bluuebunny/crossref_metadata_2025 huggingface dataset:
Featuring ultimate sensitivity of high‐resolution LC‐MS analysis of phenolics in rat plasma
Authors: Vlčková Hana Kočová , Catapano Maria Carmen , Mitašík Lucia , Kotland Ondřej , Nejmanová Iveta , Pourová Jana , Mladěnka Přemysl , Nováková Lucie
Published: March 2021

Sensitive analysis of very low‐molecular weight metabolites using liquid chromatography with quadrupole‐time‐of‐flight mass spectrometry is challenging due to the high losses of ions in a time‐of‐flight analyzer. Improvement in sensitivity for these analytes via the optimization of advanced parameters, including quadrupole profile, ion guide parameters, and duty cycle, has been achieved. The optimization of the method was carried out using a large spectrum of structurally different compounds including (iso)flavonoids and their known metabolites. These compounds can be categorized into two major groups, that is, compounds with (iso)flavonoid core and low‐molecular weight phenolics. The optimization of the duty cycle enabled up to a 15‐fold increase in analyte responses while the contribution of tuning ion optics and quadrupole profile was negligible. The limits of quantifications of our new method were assessed using both standard solutions and rat plasma. They were decreased at least 10 times for several low‐molecular weight phenolics enabling measurement of their concentrations in a range of 1‐50 ng/mL in rat plasma after protein precipitation. Concurrently, the limits of quantifications for compounds with (iso)flavonoid core did not increase distinctly allowing their detection in a range of 0.5‐10 ng/mL. The new method was used for the targeting of phenolics in biological samples from pharmacokinetics experiments.
Fear of the academic fake? Journal editorials and the amplification of the 'predatory publishing' discourse
Authors: Inouye Kelsey , Mills David
Published: March 2021

This analysis of 229 editorials and opinion pieces published in science and medical journals explores the affective discourses used to characterise so‐called predatory publishing. Most (84%, n = 193) deploy one or more of three related categories of metaphorical and figurative language (fear, fakery and exploitation) to strengthen their rhetorical case. This paper examines the deployment, co‐occurrence and amplification of this language across the science publishing system, focusing particularly on the role of major science journals in adopting and normalising this emotive discourse. The analysis shows how few editorials offer alternative perspectives on these developments (n = 9), and their relative invisibility in scholarly debates.
A buyout option alleviates implicit collusion in uniform‐price auctions
Authors: Tsuchihashi Toshihiro
Published: March 2021

Demand reduction causes extremely low revenues in uniform‐price auctions, which can be interpreted as implicit collusion among bidders. We model a uniform‐price auction with a buyout option and investigate its potential for alleviating implicit collusion. We focus on the extreme case that yields a revenue of zero with no buyout option. Our main result is that the seller obtains a positive expected revenue unless the buyout price is high. Notably, a bidder will exercise a buyout option even though the bidder is risk neutral; that is, auction aversion is fully endogenous, in contradiction to the findings of previous work.
Low‐Dose Coconut Oil Supplementation Induces Hypothalamic Inflammation, Behavioral Dysfunction, and Metabolic Damage in Healthy Mice
Authors: Veras Alana Carolina Costa , Santos Tamires dos , Martins Isis de Cássia Alves , de Souza Camilla Mendes , Amaral Camila Libardi , Franco Beatriz da Silva , Holanda Alessandro Spencer de Souza , Esteves Andrea Maculano , Milanski Marciane , Torsoni Adriana Souza , Ignacio‐Souza Leticia Martins , Torsoni Marcio Alberto
Published: March 2021

Scope

Coconut oil (CO) diets remain controversial due to the possible association with metabolic disorder and obesity. This study investigates the metabolic effects of a low amount of CO supplementation.

Methods and Results

Swiss male mice are assigned to be supplemented orally during 8 weeks with 300 µL of water for the control group (CV), 100 or 300 µL of CO (CO100 and CO300) and 100 or 300 µL of soybean oil (SO; SO100 and SO300). CO led to anxious behavior, increase in body weight gain, and adiposity. In the hypothalamus, CO and SO increase cytokines expression and pJNK, pNFKB, and TLR4 levels. Nevertheless, the adipose tissue presented increases macrophage infiltration, TNF‐α and IL‐6 after CO and SO consumption. IL‐1B and CCL2 expression, pJNK and pNFKB levels increase only in CO300. In the hepatic tissue, CO increases TNF‐α and chemokines expression. Neuronal cell line (mHypoA‐2/29) exposed to serum from CO and SO mice shows increased NFKB migration to the nucleus, TNF‐α, and NFKBia expression, but are prevented by inhibitor of TLR4 (TAK‐242).

Conclusions

These results show that a low‐dose CO changes the behavioral pattern, induces inflammatory pathway activation, TLR4 expression in healthy mice, and stimulates the pro‐inflammatory response through a TLR4‐mediated mechanism.
Adaptive CaRdiac cOne BEAm computed Tomography (ACROBEAT): Developing the next generation of cardiac cone beam CT imaging
Authors: Reynolds Tess , Dillon Owen , Prinable Joseph , Whelan Brendan , Keall Paul J. , O’Brien Ricky T.
Published: March 2021

Purpose

An important factor when considering the use of interventional cone beam computed tomography (CBCT) imaging during cardiac procedures is the trade‐off between imaging dose and image quality. Accordingly, Adaptive CaRdiac cOne BEAm computed Tomography (ACROBEAT) presents an alternative acquisition method, adapting the gantry velocity and projection rate of CBCT imaging systems in accordance with a patient’s electrocardiogram (ECG) signal in real‐time. The aim of this study was to experimentally investigate that ACROBEAT acquisitions deliver improved image quality compared to conventional cardiac CBCT imaging protocols with fewer projections acquired.

