bluuebunny/crossref_metadata_2025 huggingface dataset:
Significance of a positive tau PET scan with a negative amyloid PET scan
Authors: Robinson Carling G. , Lee Jeyeon , Min Paul H. , Przybelski Scott A. , Josephs Keith A. , Jones David T. , Graff‐Radford Jonathan , Boeve Bradley F. , Knopman David S. , Jack Clifford R. , Petersen Ronald C. , Machulda Mary M. , Fields Julie A. , Lowe Val J.
Published: December 2023

INTRODUCTION

The implications of positive tau positron emission tomography (T) with negative beta amyloid positron emission tomography (A) are not well understood. We investigated cognitive performance in participants who were T+ but A‐.

METHODS

We evaluated 98 participants from the Mayo Clinic who were T+ and A‐. Participants were matched 2:1 to A‐ and T‐ cognitively unimpaired (CU) controls. Cognitive test scores were compared between different groups.

RESULTS

The A‐T+ group demonstrated lower performance than the A‐T‐ group on the Mini‐Mental Status Exam (MMSE) (p < 0.001), Wechsler Memory Scale‐Revised Logical Memory I (p < 0.001) and Logical Memory II (p < 0.001), Auditory Verbal Learning Test (AVLT) delayed recall (p = 0.004), category fluency (animals p = 0.005; vegetables p = 0.021), Trail Making Test A and B (p < 0.001), and others. There were no significant differences in demographic features or apolipoprotein E (APOE) e4 genotype between CU A‐T+ and CI A‐T+.

DISCUSSION

A‐T+ participants show an association with lower cognitive performance.
Demographic profiles and risk factors for mortality in acute meningitis: A nationwide population‐based observational study
Authors: Akaishi Tetsuya , Tarasawa Kunio , Fushimi Kiyohide , Yaegashi Nobuo , Aoki Masashi , Fujimori Kenji
Published: December 2023

Aim

Acute meningitis encompasses bacterial, viral (aseptic), fungal, tuberculous, and carcinomatous meningitis. The rate and risks of mortality in each type remain uncertain. This study aimed to elucidate these aspects in each type of meningitis.

Methods

This study utilized Japan's nationwide administrative Diagnosis Procedure Combination (DPC) database. Patients with acute meningitis, treated at 1132 DPC‐covered hospitals from 2016 to 2022, were enrolled.

Results

Among 47,366,222 cumulative hospitalized patients, 48,758 (0.10%) were hospitalized with acute meningitis. The types of meningitis were as follows: 10,338 with bacterial, 29,486 with viral/aseptic, 965 with fungal, 678 with tuberculous, and 3790 with carcinomatous meningitis. Bacterial and viral meningitis exhibited bimodal age distributions, with the first peak occurring at 0–9 years. The median onset age was below 50 years only in viral meningitis. The mortality rate was the highest in carcinomatous meningitis (39%), followed by fungal meningitis (21%), and the lowest in viral meningitis (0.61%). Mortality rates increased with age across all meningitis types, but this trend was less prominent in carcinomatous meningitis. The duration from admission to mortality was longer in fungal and tuberculous meningitis compared with other types. Staphylococcus aureus in bacterial meningitis (adjusted odds ratio 1.71; p = 0.0016) and herpes simplex virus in viral meningitis (adjusted odds ratio 1.53; p = 0.0467) exhibited elevated mortality rates.

Conclusion

Distinct demographic profiles and mortality rates were observed among different meningitis types. The high mortality rates in less common types of meningitis emphasize the necessity to further optimize the required diagnostic and treatment strategies.
Enabling Polymer Single Crystals to Be High‐Performance Dielectric
Authors: Chen Min , Ong Wee‐Liat , Peng Boyu , Guo Xuyun , Ren Jie , Zhu Ye , Li Hanying
Published: December 2023

Semicrystalline polymer dielectrics (SPDs) are highly sought‐after state‐of‐the‐art dielectric materials. As the disorder in SPDs degrades their electrical properties, homogeneously ordered SPDs are desired. However, complex crystallization behaviors of polymers make such homogeneity elusive. Polymer lamellar single crystals (PLSCs), the most regularly‐ordered form of SPDs possible under mild crystallizing conditions, are ideal platforms for understanding and developing high‐performance dielectric materials. Here, a typical and widely used SPD, polyethylene (PE) is selected as the model material. We successfully obtained, large, uniform, and high‐quality PE PLSCs and devised a non‐destructive strategy to construct PE PLSC‐based vertical capacitors. These nanometer‐thick capacitors exhibit exceptional dielectric properties, with a high breakdown strength of 6.95 MV/cm and a low dielectric constant of 2.14±0.07, that outperform the properties of any existing neat PE. This work provides novel insights into exploring the performance possibility of ordered SPDs and reveals the PLSCs as potential high‐performance dielectric materials.
A relational understanding of the needs of siblings of children who have been sexually abused
Authors: Dwan Maeve
Published: December 2023

