bluuebunny/crossref_metadata_2025 huggingface dataset:
Per- and Polyfluoroalkyl Substances Are Positively Associated with Thyroid Hormones in an Arctic Seabird
Authors: Ask Amalie Vigdel , Jenssen Bjørn Munro , Tartu Sabrina , Angelier Frédéric , Chastel Olivier , Gabrielsen Geir Wing
Published: December 2020

Per- and polyfluoroalkyl substances (PFAS) are associated with several disrupted physiological and endocrine parameters. Regarding endocrine mechanisms, laboratory studies suggest that PFAS could disrupt the thyroid hormone system and alter circulating thyroid hormone concentrations. Thyroid hormones play a ubiquitous role—controlling thermoregulation, metabolism, and reproduction. However, evidence for disruption of thyroid hormones by PFAS remains scarce in wildlife. The present study investigated the associations between concentrations of PFAS, thyroid hormones, and body condition in an arctic seabird, the black-legged kittiwake (Rissa tridactyla). We collected blood from kittiwakes sampled in Svalbard, Norway (2013 and 2014). Plasma samples were analyzed for total thyroxine (TT4) and total triiodothyronine (TT3) concentrations; detected PFAS included branched and linear (lin) C8 perfluoroalkyl sulfonates (i.e., perfluoroctane sulfonate [PFOS]) and C9-C14 perfluoroalkyl carboxylates (PFCAs). The dominant PFAS in the kittiwakes were linPFOS and C11- and C13-PFCAs. Generally, male kittiwakes had higher concentrations of PFAS than females. We observed positive correlations between linPFOS, C10-PFCA, and TT4 in males, whereas in females C12-14-PFCAs were positively correlated to TT3. Interestingly, we observed contrasted correlations between PFAS and body condition; the direction of the relationship was sex-dependent. Although these results show relationships between PFAS and circulating thyroid hormone concentrations in kittiwakes, the study design does not allow for concluding on causal relationships related to effects of PFAS on the thyroid hormone system. Future experimental research is required to quantify this impact of PFAS on the biology of kittiwakes. The apparently different associations among PFAS and body condition for males and females are puzzling, and more research is required. Environ Toxicol Chem 2021;40:820–831. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Abstract

The thyroid hormones (THs) triiodothyronine and thyroxine and per- and polyfluoroalkyl substances (PFAS) were examined in plasma from black-legged kittiwakes (Rissa tridactyla). We found a positive association between several PFAS and the THs. T3 = triiodothyronine; T4 = thyroxine.
Subspace leakage reduced nonuniform sparse Fibonacci‐like planar array to estimate azimuth and elevation angles of both Angle of Arrival and Angle of Departure
Authors: Vethanayagam Angeline Beulah , Narasimhan Venkateswaran
Published: December 2020

Estimation of azimuth and elevation angles of both Angle of Arrival and Angle of Departure is a challenging research topic in 5G smart antenna technology. The key contributions of this work involve two novel algorithms implemented in a uniform planar array for the estimation of the arrival and departure angles using the received signal from the coherent users. One of the two algorithms reduces search complexity without any reduction in the angular resolution of the estimated angles. This is done through selection of active antennas in the uniform planar array to make it sparse without creating angle ambiguity. The second method improves the angular resolution in estimating the angles through reduction in the subspace leakage that occurs between the signal and noise subspace. Numerical simulations prove the proposed two algorithms producing a high angular resolution with reduced complexity.
The interference alignment scheme based on subspace differentiation for multicell multiuser multiple‐input‐multiple‐output uplink channels
Authors: Li Shibao , Ye Wei , Guo Lin , Liu Jianhang , Huang Tingpei , Cui Xuerong , Zhang Yucheng
Published: December 2020

The traditional subspace interference alignment (IA) schemes in the multicell multiuser multiple‐input‐multiple‐output (MIMO) network align interference into the multidimensional subspace to reduce the dimension of the interference space, but the choice of subspace is random, and the difference between users is not considered. Such schemes may leave large intercell interference when the difference between users is large. To solve this problem, this article proposes the IA scheme based on subspace differentiation for multicell multiuser MIMO uplink channels. First, based on the transmit power and the distance to base stations in other cells, each user analyzes the interference value it will cause. The interference value of each user is represented by actual interference power (AIP). Within each cell, the users are reordered according to the AIP. When performing interference reduction, the signals of the users with large interference are merged into the subspace composed of the signals of the users with small interference, which can further reduce the final intercell interference. The multidimensional merge weight is assigned according to the AIP. The smaller the interference value of the dimension, the more interference it merges. The experimental simulation data show that the scheme implemented in this article can improve the proportion of the desired signals in the received signals of the receivers, thereby improving the overall system rate. When the user difference in transmit power and distance is large, the proposed scheme has a particularly obvious advantage.
Do put warrants unwind short‐sale restrictions? Further evidence from the Taiwan Stock Exchange
Authors: Chuang Yi‐Wei , Tsai Wei‐Che , Weng Pei‐Shih , Yin Chi
Published: December 2020

This study investigates the relationship between stock short‐selling restrictions and bearish equity warrants on the Taiwan Stock Exchange to clarify the substitutive role of put warrants for underlying stocks subject to short‐sale constraints. We show that put warrant transactions increase when short selling is prohibited in the spot market and the substitutive increase in trading also leads to wider bid–ask spreads and higher implied volatility for put warrants. Moreover, we find that the increased trading activities in put warrants could subsequently affect spot market trading through warrant issuers' required dynamic hedging behaviors.
The term structure of the VXX option smirk: Pricing VXX option with a two‐factor model and asymmetry jumps
Authors: Tan Xiaoyu , Wang Chengxiang , Lin Wei , Zhang Jin E. , Li Shenghong , Zhao Xuejun , Zhang Zili
Published: December 2020