Methods

The Siemens ARTIS pheno (Siemens Healthcare, GmbH, Germany), a robotic CBCT C‐arm system, was used to compare ACROBEAT with a commercially available conventional cardiac imaging protocol that utilizes multisweep retrospective ECG‐gated acquisition. For ACROBEAT, real‐time control of the gantry position was enabled through the Siemens Test Automation Control system. ACROBEAT and conventional image acquisitions of the CIRS Dynamic Cardiac Phantom were performed, using five patient‐measured ECG traces. The traces had average heart rates of 56, 64, 76, 86, and 100 bpm. The total number of acquired projections was compared between the ACROBEAT and conventional acquisition methods. The image quality was assessed via the contrast‐to‐noise ratio (CNR), structural similarity index (SSIM), and root‐mean square error (RMSE).

Results

Compared to the conventional protocol, ACROBEAT reduced the total number of projections acquired by 90%. The visual image quality provided by the ACROBEAT acquisitions, across all traces, matched or improved compared to conventional acquisition and was independent of the patient’s heart rate. Across all traces, ACROBEAT averaged 1.4 times increase in the CNR, a 23% increase in the SSIM and a 29% decrease in the RMSE compared to conventional and was independent of the patient’s heart rate.

Conclusion

Adaptive patient imaging is feasible on a clinical robotic CBCT system, delivering higher quality images while reducing the number of projections acquired by 90% compared to conventional cardiac imaging protocols.
Validation of hair ethyl glucuronide using transdermal monitoring and self‐reported alcohol use in women of childbearing potential
Authors: Blair Andrea L. , Chiaf Ashleigh L. , Crockett Erica K. , Teague Tracy Kent , Croff Julie M.
Published: March 2021

Aim

The present study aimed to evaluate the validity of hair ethyl glucuronide concentrations compared with transdermal alcohol concentration and self‐reported alcohol use.

Methods

This trial included 25 adolescent and young adult females, aged 16‐24, who reported at least one heavy drinking episode (≥4 drinks) in the two weeks prior to baseline. All participants were asked to wear an alcohol biosensor over a one‐month prospective study. Detailed self‐report of drinking behaviors was assessed weekly. Estimates of blood alcohol concentration were computed from self‐report data using the National Highway and Transportation Safety Administration equation. Transdermal alcohol concentration and estimated blood alcohol concentration data were categorized into at‐risk (>0.05 g/dL alcohol) and high‐risk (>0.08 g/dL alcohol) drinking events. Hair ethyl glucuronide concentration, total number of drinking events, moderate (>0.05 g/dL) and high level (>0.08 g/dL) of transdermal alcohol concentration, and estimated blood alcohol concentration drinking events were analyzed with Spearman's rank correlation test for validity comparisons.

Results

No significant correlations were found between hair ethyl glucuronide values and total number, and moderate or high levels of detected drinking events by estimated blood alcohol concentration or transdermal alcohol concentration. Total number of drinking events detected and number of drinking events >0.08 g/dL using estimated blood alcohol concentration and transdermal alcohol concentration methods were significantly correlated with each other (respectively, R = .33, P < .05; R = .42, P < .05).

Conclusion

Our findings indicate that, due to the number of false negatives, hair ethyl glucuronide concentrations should be used with caution for monitoring abstinence from alcohol use.
Prioritizing the factors determining the quality in higher educational institutions—An application of fuzzy analytic hierarchy process
Authors: Goyal Amit , Gupta Sanjay , Chauhan Ajay Kumar
Published: March 2021

The aim of this paper is to understand the factors that determine the quality of higher educational institutions and to measure the relative importance of those factors from the students' perspective. A multi‐criteria decision‐making methodology (MCDM), that is, the fuzzy analytical hierarchical process has been used for measuring the relative importance of factors which determine the student satisfaction with regard to perceived quality in education. The measurement of relative weights of the factors that determine the quality of higher educational institutions as per the perception of the students has been done. Further best preference structure of the students for educational institutions has been found from the study. The study was confined to Punjab state of India that means only the perception of students of this particular region was measured. Moreover, the factors undertaken in this study are also limited which were identified from the extensive review of the literature but there is a possibility that some factors might have been ignored. The results of this study can be used to measure the internal quality by the higher educational institutions. In addition to this, the study may be helpful to higher educational institutions to identify the weak areas to be worked upon and give the students as better as possible quality from the students' perspective. The paper attempts to understand the determinants of quality and to prioritize those for educational institutions as perceived by the students.
Characterization and simulation of the nonlinear thermal field of the aramid/bismaleimide composites caused by the dielectric heating effects of the microwave radiations
Authors: Liu Kai , Xu Xiangyu , Zhang Boming
Published: March 2021

