bluuebunny/crossref_metadata_2025 huggingface dataset:
The Manufacture of Unbreakable Bionics via Multifunctional and Self‐Healing Silk–Graphene Hydrogels
Authors: Kadumudi Firoz Babu , Hasany Masoud , Pierchala Malgorzata Karolina , Jahanshahi Mohammadjavad , Taebnia Nayere , Mehrali Mehdi , Mitu Cristian Florian , Shahbazi Mohammad‐Ali , Zsurzsan Tiberiu‐Gabriel , Knott Arnold , Andresen Thomas L. , Dolatshahi‐Pirouz Alireza
Published: July 2021

Biomaterials capable of transmitting signals over longer distances than those in rigid electronics can open new opportunities for humanity by mimicking the way tissues propagate information. For seamless mirroring of the human body, they also have to display conformability to its curvilinear architecture, as well as, reproducing native‐like mechanical and electrical properties combined with the ability to self‐heal on demand like native organs and tissues. Along these lines, a multifunctional composite is developed by mixing silk fibroin and reduced graphene oxide. The material is coined “CareGum” and capitalizes on a phenolic glue to facilitate sacrificial and hierarchical hydrogen bonds. The hierarchal bonding scheme gives rise to high mechanical toughness, record‐breaking elongation capacity of ≈25 000%, excellent conformability to arbitrary and complex surfaces, 3D printability, a tenfold increase in electrical conductivity, and a fourfold increase in Young's modulus compared to its pristine counterpart. By taking advantage of these unique properties, a durable and self‐healing bionic glove is developed for hand gesture sensing and sign translation. Indeed, CareGum is a new advanced material with promising applications in fields like cyborganics, bionics, soft robotics, human–machine interfaces, 3D‐printed electronics, and flexible bioelectronics.
Hydroxyapatite Nanorods Function as Safe and Effective Growth Factors Regulating Neural Differentiation and Neuron Development
Authors: Hao Min , Zhang Zixian , Liu Chao , Tian Yue , Duan Jiazhi , He Jianlong , Sun Zhaoyang , Xia He , Zhang Shan , Wang Shuhua , Sang Yuanhua , Xing Guogang , Liu Hong
Published: July 2021

Neural stem cell (NSC) transplantation is one of the most promising therapeutic strategies for neurodegenerative diseases. However, the slow spontaneous differentiation of NSCs often hampers their application in neural repair. Although some biological growth factors accelerate the differentiation of NSCs, their high cost, short half‐life, and unpredictable behavior in vivo, as well as the complexity of the operation, hinder their clinical use. In this study, it is demonstrated that hydroxyapatite (HAp), the main component of bone, in the form of nanorods, can regulate the neural differentiation of NSCs and maturation of the newly differentiated cells. Culturing NSCs with HAp nanorods leads to the differentiation of NSCs into mature neurons that exhibit well‐defined electrophysiological behavior within 5 days. The state of these neurons is much better than when culturing the cells without HAp nanorods, which undergo a 2‐week differentiation process. Furthermore, RNA‐sequencing data reveal that the neuroactive ligand–receptor interaction pathway is dominant in the enriched differentiated neuronal population. Hence, inorganic growth factors like HAp act as a feasible, effective, safe, and practical tool for regulating the differentiation of NSCs and can potentially be used in the treatment of neurodegenerative diseases.
Energy Autonomous Sweat‐Based Wearable Systems
Authors: Manjakkal Libu , Yin Lu , Nathan Arokia , Wang Joseph , Dahiya Ravinder
Published: July 2021