This paper proposes a comprehensive jump‐to‐default extended two‐factor stochastic volatility plus asymmetry jumps model for the valuation of VXX derivatives. The model provides a more flexible modeling of the time variation in VXX options smirk and VXX options volatility term structure compared with previous model alternatives. Empirical results indicate that our model outperforms Bao et al.'s model by 28.19% in‐sample and 23.38% out‐of‐sample. Moreover, our model improves the probability that the estimated prices fall inside the quoted option bid‐ask spread and has a better fitting capacity for the term structure of VXX implied volatility, especially for out‐of‐the‐money options.
Advanced Material Against Human (Including Covid‐19) and Plant Viruses: Nanoparticles As a Feasible Strategy
Authors: Tortella Gonzalo R. , Rubilar Olga , Diez María Cristina , Padrão Jorge , Zille Andrea , Pieretti Joana C. , Seabra Amedea B.
Published: December 2020

The SARS‐CoV‐2 virus outbreak revealed that these nano‐pathogens have the ability to rapidly change lives. Undoubtedly, SARS‐CoV‐2 as well as other viruses can cause important global impacts, affecting public health, as well as, socioeconomic development. But viruses are not only a public health concern, they are also a problem in agriculture. The current treatments are often ineffective, are prone to develop resistance, or cause considerable adverse side effects. The use of nanotechnology has played an important role to combat viral diseases. In this review three main aspects are in focus: first, the potential use of nanoparticles as carriers for drug delivery. Second, its use for treatments of some human viral diseases, and third, its application as antivirals in plants. With these three themes, the aim is to give to readers an overview of the progress in this promising area of biotechnology during the 2017–2020 period, and to provide a glance at how tangible is the effectiveness of nanotechnology against viruses. Future prospects are also discussed. It is hoped that this review can be a contribution to general knowledge for both specialized and non‐specialized readers, allowing a better knowledge of this interesting topic.
Upper Cretaceous wedge‐top to foredeep architecture in the United Arab Emirates: Insights from the Faiyah Anticline
Authors: Mohammed Ibrahim Q. , Farouk Sherif , A. Lawa Fadhil , Alsuwaidi Mohammad , Morad Sadoon
Published: December 2020

Facies architecture and benthic foraminiferal biostratigraphy were interpreted to reconstruct the depositional environments of the Upper Campanian–Maastrichtian Qahlah and Simsima formations in the Faiyah Anticline Range, north‐central United Arab Emirates. Obduction of the Oman ophiolite controlled the palaeo‐configuration of the Upper Cretaceous deposits and resulted in an irregular palaeogeography which caused rapid lateral and vertical facies changes and the building up of 19 types of facies. The Qahlah Formation was deposited dominantly as an inner clastic wedge facies association containing alluvial fan, alluvial plain, and proximal shallow marine mass‐ flow deposits. The Simsima Formation is represented by deposits characteristic of variable settings, including intertidal, restricted lagoon, inner edge shallow platform, and forereef shelf that formed in the outer carbonate wedge. Towards the southwest of the Faiyah Anticline Range, the Simsima Formation exhibits distal turbidites and contains remobilized carbonate conglomerates and marl that were deposited in a foredeep environment. This lateral variation has been caused by tectonics associated with increased global sea level. A tectonically‐driven long‐time hiatus caused the absence of Danian age strata. From the sequence stratigraphic perspective, three forced sequence boundaries are reported within the Upper Campanian–Maastrichtian successions. This sequence boundaries match well with those documented from the entire Arabian Plate.
Sedimentary characteristics and detrital zircon U–Pb isotopes of the Upper Permian–Lower Triassic strata in eastern Ordos Basin, Central North China
Authors: Liu Yajun , Feng Zhiqiang , Liu Yongjiang , Li Long , Li Weimin , Liu Dongna , Wu Peng
Published: December 2020

A series of tectonic activities induced by the subduction of the Palaeo‐Asian Ocean (PAO) in the Palaeozoic have been recorded in the North China Craton (NCC). Sedimentary strata provide some precious records to reconstruct the basin evolution in the NCC. In this study, we carried out detrital zircon LA‐ICP‐MS U–Pb dating, sandstone modal analysis, bulk‐rock major, and trace elemental measurements for the Sunjiagou and Liujiagou formations in the eastern Ordos Basin to trace the material source. The results show that the sedimentary rocks were mostly sourced from active continental margins. The detrital zircon ages of the Sunjiagou and Liujiagou formations spread from >3,000 to 250 Ma with peaks of main age populations at 2,508, 1,890, 430, and 270 Ma. Based on the age comparison and the southward palaeocurrents, we consider that the source material of these sedimentary rocks comes from the northern margin of the NCC. This in turn indicates that the amalgamation of the PAO and the NCC should have finished at least by the end of the Late Permian.
How microglia sense and regulate neuronal activity
Authors: Umpierre Anthony D. , Wu Long‐Jun
Published: December 2020