The aramid/bismaleimide composites are severely affected by the dielectric heating effects of the microwave radiations during use as the microwave functional materials. This study aims to characterize and predict the nonlinear thermal fields and thermal damages of the aramid/bismaleimide composites caused by the microwave radiations. The microwave radiation experiments were performed using a tailor‐made system, and the equilibrium temperature and thermal damage threshold of the aramid/bismaleimide composites were experimentally determined. The temperature variation, thermal damage mechanism, and effect of the composite thickness associated with the dielectric heating were analyzed. Further, a simulation approach was developed to predict the nonlinear thermal fields of the composites caused by the microwave radiations. The dielectric heating process was considered an internal heat source, and a loop program was subsequently designed to implement the nonlinear thermal load. The developed simulation method efficiently predicted the equilibrium temperature and thermal damage of the composite materials due to the dielectric heating effect. The microwave radiation power was suggested to remain below 550 W for 3 mm thick aramid composites during service as a wave‐transmitting material.
Global COVID‐19 pandemic and reporting behavior ‐ An analysis of the Food and Drug Administration adverse events reporting system
Authors: Dörks Michael , Jobski Kathrin , Hoffmann Falk , Douros Antonios
Published: March 2021

Purpose

To describe the characteristics of adverse event reporting in the United States (US) Food and Drug Administration Adverse Event Reporting System (FAERS) before and after the outbreak of the COVID‐19 pandemic.

Methods

We included all FAERS reports from the US and Canada from November 7, 2019 to July 15, 2020 and divided the study period into three equal time intervals (pre‐pandemic, first pandemic, second pandemic). We focused on methotrexate, a broadly used drug unrelated to COVID‐19, and (hydroxy)chloroquine, another broadly used drug implicated in COVID‐19 treatment. Using descriptive statistics, we compared reporting characteristics before and after the COVID‐19 outbreak.

Results

During the study period, 366 998 cases (60% female, median age: 59 years) were submitted to FAERS. The daily median number of reports (1796 in the pre‐pandemic, 1810 in the second pandemic time interval) and other characteristics remained stable. The daily median number of reports for methotrexate decreased from 28 in the pre‐pandemic to 15 in the second pandemic time interval, with no considerable differences in other characteristics. The daily median number of reports for (hydroxy)chloroquine increased slightly from 1 in the pre‐pandemic to 3 in the second pandemic time interval, while there were also changes in the demographics of cases and an increase in the proportion of cases reported by health professionals.

Conclusions

The overall reporting to FAERS did not change after the outbreak of the COVID‐19 pandemic. However, some stimulated reporting was observed for (hydroxy)chloroquine, highlighting the need for caution when conducting pharmacovigilance analyses with substances related to COVID‐19.
A new approach for estimating parameters of two‐parameter bathtub‐shaped lifetime distribution under modified progressive hybrid censoring
Authors: Zhu Tiefeng
Published: March 2021

The lifetime distributions with bathtub‐shaped hazard rate functions and censoring scheme have been used widely in life testing and reliability engineering. This paper develops a new approach for estimating parameters of an important two‐parameter lifetime data analysis model with bathtub‐shaped hazard rate function under the assumption that sample is modified progressively hybrid censored. One of the most frequently used methodologies, maximum likelihood (ML) estimation, is used for estimating unknown parameters. The estimates of unknown parameters are proposed using popular Newton–Raphson algorithm because the estimators cannot be obtained in closed forms. It is well known that the convergence of Newton–Raphson algorithm is affected by an initial point. Therefore, a new Newton–Raphson algorithm with an adaptive initial point within the exact joint confidence region has been suggested to compute the ML estimation. Extensive numerical simulations show that the proposed algorithm converges all the times and it is effective. Finally, one real‐world data set from engineering is analysed to illustrate the application of the proposed  method.
Memory‐type control charts with multiple auxiliary information for process mean
Authors: Haq Abdul , Khoo Michael B. C.
Published: March 2021

Memory‐type auxiliary‐information‐based (AIB) control charts are very effective in detecting small‐to‐moderate shifts in the process mean. In this study, we first develop a unique uniformly minimum variance unbiased estimator of the process mean that requires information on the study variable as well as on several correlated auxiliary variables. Then, based on this estimator, adaptive and nonadaptive CUSUM and EWMA charts are developed with either fixed or variable sampling interval for monitoring the process mean, namely, the multiple AIB (MAIB) charts. The proposed charts encompass existing charts with or without the auxiliary information. The run length characteristics of the proposed charts are computed with the Monte Carlo simulations when sampling from a multivariate normal distribution. Based on the run length comparisons, it is found that the MAIB charts are uniformly and substantially more sensitive than the AIB charts when monitoring the process mean. Real datasets are also considered to explain the implementation of the MAIB charts.
Desorption ionization using through‐hole alumina membrane offers higher reproducibility than 2,5‐dihydroxybenzoic acid, a widely used matrix in Fourier transform ion cyclotron resonance mass spectrometry imaging analysis
Authors: Hasan Md. Mahmudul , Eto Fumihiro , Mamun Md. Al , Sato Shumpei , Islam Ariful , Waliullah A.S.M. , Chi Do Huu , Takahashi Yutaka , Kahyo Tomoaki , Naito Yasuhide , Kotani Masahiro , Ohmura Takayuki , Setou Mitsutoshi
Published: March 2021

Rationale

DIUTHAME (desorption ionization using through‐hole alumina membrane), a recently developed matrix‐free ionization‐assisting substrate, was examined for reproducibility in terms of mass accuracy and intensity using standard lipid and mouse brain sections. The impregnation property of DIUTHAME significantly improved the reproducibility of mass accuracy and intensity compared with 2,5‐dihydroxybenzoic acid (DHB).