The continuous operation of wearable electronics demands reliable sources of energy, currently met through Li‐ion batteries and various energy harvesters. These solutions are being used out of necessity despite potential safety issues and unsustainable environmental impact. Safe and sustainable energy sources can boost the use of wearables systems in diverse applications such as health monitoring, prosthetics, and sports. In this regard, sweat‐ and sweat‐equivalent‐based studies have attracted tremendous attention through the demonstration of energy‐generating biofuel cells, promising power densities as high as 3.5 mW cm−2, storage using sweat‐electrolyte‐based supercapacitors with energy and power densities of 1.36 Wh kg−1 and 329.70 W kg−1, respectively, and sweat‐activated batteries with an impressive energy density of 67 Ah kg−1. A combination of these energy generating, and storage devices can lead to fully energy‐autonomous wearables capable of providing sustainable power in the µW to mW range, which is sufficient to operate both sensing and communication devices. Here, a comprehensive review covering these advances, addressing future challenges and potential solutions related to fully energy‐autonomous wearables is presented, with emphasis on sweat‐based energy storage and energy generation elements along with sweat‐based sensors as applications.
3D Atomic‐Scale Dynamics of Laser‐Light‐Induced Restructuring of Nanoparticles Unraveled by Electron Tomography
Authors: Albrecht Wiebke , Arslan Irmak Ece , Altantzis Thomas , Pedrazo‐Tardajos Adrián , Skorikov Alexander , Deng Tian‐Song , van der Hoeven Jessi E.S. , van Blaaderen Alfons , Van Aert Sandra , Bals Sara
Published: July 2021

Understanding light–matter interactions in nanomaterials is crucial for optoelectronic, photonic, and plasmonic applications. Specifically, metal nanoparticles (NPs) strongly interact with light and can undergo shape transformations, fragmentation and ablation upon (pulsed) laser excitation. Despite being vital for technological applications, experimental insight into the underlying atomistic processes is still lacking due to the complexity of such measurements. Herein, atomic resolution electron tomography is performed on the same mesoporous‐silica‐coated gold nanorod, before and after femtosecond laser irradiation, to assess the missing information. Combined with molecular dynamics (MD) simulations based on the experimentally determined 3D atomic‐scale morphology, the complex atomistic rearrangements, causing shape deformations and defect generation, are unraveled. These rearrangements are simultaneously driven by surface diffusion, facet restructuring, and strain formation, and are influenced by subtleties in the atomic distribution at the surface.
A Biomimetic Aggregation‐Induced Emission Photosensitizer with Antigen‐Presenting and Hitchhiking Function for Lipid Droplet Targeted Photodynamic Immunotherapy
Authors: Xu Xiuli , Deng Guanjun , Sun Zhihong , Luo Yuan , Liu Junkai , Yu Xinghua , Zhao Yang , Gong Ping , Liu Guozhen , Zhang Pengfei , Pan Fan , Cai Lintao , Tang Ben Zhong
Published: July 2021

Photodynamic therapy (PDT) is a promising alternative approach for effective cancer treatment that is associated with an antitumor immune response. However, immunosuppression of the tumor microenvironment limits the immune response induced by PDT. Stimulation and proliferation of T cells is a critical step for generating immune responses and depends on the efficient presentation of tumor antigens and co‐stimulatory molecules by antigen‐presenting cells (APCs). Here, biomimetic aggregation‐induced emission (AIE) photosensitizers with antigen‐presenting and hitchhiking abilities (DC@AIEdots) are developed by coating dendritic cell (DC) membranes on the nanoaggregates of the AIEgens. Notably, the inner AIE molecules can selectively accumulate in lipid droplets of tumor cells, and the outer cell membrane can facilitate the hitchhiking of DC@AIEdots onto the endogenous T cells and enhance the tumor delivery efficiency by about 1.6 times. Furthermore, DC@AIEdots can stimulate the in vivo proliferation and activation of T cells and trigger the immune system. The potential applications of therapeutic agents targeting lipid droplets for immunotherapy are indicated and a new hitchhiking approach for drug delivery is provided. Lastly, the study presents a photoactive and artificial antigen‐presenting platform for effective T cell stimulation and cancer photodynamic immunotherapy.
Sequentially Bridged Graphene Sheets for High‐Performance Anticorrosion
Authors: Zhao Hongran , Shi Shuo , Ding Jiheng , Zhou Min , Liu Panlin , Geng Lihong , Iqbal Mohammad Irfan , Yu Haibin
Published: July 2021