Microglia are innate immune cells of the central nervous system that sense extracellular cues. Brain injuries, inflammation, and pathology evoke dynamic structural responses in microglia, altering their morphology and motility. The dynamic motility of microglia is hypothesized to be a critical first step in sensing local alterations and engaging in pattern‐specific responses. Alongside their pathological responses, microglia also sense and regulate neuronal activity. In this review, we consider the extracellular molecules, receptors, and mechanisms that allow microglia to sense neuronal activity changes under both hypoactivity and hyperactivity. We also highlight emerging in vivo evidence that microglia regulate neuronal activity, ranging from physiological to pathophysiological conditions. In addition, we discuss the emerging role of calcium signaling in microglial responses to the extracellular environment. The dynamic function of microglia in monitoring and influencing neuronal activity may be critical for brain homeostasis and circuit modification in health and disease.
FreeSurfer‐based segmentation of hippocampal subfields: A review of methods and applications, with a novel quality control procedure for ENIGMA studies and other collaborative efforts
Authors: Sämann Philipp G. , Iglesias Juan Eugenio , Gutman Boris , Grotegerd Dominik , Leenings Ramona , Flint Claas , Dannlowski Udo , Clarke‐Rubright Emily K. , Morey Rajendra A. , van Erp Theo G.M. , Whelan Christopher D. , Han Laura K. M. , van Velzen Laura S. , Cao Bo , Augustinack Jean C. , Thompson Paul M. , Jahanshad Neda , Schmaal Lianne
Published: December 2020

Structural hippocampal abnormalities are common in many neurological and psychiatric disorders, and variation in hippocampal measures is related to cognitive performance and other complex phenotypes such as stress sensitivity. Hippocampal subregions are increasingly studied, as automated algorithms have become available for mapping and volume quantification. In the context of the Enhancing Neuro Imaging Genetics through Meta Analysis Consortium, several Disease Working Groups are using the FreeSurfer software to analyze hippocampal subregion (subfield) volumes in patients with neurological and psychiatric conditions along with data from matched controls. In this overview, we explain the algorithm's principles, summarize measurement reliability studies, and demonstrate two additional aspects (subfield autocorrelation and volume/reliability correlation) with illustrative data. We then explain the rationale for a standardized hippocampal subfield segmentation quality control (QC) procedure for improved pipeline harmonization. To guide researchers to make optimal use of the algorithm, we discuss how global size and age effects can be modeled, how QC steps can be incorporated and how subfields may be aggregated into composite volumes. This discussion is based on a synopsis of 162 published neuroimaging studies (01/2013–12/2019) that applied the FreeSurfer hippocampal subfield segmentation in a broad range of domains including cognition and healthy aging, brain development and neurodegeneration, affective disorders, psychosis, stress regulation, neurotoxicity, epilepsy, inflammatory disease, childhood adversity and posttraumatic stress disorder, and candidate and whole genome (epi‐)genetics. Finally, we highlight points where FreeSurfer‐based hippocampal subfield studies may be optimized.
Chronic opioid use after laryngeal cancer treatment
Authors: Starr Nicole , Oyler Douglas R. , Schadler Aric , Aouad Rony K.
Published: December 2020

Background

Survivors of head and neck cancer may be at increased risk for chronic opioid use and questions remain about risk factors.

Methods

Retrospective study of patients with laryngeal cancer prescribed opioids utilizing the Truven Health Marketscan database. Patients had laryngeal cancer, underwent treatment, filled an opioid prescription, and were enrolled in this private insurance plan 1 year prior to and after treatment.

Results

In this study, 7484 patients were included; 17.2% developed chronic opioid use, defined as consecutive opioid fills at least 90 days after treatment cessation. Early opioid use (OR = 3.607, 95% CI [3.125–4.163]), tobacco use (OR = 1.28, 95% CI [1.117–1.467]), median morphine milligram equivalent (MME; OR = 1.001, 95% CI [1.000–1.0001]), and radiation alone (OR = 1.435, 95% CI [1.199–1.717]) were predictive of chronic opioid use.

Conclusions

Nearly one in five patients prescribed opioids during treatment developed chronic use. Providers should discuss the risk of chronic opioid use, set expectations for opioid weaning, and consider adjunct pain regimens to develop effective pain management strategies.
Ultrasound‐guided fine‐needle aspiration biopsy of thyroid nodules
Authors: Todsen Tobias , Bennedbæk Finn Noe , Kiss Katalin , Hegedüs Laszlo
Published: December 2020

Fine needle aspiration biopsy (FNAB) remains crucial in the evaluation of thyroid nodules with suspicious clinical findings or ultrasound (US) features suggestive of malignancy. The use of US‐guidance for FNAB allows real‐time visualization of the needle, but is also highly operator‐dependent. Physicians from many specialties (endocrinologists, otolaryngologists/endocrine surgeons, nuclear medicine physicians, radiologists, and pathologists) are involved in the diagnostic workup of thyroid nodules and a standardized and meticulous technique for US‐FNAB is essential for lowering the yield of nondiagnostic specimens and false‐negative results. This video, therefore, demonstrates a well‐proved technique and technical tips to increase the diagnostic results from US‐FNAB.
Pembrolizumab for refractory primary mediastinal B‐cell lymphoma with central nervous system involvement
Authors: de‐la‐Fuente Cristina , Nuñez Fidel , Cortés‐Romera Montserrat , Franch‐Sarto Mireia , Ribera Josep‐Maria , Sancho Juan‐Manuel
Published: December 2020