Methods

Frozen tissue sections were mounted on indium tin oxide‐coated glass slides. DIUTHAME and DHB were applied to individual sections. Subsequently, a solution of a phosphatidylcholine standard, PC(18:2/18:2), was poured onto the DIUTHAME and matrix. Finally, the samples were subjected to laser desorption ionization coupled with Fourier transform ion cyclotron resonance mass spectrometry. The reproducibility was tested by calculating the mean ± standard deviation values of mass errors and intensities of individual ion species.

Results

Analysis of the PC(18:2/18:2) standard showed significantly (p < 0.01) lower mass error for DIUTHAME‐MS than for MALDI‐MS. Endogenous PC(36:4) analysis in mouse brain section also showed significantly (p < 0.05) lower mass errors for DIUTHAME‐MS. Furthermore, we investigated the mass error of some abundant lipid ions in brain sections and observed similar results. DIUTHAME‐MS displayed lower signal intensity in standard PC analysis. Interestingly, it offered higher signal intensities for all the endogenous lipid ions. Lower fluctuations of both mass accuracies and signal intensities were observed in DIUTHAME‐MS.

Conclusions

Our results demonstrated that DIUTHAME‐MS offers higher reproducibility for mass accuracies and intensities than MALDI‐MS in both standard lipid and mouse brain tissue analyses. It can potentially be used instead of conventional MALDI‐MS and mass spectrometry imaging analyses to achieve highly reproducible data for mass accuracy and intensity.
Event‐triggered adaptive tracking control of uncertain switched nonlinear systems
Authors: Lian Jie , Li Can
Published: March 2021

This article is concerned with the event‐triggered adaptive tracking control of switched systems with uncertain nonlinearities and unknown control gains. The switch can occur within two consecutive sampling instants and may trigger new events that raise the mismatch problem and bring the challenge to avoid the Zeno behavior. To address these problems, we propose a novel codesign scheme composed of a switching event‐triggered mechanism and a mode‐dependent adaptive control law. A logarithmic threshold strategy is introduced into the event triggering mechanism. The absence of Zeno is proved from its formal definition. Based on the codesign scheme, the tracking error can be steered to an adjustable neighborhood of the origin. At last, a numerical example is applied to validate the obtained results.
uTPI: A utility‐based toxicity probability interval design for phase I/II dose‐finding trials
Authors: Shi Haolun , Cao Jiguo , Yuan Ying , Lin Ruitao
Published: March 2021

Unlike chemotherapy, the maximum tolerated dose (MTD) of molecularly targeted agents and immunotherapy may not pose significant clinical benefit over the lower doses. By simultaneously considering both toxicity and efficacy endpoints, phase I/II trials can identify a more clinically meaningful dose for subsequent phase II trials than traditional toxicity‐based phase I trials in terms of risk‐benefit tradeoff. To strengthen and simplify the current practice of phase I/II trials, we propose a utility‐based toxicity probability interval (uTPI) design for finding the optimal biological dose, based on a numerical utility that provides a clinically meaningful, one‐dimensional summary representation of the patient's bivariate toxicity and efficacy outcome. The uTPI design does not rely on any parametric specification of the dose‐response relationship, and it directly models the dose desirability through a quasi binomial likelihood. Toxicity probability intervals are used to screen out overly toxic dose levels, and then the dose escalation/de‐escalation decisions are made adaptively by comparing the posterior desirability distributions of the adjacent levels of the current dose. The uTPI design is flexible in accommodating various dose desirability formulations, while only requiring minimum design parameters. It has a clear decision structure such that a dose‐assignment decision table can be calculated before the trial starts and can be used throughout the trial, which simplifies the practical implementation of the design. Extensive simulation studies demonstrate that the proposed uTPI design yields desirable as well as robust performance under various scenarios.
Synthesis, Biological Evaluation and Docking Studies of Functionalized Pyrrolo[3,4‐b]pyridine Derivatives
Authors: Saigal  , Ghanem Younes S. A. , Uddin Amad , Khan Sarfaraz , Abid Mohammad , Khan Md. Musawwer
Published: March 2021

The synthesis and antibacterial studies of polysubstituted pyrrolo[3,4‐b]pyridine derivatives have been described. The preparation of pyrrolo[3,4‐b]pyridine derivatives was carried out by the reaction of enamino imides, aromatic aldehydes and malononitrile/ethyl cyanoacetate using 10 mol % of DBU (1,8‐diazabicyclo[5.4.0]undec‐7‐ene) in ethanol at 78 °C in good yields. The compounds were characterized by standard spectroscopic techniques including IR, 1H & 13C NMR and elemental analysis and also final confirmation was done by single crystal X‐ray. The antibacterial activity of all the synthesized compounds was tested against two Gram positive (S. pneumoniae MTCC 655 and E. faecalis MTCC 439) and three Gram negative (E. coli ATCC 25922, S. typhimurium MTCC 3224, and P. aeruginosa MTCC 2453) bacterial strains. Most of the tested compounds showed moderate to good antibacterial activity. Compounds pyrrolo[3,4‐b]pyridine derivatives (4 j and 4 l) were the most potent and displayed bactericidal activities against E. coli strain with MIC (minimum inhibitory concentration) values of 62.5 μg/mL and 125.0 μg/mL respectively. Growth kinetic studies against E. coli, toxicity studies using human RBCs (red blood cells) and also docking studies of the selected compounds 4 j and 4 l supported that these compounds inhibit the growth of bacterial cells, non‐toxic in nature and interact with key amino residues of DNA (deoxyribonucleic acid) duplex (PDBID: 1BNA) and have drug‐like properties.
Recent Advances in Synthesis and Study of 2D Twisted Transition Metal Dichalcogenide Bilayers
Authors: Tang Bijun , Che Bingyu , Xu Manzhang , Ang Zhi Peng , Di Jun , Gao Hong-Jun , Yang Haitao , Zhou Jiadong , Liu Zheng
Published: March 2021

