bluuebunny/crossref_metadata_2025 huggingface dataset:
Post-medieval settlement in the Isle of Lewis: a study in adaptability or change?
Authors: Campbell Stuart D
Published: April 2023

The work of historical geographers has produced a rich literature concerning medieval and later rural settlement in Scotland. This work has frequently been used in an uncritical manner by archaeologists studying this period, often to the exclusion of developing a suitable theoretical and methodological basis for archaeological research. These models might be appropriate for the 'big history' paradigms of the disciplines which generated them, but they fail to address several issues which are key to the archaeologist. This paper investigates the pre-crofting settlement of two areas of the Isle of Lewis to argue that to understand post-medieval settlement, it is necessary to utilise both conventional archaeological survey and theoretical considerations of how societies interact and react to the particular environment in which they are placed.
Prelims
Authors: - -
Published: April 2023

Front matter for Volume 139

Table of Contents

List of abbreviations commonly used in the Proceedings

Editorial board for the Proceedings Vol 139

Society of Antiquaries of Scotland Council from 1 December 2008

Patron and Honorary Fellows of the Society of Antiquaries of Scotland, 2008-9

Laws of the Society of Antiquaries of Scotland
The Representation of War in Literature A Comparative Study of 'All Quiet on the Western Front' and 'For Whom the Bell Tolls'
Authors: Waham Dr. Jihad Jaafar
Published: April 2023

This article presents a comparative study of the representation of war in literature through a analysis of two novels: "All Quiet on the Western Front" by Erich Maria Remarque and "For Whom the Bell Tolls" by Ernest Hemingway. The article explores the ways in which the authors depict the experiences of soldiers and civilians in the context of war, examining the themes of trauma, disillusionment, and the human cost of conflict. Through a close analysis of the literary techniques used in each novel, the article demonstrates how these two works offer distinct but complementary perspectives on the impact of war on individuals and societies. Ultimately, this comparative study highlights the power of literature to convey complex ideas about war and its effects on humanity. War has been a recurring theme in literature, and writers have used it to depict the horrors, tragedies, and human emotions associated with it. This comparative study analyzes two renowned works of literature that represent war- "All Quiet on the Western Front" by Erich Maria Remarque and "For Whom the Bell Tolls" by Ernest Hemingway. The analysis focuses on the similarities and differences in the representation of war in these works, the authors' perspectives on war, and their use of literary techniques. This article argues that while both authors portray war as a brutal and devastating experience, Hemingway emphasizes the political and ideological reasons behind the war, while Remarque emphasizes the human toll it takes on the soldiers. The literary techniques used by both authors, such as symbolism and irony, further highlight their differing perspectives on war.
Palliative care of nursing in the pandemic scenario according to the pacific end-of-life theory / Cuidados paliativos da enfermagem no cenário pandêmico conforme a teoria de final de vida pacífico
Authors: Matos Júnior Jonas Melo de , Pinheiro Adriana de Sá , Reis Danielle Saraiva Tuma dos , Borges William Dias , Sonobe Helena Megumi , Correa Júnior Antonio Jorge Silva
Published: April 2023

Objetivo: descrever a perspectiva assistencial da equipe de enfermagem em uma Unidade de Terapia Intensiva para os pacientes diagnosticados com COVID-19 e fora de possibilidades terapêuticas, a luz da Teoria de Final de Vida Pacífico. Métodos: estudo qualitativo com suporte da Teoria de Final de Vida Pacífico, em uma Unidade de Terapia Intensiva adulto do Norte do Brasil. A coleta no segundo semestre de 2020 obteve nove profissionais, contando com roteiro semiestruturado e posterior análise de três etapas. Resultados: inter-relação entre “Não sentir dor” e “Experiência de Conforto”, uma polissemia de perspectivas quanto a “Experiência de dignidade e respeito” e “Estar em paz”, já a “Proximidade com outros significativos” foi totalmente abalada. Considerações finais: preceitos da humanização alinharam-se a teoria, porém foi um problema a falta de padronização quanto a avaliação de dor. A exclusão dos outros significativos impossibilitou o final de vida pacífico para os pacientes com COVID-19.
Artificial Intelligence–Enabled Analysis of Statin-Related Topics and Sentiments on Social Media
Authors: Somani Sulaiman , van Buchem Marieke Meija , Sarraju Ashish , Hernandez-Boussard Tina , Rodriguez Fatima
Published: April 2023

Importance

Despite compelling evidence that statins are safe, are generally well tolerated, and reduce cardiovascular events, statins are underused even in patients with the highest risk. Social media may provide contemporary insights into public perceptions about statins.

Objective

To characterize and classify public perceptions about statins that were gleaned from more than a decade of statin-related discussions on Reddit, a widely used social media platform.

Design, Setting, and Participants

This qualitative study analyzed all statin-related discussions on the social media platform that were dated between January 1, 2009, and July 12, 2022. Statin- and cholesterol-focused communities, were identified to create a list of statin-related discussions. An artificial intelligence (AI) pipeline was developed to cluster these discussions into specific topics and overarching thematic groups. The pipeline consisted of a semisupervised natural language processing model (BERT [Bidirectional Encoder Representations from Transformers]), a dimensionality reduction technique, and a clustering algorithm. The sentiment for each discussion was labeled as positive, neutral, or negative using a pretrained BERT model.

Exposures

Statin-related posts and comments containing the terms statin and cholesterol.

Main Outcomes and Measures

Statin-related topics and thematic groups.