Graphene has been widely studied in metal protection due to its complete impermeability and ultrathin properties. However, it is still a huge challenge to fully use the unparalleled features to design and construct graphene‐based coatings with long‐term anticorrosion properties. Herein, a facile and scalable approach to design an ultrathin bioinspired graphene‐based (B–G–WEP) composite coating through sequential bridging of interfacial interactions and ordered graphene layers, is described. The combination of covalent bonding and π–π stacking greatly increases the graphene sheet ordered alignment and compatibility with epoxy matrix. This optimizes physical barrier effect, penetration resistance to sea water, and resistance to localized galvanic corrosion deterioration. The resultant B–G–WEP coating has a 190‐times reduced corrosion rate as well as a three‐orders increased impedance modulus, and keeps a high protection efficiency of 99.5% after 60 days of immersion tests. Furthermore, the coating damage function and coating damage index also decline by 2.8‐ and 10.7‐fold, respectively. This work provides overall consideration to facile, scalable, practical, high barrier and anticorrosion properties, showing great potential applications for high‐efficiency and durable metal protection.
Impact of Different Intermediate Layers on the Morphology and Crystallinity of TiO2 Grown on Carbon Nanotubes by Atomic Layer Deposition
Authors: Wang Jiao , Yin Zhigang , Hermerschmidt Felix , List‐Kratochvil Emil J. W. , Pinna Nicola
Published: July 2021

Nanocomposites of TiO2 and carbon nanotubes (CNTs) have been extensively studied in photocatalysis, sensing, and energy conversion and storage over the last decade. The unique properties of these nanocomposites are greatly dependent on the morphology, crystallinity, and homogeneity of the TiO2 coating. However, a fine control of the film microstructure is still challenging due to limited understanding of early stages of the TiO2 growth. The presence of an intermediate buffer layer can induce remarkable changes in the morphological and structural characteristics of the coatings. Here, TiO2 films deposited by atomic layer deposition (ALD) on CNTs without and with different intermediate layers (Al2O3 and ZnO) have been systematically investigated. Compared to bare CNTs, it is suggested that these two intermediate layers with higher surface energy can lead to a delay of the TiO2 crystallization, ultimately resulting in the growth of conformal and crystalline TiO2 films. This study demonstrates a strategy to tailor the microstructure and the properties of thin films via ALD by applying intermediate layers and provides information about the role of surface energy of the substrate in crystallization and growth behavior of ALD thin films.
Ultralight and Hyperelastic Nanofiber‐Reinforced MXene–Graphene Aerogel for High‐Performance Piezoresistive Sensor
Authors: Niu Fengxiao , Qin Zhen , Min Lizhen , Zhao Biao , Lv Yuhuan , Fang Xiaohui , Pan Kai
Published: July 2021

3D aerogel‐based piezoresistive sensors have attracted tremendous attention due to their high sensitivity and excellent mechanical properties. Here, a novel piezoresistive sensor with ultrahigh linear sensitivity is tactfully designed and prepared based on nanofiber‐reinforced MXene–reduced graphene oxide aerogel. The presence of MXene endows the piezoresistive sensor with high conductivity. Besides, the nanofibers can act as a scaffold to improve the compression resilience of the aerogel significantly by penetrating the entire aerogel network. Furthermore, due to the synergy effect among the multiple components, the prepared piezoresistive sensor exhibits outstanding performance, including high linear sensitivity (331 kPa−1 from 0 to 500 Pa, 126 kPa−1 from 500 Pa to 7.5 kPa), fast response time (load 71 ms, recovery 15 ms), and low detection limit (1.25 Pa). More importantly, it can maintain stable signal output even after 17 000 compression cycles. Furthermore, the prepared sensor can efficiently detect breathing, heartbeat, and vocalization of the human body in real time. Based on these advantages, the prepared sensor is expected to show significant potentials in future flexible wearable electronic devices.
Shape‐Selective Ultramicroporous Carbon Membranes for Sub‐0.1 nm Organic Liquid Separation
Authors: Seo Hyeokjun , Yoon Sunghyun , Oh Banseok , Chung Yongchul G. , Koh Dong‐Yeun
Published: July 2021