This participatory research project highlighted the views and experiences of young people who are the brothers and sisters of children and young people who have experienced child sexual abuse. By working with young people who had experienced sexual abuse and their siblings, this practitioner research sought to give these young people a voice. The research involved a group process with young people who have experienced sexual abuse and have siblings, and one‐to‐one online consultations with the brothers and sisters of young people who have experienced abuse. All the young people spoke of their sibling and family relationships as unique and requiring unique responses to these relationships by services and health‐care professionals. Siblings’ needs in the aftermath of a child sexual abuse discovery are often overlooked. This research describes how just as children who have experienced sexual abuse may feel anger, fear, guilt, shame, anxiety, and confusion, so do their siblings. Brothers and sisters of young people who have experienced sexual abuse describe significant relational trauma with intense emotional experiences of isolation, confusion, sadness, and anger. There is a real need to support young people and families to find words and develop capacities to talk about child sexual abuse ‐‐ a need to find supportive ways to speak about what has occurred and understand its impact on all. The study clearly demonstrated the significant level of need and impact on brothers and sisters of young people who have experienced sexual abuse.
LDPE/Bi2O3 nanocomposites: Enhanced mechanical, dielectric, and optical properties
Authors: Şahin Nazlıcan , Beyazay Emre , Karabul Yaşar , Kılıç Mehmet , Esmer Kadir , Güven Özdemir Zeynep
Published: December 2023

This study is focused on investigating the role of bismuth oxide (Bi2O3) nanoparticles to improve structural, optical, electrical, and mechanical properties of low‐density polyethylene (LDPE). For this purpose, Bi2O3 nanoparticles were synthesized by using the solvothermal method and examined by transmission electron microscopes (TEM), x‐ray diffraction (XRD), Fourier transformed infrared (FTIR) spectroscopy, and ultraviolet–visible (UV–Vis) light absorption methods. LDPE‐based nanocomposites were prepared by changing the nanoparticle additive ratio in the composite from 0% to 2% by weight. The composites were analyzed in the context of their FTIR spectra, atomic force microscope (AFM) images, UV–Vis light absorption spectra, stress–strain curves, and energy storage abilities. While the AFM findings indicate a smoother surface for the composites, the optical band gap analysis reveals a slightly decreased direct optical band gap energy. The analyses based on dielectric spectroscopy also highlight the LDPE/0.5% n‐Bi2O3 composite in terms of the best energy storage capability. Additionally, the highest Young's modulus, toughness, stress at break, and percentage of strain at break were also recorded for the LDPE/0.5% n‐Bi2O3 composite. In this context, the LDPE/0.5% n‐Bi2O3 composite with improved dielectric and mechanical properties can be suggested as a new promising LDPE‐based nanocomposite with better properties for industrial purposes.
Radiosynthesis and whole‐body distribution in mice of a 18F‐labeled azepino[4,3‐b]indole‐1‐one derivative with multimodal activity for the treatment of Alzheimer's disease
Authors: Lee Sang Hee , Purgatorio Rosa , Samarelli Francesco , Catto Marco , Denora Nunzio , Morgese Maria Grazia , Tucci Paolo , Trabace Luigia , Kim Hye Won , Park Hyun Soo , Kim Sang Eun , Lee Byung Chul , de Candia Modesto , Altomare Cosimo D.
Published: December 2023

Recently, the azepino[4,3‐b]indole‐1‐one derivative 1 showed in vitro nanomolar inhibition against butyrylcholinesterase (BChE), the ChE isoform that plays a role in the progression and pathophysiology of Alzheimer's disease (AD), and protects against N‐methyl‐
d‐aspartate‐induced neuronal toxicity. Three 9‐R‐substituted (R = F, Br, OMe) congeners were investigated. The 9‐F derivative (2a) was found more potent as BChE inhibitors (half‐maximal inhibitory concentration value = 21 nM) than 2b (9‐Br) and 2c (9‐OMe), achieving a residence time (38 s), assessed by surface plasmon resonance, threefold higher than that of 1. To progress in featuring the in vivo pharmacological characterization of 2a, herein the 18F‐labeled congener 2a was synthesized, by applying the aromatic 18F‐fluorination method, and its whole‐body distribution in healthy mice, including brain penetration, was evaluated through positron emission tomography imaging. [18F]2a exhibited a rapid and high brain uptake (3.35 ± 0.26% ID g−1 at 0.95 ± 0.15 min after injection), followed by a rapid clearance (t1/2 = 6.50 ± 0.93 min), showing good blood–brain barrier crossing. After a transient liver accumulation of [18F]2a, the intestinal and urinary excretion was quantified. Finally, ex vivo pharmacological experiments in mice showed that the unlabeled 2a affects the transmitters' neurochemistry, which might be favorable to reverse cognition impairment in mild‐to‐moderate AD‐related dementias.
Artificial intelligence in the information ecosystem: Affordances for everyday information seeking
Authors: Hirvonen Noora , Jylhä Ville , Lao Yucong , Larsson Stefan
Published: December 2023

In this conceptual article, we argue that artificial intelligence (AI) systems are contributing to the generation of an environment of affordances for everyday information practices through which they exert influence on people and the planet in ways that often are left unrecognized. We illustrate our insights by focusing on the practices of information seeking in everyday life, suggesting that the affordances of AI systems integrated into search engines, social media platforms, streaming services, and media generation, shape such practices in ways that may, paradoxically, result both in the increase and reduction of diversity of and access to information. We discuss the potential implications of these developments in terms of the sustainability of information ecosystems and suggest solutions for addressing them through regulation and education. Drawing from the fields of library and information science and science and technology studies and research on affordances, everyday information practices, and sustainability, the article seeks to respond to the need for more nuanced theoretical insights on the impact and implications of AI on information practices and to develop conceptual tools with which to examine the co‐evolution of humans and information systems from a systemic perspective.
Evaluation of gadolinium‐based contrast agents in juvenile CD‐1 mice including behavioral evaluations
Authors: Lewis Elise M. , Jones Paul , Clemens Guenther , Fretellier Nathalie , Bussi Simona , Hirani Ella , Czupalla Oliver , Tedoldi Fabio , Bourrinet Phillipe , Hoberman Alan M.
Published: December 2023

Introduction

Seven gadolinium‐based contrast agents (GBCAs), four linear and three macrocyclic, were evaluated for potential effects on development, including behavior of juvenile CD‐1 mice.