In recent years, twisted 2D transition metal dichalcogenides (TMDs) have attracted tremendous research interest thanks to their intriguing properties that are essential in developing future electronic and photoelectronic devices in this modernizing era. The aim of this review is to introduce recent developments in the preparation of twisted TMD (t‐TMD) bilayers, their properties investigated by photoluminescence (PL) spectroscopy, Raman spectroscopy, and other techniques, as well as the related distinctive physical phenomena. First, various strategies for synthesizing t‐TMD bilayers via the two‐step stacking method and one‐step chemical vapor deposition method are reviewed. Then, the commonly used characterization techniques in probing the interlayer coupling between the twisted layers are introduced. Moreover, the intriguing physical properties associated with twisting such as interlayer excitons and correlated electronic phases are summarized. Last but not least, challenges and future research directions are briefly discussed in light of recent advances in the field.
An Analytical Evaluation of Performance Limit for PiN diodes and IGBTs
Authors: Terashima Tomohide
Published: March 2021

This paper reports analytical evaluation for minimum reverse recovery loss and turn‐off loss of PiN diodes and IGBTs, respectively. In this evaluation, we take account of structural parameters and current continuity at the both ends of the i‐layer, and we calculate switching losses (E) from energy dissipation on the i‐layer during switching action by using position integration instead of time integration. In the case of IGBT, we assume that depletion layer spreads from the i‐layer and n+ layer interface of the PiN diode that corresponds to bottom p type layer ‐ n− layer ‐ p type backgate region of IGBT cells. We evaluate optimum structure for minimum energy dissipation of these switching actions and conduction states by newly employed index RE consists of R calculated by voltage drop at the i‐layer and both ends of the i‐layer and E. We clarify that ideal carrier profile for minimum RE, and we also evaluate structural parameters for that condition. © 2021 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.
The Calderón–Zygmund Theorem with an $$L^1$$ Mean Hörmander Condition
Authors: Suzuki Soichiro
Published: March 2021

In 2019, Grafakos and Stockdale introduced an $$L^q$$

L
q

mean Hörmander condition and proved a “limited-range” Calderón–Zygmund theorem. Comparing their theorem with the classical one, it requires weaker assumptions and implies the $$L^p$$

L
p

boundedness for the “limited-range” instead of $$1< p < \infty $$

1
<
p
<
∞

. However, in this paper, we show that the $$L^q$$

L
q

mean Hörmander condition is actually enough to obtain the $$L^p$$

L
p

boundedness for all $$1< p < \infty $$

1
<
p
<
∞

even in the worst case $$q=1$$

q
=
1

. We use a similar method to that used by Fefferman (Acta Math 124:9–36, 1970): form the Calderón–Zygmund decomposition with the bounded overlap property and approximate the bad part. Also we give a criterion of the $$L^2$$

L
2

boundedness for convolution type singular integral operators under the $$L^1$$

L
1

mean Hörmander condition.
Linalool inhibits the angiogenic activity of endothelial cells by downregulating intracellular ATP levels and activating TRPM8
Authors: Becker Vivien , Hui Xin , Nalbach Lisa , Ampofo Emmanuel , Lipp Peter , Menger Michael D. , Laschke Matthias W. , Gu Yuan
Published: March 2021

Angiogenesis crucially contributes to various diseases, such as cancer and diabetic retinopathy. Hence, anti-angiogenic therapy is considered as a powerful strategy against these diseases. Previous studies reported that the acyclic monoterpene linalool exhibits anticancer, anti-inflammatory and anti-oxidative activity. However, the effects of linalool on angiogenesis still remain elusive. Therefore, we investigated the action of (3R)-(−)-linalool, a main enantiomer of linalool, on the angiogenic activity of human dermal microvascular endothelial cells (HDMECs) by a panel of angiogenesis assays. Non-cytotoxic doses of linalool significantly inhibited HDMEC proliferation, migration, tube formation and spheroid sprouting. Linalool also suppressed the vascular sprouting from rat aortic rings. In addition, Matrigel plugs containing linalool exhibited a significantly reduced microvessel density 7 days after implantation into BALB/c mice. Mechanistic analyses revealed that linalool promotes the phosphorylation of extracellular signal-regulated kinase (ERK), downregulates the intracellular level of adenosine triphosphate (ATP) and activates the transient receptor potential cation channel subfamily M (melastatin) member (TRPM)8 in HDMECs. Inhibition of ERK signaling, supplementation of ATP and blockade of TRPM8 significantly counteracted linalool-suppressed HDMEC spheroid sprouting. Moreover, ATP supplementation completely reversed linalool-induced ERK phosphorylation. In addition, linalool-induced ERK phosphorylation inhibited the expression of bone morphogenetic protein (BMP)-2 and linalool-induced TRPM8 activation caused the inhibition of β1 integrin/focal adhesion kinase (FAK) signaling. These findings indicate an anti-angiogenic effect of linalool, which is mediated by downregulating intracellular ATP levels and activating TRPM8.
Familial Risk Factors in Relation to Recurrent Depression Among Former Adolescent Psychiatric Inpatients
Authors: Halonen Joonas , Hakko Helinä , Riala Kaisa , Riipinen Pirkko
Published: March 2021