Results

A total of 10 233 unique statin-related discussions (961 posts and 9272 comments) from 5188 unique authors were identified. The number of statin-related discussions increased by a mean (SD) of 32.9% (41.1%) per year. A total of 100 discussion topics were identified and were classified into 6 overarching thematic groups: (1) ketogenic diets, diabetes, supplements, and statins; (2) statin adverse effects; (3) statin hesitancy; (4) clinical trial appraisals; (5) pharmaceutical industry bias and statins; and (6) red yeast rice and statins. The sentiment analysis revealed that most discussions had a neutral (66.6%) or negative (30.8%) sentiment.

Conclusions and Relevance

Results of this study demonstrated the potential of an AI approach to analyze large, contemporary, publicly available social media data and generate insights into public perceptions about statins. This information may help guide strategies for addressing barriers to statin use and adherence.
Advocating for Demonstration of Disease Modification—Have We Been Approaching Clinical Trials in Early Alzheimer Disease Incorrectly?
Authors: Planche Vincent , Villain Nicolas
Published: April 2023

This Viewpoint discusses the benefits of clinical trials with a delayed-start design and analysis of downstream biomarkers to examine whether antimyeloid immunotherapy changes the course of early Alzheimer disease.
Birth-Based vs Fetuses-at-Risk Approaches for Assessing Neonatal Mortality Rate by Race
Authors: Wu Bohao , Taylor Sarah , Shabanova Veronika , Hawley Nicola L.
Published: April 2023

This cohort study assesses 5-year race-stratified neonatal mortality and prevalence of preterm births in the US using birth-based and fetuses-at-risk approaches.
Fabrication and Light‐Emission Study of Ti‐δ‐Doped Quasi‐2D γ‐Alumina by Graphene‐Assisted Atomic Layer Deposition
Authors: Kheirandish Elaheh , Spiegelhoff Yuting , Kouklin Nikolai
Published: April 2023

Crystalline quasi‐2D Ti‐δ‐doped γ‐alumina (2D‐Ti:γ‐alumina) is synthesized by a facile, precursor‐alternating atomic‐layer‐deposition technique followed by a post‐growth air‐anneal at ≈800 °C. According to energy‐dispersive X‐ray spectroscopy maps, Ti atomic concentration remains uniform and approaches ≈1.5%. Subject to several UV‐light exposures, the samples are found to develop a full strength, stable emission in the ultrawide spectral range of ≈350–850 nm. The near‐infrared (NIR) emission band centered at ≈760 nm is assigned to Ti deep defect states introduced in the alumina host. According to photoluminescence excitation–emission studies, aggregate oxygen vacancies remain a primary excitation source of the NIR emission. In addition, a broad visible‐range emission band at ≈525 nm is registered in the temperature range of ≈108–348 K, but unlike the NIR band, its temperature dependence remains Arrhenius with the non‐radiative recombination activation energy of ≈73 ± 9 meV. The resultant 2D‐Ti:γ‐alumina holds promise for applications in low‐cost alumina‐based optoelectronics, photocatalytic remediation, and spectrally wide light sources.
Chiral Plasmonic Response of 2D Ti3C2Tx Flakes: Realization and Applications
Authors: Olshtrem A. , Panov I. , Chertopalov S. , Zaruba K. , Vokata B. , Sajdl P. , Lancok J. , Storch J. , Církva V. , Svorcik V. , Kartau M. , Karimullah A. S. , Vana J. , Lyutakov O.
Published: April 2023

The circularly polarized light sensitive materials response can be reached at plasmon wavelengths through the coupling of intrinsically non‐chiral plasmonic nanostructure with chiral organic molecules. As a plasmonic background, the different types of metal nanoparticles of various shapes and sizes are successfully tested and an apparent circular dichroism (CD) signal is measured in both, nanoparticles suspensions and after nanoparticle immobilization in substrate. In this work, the creation of plasmon‐active 2D flakes of MXenes (Ti3C2Tx) is proposed, with the apparent CD response at plasmon wavelength, through the coupling of intrinsically non‐chiral flakes with helically shaped helicene enantiomers. This work provides the first demonstration of chiral and plasmon‐active 2D material, which shows the absorption sensitive to light intrinsic circular polarization even in plasmon wavelengths range. The appearance of the induced CD signal is additionally confirmed by several theoretical calculations. After the experimental and theoretical confirmation of the optical chirality at plasmon wavelengths, the flakes are utilized for the polarization sensitive conversion of light to heat, as well as for polarization dependent triggering of plasmon‐assisted chemical transformation.
In Situ Thermolysis of a Ni Salt on Amorphous Carbon and Graphene Oxide Substrates
Authors: Tamadoni Saray Mahmound , Yurkiv Vitaliy , Shahbazian‐Yassar Reza
Published: April 2023

Understanding the thermal decomposition of metal salt precursors on carbon structures is essential for the controlled synthesis of metal‐decorated carbon nanomaterials. Here, the thermolysis of a Ni precursor salt, NiCl2·6H2O, on amorphous carbon (a‐C) and graphene oxide (GO) substrates is explored using in situ transmission electron microscopy. Thermal decomposition of NiCl2·6H2O on GO occurs at higher temperatures and slower kinetics than on a‐C substrate. This is correlated to a higher activation barrier for Cl2 removal calculated by the density functional theory, strong Ni‐GO interaction, high‐density oxygen functional groups, defects, and weak van der Waals using GO substrate. The thermolysis of NiCl2·6H2O proceeds via multistep decomposition stages into the formation of Ni nanoparticles with significant differences in their size and distribution depending on the substrate. Using GO substrates leads to nanoparticles with 500% smaller average sizes and higher thermal stability than a‐C substrate. Ni nanoparticles showcase the fcc crystal structure, and no size effect on the stability of the crystal structure is observed. These findings demonstrate the significant role of carbon substrate on nanoparticle formation and growth during the thermolysis of carbon–metal heterostructures. This opens new venues to engineer stable, supported catalysts and new carbon‐based sensors and filtering devices.
Self‐Tandem Bio‐Heterojunctions Empower Orthopedic Implants with Amplified Chemo‐Photodynamic Anti‐Pathogenic Therapy and Boosted Diabetic Osseointegration
Authors: Shu Rui , Sun Jiamin , Li Bin , Gao Xiangyu , He Miaomiao , Chan Yau Kei , Shi Jiacheng , Bai Ding , Yang Weizhong , Deng Yi
Published: April 2023