Primary mediastinal large B‐cell lymphoma (PMBCL) is a rare aggressive B‐cell lymphoma characterized by the frequent presence of amplification and translocation events at 9p24.1, resulting in the expression of the programmed cell death‐1 (PD‐1) ligands PD‐L1 and PD‐L2. Pembrolizumab, a humanized anti‐PD‐1 monoclonal antibody, binds PD‐1 and blocks this interaction, enhancing the activity of the immune system against tumor cells, and has shown activity in PMBCL and in some cases of primary and secondary central nervous system (CNS) lymphoma. We report the case of a 40‐year‐old woman diagnosed with relapsed PMBCL and secondary CNS involvement who responded to pembrolizumab monotherapy, allowing for a later allogeneic stem cell transplant.
A two‐component modeling for free stream velocity in magnetohydrodynamic nanofluid flow with radiation and chemical reaction over a stretching cylinder
Authors: Vinita  , Poply Vikas , Devi Renu
Published: December 2020

This analysis explores the influence of magnetohydrodynamic (MHD) nanofluid flow over a stretching cylinder with radiation effect in presence of chemically reactive species. The thermal radiation phenomenon is incorporated in the temperature equation. The mathematical modeling of the physical problem produces nonlinear set of partial differential equations corresponding to the momentum and energy equations that can be transformed into simultaneous system of ordinary differential equations with appropriate boundary conditions by applying similarity transformations. Shooting technique is used to solve the molded equations after adoption of Runge–Kutta–Fehlberg approach and ODE45 solver in MATLAB. A parametric analysis has been carried out to investigate the impacts of physical parameters that are considered in the current study. The attractive pattern studied the consequence of Brownian motion along with thermophoresis parameter. The outcomes of prominent fluid parameters, especially heat radiation, Lewis number, free stream velocity, chemical reaction, thermophoresis, and Brownian motion on the concentration, temperature, as well as velocity have been examined and are displayed through graphs and tables. The present study reveals that the temperature phenomenon enhances with an increase in radiation parameter, while nanoparticle concentration phenomenon reduces with an increase in chemical reaction parameter.
Tea bioactive components prevent carcinogenesis via anti‐pathogen, anti‐inflammation, and cell survival pathways
Authors: Fan Xiangqi , Xiao Xiangjun , Mao Xiangbing , Chen Daiwen , Yu Bing , Wang Jianping , Yan Hui
Published: December 2020

Cancer seriously impairs human health and survival. Many perturbations, such as increased oxidative stress, pathogen infection, and inflammation, promote the accumulation of DNA mutations, and ultimately lead to carcinogenesis. Tea is one of the most highly consumed beverages worldwide and has been linked to improvements in human health. Tea contains many active components, including tea polyphenols, tea polysaccharides, L‐theanine, tea pigments, and caffeine among other common components. Several studies have identified components in tea that can directly or indirectly reduce carcinogenesis with some being used in a clinical setting. Many previous studies, in vitro and in vivo, have focused on the mechanisms that functional components of tea utilized to protect against cancer. One particular mechanism that has been well described is an improvement in antioxidant capacity seen with tea consumption. However, other mechanisms, including anti‐pathogen, anti‐inflammation and alterations in cell survival pathways, are also involved. The current review focuses on these anti‐cancer mechanisms. This will be beneficial for clinical utilization of tea components in preventing and treating cancer in the future.
Synthesis and biological evaluation of a new series of benzofuran‐1,3,4‐oxadiazole containing 1,2,3‐triazole‐acetamides as potential α‐glucosidase inhibitors
Authors: Abedinifar Fahimeh , Mohammadi‐Khanaposhtani Maryam , Asemanipoor Nafise , Mojtabavi Somayeh , Faramarzi Mohammad A. , Mahdavi Mohammad , Biglar Mahmood , Larijani Bagher , Hamedifar Haleh , Hajimiri Mir H.
Published: December 2020

A series of new benzofuran‐1,3,4‐oxadiazole containing 1,2,3‐triazole‐acetamides 12a‐n as potential anti‐α‐glucosidase agents were designed and synthesized. α‐Glucosidase inhibition assay demonstrated that all the synthesized compounds 12a‐n (half‐maximal inhibitory concentration [IC50] values in the range of 40.7 ± 0.3–173.6 ± 1.9 μM) were more potent than standard inhibitor acarbose (IC50 = 750.0 ± 12.5 µM). Among them, the most potent compound was compound 12c, with inhibitory activity around 19‐fold higher than acarbose. Since the most potent compound inhibited α‐glucosidase in a competitive mode, a docking study of this compound was also performed into the active site of α‐glucosidase. In vitro and in silico toxicity assays of the title compounds were also performed.
LncRNA PART1 promotes cell proliferation and progression in non‐small‐cell lung cancer cells via sponging miR‐17‐5p
Authors: Chen Yeye , Zhou Xiaoyun , Huang Cheng , Li Li , Qin Yingzhi , Tian Zhenhuan , He Jia , Liu Hongsheng
Published: December 2020

