehydes have been designed and synthesized for sensing of heavy metal ions. Synthesized receptors were well characterized by various standard spectroscopic techniques. The receptor R1 exhibited multi‐ion selectivity for Cd2+, Hg2+, Pb2+, Cu2+ ions and showed lowest detection limit of 1.9 ppb, for Cd2+ & Hg2+ ions. The receptors R2 and R3 displayed dual ion selectivity (R2 for Hg2+, Cu2+, and R3 for Cu2+, AsO2– ions) in an aqueous medium at ppb levels. The UV–Vis and colorimetric studies confirmed the selectivity and sensitivity of chemosensors R1–R3 in the presence of other interfering metal ions. Further, using the B–H plot, FT‐IR, and mass analysis data, the binding modes, stoichiometric ratios of receptors R1–R3 with the metal ions were investigated. The estimated association constant values were found to be 104 to 105 M–1/M–2. The experimental results are well concordant with that of calculated theoretical DFT results. The receptors R1–R3 exhibited good sensitivity and selectivity compared to literature reports and successfully demonstrated for test strip applications.
Structural, Quantum Chemical and Spectroscopic Investigations on Photophysical Properties of Fluorescent Saccharide Sensor: Theoretical and Experimental Studies
Authors: Khamees Hussien A. , Revanna Bhavya N. , Madegowda Mahendra , Sebastian Jeyaseelan , Haruvegowda Doreswamy B. , Kumar Shamantha
Published: May 2020

Structure, Hirshfeld surface, spectra and photophysical properties of boronic acid‐based carbohydrate sensor (5‐fluoro‐2‐methoxyphenyl) boronic acid (BA8) has been reported by experimental methods (XRD/FT‐IR/UV/steady state fluorescence) and theoretically by Density functional theory (DFT) model with most accurate functionals (B3LYP/CAM−B3LYP/ M06‐2X). The comparison of theoretical and experimental data exhibited good agreement. Natural bond orbital (NBO) and frontier molecular orbitals (FMOs) have been analysed. The sensing ability of the compound with carbohydrates (D‐glucose and D‐fructose) were studied by UV/fluorescence spectra. The variation of absorbance and fluorescence on pH was rationale with the estimated acid‐base dissociation constants (pKa). Quantum yield (Φ) and fluorescence lifetimes (τ) for the compound and its esters with sugars were calculated. The results of absorbance, fluorescence measurements and calculated photophysical properties indicated fairly selectivity of BA8 with fructose more than the glucose, which is ascertained from both experimental and theoretical results.