Hyperglycemic microenvironment in diabetes mellitus inevitably stalls the normal orchestrated course of bone regeneration and encourages pathogenic multiplication. Photodynamic therapy (PDT) and chemo‐dynamic therapy (CDT) are extensively harnessed to combat pathogens, yet deep‐seated diabetic bone defect has difficulty in supplying sufficient oxygen (O2) and hydrogen peroxide (H2O2) stocks, resulting in inferior therapeutic efficiency. To address the tough plaguing, the self‐tandem bio‐heterojunctions (bio‐HJs) consisting of molybdenum disulfide (MoS2), graphene oxide (GO), and glucose oxidase (GOx) are constructed on orthopedic polyetheretherketone (PEEK) implants (SP‐Mo/G@GOx) for amplified chemo‐photodynamic anti‐pathogenic therapy and boosted osseointegration in the deep‐seated diabetic micromilieu. In this system, GOx exhausts glucose to generate H2O2, which provides an abundant stock for CDT. Besides, the bio‐HJs produce hyperthermia upon near‐infrared light (NIR) to accelerate the dynamic process, which amplifies the antibacterial potency of PDT by promoting the vast yield of singlet oxygen (1O2) in a self‐tandem manner. More importantly, in vivo and in vitro assays demonstrate that the engineered implants exert a captivated bactericidal ability and significantly boost osseointegration in an infectious diabetic bone defect model. As envisaged, this study furnishes a novel tactic to arm orthopedic implants with self‐tandem capability for the remedy of infectious diabetic bone defects.
Multistage‐Responsive Dual‐Enzyme Nanocascades for Synergistic Radiosensitization‐Starvation Cancer Therapy
Authors: Zhao Ming , Zhu Anni , Zheng Xueyun , Qian Xiaomin , Zhang Shujun , Wu Chenyu , Yu Congwei , Zhang Jiaheng , Li Jingchao
Published: April 2023

Radiotherapy is a common cancer treatment approach in clinical practice, yet its efficacy has been restricted by tumor hypoxia. Nanomaterials‐mediated systemic delivery of glucose oxidase (GOx) and catalase (CAT) or CAT‐like nanoenzymes holds the potential to enhance tumor oxygenation. However, they face the challenge of intermediate (hydrogen peroxide [H2O2]) escape during systemic circulation if the enzyme pair is not closely placed to largely decompose H2O2, leading to oxidative stress on normal tissues. In the present study, a oxygen‐generating nanocascade, n(GOx‐CAT)C7A, constructed by strategically placing an enzymatic cascade (GOx and CAT) within a polymeric coating rich in hexamethyleneimine (C7A) moieties, is reported. During blood circulation, C7A remains predominantly non‐protonated , achieving prolonged blood circulation due to its low‐fouling surface. Once n(GOx‐CAT)C7Areaches the tumor site, the acidic tumor microenvironment (TME) induces protonation of C7A moieties, resulting in a positively charged surface for enhanced tumor transcytosis. Moreover, GOx and CAT are covalently conjugated into close spatial proximity (<10 nm) for effective H2O2 elimination. As demonstrated by the in vivo results, n(GOx‐CAT)C7Aachieves effective tumor retention and oxygenation, potent radiosensitization and antitumor effects. Such a dual‐enzyme nanocascade for smart O2 delivery holds great potential for enhancing the hypoxia‐compromised cancer therapies.
Curved Nanographenes: Multiple Emission, Thermally Activated Delayed Fluorescence, and Non‐Radiative Decay
Authors: Ramírez‐Barroso Sergio , Romeo‐Gella Fernando , Fernández‐García Jesús M. , Feng Siyang , Martínez‐Fernández Lara , García‐Fresnadillo David , Corral Inés , Martín Nazario , Wannemacher Reinhold
Published: April 2023

The intriguing and rich photophysical properties of three curved nanographenes (CNG 6, 7, and 8) are investigated by time‐resolved and temperature‐dependent photoluminescence (PL) spectroscopy. CNG 7 and 8 exhibit dual fluorescence, as well as dual phosphorescence at low temperature in the main PL bands. In addition, hot bands are detected in fluorescence as well as phosphorescence, and, in the narrow temperature range of 100–140 K, thermally activated delayed fluorescence (TADF) with lifetimes on the millisecond time‐scale is observed. These findings are rationalized by quantum‐chemical simulations, which predict a single minimum of the S1 potential of CNG 6, but two S1 minima for CNG 7 and CNG 8, with considerable geometric reorganization between them, in agreement with the experimental findings. Additionally, a higher‐lying S2 minimum close to S1 is optimized for the three CNG, from where emission is also possible due to thermal activation and, hence, non‐Kasha behavior. The presence of higher‐lying dark triplet states close to the S1 minima provides mechanistic evidence for the TADF phenomena observed. Non‐radiative decay of the T1 state appears to be thermally activated with activation energies of roughly 100 meV and leads to disappearance of phosphorescence and TADF at T > 140 K.
Metasurfaces‐Driven Hyperspectral Imaging via Multiplexed Plasmonic Resonance Energy Transfer
Authors: Kim Inki , Kim Hongyoon , Han Seungyeon , Kim Joohoon , Kim Yangkyu , Eom Seonghyeon , Barulin Aleksandr , Choi Inhee , Rho Junsuk , Lee Luke P.
Published: April 2023

