bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dose/exposure–response modeling in dose titration trials: Overcoming the titration paradox
Authors: Kristensen Niels Rode , Agersø Henrik 
Published: September 2022

AbstractResponse‐based dose individualization or dose titration is a powerful approach to achieve precision dosing. Yet, titration as an individualization strategy is underused in drug development and therefore not reflected in labeling, possibly partly because of the data analysis challenges associated with assessing dose/exposure–response under dose titration, where there is an inherent risk of selection bias because poor responders would get high doses, whereas good responders would get low doses. In a recent article, this issue of selection bias was termed the “titration paradox.” In this study, we demonstrate by means of simulation that the titration paradox may be overcome if longitudinal data from dose titration trials is analyzed using a population approach that accounts for the fact that dose/exposure–response relationships differ between individuals. We show that with an appropriate sample size and missing data missing at random, stepwise dose/exposure–response modeling based on data obtained under dose titration is not by definition subject to model selection bias or bias in parameter estimates. We also illustrate the challenges of graphical exploration of data obtained under dose titration and discuss the use of model diagnostic tools with such data. Our study shows that if, at every timepoint in the course of a trial, there is a clear causal relationship between the response and the dose/exposure level, and a population approach is used, it will in many cases be possible to develop, estimate, and appropriately qualify a dose/exposure–response model also for data obtained under dose titration, thus overcoming the titration paradox.
Boosting Electrocatalytic Reduction of CO2 to HCOOH on Ni Single Atom Anchored WTe2 Monolayer
Authors: Zhang Yuefeng , Yang Ruijie , Li Hao , Zeng Zhiyuan 
Published: September 2022

AbstractAchieving efficient conversion of carbon dioxide (CO2) to formic acid (HCOOH) at mild conditions is a promising means to reduce greenhouse gas emission and mitigate the energy crisis. Herein, spin‐polarized density functional theory calculations with van der Waals corrections (DFT+D3) are performed to analyze the catalytic activity of seven metals (Ti, Fe, Ni, Cu, Zn, In, and Sn) anchored on a tungsten ditelluride monolayer (M@WTe2) and screen favorable CO2 reduction pathways. These results demonstrate that Ni single atoms strongly bind to the WTe2 monolayer and exist in isolated form due to the high diffusion barriers. Also, Ni‐anchored WTe2 monolayer (Ni@WTe2) possesses a considerably low limiting‐potential (−0.11 V vs reversible hydrogen electrode) to convert CO2 to HCOOH due to moderate OCHO adsorption energy and a suppressed competing hydrogen evolution reaction (HER). Therefore, Ni@WTe2 monolayer is a promising electrocatalytic material for the CO2 reduction reaction (CO2RR). This study sheds light on strategies of designing single metal atom anchored WTe2 catalysts for improved CO2RR performances.
Inverter Based Ultra‐Low Power Demodulation Circuit for AM Receivers
Authors: Masui Yoshihiro 
Published: September 2022

AbstractWireless communication with AM (Amplitude Modulation) is widely used. If the power consumption of the AM receiver is reduced to the utmost limit, the power source can be replaced with an energy harvest, which is very convenient. Power lines will not be needed and batteries will no longer need to be replaced or recharged. Therefore, we propose an ultra‐low power demodulation circuit for AM receivers. The proposed demodulator achieved a peak SNDR of 47.8 dB and a power consumption of 3.36 μW at a carrier frequency of 1 MHz. © 2022 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.
Abnormal cerebrospinal fluid levels of amyloid and tau are associated with cognitive decline over time in cognitively normal older adults: A monozygotic twin study
Authors: Tomassen Jori , den Braber Anouk , van der Landen Sophie M. , Konijnenberg Elles , Teunissen Charlotte E. , Vermunt Lisa , de Geus Eco J. C. , Boomsma Dorret I. , Scheltens Philip , Tijms Betty M. , Visser Pieter Jelle 
Published: September 2022