Liquid‐phase chemical separations from complex mixtures of hydrocarbon molecules into singular components are large‐scale and energy‐intensive processes. Membranes with molecular specificity that efficiently separate molecules of similar size and shape can avoid phase changes, thereby reducing the energy intensity of the process. Here, forward osmosis molecular differentiation of hexane isomers through a combination of size‐ and shape‐based separation of molecules is demonstrated. An ultramicroporous carbon membrane produced with 6FDA‐polyimides realized the separation of isomers for different shapes of di‐branched, mono‐branched, and linear molecules. The draw solvents provide the driving force for fractionation of hexane isomers with a sub‐0.1 nm size difference at room temperature without liquid‐phase pressurization. Such membranes could perform bulk chemical separations of organic liquids to achieve major reductions in the energy intensity of the separation processes.
Identification and Characterization of Robust Hepatocellular Carcinoma Prognostic Subtypes Based on an Integrative Metabolite‐Protein Interaction Network
Authors: Chen Di , Zhang Yiran , Wang Wen , Chen Huan , Ling Ting , Yang Renyu , Wang Yawei , Duan Chao , Liu Yu , Guo Xin , Fang Lei , Liu Wuguang , Liu Xiumei , Liu Jing , Otkur Wuxiyar , Qi Huan , Liu Xiaolong , Xia Tian , Liu Hong‐Xu , Piao Hai‐long
Published: July 2021

Metabolite‐protein interactions (MPIs) play key roles in cancer metabolism. However, our current knowledge about MPIs in cancers remains limited due to the complexity of cancer cells. Herein, the authors construct an integrative MPI network and propose a MPI network based hepatocellular carcinoma (HCC) subtyping and mechanism exploration workflow. Based on the expressions of hub proteins on the MPI network, two prognosis‐distinctive HCC subtypes are identified. Meanwhile, multiple interdependent features of the poor prognostic subtype are observed, including hypoxia, DNA hypermethylation of metabolic pathways, fatty acid accumulation, immune pathway up‐regulation, and exhausted T‐cell infiltration. Notably, the immune pathway up‐regulation is probably induced by accumulated unsaturated fatty acids which are predicted to interact with multiple immune regulators like SRC and TGFB1. Moreover, based on tumor microenvironment compositions, the poor prognostic subtype is further divided into two sub‐populations showing remarkable differences in metabolism. The subtyping shows a strong consistency across multiple HCC cohorts including early‐stage HCC. Overall, the authors redefine robust HCC prognosis subtypes and identify potential MPIs linking metabolism to immune regulations, thus promoting understanding and clinical applications about HCC metabolism heterogeneity.
Pten Regulates Cardiomyocyte Differentiation by Modulating Non‐CG Methylation via Dnmt3
Authors: Wang Wuming , Lu Gang , Liu Hong‐Bin , Xiong Zhiqiang , Leung Ho‐Duen , Cao Ruican , Pang Alan Lap‐Yin , Su Xianwei , Law Patrick Wai Nok , Zhao Zhiju , Chen Zi‐Jiang , Chan Wai‐Yee
Published: July 2021