Obtaining single–molecular–level fingerprints of biomolecules and electron–transfer dynamic imaging in living cells are critically demanded in postgenomic life sciences and medicine. However, the possible solution called plasmonic resonance energy transfer (PRET) spectroscopy remains challenging due to the fixed scattering spectrum of a plasmonic nanoparticle and limited multiplexing. Here, multiplexed metasurfaces‐driven PRET hyperspectral imaging, to probe biological light–matter interactions, is reported. Pixelated metasurfaces with engineered scattering spectra are first designed over the entire visible range by the precision nanoengineering of gap plasmon and grating effects of metasurface clusters. Pixelated metasurfaces are created and their full dark‐field coloration is optically characterized with visible color palettes and high‐resolution color printings of the art pieces. Furthermore, three different biomolecules (i.e., chlorophyll a, chlorophyll b, and cytochrome c) are applied on metasurfaces for color palettes to obtain selective molecular fingerprint imaging due to the unique biological light–matter interactions with application‐specific biomedical metasurfaces. This metasurface‐driven PRET hyperspectral imaging will open up a new path for multiplexed real‐time molecular sensing and imaging methods.
Multifunctional Reflective Metasurface to Independently and Simultaneously Control Amplitude and Phase with Frequency Tunability
Authors: Phon Ratanak , Lee Minjae , Lor Chhunheng , Lim Sungjoon
Published: April 2023

The capability to dynamically modulate electromagnetic wavefronts can revolutionize and be crucial for future wireless technology. Electromagnetic waves can be fundamentally described in terms of amplitude, phase, polarization, and angular frequency. However, reported reconfigurable metasurfaces can only control one or two fundamental parameters and require different tuning/switching elements or materials that remain challenging to control those continuously. In this work, an approach is presented for designing electrically tunable reflective metasurfaces that enable independent and simultaneous control of amplitude and phase, while also providing frequency tuning capability. This is achieved by arranging two varactor diodes on the top layer and a lumped resistor on the bottom layer. The proposed metasurface is fabricated and several electromagnetic functionalities experimentally demonstrated as proof‐of‐concept applications, including reflector, radar absorbing, dual and single‐beam steering, and amplitude control. The proposed metasurface will open avenues for realizing advanced multifunctional devices to fully control electromagnetic parameters, offering numerous applications in future communication technologies, radar systems, and information processing.
All‐Optical Nonlinear Neuron Based on Metallic Quantum Wells
Authors: Niu Junru , Shao Hua , Feng Yiming , Gao Bingtao , Zhang Yiyun , Li Ying , Chen Hongsheng , Qian Haoliang
Published: April 2023

Optical nonlinear neuron, as an essential implementation method for optical interconnection, could greatly promote the development of optical neuron networks, which appears to be a promising alternative to electronic neural networks that are limited by computing speed and the end of Moore's law. However, restricted by weak nonlinearities, the modulation performance of optical nonlinear neuron networks is much lower compared to their electronic counterparts. Therefore, an effectual all‐optical nonlinear neuron is proposed by combining a double‐ring resonator with field‐enhancement and metallic quantum wells (MQWs) with a large Kerr nonlinear response. Based on the large and ultrafast Kerr nonlinearity provided by MQWs, the device can achieve a modulation extinction ratio of 18.78 dB and a transition rate of 13 GW cm−2 per 3 dB. The work may provide a new route for integrated, ultrafast, and high‐efficient optical nonlinear neurons for on‐chip neuron networks.
Influence of the Reference Electrode on the Performance of Single‐Electrode Triboelectric Nanogenerators and the Optimization Strategies
Authors: Chen Zetong , Dai Keren , Chen Jiaxiang , Zhuo Jingting , Zhao Danna , Ma Rui , Zhang Xujing , Li Xubiao , Wang Xiaofeng , Yang Guowei , Yi Fang
Published: April 2023

Owing to their unique advantages, single‐electrode triboelectric nanogenerators (SETENGs) have gained wide attention and have been applied in myriad areas, especially in the burgeoning flexible/wearable electronics. However, there is still a lack of a clear understanding of SETENGs. For example, previous simulation models generally put the reference electrode perpendicularly below the working part, but in practice, the reference electrode is designed in various scenarios and noticeable differences in outputs often occur when the reference electrode changes. With SETENGs developing towards wearability and portability, its reference electrode is often required to be constructed inside the device. Consequently, to achieve optimum performance, it is essential to understand the reference electrode's influence on the outputs. Here, the influence of the reference electrode on the performance of SETENGs is systematically investigated and the targeted optimization strategies are thoroughly revealed. First, theoretical simulations are conducted to investigate the reference electrode's effect on the performance of SETENGs with different structures and in various working modes. Secondly, the theoretical results are certified through corresponding experiments. Based on the results, the targeted optimization strategies for SETENGs are comprehensively demonstrated. This work provides fundamental guidance for the development of TENGs and the design and fabrication of new electronic devices.
Multi‐Fold Fan‐Shape Surface State Induced by an Isolated Weyl Phonon Beyond No‐Go Theorem
Authors: Fu Hua‐Hua , Liu Qing‐Bo , Wang Zhe‐Qi , Yang Xiang‐Feng
Published: April 2023