It has been demonstrated in previous studies that lncPART1 is dysregulated in non‐small cell lung cancer (NSCLC). However, the function of lncPART1 in NSCLC is unclear. Therefore, this experimental design was based on LncPART1 to explore the pathogenesis of NSCLC. Real‐time polymerase chain reaction was used to detect the expression of lncPART1 and miR‐17‐5p in NSCLC. Cell Counting Kit ‐8, colony formation, and transwell assays were used to examine the effects of lncPART1 and miR‐17‐5p on NSCLC cell proliferation and migration invasiveness. Target gene prediction, luciferase reporter assays were used to validate downstream target genes for lncPART1 and miR‐17‐5p. Western blot analysis was used to detect the expression of TGFBETAR2. LncPART1 was highly expressed in NSCLC. LncPART1 significantly promoted cell proliferation of NSCLC cells. miR‐17‐5p was down‐expressed in NSCLC. miR‐17‐5p overexpression inhibited cell proliferation and migration invasion in NSCLC cells. LncPART1 was able to inhibit miR‐17‐5p expression and upregulate the expression level of TGFBETAR2. The results of in vivo animal models confirmed that lncPART1 promoted NSCLC progression by miR‐17‐5p/TGFBETAR2 axis. LncPART1 promoted the progression of NSCLC by miR‐17‐5p/TGFBETAR2 axis.
Atypical structure and function of integrin αVβ8
Authors: Song Guannan , Luo Bing‐Hao
Published: December 2020

Integrins are heterodimeric transmembrane proteins that play important roles in various biological processes. Most integrins serve as adhesion molecules and transmit bidirectional signaling across the cell membrane through global conformational changes from the bent closed to the extended open conformation. However, integrin β8 is distinctive in structure and function. Its cytoplasmic domain lacks the conserved protein‐binding sequence, which is important in transmitting inside‐out signals, suggesting that integrin β8 may have a different activation mechanism or lack such signaling. In addition, the ligand‐binding or activating metal ion Mn2+ does not induce a global conformational change in integrin β8. It may have only one conformation, that is, an extended, closed conformation, but with high affinity for ligands under physiological conditions, and is, therefore, considered an atypical integrin member. The extended structure and high ligand‐binding affinity of integrin αvβ8 make it ideal for encountering and binding ligands expressed on an opposing cell or in the extracellular matrix. In this review, we summarize the progress in integrin β8 research with a focus on its distinctive function and structure among integrin members.
Pharmacokinetic and Pharmacodynamic Modeling of Tezepelumab to Guide Phase 3 Dose Selection for Patients With Severe Asthma
Authors: Ly Neang , Zheng Yanan , Griffiths Janet M. , van der Merwe Rene , Agoram Balaji , Parnes Jane R. , Roskos Lorin
Published: December 2020

Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin, an epithelial cytokine involved in asthma pathogenesis. In the phase 2b PATHWAY study (ClinicalTrials.gov identifier: NCT02054130), tezepelumab significantly reduced exacerbations in adults with severe, uncontrolled asthma. We used pharmacokinetic (PK) and pharmacodynamic (PD) modeling to guide tezepelumab dose selection for phase 3 trials in patients with severe asthma. PK data from 7 clinical studies were used to develop a population PK model. Population PK‐PD models were developed to characterize the relationship between tezepelumab PK and asthma exacerbation rate (AER) and fractional exhaled nitric oxide (FeNO) levels (using phase 2b PD data only). Tezepelumab PK were well described by a 2‐compartment model with first‐order absorption; PK parameter estimates were consistent with those of other immunoglobulin G2 antibodies. PK‐PD models predicted that subcutaneous dosing at 210 mg every 4 weeks was associated with ≈90% of the maximum drug effect of tezepelumab on AER and FeNO; further dose increases were not expected to result in additional, clinically meaningful treatment benefit. No clinically significant covariates of treatment effects on AER and FeNO were identified. Population PK simulations, exposure‐response relationships and safety profiles of tezepelumab at doses up to 280 mg every 2 weeks suggested that no dose adjustment based on body weight or for adolescents was required. These results support the selection of 210 mg every 4 weeks subcutaneously as the dose for phase 3 studies of tezepelumab in adults and adolescents with severe asthma.
A Population Pharmacokinetic Model of (R)‐ and (S‐) Oxybutynin and Its Active Metabolites After Oral and Intravesical Administration to Healthy Volunteers
Authors: Kretschmar Melanie , Suleiman Ahmed Abbas , Krause Petra , Albrecht Uwe , Stein Raimund , Rubenwolf Peter , Fuhr Uwe , Taubert Max
Published: December 2020

Oxybutynin is a racemic anticholinergic drug used for the symptomatic treatment of detrusor overactivity. The formation of active metabolites related to tolerability problems depends on the route of administration. The objective of this evaluation was to develop a pharmacokinetic model for oral/intravesical administration as the basis for simulations with different dosages. Data from a published changeover clinical study with 18 healthy adults receiving a single oral dose of 5 mg immediate‐release oxybutynin and single and multiple intravesical doses of 10 mg oxybutynin solution was evaluated. Enantioselective plasma concentrations of oxybutynin and N‐desethyloxybutynin (NDO) were used to establish a population pharmacokinetic model using nonlinear mixed‐effects modeling with NONMEM 7.4.1. For both enantiomers, the data were described well by a 2‐compartment model for oxybutynin with an additional compartment for NDO. Oxybutynin absorption was modeled by transit compartments for oral and first‐order absorption for intravesical application. Bioavailability of the more active (R)‐enantiomer was 7% for oral and 10%‐22% for intravesical administration. In simulations, intravesical doses of 5 to 15 mg (R)‐oxybutynin administered 2 to 3 times daily decreased peak‐trough fluctuations of NDO to 8% compared with 24% after oral administration. The NDO/oxybutynin ratio was reduced from 17 after oral administration to unity. Chronic intravesical versus oral administration of (R)‐oxybutynin generates distinctly lower and less variable concentrations of (R)‐NDO. Pharmacokinetic simulations suggest that exposure for 12.5 mg (R)‐oxybutynin administered twice daily might not compromise efficacy and tolerability compared with exposure for standard thrice‐daily administrations. This assumption needs to be assessed in clinical studies.
An overview of key papers preceding Sidman equivalence
Authors: Arntzen Erik , Sætherbakken Per Stian
Published: December 2020