Treating recurrent depression is a challenge for clinical practitioners. We investigated which family environmental factors contribute to differences between recurrent and non-recurrent depression by the young adulthood of the former adolescent inpatients. The initial sample covered 237 adolescent psychiatric inpatients with depression, of which 35.4% had later diagnosed with recurrent depression. Recurrence in depression was associated to distant maternal relationships in both male (p = 0.022) and female patients (p = 0.042). In females, the likelihood for recurrent depression was also related to psychiatric problems of the father (p = 0.013) and siblings (OR = 3.7, p = 0.032), and having a grand multiparous mother (p = 0.005). Our results emphasise the need for effective family-centred approaches in treatment of adolescents with depression.
Effective identification of cancer predisposition syndromes in children with cancer employing a questionnaire
Authors: Schwermer Miriam , Behnert Astrid , Dörgeloh Beate , Ripperger Tim , Kratz Christian P.
Published: March 2021

Approximately 10% of children with newly diagnosed cancer have a cancer predisposition syndrome (CPS). The optimal diagnostic approach to identify them among children diagnosed with cancer is unknown. Objective: To determine whether the use of a one-page questionnaire can improve the CPS diagnosis among children with an oncologic condition. Design: Comparative effectiveness research. Setting: Referral center for children with cancer. Results: 739 children diagnosed with an oncologic condition between 2012 and 2019. All children with a newly diagnosed oncologic condition presenting to Hannover Medical School between January 1st 2017 and December 31st 2019 were prospectively evaluated with a CPS questionnaire. Children in whom the questionnaire suggested the need of a genetic workup were further evaluated. All children diagnosed with an oncologic condition between January 1st 2012 and December 31st 2016 served as control. The CPS diagnoses established during both time periods were evaluated and compared. A CPS was diagnosed in 27 out of 287 children (9.4%) during the questionnaire period versus 24 out of 452 children (5.3%) during the control period (P = 0.032). Conclusion: The CPS questionnaire appears to significantly improve the diagnosis of children with CPS among children with a newly diagnosed oncologic condition.
Secondary Forests and Agrarian Transitions: Insights from Nepal and Peru
Authors: Pain Adam , Marquardt Kristina , Khatri Dil
Published: March 2021

We provide an analytical contrast of the dynamics of secondary forest regeneration in Nepal and Peru framed by a set of common themes: land access, boundaries, territories, and rights, seemingly more secure in Nepal than Peru; processes of agrarian change and their consequences for forest-agriculture interactions and the role of secondary forest in the landscape, more marked in Peru, where San Martín is experiencing apparent agricultural intensification, than in Nepal; and finally processes of social differentiation that have consequences for different social groups, livelihood construction and their engagement with trees, common to both countries. These themes address the broader issue of the necessary conditions for secondary forest regeneration and the extent to which the rights and livelihood benefits of those actively managing it are secured.
Gaṅgeśa on Epistemic Luck
Authors: Das Nilanjan
Published: March 2021

This essay explores a problem for Nyāya epistemologists. It concerns the notion of pramā. Roughly speaking, a pramā is a conscious mental event of knowledge-acquisition, i.e., a conscious experience or thought in undergoing which an agent learns or comes to know something. Call any event of this sort a knowledge-event. The problem is this. On the one hand, many Naiyāyikas accept what I will call the Nyāya Definition of Knowledge, the view that a conscious experience or thought is a knowledge-event just in case it is true and non-recollective. On the other hand, they are also committed to what I shall call Nyāya Infallibilism, the thesis that every knowledge-event is produced by causes that couldn’t have given rise to an error. These two commitments seem to conflict with each other in cases of epistemic luck, i.e., cases where an agent arrives a true judgement accidentally or as a matter of luck. While the Nyāya Definition of Knowledge seems to predict that these judgements are knowledge-events, Nyāya Infallibilism seems to entail that they aren’t. In this essay, I show that Gaṅgeśa Upādhyāya, the 14th century Naiyāyika, solves this problem by adopting what I call epistemic localism, the view that upstream causal factors play no epistemically significant role in the production of knowledge.
Pupillary unrest, opioid intensity, and the impact of environmental stimulation on respiratory depression
Authors: McKay Rachel Eshima , Kohn Michael A. , Larson Merlin D.
Published: March 2021