Methods

The GBCAs were administered via intravenous injection once daily on postnatal day (PND) 9, 12, 15, 18, and 21 (PND 1 was the day of delivery) at doses up to twice the human equivalent clinical dose (i.e., 0.63 mmol Gd/kg for gadoxetate disodium and 2.5 mmol Gd/kg for the other GBCAs). Mice were bled for evaluation of exposure (plasma) to gadolinium (Gd) on PND 9, 12, and 70. At scheduled euthanasia, the liver, spleen, brain, skin (dorsal surface), bone (left femur), and kidneys were excised from up to six mice/sex/group on PND 10, 22, or 70 for the determination of Gd levels and histopathological analysis. All mice were monitored for toxicity, growth and survival, sexual maturation, and behavior.

Conclusion

Gd was quantifiable in the brain tissues with levels declining over time. There was no long‐term effect on the growth and development for mice exposed to any of the GBCAs. There was no impact on neurodevelopment as assessed by brain histology and validated neurobehavioral tests, including a functional observational battery, motor activity, and learning and memory as evaluated in the Morris water maze. For all GBCAs, the highest dose tested represented the no‐observable‐adverse‐effect level in juvenile mice.
Use of surgical grafting as a part of multidisciplinary treatment for a patient treated with fixed orthodontic therapy to improve treatment outcomes
Authors: Viet Hoang , Phuoc Tran Hong , Tuyen Hoang Ming , Marya Anand
Published: December 2023

Key Clinical Abstract

Multidisciplinary treatment options can help provide good clinical outcomes if these are appropriately sequenced and carried out correctly. This case exemplifies interdisciplinary involvement to ensure the patient received an improved esthetic outcome.

The presence of anterior diastemas may compromise the esthetics of a patient's smile, causing mental, and social trauma in many patients. After careful evaluation Periodontal, surgical, and prosthodontic treatments are sometimes required to ensure successful treatment outcomes using a multidisciplinary staged treatment approach. These approaches must be carefully planned to ensure timely treatment progress. Surgical intervention must be planned at the right point in treatment to ensure adequate healing before placement of esthetic restorations.
Bioheterojunction‐Engineered System: A New Mechanism of BP/MoS2 Photothermal‐Photocatalytic Dual‐Power Synergistic Sterilization under NIR
Authors: Zhang Shuyan , Pan Yueqi , Chen Yihan , Yang Zhiwei , He Dongcai , Feng Nan , Wang Weijie , Li Yunfeng , Chen Danna , Chen Xianchun , Zhang Jing
Published: December 2023

In this research, a high‐efficiency nano‐fungicide with synergistic effect was obtained by combining polycrystalline MoS2 with layered nano‐BP to form heterojunction, which had a new photothermal‐photocatalytic antibacterial mechanism to Gram‐positive bacteria, Gram‐negative and drug‐resistance bacteria under NIR. BP/MoS2 whose lethality of bacteria could reach nearly 100 % at 400 μg/L, exhibited the highest photothermal lysis efficiency against E. coli, B. pumilus and A. baumannii. It was found that the heterojunction could be heated up to 51.8 °C within 5 minutes by photothermal conversion, and it also had an excellent performance of photothermal cycle. High temperature and stability of the material endowed it with an outstanding and long‐lasting bactericidal effect. In addition, a series of in vitro free radical experiments was designed, the existence of ⋅O2− and 1O2 in BP/MoS2‐NIR system was verified. And the Way of ROS production and the mechanism of action were discussed by EPR test. Subsequently, two mechanisms of synergistic antibacterial action were summarized, that is, abundant ROS and high temperature could destroy cell wall damage and lysis of bacteria effectively. This study provides a theoretical basis for the synergistic antibacterial action of NIR photothermal and photocatalysis of BP system.
Binding of Acetylated Lysine by Using a Water Soluble Aryl Extended Calix[4]pyrrole
Authors: Orlandini Martina , Pedrini Alessandro , Marchetti Danilo , Li Yifan , Aragay Gemma , Dalcanale Enrico , Ballester Pablo , Pinalli Roberta
Published: December 2023

Post‐translational modifications of lysine in histones, as methylation and acetylation, have well established functions in epigenetics and are emerging as important actors in broader biological regulation. Currently, the detection of acetylated lysine (Kac) in water solution as free amino acid or protein residue remains challenging. Acetylated lysine is a neutral amino acid, and the lack of ion–dipole interactions causes the decrease in binding affinity displayed by synthetic molecular receptors with respect to the other lysine modifications. Here, we report molecular modeling calculations and 1H NMR experiments to investigate the binding properties of two different calix[4]pyrrole receptors towards Kac. Computational analyses reveal that tetra‐aryl‐extended calix[4]pyrrole (1) preferentially binds the cis‐Kac conformer over the trans one due to steric considerations and more favorable interactions. Experimental 1H NMR titration experiments confirm the formation of a 1 : 1 complex between receptor 1 and cis‐Kac, with a Ka exceeding 103 M−1. Conversely, the super‐aryl‐extended calix[4]pyrrole 2 is less efficient in binding Kac, due to unfavorable solvation/desolvation effects, as proven by 1H NMR experiments. Moreover, receptor 1 showed a higher affinity for Kac over other lysine modifications, such as methylated lysines.
A distributed reliable collusion‐free algorithm for selecting multiple coordinators in IOTA using fog computing
Authors: Alavizadeh Alavieh Sadat , Erfani Seyed Hossein , Mirabi Meghdad , Sahafi Amir
Published: December 2023