In behavior analysis, research on stimulus equivalence has been an area of high activity for more than 45 years. Murray Sidman's contribution was crucial in the development of this field, and, thus, it seems informative to highlight the experiments that were necessary in the development of the descriptive model of equivalence relations and behavior. The purpose of this paper is to provide an overview of the significant work that gave the historical context for Sidman and colleagues' conceptualization of stimulus equivalence as it was presented in 1982. This article emphasizes the 31 papers and chapters written by Sidman and colleagues that focus on research questions within stimulus control. The chapters and papers are organized according to their dimensions in behavior analysis and according to whether they can be categorized as instruction programs or experimental studies. The issues discussed regarding these papers and chapters include types of stimuli, matching, discriminations, and others. Collectively, this early work influenced methods and considerations about stimulus control issues that have been important to the development of stimulus equivalence.
Increased serum amylase and/or lipase in coronavirus disease 2019 (COVID‐19) patients: Is it really pancreatic injury?
Authors: Pribadi Rabbinu R , Simadibrata Marcellus
Published: December 2020

Coronavirus disease 2019 (COVID‐19) is a novel disorder caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Although it mainly affects the respiratory system, the pancreas could also become the virus' target. The issue regarding pancreatic involvement in COVID‐19 has been raised by several researchers. They found increased serum amylase and/or lipase in COVID‐19 patients, which suggested pancreatic injury. We aimed to critically review the evidence to provide insights and to answer the very question of the possibility of pancreatic injury. Current evidence shows that increased amylase and/or lipase is not necessarily a pancreatic injury in COVID‐19 patients. Those increased enzymes might also be found in other clinical conditions.
Microwave‐assisted synthesis of 2‐styrylquinoline‐4‐carboxylic acid derivatives to improve the toxic effect against Leishmania (Leishmania) amazonensis
Authors: Luczywo Ayelen , Sauter Ismael Pretto , da Silva Ferreira Thalita Camêlo , Cortez Mauro , Romanelli Gustavo P. , Sathicq Gabriel , Asís Silvia E.
Published: December 2020

The identification of new compounds is urgent to develop safe and efficacious candidates for leishmaniasis treatment, especially from natural products as a potential source of active molecules against neglected tropical parasite diseases. Inspired by the efficacious quinoline alkaloid microbial effects, we have previously reported the synthesis and biological activity of 2‐phenylquinoline‐4‐carboxylic acids and poly‐substituted quinolines against parasites. In this work, a series of eighteen 2‐styryl‐4‐quinolinecarboxylic acids were synthesized under microwave irradiation settings obtaining from good to excellent yields (60%‐90%), shorter reaction times (2 minutes), and eco‐friendly experimental conditions. All these products were evaluated against infective forms of Leishmania (Leishmania) amazonensis, such as promastigotes and intracellular amastigotes, based on cytotoxicity assays, including host macrophage infection assays. Compounds 4 and 5 possessing a 2‐chloro or 4‐chlorostyryl moiety, respectively, were considered the most promising antileishmanial agents due to the parasite killing effect in intracellular forms inside infected macrophages. Thus, our results revealed that the 2‐styryl‐4‐quinolinecarboxylic acid backbone structure was essential for the activity against intracellular pathogens like L. (L.) amazonensis.
Hysterosalpingo‐Foam Sonography for the Diagnosis of Tubal Occlusion
Authors: Melcer Yaakov , Zilberman Sharon Nataly , Nimrodi Maya , Pekar‐Zlotin Marina , Gat Itai , Maymon Ron
Published: December 2020

This systematic review and meta‐analysis evaluated the diagnostic accuracy of hysterosalpingo‐foam sonography in suspected cases of tubal occlusion. The combined sensitivity and specificity estimates were 0.99 (95% confidence interval [CI], 0.89–0.99) and 0.91 (95% CI, 0.53–0.98), respectively, with positive and negative likelihood ratios of 11.5 (95% CI, 1.5–87.5) and 0.006 (95% CI, 0.0003–0.12), respectively. The diagnostic odds ratio was 1931.008 (95% CI, 69.7–53,460.8). These findings confirm hysterosalpingo‐foam sonography as a highly accurate test for the diagnosis of tubal occlusion and show that it is on a par with standard tests.
Deep Learning for Classification of Pediatric Otitis Media
Authors: Wu Zebin , Lin Zheqi , Li Lan , Pan Hongguang , Chen Guowei , Fu Yuqing , Qiu Qianhui
Published: December 2020

Objectives/Hypothesis

To create a new strategy for monitoring pediatric otitis media (OM), we developed a brief, reliable, and objective method for automated classification using convolutional neural networks (CNNs) with images from otoscope.

Study Design

Prospective study.