Absence of any surface arc state has been regarded as the fundamental property of singular Weyl points, because they are circumvented from the Nielsen‐Ninomiya no‐go theorem. In this work, through systematic investigations on topological properties of isolated Weyl phonons (IWPs) surrounded by closed Weyl nodal walls (WNWs), which are located at the Brillouin zone (BZ) boundaries of bosonic systems, it uncovers that a new kind of phononic surface state, that is, the multi‐fold fan‐shape surface state named by us, is exhibited to connect the projections of IWP and WNWs. Importantly, the number of fan leaves in this surface state is associated with the Chern number of IWP. Moreover, the topological features of charge‐two IWP in K2Mg2O3(SG No. 96) and charge‐four IWP in Nb3Al2N (SG No. 213) confirm further the above fundamental properties of this kind of surface state. The theoretical work not only provides an effective way to seek for IWPs as well as to determine their Chern number in real materials, but also uncovers a new class of surface states in the topological Weyl complex composed of IWPs and WNWs.
Large‐Area Field Potential Imaging Having Single Neuron Resolution Using 236 880 Electrodes CMOS‐MEA Technology
Authors: Suzuki Ikuro , Matsuda Naoki , Han Xiaobo , Noji Shuhei , Shibata Mikako , Nagafuku Nami , Ishibashi Yuto
Published: April 2023

The electrophysiological technology having a high spatiotemporal resolution at the single‐cell level and noninvasive measurements of large areas provide insights on underlying neuronal function. Here, a complementary metal‐oxide semiconductor (CMOS)‐microelectrode array (MEA) is used that uses 236 880 electrodes each with an electrode size of 11.22 × 11.22 µm and 236 880 covering a wide area of 5.5 × 5.9 mm in presenting a detailed and single‐cell‐level neural activity analysis platform for brain slices, human iPS cell‐derived cortical networks, peripheral neurons, and human brain organoids. Propagation pattern characteristics between brain regions changes the synaptic propagation into compounds based on single‐cell time‐series patterns, classification based on single DRG neuron firing patterns and compound responses, axonal conduction characteristics and changes to anticancer drugs, and network activities and transition to compounds in brain organoids are extracted. This detailed analysis of neural activity at the single‐cell level using the CMOS‐MEA provides a new understanding of the basic mechanisms of brain circuits in vitro and ex vivo, on human neurological diseases for drug discovery, and compound toxicity assessment.
High‐Throughput Electromechanical Coupling Chip Systems for Real‐Time 3D Invasion/Migration Assay of Cells
Authors: Jiang Nan , Xu Liang , Han Yiming , Wang Shuyi , Duan Xiaocen , Dai Jingyao , Hu Yunxing , Liu Xiaozhi , Liu Zhiqiang , Huang Jianyong
Published: April 2023

Cell invasion/migration through three‐dimensional (3D) tissues is not only essential for physiological/pathological processes, but a hallmark of cancer malignancy. However, how to quantify spatiotemporal dynamics of 3D cell migration/invasion is challenging. Here, this work reports a 3D cell invasion/migration assay (3D‐CIMA) based on electromechanical coupling chip systems, which can monitor spatiotemporal dynamics of 3D cell invasion/migration in a real‐time, label‐free, nondestructive, and high‐throughput way. In combination with 3D topological networks and complex impedance detection technology, this work shows that 3D‐CIMA can quantitively characterize collective invasion/migration dynamics of cancer cells in 3D extracellular matrix (ECM) with controllable biophysical/biomechanical properties. More importantly, this work further reveals that it has the capability to not only carry out quantitative evaluation of anti‐tumor drugs in 3D microenvironments that minimize the impact of cell culture dimensions, but also grade clinical cancer specimens. The proposed 3D‐CIMA offers a new quantitative methodology for investigating cell interactions with 3D extracellular microenvironments, which has potential applications in various fields like mechanobiology, drug screening, and even precision medicine.
Fast Delivery of Multifunctional NIR‐II Theranostic Nanoaggregates Enabled by the Photoinduced Thermoacoustic Process
Authors: Xie Huilin , Zhang Chen , Li Tingting , Hu Lianrui , Zhang Jianquan , Guo Heng , Liu Zhao , Peng Dinglu , Li Zeshun , Wu Weijun , Gao Ji , Bi Zhenyu , Wang Jinghan , Zhang Pengfei , Kwok Ryan T. K. , Lam Jacky W. Y. , Guo Zhihong , Xi Lei , Li Kai , Tang Ben Zhong
Published: April 2023

Multifunctional nanoaggregates are widely used in cancer phototheranostics. However, it is challenging to construct their multifunctionality with a single component, and deliver them rapidly and efficiently without complex modifications. Herein, a NIR‐absorbing small molecule named TBT‐2(TP‐DPA) is designed and certify its theranostic potentials. Then, their nanoaggregates, which are simply encapsulated by DSPE‐PEG, demonstrate a photothermal efficiency of 51% while keeping a high photoluminescence quantum yield in the NIR region. Moreover, the nanoaggregates can be excited and delivered by an 808 nm pulse laser to solid tumors within only 40 min. The delivery efficiency and theranostic efficacy are better than that of the traditional enhanced permeability and retention (EPR) effect (generally longer than 24 hours). This platform is first termed as the photoinduced thermoacoustic (PTA) process, and confirm its application requires both NIR‐responsive materials and pulse laser irradiation. This study not only inspires the design of multifunctional nanoaggregates, but also offers a feasible approach to their fast delivery. The platform reported here provides a promising prospect to boost the development of multifunctional theranostic drugs and maximize the efficacy of used medicines for their clinical applications.
Biomaterials Facilitating Dendritic Cell‐Mediated Cancer Immunotherapy
Authors: Dong Heng , Li Qiang , Zhang Yu , Ding Meng , Teng Zhaogang , Mou Yongbin
Published: April 2023