The regulation of cardiomyocyte differentiation is a fundamental aspect of cardiac development and regenerative medicine. PTEN plays important roles during embryonic development. However, its role in cardiomyocyte differentiation remains unknown. In this study, a low‐cost protocol for cardiomyocyte differentiation from mouse embryonic stem cells (ESCs) is presented and it is shown that Pten deletion potently suppresses cardiomyocyte differentiation. Transcriptome analysis shows that the expression of a series of cardiomyocyte marker genes is downregulated in Pten−/− cardiomyocytes. Pten ablation induces Dnmt3b expression via the AKT/FoxO3a pathway and regulates the expression of a series of imprinted genes, including Igf2. Double knockout of Dnmt3l and Dnmt3b rescues the deficiency of cardiomyocyte differentiation of Pten−/− ESCs. The DNA methylomes from wild‐type and Pten−/− embryoid bodies and cardiomyocytes are analyzed by whole‐genome bisulfite sequencing. Pten deletion significantly promotes the non‐CG (CHG and CHH) methylation levels of genomic DNA during cardiomyocyte differentiation, and the non‐CG methylation levels of cardiomyocyte genes and Igf2 are increased in Pten−/− cardiomyocytes. Igf2 or Igf1r deletion also suppresses cardiomyocyte differentiation through the MAPK/ERK signaling pathway, and IGF2 supplementation partially rescues the cardiomyocyte differentiation. Finally, Pten conditional knockout mice are generated and the role of PTEN in cardiomyocyte differentiation is verified in vivo.
De Novo Design of Peptidic Positive Allosteric Modulators Targeting TRPV1 with Analgesic Effects
Authors: Xu Lizhen , Zhang Heng , Wang Yunfei , Lu Xiancui , Zhao Zhenye , Ma Cheng , Yang Shilong , Yarov‐Yarovoy Vladimir , Tian Yuhua , Zheng Jie , Yang Fan
Published: July 2021

Transient receptor potential vanilloid 1 (TRPV1) ion channel is a nociceptor critically involved in pain sensation. Direct blockade of TRPV1 exhibits significant analgesic effects but also incurs severe side effects such as hyperthermia, causing failures of TRPV1 inhibitors in clinical trials. In order to selectively target TRPV1 channels that are actively involved in pain‐sensing, peptidic positive allosteric modulators (PAMs) based on the high‐resolution structure of the TRPV1 intracellular ankyrin‐repeat like domain are de novo designed. The hotspot centric approach is optimized for protein design; its usage in Rosetta increases the success rate in protein binder design. It is demonstrated experimentally, with a combination of fluorescence resonance energy transfer (FRET) imaging, surface plasmon resonance, and patch‐clamp recording, that the designed PAMs bind to TRPV1 with nanomolar affinity and allosterically enhance its response to ligand activation as it is designed. It is further demonstrated that the designed PAM exhibits long‐lasting in vivo analgesic effects in rats without changing their body temperature, suggesting that they have potentials for developing into novel analgesics.
Probing Ferrimagnetic Semiconductor with Enhanced Negative Magnetoresistance: 2D Chromium Sulfide
Authors: Moinuddin Mohamad G. , Srinivasan Srikant , Sharma Satinder K.
Published: July 2021

Magnetic 2D materials have emerged as a great interest in spintronics due to atomic thickness scaling, low energy switching, and ease in the manipulation of spins. This report demonstrates a facile, bottom‐up, chemical vapor deposition approach for non‐van der Waals (non‐vdWs), 2D chromium (III) sulfide (Cr2S3) with c‐axis orientation, out‐of‐plane magnetic anisotropy (easy axis), and ferrimagnetic ordering. Importantly, the anisotropic magnetic saturation and resistivity of 10.23 mΩ cm reveal a narrow bandgap ferrimagnetism in Cr2S3 (∆EActivation ≈ 22 meV and Eg ≈ 40 meV). The prototype lateral spin‐channel Al/Cr2S3/Al devices exhibit a negative magnetoresistance of ≈25% and ≈15% at 100 K (below Néel temperature) for few‐layer (≈8 nm) and thin‐film (≈50 nm) device structures, respectively, owing to itinerant ferrimagnetism of Cr2S3. The magnetic field‐induced spin polaron formations are quite resilient and enhance the field‐dependent carrier conduction, making it greatly useful for negative magnetoresistance operation. These prototype Al/Cr2S3/Al structures have demonstrated a low power (≈2 µW for 8 µm channel at 10 µA current) operation with a negative field‐dependent resistance coefficient (rM) of ≈−5 × 10−4 Oe−1. The computed rM magnitude is tenfold higher than the bulk Cr2S3. This study identifies the potential of non‐vdW Cr2S3 toward new and robust 2D‐based spintronic applications.
Bifunctional Catalytic Activity Guided by Rich Crystal Defects in Ti3C2 MXene Quantum Dot Clusters for Li–O2 Batteries
Authors: Wang Peng , Zhao Danyang , Hui Xiaobin , Qian Zhao , Zhang Peng , Ren Yingying , Lin Yue , Zhang Zhiwei , Yin Longwei
Published: July 2021