IOTA is a distributed ledger technology with a new structure called Tangle, which offers high scalability, no fees, and near‐instant transfers for the internet‐of‐things (IoT) networks. The most important issue of IOTA is consensus achievement, which is handled by a single node acting as a coordinator. A single and default coordinator node exposes IOTA to the single point of failure and incomplete distribution issues. In this paper, a novel algorithm for selecting multiple coordinators to participate in the consensus process at milestones is proposed (i.e., MCS algorithm) to overcome the problem of a single coordinator in IOTA network. The MCS algorithm is applied in a two‐layered architecture including IoT devices (i.e., Layer 1) and fog nodes (i.e., Layer 2). We define and formulate four different properties as metrics to select multiple coordinators in this architecture. Moreover, a collusion list is defined to decrease the risk of collusion between fog nodes in the network. Experimental results show that using multiple fog nodes as coordinators in IOTA network can improve the average response time and average throughput while does not considerably sacrifice the total cost and system utilization in comparison with the use of a single default coordinator in IOTA network.
A Phase I, Randomized, Multi‐Dose Study to Evaluate the Enteric Selectivity and Safety of JAK Inhibitor, Lorpucitinib, in Healthy Participants
Authors: Ma Xuewen , Borzillo Gary , Kothe Martine J. Christine , Sanga Madhu , Chu Gerald , Greger James G. , Deiteren Annemie , Attiyeh Edward
Published: December 2023

Janus kinase (JAK) signaling has been implicated in human inflammatory diseases, including psoriasis, rheumatoid arthritis, and inflammatory bowel disease. Lorpucitinib (JNJ‐64251330) is an oral, small molecule, pan‐JAK inhibitor. Unlike systemic JAK antagonists, lorpucitinib was found to have enteric (gut)‐selective properties, providing possible applications in diseases of the human gastrointestinal tract. Here, lorpucitinib was evaluated in a phase I, two‐part, dosing study (NCT04552197) to assess pharmacokinetics, pharmacodynamic biomarkers, and safety in healthy participants. In part 1, 24 participants were randomized to 1 of 4 treatment arms receiving either lorpucitinib (30 mg daily, 30 mg every 12 hours (q12h), or 75 mg q12h) or tofacitinib (5 mg q12h) for 5 days. Part 2 was a food‐effect study in which 12 participants received a single 75‐mg dose of lorpucitinib under either fasting or fed conditions. In part 1, plasma and gut tissue concentrations of lorpucitinib showed approximately dose‐proportional increases. At all doses, lorpucitinib concentrations were significantly higher (392‐ to 1928‐fold) in the gut mucosal biopsies vs. the corresponding plasma samples, demonstrating high enteric selectivity and significantly exceeding both the tissue concentrations (> 200‐fold) and tissue/plasma ratios observed with tofacitinib. JAK inhibition in biopsies was confirmed via reduction in pSTAT‐3 levels. In part 2, lorpucitinib plasma concentrations were detectable but at low levels, with no statistical differences in PK parameters between the fed and fasted groups. Lorpucitinib was safe and well‐tolerated, and the data may be useful in designing studies to evaluate lorpucitinib in patients with JAK/STAT‐driven gastrointestinal diseases.
Amelioration of Acute Radiation Dermatitis in Breast Cancer Patients by a Bioadhesive Barrier‐Forming Gel (Episil): A Single‐Center, Open, Parallel, Randomized, Phase I/II Controlled Trial
Authors: Li Qian , Feng Shanhui , Yu Zeshun , Wang Yue , Tian Lijun , Geng Haitao , Guo Chen , Ning Fangling , Luo Judong , Liu Changmin
Published: December 2023

Episil is a bioadhesive barrier‐forming liquid gel that can relieve mucositis caused by radiotherapy (RT) and effectively relieve pain. The purpose of this trial is to compare the efficacy and safety of Episil in improving acute radiation dermatitis (ARD) in patients with breast cancer. This study included patients who met the criteria for postoperative RT for breast cancer. The primary end point was the grade of RD during treatment. A total of 102 patients were included in this study. The patients were grouped in a 2:1 ratio using the randomized number table method: 67 patients received Episil combined with conventional skin care (the Episil group), whereas the remaining 35 patients served as the control group and received conventional skin care only (the control group). According to the grading criteria of the Radiation Therapy Oncology Group (RTOG), the skin reaction rate and severity were significantly better in the Episil group than the control group (24.62%, 72.31%, 3.08, 0, 0 vs. 0, 85.71%, 14.29%, 0, 0, 0) across grades 0 to 4 (P < 0.05). The itchiness score exhibited s significant reduction in the Episil group as compared with the control group (P < 0.05). The results of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ‐C30) showed that the overall health (z = −5.855, P < 0.001) and overall quality of life (z = −6.583, P < 0.001) were better in the Episil group than the control group after RT. Overall, in patients with breast cancer receiving RT, the topical application of Episil may significantly reduce the grading of ARD, alleviate patient symptoms, and improve the patient's overall quality of life.
Minimal light requirements and performance under reduced photosynthetic photon flux of GA2ox‐transformed and conventional Kentucky bluegrass
Authors: Reed C. , Harriman R. , Koch M. , Baldwin C. , Gardner D. , Chang B. , Wherley B.
Published: December 2023