Methods

An otoscopic image classifier for pediatric OM was built upon the idea of deep learning and transfer learning using the two most widely used CNN architectures named Xception and MobileNet‐V2. Otoscopic images, including acute otitis media (AOM), otitis media with effusion (OME), and normal ears were obtained from our institution. Among qualified otoendoscopic images, 10,703 images were used for training, and 1,500 images were used for testing. In addition, 102 images captured by smartphone with WI‐FI connected otoscope were used as a prospective test set to evaluate the model for home screening and monitoring.

Results

For all diagnoses combined in the test set, the Xception model and the MobileNet‐V2 model had similar overall accuracies of 97.45% (95% CI 96.81%–97.94%) and 95.72% (95% CI 95.12%–96.16%). The overall accuracies of two models with smartphone images were 90.66% (95% CI 90.21%–90.98%) and 88.56% (95% CI 87.86%–90.05%). The class activation map results showed that the extracted features of smartphone images were the same as those of otoendoscopic images.

Conclusions

We have developed deep learning algorithms for the successfully automated classification of pediatric AOM and OME with otoscopic images. With a smartphone‐enabled wireless otoscope, artificial intelligence may assist parents in early detection and continuous monitoring at home to decrease the visit frequencies.

Level of Evidence

NA Laryngoscope, 131:E2344–E2351, 2021
Taming Ultrafast Laser Filaments for Optimized Semiconductor–Metal Welding
Authors: Chambonneau Maxime , Li Qingfeng , Fedorov Vladimir Yu. , Blothe Markus , Schaarschmidt Kay , Lorenz Martin , Tzortzakis Stelios , Nolte Stefan
Published: December 2020

Ultrafast laser welding is a fast, clean, and contactless technique for joining a broad range of materials. Nevertheless, this technique cannot be applied for bonding semiconductors and metals. By investigating the nonlinear propagation of picosecond laser pulses in silicon, it is elucidated how the evolution of filaments during propagation prevents the energy deposition at the semiconductor–metal interface. While the restrictions imposed by nonlinear propagation effects in semiconductors usually inhibit countless applications, the possibility to perform semiconductor–metal ultrafast laser welding is demonstrated. This technique relies on the determination and the precompensation of the nonlinear focal shift for relocating filaments and thus optimizing the energy deposition at the interface between the materials. The resulting welds show remarkable shear joining strengths (up to 2.2 MPa) compatible with applications in microelectronics. Material analyses shed light on the physical mechanisms involved during the interaction.
Polymer‐silica additive as a modifier of tribological properties of ecological grease, improvement of fatigue resistance
Authors: Drabik Jolanta , Trzos Magdalena
Published: December 2020

The influence of polymer additive (polytetrafluoroethylene) in grease based on paraffin oil on the resistance to fatigue wear (pitting) was investigated of rolling contact. The research results revealed that grease containing a polymer caused an increase in resistance to fatigue. It was examined whether the additive affects the properties of the grease, including rheological (investigated with the use of rheometer operated in the cone/plate configuration) and thermal (determined using the Differential Scanning Calorimetry) to check their relationship with a resistance to fatigue. A scanning electron microscope equipped with an energy dispersive spectrometer was used to determine if a polymer was present on wear trace. Then the sources of chemical elements were analysed with the use of X‐ray photoelectron spectroscopy to explain the improvement of resistance to fatigue. The relation between rheological properties and resistance to fatigue was shown, and the presence of polymer in friction contact was observed.
Preparation of Iron Filler‐Based Photocomposites and Application in 3D Printing
Authors: Xu Yangyang , Ding Zhaofu , Zhu Haibin , Zhang Yijun , Knopf Stephan , Xiao Pu , Lalevée Jacques
Published: December 2020

The introduction of metallic fillers to polymers via the photopolymerization approach can endow the composite materials with some unique properties, but the relevant research is still scarce due to the issue of light penetration and inner filter effect. Herein, for the first time the fabrication of photocomposites based on fine iron powder (i.e., a typical kind of metallic filler) is reported in this work. The free radical polymerization of two different acrylate monomers, poly(ethylene glycol) diacrylate and trimethylolpropane triacrylate, is performed in the presence of iron filler under mild conditions (i.e., light emitting diode (LED)@405 nm irradiation at room temperature under air). And the real‐time Fourier transform infrared spectroscopy reveals remarkable photopolymerization kinetics of acrylates with high final conversions and fast polymerization rates despite the increasing contents of iron filler in the composites. Interestingly, the 3D printing technique is applied to the iron filler‐based composites to produce tridimensional patterns with excellent spatial resolution. This work not only paves the way for the investigation of photocomposites based on metallic fillers through photochemical methods, but also broadens the potential application prospects.
Nielsen's beta function and some infinitely divisible distributions
Authors: Berg Christian , Koumandos Stamatis , Pedersen Henrik L.
Published: December 2020

We show that a large collection of special functions, in particular Nielsen's beta function, are generalized Stieltjes functions of order 2, and therefore logarithmically completely monotonic. This includes the Laplace transform of functions of the form , where f is itself the Laplace transform of a sum of dilations and translations of periodic functions. Our methods are also applied to ratios of Gamma functions, and to the remainders in asymptotic expansions of the double Gamma function of Barnes.
Flexibility of Gut Microbiota in Ageing Individuals during Dietary Fiber Long‐Chain Inulin Intake
Authors: Kiewiet Mensiena B. G. , Elderman Marlies E. , El Aidy Sahar , Burgerhof Johannes G. M. , Visser Hester , Vaughan Elaine E. , Faas Marijke M. , de Vos Paul
Published: December 2020

Scope

During ageing, dysbiosis in the intestinal microbiota may occur and impact health. There is a paucity of studies on the effect of fiber on the elderly microbiota and the flexibility of the aged microbiota upon prebiotic intake. It is hypothesized that chicory long‐chain inulin consumption can change microbiota composition, microbial fermentation products, and immunity in the elderly.