AbstractIntroductionThe contribution of genetic and environmental factors to the relation between cerebrospinal fluid (CSF) biomarkers and cognitive decline in preclinical Alzheimer's disease remains unclear. We studied this in initially cognitively normal monozygotic twins.MethodsWe included 122 cognitively normal monozygotic twins (51 pairs) with a follow‐up of 4.3 ± 0.4 years. We first tested associations of baseline CSF Aβ1‐42/1‐40 ratio, total tau (t‐tau), and 181‐phosphorylated‐tau (p‐tau) status with subsequent cognitive decline using linear mixed models, and then performed twin specific analyses.ResultsBaseline abnormal amyloid‐β and tau CSF markers predicted steeper decline on memory (p ≤ .003) and language (p ≤ 0.04). Amyloid‐β and p‐tau markers in one twin predicted decline in memory in the co‐twin and tau markers in one twin predicted decline in language in the co‐twin (r range ‐0.26,0.39; p’s ≤ .02).DiscussionThese results suggest that memory and language decline are early features of AD that are in part determined by the same genetic factors that influence amyloid‐β and tau regulation.
Rapid autologous point‐of‐care transplantation of the adipose‐derived stromal vascular fraction in a dog with cubarthrosis
Authors: Schroers Maike , Schermuck Yyonne , Steigmeier‐Raith Stephanie , Waselau Anja‐Christina , Meyer‐Lindenberg Andrea 
Published: September 2022

AbstractA 1‐year‐old shepherd dog was presented in the veterinary hospital due to left‐sided cubarthrosis and persisting weight‐bearing lameness of the left forelimb after a fragmented coronoid process in the left elbow joint had been removed at the age of 6 months. An autologous point‐of‐care transplantation of adipose tissue‐derived regenerative cells was performed using ARC System (InGeneron, Houston, TX, USA). Pre‐ and postoperative investigations included orthopaedic and radiographic examinations, gait analyses as well as two owner questionnaires, Liverpool Osteoarthritis in Dogs and Canine Brief Pain Inventory. After 1, 2, 3, 6 and 12 months of treatment, the dog showed an improvement of peak vertical force and vertical impulse in the gait analyses as well as. The Canine Brief Pain Inventory and the Liverpool Osteoarthritis in Dogs revealed an improvement of the quality of life within all further control visits up to 12 months after the therapy.
Die α-Mannosidose: eine seltene, aber unterdiagnostizierte Erkrankung?
Authors: Hennermann Julia B. 
Published: September 2022

ZusammenfassungBei der α‑Mannosidose handelt es sich um eine seltene lysosomale Speichererkrankung, bedingt durch eine autosomal-rezessiv vererbte Defizienz der α‑Mannosidase. Die Erkrankung weist ein breites klinisches Spektrum mit chronisch progredientem Verlauf auf. Charakteristische klinische Zeichen in den ersten Lebensjahren sind Hörminderung, Entwicklungsverzögerung, rezidivierende Infekte und/oder faziale Dysmorphie. Im weiteren Verlauf der Erkrankung manifestieren sich zunehmende skeletale Probleme und eine Ataxie, beide zu Immobilität führend. Im Gegensatz zu anderen lysosomalen Speichererkrankungen zeigt sich nach dem 20. Lebensjahr meist kein weiterer Verlust kognitiver Fähigkeiten. Ab dem Alter von 15 Jahren entwickeln ca. 25 % der Patienten psychiatrische Symptome. Aufgrund der Seltenheit der Erkrankung werden viele Patienten verspätet, z. T. erst im Erwachsenenalter, diagnostiziert.Mittlerweile stehen 2 Therapieoptionen zur Behandlung der α‑Mannosidose zur Verfügung. Bei frühzeitiger Diagnosestellung ist die hämatopoetische Stammzelltransplantation eine wichtige therapeutische Option mit potenziell positivem Effekt auf die neurokognitive Entwicklung. Die Enzymersatztherapie mit Velmanase alfa ist seit 2018 in Europa zugelassen und eine therapeutische Option zur Behandlung der nichtneurologischen Manifestationen bei α‑Mannosidose. Sie hat jedoch keinen Einfluss auf neurologische Manifestationen der Erkrankung.Zur Verbesserung der Diagnostik von Kindern und Jugendlichen mit der seltenen Erkrankung α‑Mannosidose möchte dieser Beitrag das Wissen um und das Bewusstsein für diese Erkrankung schärfen. Die frühe Diagnose einer α‑Mannosidose erspart nicht nur den Familien einen jahrelangen diagnostischen Leidensweg, sondern ermöglicht auch den betroffenen Patienten ein verbessertes Auskommen durch einen frühen Therapiestart.
A population pharmacokinetic model of remdesivir and its major metabolites based on published mean values from healthy subjects
Authors: Abouellil Ahmed , Bilal Muhammad , Taubert Max , Fuhr Uwe 
Published: September 2022