Shade stress is a common problem encountered in turfgrass management situations worldwide. Shade reduces photosynthetic photon flux (PPF), alters light quality, reduces air movement, and may introduce tree root competition. As a species, Kentucky bluegrass (Poa pratensis L.) possesses relatively poor shade tolerance, which limits its use in reduced light environments. However, genetic alteration of the gibberellic acid enzyme pathway has shown promise in some plant species for improving growth in shade. The objective of this 2‐year field study was to determine the comparative performance under reduced PPF and determine minimal daily light integral (DLIm) requirements for acceptable quality of a conventional (CONV) Kentucky bluegrass (KBG) blend and gibberellic acid 2‐oxidase (GA2ox) transformed “ProVista” (PV) KBG. A 2‐year field study was conducted under neutral density shade treatments producing monthly daily light integrals averaging from ∼5.8 (90% shade) to 48 mol m−2 day−1 (full sun) for mid‐June through October study periods. Based on nonlinear regression of mean monthly DLI during the study period versus turfgrass quality (TQ) at the end of each study period, DLIm was found to range from 7.5 to 10 mol m−2 day−1 for PV and from 22.5 to 26.2 mol m−2 day−1 for CONV KBG. Improved TQ of PV under low light intensities may be associated with reduced rates of leaf elongation, greater stand density, higher chlorophyll concentrations, and darker green color compared to CONV KBG. Although shade duration did not exceed 4 months, the results suggest that GA2ox‐transformed PV KBG possesses improved tolerance to reduced PPF compared to CONV KBG.
Living the American Dream: Playlist GTA in the Third World Country
Authors: Dhara Animesh
Published: December 2023

This research critically examines the nexus between video games, specifically the Grand Theft Auto (GTA) series, and the nuanced perceptions of the American Dream among teenagers in developing nations, primarily focusing on India. Situated within the broader exploration of the American Dream across academic disciplines, my qualitative research employs semi‐structured interviews and online surveys. Targeting participants aged 13 to 22 with extensive GTA exposure, my purposive sampling strategy ensures diverse perspectives. Thematic analysis of game content, encompassing narratives, characters, and themes, serves as the methodological core. Adopting a case study approach, this study aims to investigate the influence of the GTA game series on teenagers from developing nations, particularly India, and how it shapes their perception of the American Dream.
Cluster‐based context‐aware route service management for smart intelligent autonomous vehicles with industrial transport system
Authors: Nagappan G. , Maheswari K. G. , Siva C. , Shobana M.
Published: December 2023

Industrial transport system refers to the movement of goods, raw materials, and finished products within and between industrial facilities such as factories, warehouses, and distribution centers. It includes a variety of modes of transport such as trucks, forklifts, conveyor belts, and automated guided vehicles (AGVs). Context‐aware route service management refers to system that can dynamically manage and optimize the routes taken by vehicles in transportation system based on contextual information. Our proposed framework for industrial transport systems and smart intelligent autonomous vehicles utilizes cluster‐based context‐aware routing (CCAR), which includes several significant contributions. Firstly, modified elephant herding optimization (MEHO) algorithm is used to efficiently group autonomous vehicles for routing. Secondly, an improved gravitational search (IGS) algorithm is used for cluster head (CH) selection responsible for transferring context information between vehicles (V2V). Thirdly, a deep hybrid multi‐graph neural network (DHMG‐NN) is designed for optimal neighboring roadside unit (RSU) node selection through different design constraints to ensure data dissemination between vehicles and infrastructure (V2I). Finally, we validate the effectiveness of our CCAR framework using various simulation scenarios. Our framework achieves a reduction of up to 78% in computation time and an improvement of up to 25% in customer satisfaction ratio and 15% higher than the overall performance ratio compared to the existing frameworks.
Influence of carbon side chain length on the in vivo pharmacokinetic and pharmacodynamic characteristics of illicitly manufactured fentanyls
Authors: Canfield Jeremy R. , Sprague Jon E.
Published: December 2023

Since 2016, illicitly manufactured fentanyls and fentanyl analogs (referred to as IMFs) have contributed to an increase in drug overdoses. Although fentanyl has been characterized and evaluated extensively in animals and humans, many of the clandestinely synthesized analogs of fentanyl have not and users may unknowingly ingest these IMFs leading to overdose and potentially death. The pharmacodynamic (PD) and pharmacokinetic (PK) properties of four IMFs and fentanyl were evaluated in Sprague–Dawley rats. A 300‐μg/kg subcutaneous dose of each compound (fentanyl, acetylfentanyl, cyclopropylfentanyl, butyrylfentanyl, and valerylfentanyl) was given. PD parameters were measured using a tail flick meter and core body temperature. Blood was drawn to evaluate PK parameters utilizing liquid chromatography tandem mass spectrometry (LC–MS/MS). Fentanyl displayed the greatest and longest lasting analgesia with a tail flick response of 10 s (the maximum cutoff). Additionally, fentanyl produced an average −4.9°C in core body temperature resulting in the greatest decrease in core body temperature. Acetylfentanyl, with the shortest carbon side chain, displayed the shortest T½, and lowest AUC and Cmax and resulted in an increase in body temperature. There were no other PK differences among the IMFs assessed. As IMFs are commonly seen on the streets and can pose significant risks to users (although these risks do depend on other factors such as dose and route of administration), there is a benefit to having the pharmacological properties of these compounds characterized to better understand the potential harm to humans.
Advances in boron nitride‐based materials for electrochemical energy storage and conversion
Authors: Sun Dandan , Sun Zhipeng , Yang Dehong , Jiang Xiangfen , Tang Jie , Wang Xuebin
Published: December 2023