Methods and Results

A double‐blind, placebo‐controlled trial is performed in healthy individuals (55–80 years), in which microbiota composition is studied before, during, and after two months of chicory long‐chain inulin consumption. Fecal short chain fatty acid concentrations, T cell subsets, and antibody responses against a Hepatitis B (HB) vaccine are measured as well. Inulin consumption modified the microbiota composition, as measured by 16S rRNA sequencing. Participants consuming inulin have higher microbial diversity and a relatively higher abundance of the Bifidobacterium genus, as well as Alistipes shahii, Anaerostipes hadrus, and Parabacteroides distasonis. While the immune responses remain unchanged, the isobutyric acid levels, an undesired fermentation product, tend to be lower in the inulin group.

Conclusions

Overall, it is shown that the gut microbiota composition is still sensitive to chicory long‐chain inulin induced changes in an ageing population, although this did not translate into an improved immune response to an HB vaccine.
Longitudinal acquisition repeatability of MRI radiomics features: An ACR MRI phantom study on two MRI scanners using a 3D T1W TSE sequence
Authors: Wong Oi Lei , Yuan JIng , Zhou Yihang , Yu Siu Ki , Cheung Kin Yin
Published: December 2020

Purpose

The purpose of this study was to quantitatively assess the longitudinal acquisition repeatability of MRI radiomics features in a three‐dimensional (3D) T1‐weighted (T1W) TSE sequence via a well‐controlled prospective phantom study.

Methods

Thirty consecutive daily datasets of an ACR‐MRI phantom were acquired on two 1.5T MRI simulators using a 3D T1W TSE sequence. Images were blindly segmented by two observers. Post‐acquisition processing was minimized but an intensity discretization (fixed bin size of 25). One hundred and one radiomics features (shape n = 12; first order n = 16; texture n = 73) were extracted. Longitudinal repeatability of each feature was evaluated by Pearson correlation and coefficient of variance (CV68%). Interobserver feature value agreement was also quantified using intraclass correlation coefficient (ICC) and Bland–Altman analysis. A most repeatable radiomics feature set on both scanners was determined by feature coefficient of variance (CV68%<5%), ICC (>0.75), and the ratio of the interobserver difference to the interobserver mean δ<5%.

Results

No trend of radiomics feature value changed with time. Longitudinal feature repeatability CV68% ranged 0.01–38.60% (mean/median: 12.5%/9.9%), and 0.01–40.47%, (8.49%/7.34%) on the scanners A and B. Shape features exhibited significantly better repeatability than first‐order and texture features (all P < 0.01). Significant longitudinal repeatability difference was observed in texture features (P < 0.001) between the two scanners, but not in shape and first‐order features (P > 0.30). First‐order and texture features had smaller interobserver‐dependent variation than acquisition‐dependent variation. They also showed good interobserver agreement on both scanners (A:ICC = 0.80 ± 0.23; B:ICC = 0.80 ± 0.22), independent of acquisition repeatability. The repeatable radiomics features in common on both scanners, including 12 shape features, 0 first‐order features, and 3 texture features, were determined as the most repeatable MRI radiomics feature set.

Conclusions

Radiomics features exhibited heterogeneous longitudinal repeatability, while the shape features were the most repeatable, in this phantom study with a 3D T1W TSE acquisition. The most repeatable radiomics feature set derived in this study should be helpful for the selection of reliable radiomics features in the future clinical use.
Do Carbonated Beverages Reduce Bleeding from Gill Injuries in Angled Northern Pike?
Authors: Trahan Alexandria T. , Chhor Auston D. , Lawrence Michael J. , Brownscombe Jacob W. , Glassman Daniel M. , Reid Connor H. , Abrams Alice E. I. , Danylchuk Andy J. , Cooke Steven J.
Published: December 2020

The premise of catch-and-release recreational angling is that postrelease survival is high. Therefore, it is common for anglers, management agencies, and conservation organizations to share information on handling practices and other strategies that are believed to improve the welfare and survival of fish that are released. A recent surge in popularity has sensationalized the use of carbonated beverages to treat bleeding fish—an intervention that is purported to stop bleeding but has yet to be validated scientifically. We captured Northern Pike Esox lucius via hook and line and experimentally injured their gills in a standardized manner. Gill injuries were treated with Mountain Dew, Coca-Cola, or carbonated lake water. The duration and intensity of bleeding as well as overall blood loss (using gill color as a proxy) were observed while the fish were held in a lake water bath. As a control, we used a group of experimentally injured fish that did not have liquid poured over their gills before the observation period. All treatments and the control were conducted at two different water temperatures (11–18°C and 24–27°C) to determine whether the effects of pouring carbonated beverages over injured gills are seasonally dependent. When compared to the control, we found that the duration and intensity of bleeding increased regardless of the type of carbonated beverage used in this study, and there was no effect of season. Use of chilled versus ambient-temperature beverages similarly had no influence on outcomes. As such, there is no scientific evidence to support the use of carbonated beverages for reducing or stopping blood loss in fish that receive gill injuries during recreational angling based on the context studied here. Our study reinforces the need to scientifically test angler anecdotes and theories regarding best practices for catch-and-release fishing.