Dendritic cell (DC)‐based cancer immunotherapy has exhibited remarkable clinical prospects because DCs play a central role in initiating and regulating adaptive immune responses. However, the application of traditional DC‐mediated immunotherapy is limited due to insufficient antigen delivery, inadequate antigen presentation, and high levels of immunosuppression. To address these challenges, engineered biomaterials have been exploited to enhance DC‐mediated immunotherapeutic effects. In this review, vital principal components that can enhance DC‐mediated immunotherapeutic effects are first introduced. The parameters considered in the rational design of biomaterials, including targeting modifications, size, shape, surface, and mechanical properties, which can affect biomaterial optimization of DC functions, are further summarized. Moreover, recent applications of various engineered biomaterials in the field of DC‐mediated immunotherapy are reviewed, including those serve as immune component delivery platforms, remodel the tumor microenvironment, and synergistically enhance the effects of other antitumor therapies. Overall, the present review comprehensively and systematically summarizes biomaterials related to the promotion of DC functions; and specifically focuses on the recent advances in biomaterial designs for DC activation to eradicate tumors. The challenges and opportunities of treatment strategies designed to amplify DCs via the application of biomaterials are discussed with the aim of inspiring the clinical translation of future DC‐mediated cancer immunotherapies.
Biosignal Amplifiers Based on Low‐Noise Organic Transistors with Printed Electrodes
Authors: Kimura Tomoharu , Uemura Takafumi , Shibafuji Yayoi , Suyama Takeshi , Ueno Hiroyuki , Sekitani Tsuyoshi
Published: April 2023

The monitoring of microvolt‐level biosignals such as electroencephalograms requires the application of low‐noise signal amplifier circuits, which, for single‐use cases, must be fabricated for disposability using low‐cost manufacturing techniques. One promising solution for the production of low‐cost amplifier circuits for digital biosensing is the emerging technology of low‐noise printed circuits. Here, a low‐noise‐electrode printing process for organic transistors that can carry out precision measurement of brain activity using a low‐noise organic amplifier is proposed. In the transistor fabrication process, Ag electrodes are processed via flat stamp parallel printing, and fine‐process optimization to minimize the charge‐trapping effect enables a three‐order reduction in transistor noise. The low‐noise transistors are used to produce an organic pseudo‐complementary metal‐oxide‐semiconductor amplifier with a small noise level of 2.2 µVp‐p at 10 Hz, which enables precision brain wave monitoring in a close correlation with signals obtained using a commercialized measurement system.
Direct Conversion of Waste Battery Cathodes to High‐Volumetric‐Capacity Anodes with Assembled Secondary‐Particle Morphology
Authors: Liao Hengyi , Zhao Siwei , Cai Mingzhi , Dong Yanhao , Huang Fuqiang
Published: April 2023

The growing consumption of lithium‐ion batteries calls for recycling of electrode materials. Conventional direct recycling mainly consists of cathode‐to‐cathode and anode‐to‐anode strategies. In this work, a cathode‐to‐anode approach is proposed using a LiCoO2 model system and extending to Co‐lean/Co‐free cathodes (LiNi0.8Co0.1Mn0.1O2, LiMn2O4, and LiFePO4). Commercial cathodes are featured with single‐crystalline or secondary‐particle polycrystalline morphology, thus exhibiting higher tap density than anodes (LiCoO2 2.7 g cm−3 vs Si 0.25 g cm−3). By means of an intuitively direct conversion, the anodes are bestowed with well‐assembled morphology and high tap density from cathodes. During discharging, a dual conductive network is formed to facilitate lithium storage, where the binder‐derived carbon functions as electronic‐conductive and LiF/Li2O as ionic‐conductive motifs. Recycled cathodes exhibit an outstanding rate volumetric capacity (883 mAh cm−3, 5 A g−1, LiCoO2) and cyclic performance (1286 mAh cm−3, 1000 cycles, 2 A g−1, LiMn2O4). The morphologically inherited cathode‐to‐anode strategy proves to be a universal method for battery recycling toward high volumetric energy density.
Phase I study of neoadjuvant S‐1 plus cisplatin with concurrent radiation for biliary tract cancer (Tokyo Study Group for Biliary Cancer: TOSBIC02)
Authors: Abe Yuta , Itano Osamu , Takemura Yusuke , Minagawa Takuya , Ojima Hidenori , Shinoda Masahiro , Kitago Minoru , Obara Hideaki , Shigematsu Naoyuki , Kitagawa Yuko
Published: April 2023

Aim

Neoadjuvant chemoradiotherapy may improve survival in patients with advanced cholangiocarcinoma. This Phase I study aimed to determine the recommended dose of neoadjuvant chemoradiotherapy and decide whether to move to a Phase II study.

Methods

Patients diagnosed with resectable stage II–IVa cholangiocarcinoma were administered cisplatin (40 [level 0], 50 [level 1 as starting dose], or 60 [level 2] mg/m2), 80 mg/m2 of S‐1, and 50.4 Gy of external beam radiation. The recommended dose was defined as a dose one‐step lower than the maximum‐tolerated dose, which was defined when dose‐limiting toxicity was observed in three or more of the six patients.

Results

Twelve patients were eligible from November 2012 to May 2016. Ten patients had perihilar cholangiocarcinoma and two patients had distal cholangiocarcinoma. Dose‐limiting toxicity was observed in one of the first six patients at level 1 and two of the next six patients at level 2; thus, the maximum‐tolerated dose was not determined even at level 2 and the recommended dose was determined as level 2. Four patients had partial response, four patients had stable disease, and two patients had progression of disease because of liver metastases. Finally, nine patients underwent radical surgery and seven cases achieved R0 resection. However, five cases suffered biliary leakage and one suffered intrahospital death due to rupture of the hepatic artery.