Ameliorating round‐trip efficiency and mitigating parasitic reaction play a key role in enhancing the activity and durability of lithium–oxygen batteries. Herein, it is first reported that Ti3C2 MXene quantum dot clusters full of rich crystal defects anchored on N‐doped carbon nanosheets (Ti3C2 QDC/N‐C) can operate well as bifunctional catalyst for Li–O2 batteries. The well‐defined grain boundary and edge defects make crucial contributions in modulating the local unsaturated coordination state of active titanium atoms and thus the electronic structure of Ti3C2 QDC/N‐C, greatly enhancing the catalytic capability. Furthermore, density functional theory calculations disclose that the fruitful crystal defects governed catalytic centers endow substantial benefits for inducing charge density delocalization, regulating the LixOy intermediate adsorption and reducing the oxidation‐reduction energy barriers. The geometric morphology and distribution of final Li2O2 accommodations are distinctly altered with optimized decomposition reversibility, which strengthens electro‐catalytic kinetics and lowers redox voltage gaps. As expected, Li–O2 cells based on Ti3C2 QDC/N‐C show favorable long‐period stability (240 cycles at 200 mA g−1) with minimal side reactions and distinguished discharge/charge overpotential (0.62 V). Critically, this crystal defect strategy paves a new way for expanding the active sites in MXenes for catalytic applications.
Aerosol Assisted Solvent Treatment: A Universal Method for Performance and Stability Enhancements in Perovskite Solar Cells
Authors: Du Tian , Ratnasingham Sinclair R. , Kosasih Felix U. , Macdonald Thomas J. , Mohan Lokeshwari , Augurio Adriana , Ahli Huda , Lin Chieh‐Ting , Xu Shengda , Xu Weidong , Binions Russell , Ducati Caterina , Durrant James R. , Briscoe Joe , McLachlan Martyn A.
Published: July 2021

Metal‐halide perovskite solar cells (PSCs) have had a transformative impact on the renewable energy landscape since they were first demonstrated just over a decade ago. Outstanding improvements in performance have been demonstrated through structural, compositional, and morphological control of devices, with commercialization now being a reality. Here the authors present an aerosol assisted solvent treatment as a universal method to obtain performance and stability enhancements in PSCs, demonstrating their methodology as a convenient, scalable, and reproducible post‐deposition treatment for PSCs. Their results identify improvements in crystallinity and grain size, accompanied by a narrowing in grain size distribution as the underlying physical changes that drive reductions of electronic and ionic defects. These changes lead to prolonged charge‐carrier lifetimes and ultimately increased device efficiencies. The versatility of the process is demonstrated for PSCs with thick (>1 µm) active layers, large‐areas (>1 cm2) and a variety of device architectures and active layer compositions. This simple post‐deposition process is widely transferable across the field of perovskites, thereby improving the future design principles of these materials to develop large‐area, stable, and efficient PSCs.
Tactile and Vision Perception for Intelligent Humanoids
Authors: Gao Shuo , Dai Yanning , Nathan Arokia
Published: July 2021

Touch and vision perception are two important functions humans use to interact with the real world. To mimic human‐like abilities, tactile‐ and visual‐sensing‐based intelligent humanoids have emerged and are going through a fast phase of development. Studies have demonstrated that the combination of tactile and visual information not only enables humanoids to better learn the environment, but also allows them to have pseudocognitive ability. Being a new and rapidly developing field of research, a significant growth in articles reporting different aspects of sensing and related machine learning is being witnessed. To help readers comprehensively understand the fundamentals and insights, and the current state of the art, this review is compiled to explain the working mechanisms of tactile and visual sensing, introduce the application of intelligent humanoids in diverse scenarios, discuss current challenges, and predict future trends.
Azobenzene‐Based Photomechanical Biomaterials
Authors: Sun Jing , Wang Fan , Zhang Hongjie , Liu Kai
Published: July 2021