AbstractRemdesivir is a direct-acting anti-viral agent. It was originally evaluated against filoviruses. However, during the COVID-19 pandemic, it was investigated due to its anti-viral activities against (SARS-CoV-2) virus. Therefore remdesivir received conditional approval for treatment of patients with severe coronavirus disease. Yet, its pharmacokinetic properties are inadequately understood. This report describes the population pharmacokinetics of remdesivir and its two plasma-detectable metabolites (GS-704277 and GS-441524) in healthy volunteers. The data was extracted from published phase I single escalating and multiple i.v remdesivir dose studies conducted by the manufacturer. The model was developed by standard methods using non-linear mixed effect modeling. Also, a series of simulations were carried out to test suggested clinical doses. The model describes the distribution of remdesivir and each of its metabolites by respective two compartments with sequential metabolism between moieties, and elimination from central compartments. As individual data were not available, only inter-cohort variability could be assessed. The estimated point estimates for central (and peripheral) volumes of distribution for remdesivir, GS-704277, and GS-441524 were 4.89 L (46.5 L), 96.4 L (8.64 L), and 26.2 L (66.2 L), respectively. The estimated elimination clearances of remdesivir, GS704277, and GS-441524 reached 18.1 L/h, 36.9 L/h, and 4.74 L/h, respectively. The developed model described the data well. Simulations of clinically approved doses showed that GS-441524 concentrations in plasma exceeded the reported EC50 values during the complete duration of treatment. Nonetheless, further studies are needed to explore the pharmacokinetics of remdesivir and its relationship to clinical efficacy, and the present model may serve as a useful starting point for additional evaluations.
Emotion recognition profiles in clusters of youth based on levels of callous-unemotional traits and reactive and proactive aggression
Authors: Kleine Deters Renee , Naaijen Jilly , Holz Nathalie E. , Banaschewski Tobias , Schulze Ulrike M. E. , Sethi Arjun , Craig Michael C. , Sagar-Ouriaghli Ilyas , Santosh Paramala , Rosa Mireia , Castro-Fornieles Josefina , Penzol María José , Arango Celso , Brandeis Daniel , Franke Barbara , Glennon Jeffrey C. , Buitelaar Jan K. , Hoekstra Pieter J. , Dietrich Andrea 
Published: September 2022

AbstractYouth with disruptive behavior showing high callous-unemotional (CU) traits and proactive aggression are often assumed to exhibit distinct impairments in emotion recognition from those showing mainly reactive aggression. Yet, reactive and proactive aggression and CU traits may co-occur to varying degrees across individuals. We aimed to investigate emotion recognition in more homogeneous clusters based on these three dimensions. In a sample of 243 youth (149 with disruptive behavior problems and 94 controls) aged 8–18 years, we used model-based clustering on self-report measures of CU traits and reactive and proactive aggression and compared the resulting clusters on emotion recognition (accuracy and response bias) and working memory. In addition to a Low and Low-Moderate symptom cluster, we identified two high CU clusters. The CU-Reactive cluster showed high reactive and low-to-medium proactive aggression; the CU-Mixed cluster showed high reactive and proactive aggression. Both CU clusters showed impaired fear recognition and working memory, whereas the CU-Reactive cluster also showed impaired recognition of disgust and sadness, partly explained by poor working memory, as well as a response bias for anger and happiness. Our results confirm the importance of CU traits as a core dimension along which youth with disruptive behavior may be characterized, yet challenge the view that high CU traits are closely linked to high proactive aggression per se. Notably, distinct neurocognitive processes may play a role in youth with high CU traits and reactive aggression with lower versus higher proactive aggression.
IL-17A promotes Helicobacter pylori-induced gastric carcinogenesis via interactions with IL-17RC
Authors: Kang Jee Hyun , Park Suyoung , Rho Jinhyung , Hong Eun-Ju , Cho Young-Eun , Won Young-Suk , Kwon Hyo-Jung 
Published: September 2022

Abstract
Background
Gastric cancer (GC) is a common malignancy worldwide, with a major attribution to Helicobacter pylori. Interleukin (IL)-17A has been reported to be up-regulated in serum and tumor of GC patients, but the precise mechanisms underlying its involvement in gastric tumorigenesis are yet to be established. Here, we investigated the roles of IL-17A in the pathogenesis of H. pylori-induced GC.