Energy storage and conversion (ESC) devices are regarded as predominant technologies to reach zero emission of carbon dioxide, which still face many challenges, such as poor safety, limited cycle life, low efficiency, etc. Hexagonal boron nitride (h‐BN), distinguished by its robust mechanical strength, chemical inertness, exceptional thermal stability, and superior ion conductivity, has appeared to meet some challenges of ESC devices. Typically, h‐BN can act as a perfect modifier to enhance the safety of batteries by improving the mechanical strength and heat dissipation of separators, extend cycle life of Li metal batteries by protecting solid state electrolyte from reducing and increase efficiency of fuel cells by improving the proton conductivity of membranes. Besides, recent progress on doping, surface modification, tailoring quantum dots, heterostructures, and hybridizations with other nanomaterials has made it possible to extensively apply h‐BN to other ESC technologies. This review provides a comprehensive overview of the up‐to‐date synthetic strategies for BN‐based materials and discusses the most recent breakthroughs on their application in electrochemical ESC technologies. Also, the challenges and future development for BN‐based materials in these fields are assessed.
Optimal detection protocol of Tetracapsuloides bryosalmonae by environmental DNA: A comparison of qPCR and ddPCR approaches
Authors: Stelzer Moritz , Ord James , Neyrinck Sabrina , Steiner Jonas , Hartikainen Hanna , Brys Rein , Schmidt‐Posthaus Heike
Published: December 2023

Investigation of environmental DNA (eDNA) is increasingly used to precisely and non‐invasively detect and monitor pathogens. Among these, Tetracapsuloides bryosalmonae is a myxozoan endoparasite that causes proliferative kidney disease (PKD) in salmonid fish. Although the detection of T. bryosalmonae DNA in water samples has been shown to be promising and successful, method comparison and cross‐validation are currently lacking. This study aims to directly compare the sensitivity of different eDNA‐based methods in field and laboratory applications, and to develop an easy‐to‐apply and sensitive protocol to monitor T. bryosalmonae occurrence non‐invasively by its eDNA in water samples. First, we tested three existing probe‐based T. bryosalmonae‐specific detection assays in parallel by comparing the limit of detection (LOD) and limit of quantification (LOQ) using quantitative PCR (qPCR) and digital droplet PCR (ddPCR) platforms. Second, the impact of different filter types and water volumes on the detection probability was tested by sampling water directly from riverbanks with a syringe‐based protocol. The most sensitive detection protocol was the combination of the probe‐based assay published by Bettge et al. run via ddPCR, resulting in a LOD of 1.65 copies/μL input (6.6 copies/reaction) and a LOQ of 3.66 copies/μL input (14.67 copies/reaction). The type of filter (Sterivex™ compared to Millex®) did not significantly influence detection probability, however, the volume of water sampled (600 mL compared to 300 mL) significantly affected the probability of capturing eDNA in a sample. Based on modeled probabilities of eDNA capture and detection, we calculated that using the Bettge et al. assay via the ddPCR platform for data collection, 95% overall detection probability could be achieved with three replicates of 600 mL filtered water with Sterivex™ filters. Based on this cross‐validation of assays and detection platforms, we provide a cost‐effective, straightforward, and highly sensitive laboratory analysis workflow to detect DNA of T. bryosalmonae from water samples.
Application of Buffer Layer to Improve the Efficiency of Organic Solar Cells
Authors: Li Shuxin , Bachagha Kareem
Published: December 2023

Organic solar cells (OSCs) are widely studied for their advantages such as simple production, low cost, good flexibility, and large‐area printing. The buffer layer between electrodes and the photoactive layer has a significant impact on the efficiency and stability of OSCs. In order to lower the energy barrier height at the interface, provide an Ohmic contact with lower series resistance, and increase the charge collection efficiency of the corresponding electrodes for either holes or electrons, suitable electrode buffer materials can be chosen. The selection of electrode buffer layer has an important effect on the photoelectric conversion efficiency. Therefore, the study of buffer layer characteristics has certain guiding significance for the improvement of device structure and performance optimization. At present, the buffer layer materials used in OSCs are mainly organic polymer materials, organic small molecule materials, metal fluoride, metal oxides, and so on. Herein, the structure and working principle of OSCs are introduced first. Then, the properties and function of buffer layer in OSCs are summarized and discussed. Finally, the application of common buffer layer materials in OSCs is summarized, and how to improve the performance of the device is described.
Analysis of engineering properties, milling characteristics, antioxidant potential, and nutritional benefits of purple wheat and its bran
Authors: Saini Praveen , Kumar Nitin , Kumar Sunil , Panghal Anil , Attkan Arun K.
Published: December 2023