Biomaterials with stimuli sensitivity and good mechanical properties are garnering interest as an important branch of stimuli‐responsive materials. Among them, photomechanical biomaterials are an emerging class of eco‐friendly materials for the development of various biomedical devices because they offer high spatiotemporal control, on‐demand response, and noninvasive manipulation. In particular, azobenzene can be reversibly converted from the trans to the cis isomer under irradiation by different wavelengths of light. The significant changes in structural geometry and excellent fatigue resistance of azobenzene upon isomerization allow its use in the fabrication of materials with photoresponsive properties, such as bending, twisting, coiling, buckling, expansion, or even jumping. However, studies on the photomodulated mechanical performance of azobenzene‐based bulk biomaterials have rarely been reported. This review focuses on the photomechanical effects that occur in various systems incorporated with azobenzene moieties. Within this framework, the advantages of azobenzene in different photomechanical materials, including liquid crystals, bulk films, gels, and bulk fibers, are discussed. In each section, the light‐induced modulation of mechanical properties, including tensile strength, modulus, and toughness, is highlighted. Finally, a summary and outlook for the development of azobenzene‐based photomechanical materials is presented.
Efficient, doubly robust estimation of the effect of dose switching for switchers in a randomized clinical trial
Authors: Van Lancker Kelly , Vandebosch An , Vansteelandt Stijn
Published: July 2021

Motivated by a clinical trial conducted by Janssen Pharmaceutica in which a flexible dosing regimen is compared to placebo, we evaluate how switchers in the treatment arm (i.e., patients who were switched to the higher dose) would have fared had they been kept on the low dose. This is done in order to understand whether flexible dosing is potentially beneficial for them. Simply comparing these patients' responses with those of patients who stayed on the low dose does not likely entail a satisfactory evaluation because the latter patients are usually in a better health condition. Because the available information in the considered trial is too limited to enable a reliable adjustment, we will instead transport data from a fixed dosing trial that has been conducted concurrently on the same target, albeit not in an identical patient population. In particular, we propose an estimator that relies on an outcome model, a model for switching, and a propensity score model for the association between study and patient characteristics. The proposed estimator is asymptotically unbiased if either the outcome or the propensity score model is correctly specified, and efficient (under the semiparametric model where the randomization probabilities are known and independent of baseline covariates) when all models are correctly specified. The proposed method for transporting information from an external study is more broadly applicable in studies where a classical confounding adjustment is not possible due to near positivity violation (e.g., studies where switching takes place in a (near) deterministic manner). Monte Carlo simulations and application to the motivating study demonstrate adequate performance.
Production of MSTN‐mutated cattle without exogenous gene integration using CRISPR‐Cas9
Authors: Gim Gyeong‐Min , Kwon Dong‐Hyeok , Eom Kyeong‐Hyun , Moon JoonHo , Park Ji‐Hyun , Lee Won‐Wu , Jung Dae‐Jin , Kim Dae‐Hyun , Yi Jun‐Koo , Ha Jae‐Jung , Lim Ka‐Yeong , Kim Jin‐Soo , Jang Goo
Published: July 2021

Many genome‐edited animals have been produced using clustered regularly interspaced short palindromic repeats (CRISPR)‐Cas9 technology to edit specific genes. However, there are few guidelines for the application of this technique to cattle. The goal of this study was to produce trait‐improved cattle using the genome‐editing technology CRISPR–Cas9. Myostatin (MSTN) was selected as a target locus, and synthetic mRNA of sgRNA and Cas9 were microinjected into fertilized bovine embryos in vitro. As a result, 17 healthy calves were born, and three of them showed MSTN mutation rates of 10.5%, 45.4%, and 99.9%, respectively. Importantly, the offspring with the 99.9% MSTN mutation rate had a biallelic mutation (‐12 bps) and a double‐muscling phenotype. In conclusion, we demonstrate that the genome‐editing technology CRISPR‐Cas9 can produce genetically modified calves with improved traits.
Understanding suicidality and reasons for living amongst Doctoral Researchers: A thematic analysis of qualitative U‐DOC survey data
Authors: Hazell Cassie M. , Berry Clio , Niven Jeremy E. , Mackenzie Jay‐Marie
Published: July 2021