Methods
GC was induced in IL-17A knockout (KO) and wild-type (WT) mice via N-methyl-N-nitrosourea (MNU) treatment and H. pylori infection. At 50 weeks after treatment, gastric tissues were examined by histopathology, immunohistochemistry, and immunoblot analyses. In vitro experiments on the human GC cell lines were additionally performed to elucidate the underlying mechanisms.

Results
Deletion of IL-17A suppressed MNU and H. pylori-induced gastric tumor development accompanied by a decrease in gastric epithelial cell growth, oxidative stress, and expression of gastric epithelial stem cells markers. In AGS cells, recombinant human IL-17A (rhIL-17A) inhibited apoptosis and G1/S phase transition arrest while promoting reactive oxygen species production, sphere formation ability of cancer stem cells (CSC), and expression of stemness-related genes. In addition, rhIL-17A induced expression of IL-17RC, leading to NF-κB activation and increased NADPH oxidase 1 (NOX1) levels. Inhibition of NOX1 with GKT136901 attenuated rhIL-17A-mediated elevation of GC cell growth, ROS generation, and CSC stemness. Clinically, IL-17RC expressions were significantly upregulated in human GC compared with normal gastric tissues.

Conclusion
Our results suggest that IL-17A promotes gastric carcinogenesis, in part, by regulating IL-17RC/NF-κB/NOX1 pathway, supporting its potential as a target in human GC therapy.
A view of computational models for image segmentation
Authors: Antonelli Laura , De Simone Valentina , di Serafino Daniela 
Published: September 2022

AbstractImage segmentation is a central topic in image processing and computer vision and a key issue in many applications, e.g., in medical imaging, microscopy, document analysis and remote sensing. According to the human perception, image segmentation is the process of dividing an image into non-overlapping regions. These regions, which may correspond, e.g., to different objects, are fundamental for the correct interpretation and classification of the scene represented by the image. The division into regions is not unique, but it depends on the application, i.e., it must be driven by the final goal of the segmentation and hence by the most significant features with respect to that goal. Thus, image segmentation can be regarded as a strongly ill-posed problem. A classical approach to deal with ill posedness consists in incorporating in the model a-priori information about the solution, e.g., in the form of penalty terms. In this work we provide a brief overview of basic computational models for image segmentation, focusing on edge-based and region-based variational models, as well as on statistical and machine-learning approaches. We also sketch numerical methods that are applied in computing solutions to these models. In our opinion, our view can help the readers identify suitable classes of methods for solving their specific problems.
Experimental study on the evaluation of surfactant/polymer flooding for enhancing oil recovery in Kumkol Oil Field
Authors: Zhao Lun , Wang Jincai , Zhang Xiangzhong , Guo Xuejing , Chen Li , Zhang Angang , Cao Kechuan , Li Junjian 
Published: September 2022

AbstractChemical enhanced oil recovery (EOR) methods are shown to sweep the residual oil by altering physical properties of fluids after waterflooding to improve oil recovery. This work presents an experimental study on the surfactant/polymer injection for EOR in sandstone reservoirs. Interfacial tension measurements, emulsification and rheology tests are performed to select the best candidates from thirteen commercial surfactants and five commercial polymers. The performance of the preferred surfactant and polymer candidates in EOR is evaluated through a series of core flooding experiments on both homogeneous and heterogenous sand packs. Different injection schemes are investigated. The results show that the polymer injection and polymer-surfactant-mixture slug can effectively displace the residual oil as the polymer injection improves efficiency of the sweeping front. Core flooding experiments on the heterogenous sand pack show that injecting polymer in the first, followed by surfactant slug yields the better performance compared with combined polymer-surfactant-mixture injection as the polymer pre-flush improves the vertical conformance of the surfactant solution and the final recovery.
Our Current Understanding of Chagas Disease and Trypanosoma cruzi Infection in the State of Florida — an Update on Research in this Region of the USA
Authors: Beatty Norman L. , Forsyth Colin J. , Burkett-Cadena Nathan , Wisely Samantha M. 
Published: September 2022