With evolving lifestyle preferences, consumer interest has shifted toward diets rich in antioxidants, notably anthocyanins. This study evaluates the engineering, milling, and nutritional properties of three colored wheat types (Amber, Purple P1, and Purple P2) as well as their bran fractions. Moisture levels (12%, 14%, and 16%) were investigated for their effects on engineering and debranning characteristics. The bran and flour samples of the selected wheat samples were examined for their nutritional and antioxidant characteristics. Purple P1 wheat demonstrated the highest protein, fiber, ash, and phytic acid content. Purple P2 had elevated crude fat content, while Amber exhibited increased starch content in both whole wheat flour and pearled bran. Bran consistently contained nearly double the anthocyanin content compared to flour, with Purple P1 wheat exhibiting the highest levels. Purple P1 also displayed superior polyphenol content, total flavonoids, and total antioxidant activity, while Amber samples showed minimum antioxidant activity. Considering the high nutritional and antioxidant qualities of wheat bran, their utilization as functional food seems promising. Also, there is good scope to incorporate wheat bran into different food products (like cookies, bread, noodles, etc.). The application of different modification treatments especially biological modification can further enhance their health‐promoting and functional properties.
Associations of prior concussion severity with brain microstructure using mean apparent propagator magnetic resonance imaging
Authors: Goeckner Bryna D. , Brett Benjamin L. , Mayer Andrew R. , España Lezlie Y. , Banerjee Anjishnu , Muftuler L. Tugan , Meier Timothy B.
Published: December 2023

Magnetic resonance imaging (MRI) diffusion studies have shown chronic microstructural tissue abnormalities in athletes with history of concussion, but with inconsistent findings. Concussions with post‐traumatic amnesia (PTA) and/or loss of consciousness (LOC) have been connected to greater physiological injury. The novel mean apparent propagator (MAP) MRI is expected to be more sensitive to such tissue injury than the conventional diffusion tensor imaging. This study examined effects of prior concussion severity on microstructure with MAP‐MRI. Collegiate‐aged athletes (N = 111, 38 females; ≥6 months since most recent concussion, if present) completed semistructured interviews to determine the presence of prior concussion and associated injury characteristics, including PTA and LOC. MAP‐MRI metrics (mean non‐Gaussian diffusion [NG Mean], return‐to‐origin probability [RTOP], and mean square displacement [MSD]) were calculated from multi‐shell diffusion data, then evaluated for associations with concussion severity through group comparisons in a primary model (athletes with/without prior concussion) and two secondary models (athletes with/without prior concussion with PTA and/or LOC, and athletes with/without prior concussion with LOC only). Bayesian multilevel modeling estimated models in regions of interest (ROI) in white matter and subcortical gray matter, separately. In gray matter, the primary model showed decreased NG Mean and RTOP in the bilateral pallidum and decreased NG Mean in the left putamen with prior concussion. In white matter, lower NG Mean with prior concussion was present in all ROI across all models and was further decreased with LOC. However, only prior concussion with LOC was associated with decreased RTOP and increased MSD across ROI. Exploratory analyses conducted separately in male and female athletes indicate associations in the primary model may differ by sex. Results suggest microstructural measures in gray matter are associated with a general history of concussion, while a severity‐dependent association of prior concussion may exist in white matter.
Challenges in Early Verification and Validation of System Requirements
Authors: Bacquet Cyril , Marangé Pascale , Bonjour Éric , Kerbrat Alain
Published: December 2023

Today, requirements engineering (RE) is a key process in the development of complex systems‐(ISO/IEC/IEEE 2015). Requirements containing quality issues such as ambiguity or inconsistency can lead to late error detection in systems design, resulting in high project cost overruns. This paper presents challenges for early system requirements verification and validation associated to an executable model‐based requirements engineering (eMBRE) process proposal.
Challenges in Developing a Method to Support the Adoption of a Model‐Based Systems Engineering Methodology
Authors: Kozak Léa , Bonjour Eric , Mayer Frédérique , Micaëlli Jean‐Pierre
Published: December 2023

To improve design performance and achieve sustainability, organisations are looking to change their systems engineering practices. A model‐based systems engineering (MBSE) methodology provides a framework for integrating, associating, orchestrating, and connecting executable and interactive models. It improves early verification and validation of system specifications and architectures, as well as communication and collaboration between project stakeholders. In this sense, MBSE has a truly systemic aspect. The variables to be considered when designing a support strategy are numerous and multidimensional. As a result, this situation can lead to contradictions in the choice of actions to be implemented, or to paradoxes that are likely to slow down the progress of the deployment project with the engineers. Currently, there is no method to support teams in charge of a methodological transformation (for example, in MBSE) to facilitate the adoption of this methodology. This article identifies the main challenges involved in developing such a methodology.
Project Engineering for the Depollution of Industrial Sites: a Model‐Based and Systems‐of‐Systems Approach
Authors: Mayssa Chebbi , Chapurlat Vincent , Wienin Jean‐Samuel , Aprin Laurent , Girones Philippe
Published: December 2023

This work addresses the challenges associated with depolluting brownfields or industrial sites, emphasizing the significant societal, financial, and environmental implications. Current depollution projects are often treated in an ad‐hoc manner, lacking a systematic and industrial perspective, despite the growing number of such projects. The proposed method advocates for a structured approach grounded in systems engineering principles, aiming to enhance collaboration among stakeholders, preserve knowledge, and facilitate the industrial transformation of depollution efforts. The method encompasses elements such as establishing a common vocabulary, employing modeling languages, implementing a double operational approach, providing supportive tools, and managing shared knowledge to improve project design, execution, and collaboration across multiple companies.
Early Validation of Functional Requirements
Authors: Assioua Yasmine , Ameur‐Boulifa Rabea , Pacalet Renaud , Guitton‐Ouhamou Patricia
Published: December 2023