Conclusion

We determined the recommended dose of neoadjuvant chemoradiotherapy for resectable cholangiocarcinoma. However, we terminated the trial due to a high incidence of morbidity and unexpected mortality.
U2AF2 variant in a patient with developmental delay, dysmorphic features, and epilepsy
Authors: Kittock Claire M. , Saifeddine Mohamad , Straight Lisa , Ward D. Isum
Published: April 2023

Variants in the RNA binding protein (RBP) U2AF2 are hypothesized to cause a novel neurodevelopmental disorder. Here, we report a patient with a de novo missense variant in U2AF2, the second case report of the same variant, and third case report overall. The patient in this report has a history of global developmental delay, dysmorphic features, and epilepsy. This presentation is consistent with the previous case report with the same U2AF2 variant and with a recent case report of another U2AF2 variant, strengthening the evidence that variants in U2AF2 are the cause of a novel neurodevelopmental disorder.
Magnon Blockade and Magnon–Atom Entanglement Induced by a Qutrit Coupled to a Ferromagnetic YIG Sphere
Authors: Setodeh Kheirabady M. , Ghasemian E. , Tavassoly M. K.
Published: April 2023

Hybridized magnonic–photonic systems promise novel applications for future information processing technologies. Here, a hybrid magnonic system comprising of a qutrit (Λ‐type three‐level atom) and a ferromagnetic YIG sphere is considered. Indeed, the whole system is driven by two light fields under the influence of the thermal environment. The indirect magnon–atom interaction is established via the virtual photon exchange. The associated Lindblad master equation is derived and its solution is found to investigate the nonclassical feature, especially in the steady‐state solution. Generally, the system shows considerable nonclassicality, that is, strong magnon antibunching and magnon blockade. In fact, the feasibility of using such a hybrid system to prepare a single‐magnon source based on magnon blockade effects we theoretically demonstrated. Besides, the considered system may be exploited to generate robust and stable magnon–atom entanglement. The appearance of magnon blockade and magnon–atom entanglement in the Λ‐type atom may have its origin in the fact that the atom is trapped in different superposition states, induced by the quantum interference phenomenon. The proposed model and the corresponding results may open up an intriguing prospect to prepare a single‐magnon source and provide further benefits through concatenating with photons in optomagnonic systems.
Regiodivergente C−H‐Acylierung von Aromaten durch Wechsel von ionischer zu radikalischer Chemie unter Verwendung von NHC‐Katalyse
Authors: Reimler Jannik , Yu Xiao‐Ye , Spreckelmeyer Nico , Daniliuc Constantin G. , Studer Armido
Published: April 2023

Die Friedel–Crafts‐Acylierung, die zur Klasse der elektrophilen aromatischen Substitutionen gehört, ist eine äußerst wertvolle und vielseitige Reaktion in der Synthese. Die Regioselektivität ist gut vorhersagbar und wird sowohl durch elektronische als auch durch sterische Faktoren des verwendeten (Hetero)Aromaten bestimmt. In dieser Mitteilung wird ein radikalischer Ansatz für die Acylierung von Aromaten und Heteroaromaten vorgestellt. Die C−H‐Acylierung erfolgt durch milde kooperative Photoredox/NHC‐Radikal‐Katalyse mit der Kreuzkupplung eines Arenradikalkations mit einem NHC‐gebundenen Ketylradikal als Schlüsselschritt. Im Vergleich zur klassischen Friedel–Crafts‐Acylierung wird beim Wechsel vom ionischen zum radikalischen Modus ein regiodivergentes Ergebnis beobachtet. Bei diesen divergenten Reaktionen fungieren Aroylfluoride als Acylierungsreagenzien sowohl im ionischen als auch im radikalischen Prozess.
Regiodivergent C−H Acylation of Arenes by Switching from Ionic‐ to Radical‐Type Chemistry Using NHC Catalysis
Authors: Reimler Jannik , Yu Xiao‐Ye , Spreckelmeyer Nico , Daniliuc Constantin G. , Studer Armido
Published: April 2023

The Friedel–Crafts acylation reaction, which belongs to the class of electrophilic aromatic substitutions is a highly valuable and versatile reaction in synthesis. Regioselectivity is predictable and determined by electronic as well as steric factors of the (hetero)arene substrate. Herein, a radical approach for the acylation of arenes and heteroarenes is presented. C−H acylation is achieved through mild cooperative photoredox/NHC radical catalysis with the cross‐coupling of an arene radical cation with an NHC‐bound ketyl radical as a key step. As compared to the classical Friedel–Crafts acylation, a regiodivergent outcome is observed upon switching from the ionic to the radical mode. In these divergent reactions, aroyl fluorides act as the acylation reagents in both the ionic as well as the radical process.
Preclinical Characterization of Pharmacologic NAD+ Boosting as a Promising Therapeutic Approach in Rheumatoid Arthritis
Authors: Perez‐Sanchez Carlos , Escudero‐Contreras Alejandro , Cerdó Tomás , Sánchez‐Mendoza Luz Marina , Llamas‐Urbano Adrián , la Rosa Iván Arias‐de , Pérez‐Rodriguez Miguel , Muñoz‐Barrera Laura , del Carmen Abalos‐Aguilera María , Barbarroja Nuria , Calvo Jerusalem , Ortega‐Castro Rafaela , Ruiz‐Vilchez Desiree , Moreno Juan Antonio , Burón María Isabel , González‐Reyes José Antonio , Collantes‐Estevez Eduardo , Lopez‐Pedrera Chary , Villalba José Manuel
Published: April 2023

Objective

We analyzed NAD+ metabolism in patients with rheumatoid arthritis (RA), its association with disease activity and clinical outcomes of RA, and the therapeutic potential of pharmacologic NAD+ boosting.