Abstract
Purpose of Review
Chagas disease (CD) is a neglected tropical disease caused by the protozoan parasite, Trypanosoma cruzi. Parasite transmission primarily occurs through direct interaction with an infected triatomine insect vector (kissing bug), but other routes are known. We aim to review the literature and discuss the unique circumstances of CD in the US state of Florida.

Recent Findings
Florida is home to naturally occurring kissing bugs that are invading homes and harbor T. cruzi. The state is also home to a diverse population of immigrants from Chagas-endemic regions in Latin America. In the USA, Florida is the state with the third highest estimated burden of CD, although the true prevalence is unknown.

Summary
Chagas disease is a chronic infection that often remains silent for decades. Those who manifest chronic disease may eventually die from debilitating cardiac and/or gastrointestinal manifestations. Florida is an opportune region of the USA for the study of CD, due to the existence of endemic transmission cycles in addition to the burden among people born in Chagas-endemic regions.
Primary node election based on probabilistic linguistic term set with confidence interval in the PBFT consensus mechanism for blockchain
Authors: Xie Mingyue , Liu Jun , Chen Shuyu , Xu Guangxia , Lin Mingwei 
Published: September 2022

AbstractThis study proposes a primary node election method based on probabilistic linguistic term set (PLTS) for the practical Byzantine fault tolerance (PBFT) consensus mechanism to effectively enhance the efficiency of reaching consensus. Specifically, a novel concept of the probabilistic linguistic term set with a confidence interval (PLTS-CI) is presented to express the uncertain complex voting information of nodes during primary node election. Then, a novel score function based on the exponential semantic value and confidence approximation value for the PLTS-CI, called Score-ESCA, is used to solve the problems of comparing different nodes with various voting attitudes. This method helps select the node with the highest score by utilizing complex decision attitudes, making it an accurate primary node election solution. Furthermore, the feasibility of our proposed method is proved by both theoretical analysis and experimental evaluations.
Influence of Al11Ce3 Size and Distribution on the Electrochemical Properties of Sonoprocessed Al-10 wt.% Ce Alloy
Authors: El-Hadad S. , Moussa M. E. , Shoeib M. 
Published: September 2022

AbstractSolidification of Al–Ce alloys under ultrasonic vibrations (Sonoprocessing) has a significant effect on the refining of Al11Ce3 intermetallic, which plays a key role in controlling the properties of this group of high-performance characteristics. In the current research, a group of as-received Al-10 wt% Ce alloys that were sonoprocessed under different temperatures was characterized. The influence of Al11Ce3 intermetallic size and distribution on the electrochemical properties of these alloys was investigated. Polarization tests in 3.5% NaCl solution were carried out and the recorded Tafel and impedance curves were studied. The corrosion test results were related to the microstructure characteristics as affected by sonoprocessing. Investigation of the as-received samples showed that ultrasonic vibrations broke the long lath-shaped particles of Al11Ce3 and obviously decreased their size and increased their surface area fraction. Sonoprocessing at the optimum temperature, 655 °C, reduced the Al11Ce3 particles size by 90% and enhanced their distribution in the matrix. This in its turn resulted in significant effects on their electrochemical behavior. Polarization tests showed that the corrosion rate of the un-sonoprocessed specimen decreased from ~ 0.00068 to 0.00006 mm/year after processing at the optimum condition (655 °C), and the polarization resistance increased from ~ 71 to 343 kΩ. By increasing the temperature of ultrasonic treatment beyond 655 °C, and the corresponding coarsening of the intermetallic particles, the corrosion rate slowly increased again, and concurrently, the polarization resistance decreased. The size and distribution of the intermetallic particles also influenced the formation of the corrosion pits, where the optimum sample showed shallow pits compared to those observed in the unprocessed specimen. This emphasizes the role of sonoprocessing in controlling the microstructure features and hence the electrochemical properties of Al-10 wt% Ce alloys.