Opioid-induced respiratory depression (OIRD) confers significant morbidity, but its onset can be challenging to recognize. Pain or stimulation effects of conversation may mask or attenuate common clinical manifestations of OIRD. We asked whether pupillary unrest could provide an objective signal of opioid exposure, and whether this signal would be independent from the confounding influence of extrinsic stimulation. We conducted a cross-over trial of healthy volunteers using identical remifentanil infusions separated by a washout period; in both, pupillary unrest in ambient light (PUAL) was measured at 2.5-min intervals. During one infusion, investigators continuously engaged the subject in conversation, while in the other, a quiet environment was maintained; measures of respiratory depression were compared under each condition. We tested PUAL’s relationship to estimated opioid concentration under quiet conditions, measured PUAL’s discrimination of lower versus higher opioid exposure using receiver operating characteristic (ROC) analysis, and assessed the effect of stimulation on PUAL versus opioid using mixed effects regression. Respiratory depression occurred more frequently under quiet conditions (p < 0.0001). Under both conditions, PUAL declined significantly over the course of the remifentanil infusion and rose during recovery (p < 0.0001). PUAL showed excellent discrimination in distinguishing higher versus absent-moderate opioid exposure (AUROC = 0.957 [0.929 to 0.985]), but was unaffected by interactive versus quiet conditions (mean difference, interactive – quiet = − 0.007, 95% CI − 0.016 to 0.002). PUAL is a consistent indicator of opioid effect, and distinguishes higher opioid concentrations independently of the stimulating effects of conversational interaction. Under equivalent opioid exposure, conversational interaction delayed the onset and minimized the severity of OIRD.

Clinical trial registration: NCT 04301895
Fiber-based modeling and simulation of skeletal muscles
Authors: Gfrerer M. H. , Simeon B.
Published: March 2021

This paper presents a novel fiber-based muscle model for the forward dynamics of the musculoskeletal system. While bones are represented by rigid bodies, the muscles are taken into account by means of one-dimensional cables that obey the laws of continuum mechanics. In contrast to standard force elements such as the Hill-type muscle model, this approach is close to the real physiology and also avoids the issue of wobbling masses. On the other hand, the computational cost is rather low in comparison with full 3D continuum mechanics simulations. The cable model includes sliding contact between individual fibers as well as between fibers and bones. For the discretization, cubic finite elements are employed in combination with implicit time stepping. Several validation studies and the simulation of a motion scenario for the upper limb demonstrate the potential of the fiber-based approach.
LAG-3 expression in the inflammatory microenvironment of glioma
Authors: Mair Maximilian J. , Kiesel Barbara , Feldmann Katharina , Widhalm Georg , Dieckmann Karin , Wöhrer Adelheid , Müllauer Leonhard , Preusser Matthias , Berghoff Anna S.
Published: March 2021

Purpose

Immune modulatory therapies including immune checkpoint inhibitors have so far failed to result in clinically meaningful efficacy in glioma. We aimed to investigate lymphocyte activation gene 3 (LAG-3), an inhibitory receptor on immune cells and target of second-generation immune checkpoint inhibitors, in glioma.

Methods

97 patients with diffuse glioma (68 with glioblastoma, 29 with WHO grade II-III glioma) were identified from the Neuro-Biobank of the Medical University of Vienna. LAG-3 expression in the inflammatory microenvironment was assessed by immunohistochemistry (monoclonal anti-LAG-3 antibody, clone 17B4) and correlated to CD3+ , CD8+ , CD20+ and PD-1+ tumor-infiltrating lymphocytes (TILs) and PD-L1 expression on tumor cells.

Results

LAG-3+ TILs could be observed in 10/97 (10.3%) IDH-wildtype samples and in none of the included IDH-mutant glioma samples (p = 0.057). Further, LAG-3+ TILs were only observed in WHO grade IV glioblastoma, while none of the investigated WHO grade II–III glioma presented with LAG-3+ TILs (p = 0.03). No association of O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation and presence of LAG-3+ TILs was observed (p = 0.726). LAG-3 expression was associated with the presence of CD3+ (p = 0.029), CD8+ (p = 0.001), PD-1+ (p < 0.001) TILs and PD-L1+ tumor cells (p = 0.021), respectively. No association of overall survival with LAG-3+ TIL infiltration was evident (median OS 9.9 vs. 14.2 months, p = 0.95).

Conclusions

LAG-3 is only rarely expressed on TILs in IDH-wildtype glioma and associated with active inflammatory milieu as defined by higher TIL density. Immune microenvironment diversity should be considered in the design of future immunotherapy trials in glioma.
The impact of clinical symptoms and endoscopic and histologic disease activity on health-related quality of life in patients with ulcerative colitis following treatment with multimatrix mesalazine
Authors: Yarlas Aaron , Willian Mary Kaye , Nag Arpita
Published: March 2021

Purpose

Studies of patients with ulcerative colitis (UC) report that reduced clinical symptoms and endoscopic activity predict better health-related quality of life (HRQoL). However, no study has examined the joint and unique associations of clinical and endoscopic activity with HRQoL, nor of histologic inflammation and HRQoL. These post hoc analyses evaluated whether reduced clinical, endoscopic, and histologic disease activity were uniquely associated with improved HRQoL for adults with active mild-to-moderate UC receiving once-daily 4.8 g/day multimatrix mesalazine for 8 weeks.

Methods

Assessments at baseline and week 8 (i.e., treatment completion) included clinical and endoscopic activity (modified UC-Disease Activity Index), histology (Geboes scoring), and HRQoL (Short Inflammatory Bowel Disease Questionnaire [SIBDQ]; SF-12v2® Health Survey [SF-12v2]). Associations among each type of disease activity and HRQoL were examined by correlations and by mean changes in SIBDQ and SF-12v2 scores between disease activity subgroups (e.g., achievement of clinical remission; mucosal healing). Regression models estimated unique variance in HRQoL accounted by each type of disease activity.