Methods

Our study included 253 participants. In the first cohort, comprising 153 RA patients and 56 healthy donors, we assessed NAD+ levels and NAD+‐related gene pathways. We analyzed 92 inflammatory molecules by proximity extension assay. In the second cohort, comprising 44 RA patients starting anti–tumor necrosis factor (anti‐TNF) drugs, we evaluated changes in NAD+ levels and their association with clinical response after 3 months. Mechanistic studies were performed ex vivo on peripheral blood mononuclear cells (PBMCs) from patients with RA to test the beneficial effects of NAD+ boosters, such as nicotinamide and nicotinamide riboside.

Results

Reduced NAD+ levels were found in RA samples, in line with altered activity and expression of genes involved in NAD+ consumption (sirtuins, poly[ADP‐ribose] polymerase, CD38), transport (connexin 43), and biosynthesis (NAMPT, NMNATs). Unsupervised clustering analysis identified a group of RA patients with the highest inflammatory profile, the lowest NAD+ levels, and the highest disease activity (as shown by the Disease Activity Score in 28 joints). NAD+ levels were modulated by anti‐TNF therapy in parallel with the clinical response. In vitro studies using PBMCs from RA patients showed that nicotinamide riboside and nicotinamide increased NAD+ levels via NAMPT and NMNAT and reduced their prooxidative, proapoptotic, and proinflammatory status.

Conclusion

RA patients display altered NAD+ metabolism, directly linked to their inflammatory and disease activity status, which was reverted by anti‐TNF therapy. The preclinical beneficial effects of NAD+ boosters, as shown in leukocytes from RA patients, along with their proven clinical safety, might pave the way for the development of clinical trials using these compounds.
On robust state derivative feedback control for uncertain polytopic systems with uncertain sampling period and network‐induced delay
Authors: Leandro Marco A. C. , Pereira Renan L.
Published: April 2023

This paper addresses the state derivative feedback control problem for uncertain polytopic systems subject to an uncertain sampling period and network‐induced delay. The distinctive contribution relies on the direct design of a robust state derivative feedback controller employing an augmented discretized model derived in terms of the state derivative feedback such that network‐induced delay and uncertain sampling periods can be incorporated from the original continuous‐time state‐space representation into the discretized model. Two augmented models are provided to handle longer input time delays, as well as delays less or equal to the sampling period. In this work, all the uncertain parameters are modeled as a polytopic form whose resulting discrete‐time model has matrices with polynomial dependence on the uncertain parameters and an additive norm‐bounded term featuring the discretization residual error. Moreover, synthesis conditions are derived using a set of linear matrix inequalities (LMI) to solve the stabilization problem for this class of systems under different input time delays. Finally, numerical simulations are carried out to evaluate the effectiveness of the proposed method.
Achieving Enhanced Electrochemical Performance for Cobalt‐Free Layered Cathode Material by Aluminum Doping
Authors: Ma Mingyuan , Yang Dan , Ji Yongsheng , Qie Long , Liu Zhikang , Huang Yunhui
Published: April 2023

We introduce a facile strategy to greatly improve the electrochemical reversibility of cobalt‐free cathode material by doping trace quantity of aluminum (Al) in LiNi0.65Mn0.35O2. X‐ray diffraction and X‐ray photoelectron spectroscopy results reveal that Al doping reduces the cation disorder consequently and hence increases structural stability. Electrochemical measurements show that rate capability and cycling stability are remarkably enhanced by Al doping. Al‐doped LiNi0.65Mn0.35O2 exhibits the optimized electrochemical performance with a capacity retention of 94.2 % after 200 cycles at 2 C in voltage range of 2.75–4.2 V in cylindrical full cell, demonstrating that Al‐doped cathode exhibits enhanced cyclability, reduced polarization and high‐rate capability during charge/discharge process. Moreover, the full cell shows good low‐temperature performance with more than 70 % capacity retention at −20 °C. The improved performances can be ascribed to the enhanced stability in layered structure of the Co‐free material by the support of doped Al ions.
The endocannabinoidome in human placenta: Possible contribution to the pathogenesis of preeclampsia
Authors: Maia João , Iannotti Fabio Arturo , Piscitelli Fabiana , Fonseca Bruno Miguel , Braga António , Braga Jorge , Teixeira Natércia , Di Marzo Vincenzo , Correia‐da‐Silva Georgina
Published: April 2023

Preeclampsia (PE) was first reported thousands of years ago, yet there is still a shortage of biomarkers to determine the severity and type of PE. The importance of the expanded endocannabinoid system, or endocannabinoidome (eCBome), has emerged recently in placental physiology and pathology, though the potential alterations of the eCBome in PE have not been fully explored. Analysis by qRT‐PCR using placental samples of normotensive and PE women demonstrate for the first time the presence of ABHD4, GDE1, and DAGLβ in both normotensive and PE placental tissues. Interestingly, NAPE‐PLD, FAAH‐1, DAGLα, MAGL, and ABHD6 mRNA levels were increased in the placental tissues of PE patients. Quantification in plasma and placental tissues showed a decrease for anandamide (AEA), N‐oleoylethanolamine (OEA), and N‐docosahexaenoylethanolamine (DHEA) in the placenta, accompanied only by a decrease in plasma levels of AEA. In addition, a strong negative correlation was obtained between OEA and the biomarker of PE, soluble fms‐like tyrosine kinase‐1. Given the inflammatory nature of PE and the anti‐inflammatory role of OEA and DHEA, the decrease in the local levels of these mediators may underlie the inflammatory component of this pathology. Additionally, lower AEA levels in both placenta and plasma may contribute to the atypical alterations of the spiral arteries in PE due to the vasorelaxation effects of AEA. These results add new information to the role of the eCBome members in placental development, while also pointing to a potential role as biomarkers of PE.