Technical specifications and intended functionalities are often gathered in documents that include requirements written in constrained natural language, that is, natural‐like language with restricted syntax. In the automotive industry one challenge is the ability to produce safe vehicles, emphasizing the importance of safety by design. In the framework of case studies based on functions of autonomous vehicles, we introduce a systematic process for building formal models from automotive requirements written in constrained natural language, and for verifying them. By allowing formal verification at the earliest stages of the development cycle our aim is to avoid the costly discovery of errors at later stages.
Interoperability Forum for Requirements Exchange
Authors: Koumlah Mbey Christian , Darré Frédéric , El Amrani El‐Mehdi , Lévy Albert , Hubert Pascal
Published: December 2023

This article illustrates requirement exchanges based on the STEP AP242 application protocol. These results are the outcomes of the systems engineering interoperability forum (SE‐IF) of the ATLAS program, a working group sponsored by the French industry and the French government. The SE‐IF is composed of manufacturers, who define use cases and assign priorities and solution providers, who implement the standard, carry out interoperability tests and establish recommended practices. The objective of this forum is to enable exchange of requirements and their attributes in a fluid and tool‐agnostic way, to facilitate collaborative work in the context of the extended enterprise. This work gives promising perspectives for standardized transfers of all other systems engineering data.
Model‐Based Systems Engineering Approach for an Indoor Multi‐Usages System Development
Authors: Razafimahazo Eric , de Saqui‐Sannes Pierre , Vingerhoeds Rob , Soula Julien , Mège Romain
Published: December 2023

This paper discusses the design of multi‐usage systems able to perform various missions inside buildings, including inspection, digitization, monitoring of construction work, and evaluation of technical performances of the building. Designing such systems, carrying out various missions in different operational environments, is a complex task and requires adopting a well‐defined engineering approach. A model‐based systems engineering (MBSE) approach is proposed and applied to address the complexity of the indoor multi‐usages system and to lead its development. The proposed method provides several complementary and comprehensive views of the system.
Enhancement of energy decomposition analysis in fragment molecular orbital calculations
Authors: Matsuoka Sota , Sakakura Kota , Akinaga Yoshinobu , Akisawa Kazuki , Okuwaki Koji , Doi Hideo , Mochizuki Yuji
Published: December 2023

Energy decomposition analysis is one of the most attractive features of fragment molecular orbital (FMO) calculations from the point of view of practical applications. Here we report some enhancements for PIEDA in the ABINIT‐MP program. One is a separation of the dispersion‐type stabilization from the electron correlation energy, traditionally referred to as the “dispersion interaction” (DI). Another is an alternative evaluation of the electrostatic (ES) interaction using the restrained electrostatic potential (RESP) charges. The GA:CT stacked base pair and the Trp‐Cage miniprotein were used as illustrative examples.
Noninvasive scores are poorly predictive of histological fibrosis in paediatric fatty liver disease
Authors: Kalveram Laura , Baumann Ulrich , De Bruyne Ruth , Draijer Laura , Janczyk Wojciech , Kelly Deirdre , Koot Bart G. , Lacaille Florence , Lefere Sander , Lev Hadar Moran , Lubrecht Judith , Mann Jake P. , Mosca Antonella , Rajwal Sanjay , Socha Piotr , Vreugdenhil Anita , Alisi Anna , Hudert Christian A. ,   ESPGHAN Fatty Liver Special Interest Group
Published: December 2023

Objectives

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children. Roughly a quarter of paediatric patients with NAFLD develop nonalcoholic steatohepatitis and fibrosis. Here, we evaluated the diagnostic accuracy of previously published noninvasive fibrosis scores to predict liver fibrosis in a large European cohort of paediatric patients with NAFLD.

Methods

The 457 patients with biopsy‐proven NAFLD from 10 specialized centers were included. We assessed diagnostic accuracy for the prediction of any (F ≥ 1), moderate (F ≥ 2) or advanced (F ≥ 3) fibrosis for the AST/platelet ratio (APRI), Fibrosis 4 score (FIB‐4), paediatric NAFLD fibrosis score (PNFS) and paediatric NAFLD fibrosis index (PNFI).

Results

Patients covered the full spectrum of fibrosis (F0: n = 103; F1: n = 230; F2: n = 78; F3: n = 44; F4: n = 2). None of the scores were able to accurately distinguish the presence of any fibrosis from no fibrosis. For the detection of moderate fibrosis, area under the receiver operating characteristic curve (AUROC) were: APRI: 0.697, FIB‐4: 0.663, PNFI: 0.515, PNFS: 0.665, while for detection of advanced fibrosis AUROCs were: APRI: 0.759, FIB‐4: 0.611, PNFI: 0.521, PNFS: 0.712. Fibrosis scores showed no diagnostic benefit over using ALT ≤ 50/ > 50 IU/L as a cut‐off.

Conclusions

Established fibrosis scores lack diagnostic accuracy to replace liver biopsy for staging of fibrosis, giving similar results as compared to using ALT alone. New diagnostic tools are needed for Noninvasive risk‐stratification in paediatric NAFLD.