Results

Within the analysis sample (n = 717), patients with reduced clinical and endoscopic activity had significantly larger improvements in all HRQoL domains (p < 0.001), as did patients in both endoscopic and clinical remission compared to patients in endoscopic remission only (p < 0.05). Patients with histologic activity post-treatment scored significantly worse on all HRQoL domains than patients with no activity (p < 0.05). Correlations and regression models found that decreases in clinical and endoscopic activity were associated with improvements in HRQoL domain scores.

Conclusions

Clinical symptoms and mucosal health have separable, distinct impacts on UC patients’ HRQoL.
Against Polanyian orthodoxy: a reply to Hannes Lacher
Authors: Somers Margaret , Block Fred
Published: March 2021

Hannes Lacher’s article (2019) misrepresents and then denounces both the substance and the spirit of our book, The Power of Market Fundamentalism: Karl Polanyi’s Critique (2014). Lacher claims his interpretation of Polanyi to be the only acceptable one, and vociferously alerts readers to beware the dangerous influence of our work. Because we continue to believe that familiarity with Polanyi’s  theoretical framework is valuable for those resisting the depredations of neoliberalism and authoritarianism, we restate our commitment to interpreting Polanyi’s work in the most capacious way possible, treating it not as Scripture but as a body of work multidimensional enough for varying perspectives. In our reply to Lacher, we revisit several themes central to our book, including Polanyi’s complex use of “utopianism”; the “always-instituted economy”; the gold standard’s attack on the “democratic virus” and the rise of fascism; and Polanyi’s socialist commitment to democratizing the economy. We also suggest that by exploring several apparent puzzles in the text of GT it is possible to derive a more fruitful and powerful interpretation of Polanyi’s thinking.
Sleeping beauties gain impact in overdrive mode
Authors: van Raan Anthony F. J.
Published: March 2021

In this study we focus on characteristics of SBs that have not or hardly been investigated previously. We find that the choice of the awakening period in the selection of SBs has consequences for the measured citation patterns. Focusing on medical SBs we analyze patterns in the time-development of the citation impact of SBs; the influence of self-citations on the awakening process; and the occurrence of medical research fields to which the SBs and their citing papers belong. An important finding is that SBs are generally characterized by a sleep that becomes less and less deep instead of a permanent deep sleep. The sleeping period is followed by a phase-transition-like jump as a start of the awakening period and a remarkable regularity is found for the citation impact immediately before and after the jump.
Evaluation Metrics for Conditional Image Generation
Authors: Benny Yaniv , Galanti Tomer , Benaim Sagie , Wolf Lior
Published: March 2021

We present two new metrics for evaluating generative models in the class-conditional image generation setting. These metrics are obtained by generalizing the two most popular unconditional metrics: the Inception Score (IS) and the Fréchet Inception Distance (FID). A theoretical analysis shows the motivation behind each proposed metric and links the novel metrics to their unconditional counterparts. The link takes the form of a product in the case of IS or an upper bound in the FID case. We provide an extensive empirical evaluation, comparing the metrics to their unconditional variants and to other metrics, and utilize them to analyze existing generative models, thus providing additional insights about their performance, from unlearned classes to mode collapse.
Failure Analysis of Premature Corrosion of HF Seam-Welded Steel Pipe in Central Heating System
Authors: Tyrala Dorota , Pawlowski Bogdan
Published: March 2021

Premature corrosion in the form of longitudinal cracking in a high-frequency (HF) induction seam-welded steel pipe occurred after just 24 months in service. The failed pipe was investigated to reveal the main cause of its failure, and the results of microstructural examinations (light optical microscopy, scanning electron microscopy with energy-dispersive spectrometry) suggest that the failure resulted from an HF induction welding process defect—a so-called cast weld, that is, a huge number of iron oxides in the weld line caused by insufficient ejection of the molten metal from the bond line.
One-shot Cluster-Based Approach for the Detection of COVID–19 from Chest X–ray Images
Authors: Aradhya V. N. Manjunath , Mahmud Mufti , Guru D. S. , Agarwal Basant , Kaiser M. Shamim
Published: March 2021

Coronavirus disease (COVID-19) has infected over more than 28.3 million people around the globe and killed 913K people worldwide as on 11 September 2020. With this pandemic, to combat the spreading of COVID-19, effective testing methodologies and immediate medical treatments are much required. Chest X-rays are the widely available modalities for immediate diagnosis of COVID-19. Hence, automation of detection of COVID-19 from chest X-ray images using machine learning approaches is of greater demand. A model for detecting COVID-19 from chest X-ray images is proposed in this paper. A novel concept of cluster-based one-shot learning is introduced in this work. The introduced concept has an advantage of learning from a few samples against learning from many samples in case of deep leaning architectures. The proposed model is a multi-class classification model as it classifies images of four classes, viz., pneumonia bacterial, pneumonia virus, normal, and COVID-19. The proposed model is based on ensemble of Generalized Regression Neural Network (GRNN) and Probabilistic Neural Network (PNN) classifiers at decision level. The effectiveness of the proposed model has been demonstrated through extensive experimentation on a publicly available dataset consisting of 306 images. The proposed cluster-based one-shot learning has been found to be more effective on GRNN and PNN ensembled model to distinguish COVID-19 images from that of the other three classes. It has also been experimentally observed that the model has a superior performance over contemporary deep learning architectures. The concept of one-shot cluster-based learning is being first of its kind in literature, expected to open up several new dimensions in the field of machine learning which require further researching for various applications.