Evidence regarding the mental health of doctoral researchers (DRs) is very limited; that which exists suggests DRs are particularly vulnerable to experiencing mental health difficulties during their PhD. Despite the associated jeopardy, however, to our knowledge there are no data published nor in the grey literature, reporting on suicidality amongst DRs. Using an online survey, we invited UK DRs to complete the Suicide Behaviour Questionnaire‐Revised and qualitatively describe their experience of suicidality and its association with their PhD studies. A total of 1,263 DRs provided these data, with 40% of these participants meeting Suicide Behaviour Questionnaire‐Revised criteria for being at high risk of suicide. Within the qualitative data, we identified three higher‐order themes: (a) lived experience of suicidality; (b) PhD: the good, the bad, the ugly; and (c) life outside the PhD. Our findings suggest that suicidality is a common, yet complex and nuanced, experience amongst doctoral researchers. Identifiable elements of the PhD and personal lives can increase or protect against suicidality. The risk and protective factors identified here require verification using quantitative methods, but still support the immediate need for universities to respond to the risk of suicidality amongst their DRs.
IK: A novel cell mitosis regulator that contributes to carcinogenesis
Authors: Gao Chao , Han Yanyan , Bai Lu , Wang Yingmei , Xue Fengxia
Published: July 2021

Carcinogenesis is characterized by abnormal regulation of cell growth and cell death. IK is a novel cell mitosis regulator that may contribute to carcinogenesis. Previous studies showed that the loss of IK expression resulted in cell mitotic arrest and even cell death. Besides, IK can also inhibit the interferon gamma (IFN‐γ)‐induced expression of human leukocyte antigen (HLA) class II antigen, which is associated with tumour immune microenvironment. To gain insight into the current research progress regarding IK, we conducted a review and searched the limited literature on IK using PubMed or Web of Science. In this review, we discussed the possible biological functions and mechanisms of IK in cancer and its immune microenvironment. Future perspectives of IK were also mentioned to explore its clinical significance.
COVID‐19 in a pregnant patient with beta‐thalassemia major: A case report
Authors: Hailan Yousef Mohammed Ali , Sayed Gamal , Yassin Mohamed A.
Published: July 2021

Further studies are needed on this unique population to better manage them and increase their chances of normal pregnancy and fewer complications and more favorable outcomes.
PROTOCOL: Language interventions for improving the L1 and L2 development of dual language learners in early education and care: A systematic review and meta‐analysis
Authors: Egert Franziska , Sachse Steffi , Groth Katarina
Published: July 2021

The aim of the current systematic review and meta‐analysis is to comprehensively synthesize the effectiveness of language promotion interventions in early childhood education and care (ECEC) settings on L1 and L2 development of dual language learners (DLLs). We will use the PICOC‐Strategy (Population, Intervention, Comparison, Outcome, Context) suggested by Petticrew et al. to frame our research questions. Specifically, this review has the following research questions: (1) To which extent do language interventions accomplished in ECEC settings effect the L2 development (in the society language) of DLLs? (2) To which extent do bilingual language interventions (with L1 as language of instruction) accomplished in ECEC effect the L1 development (in the family language) of DLLs? (3) Are there significant differences in the effectiveness of different language interventions (additive vs. integrated vs. bilingual/two‐way‐immersion) to promote the L2 development of DLLs? (4) Are language interventions accomplished in ECEC settings more effective in supporting the L2 development (in the society language) of DLLs, when they start early in life (before the age of three)? (5) Are language interventions more effective in supporting the L2 development (in the society language) of DLLs when they are implemented with high fidelity/high quality? (6) Are language interventions with teachers as implementers more effective in supporting the L2 development (in the society language) of DLLs than language interventions with external implementers? (7) Are language interventions with higher intervention dosage (exposure × attention) more effective in supporting the L2 development (in the society language) of DLLs?
The distribution, number, and certain neurochemical identities of infracortical white matter neurons in the brains of a southern lesser galago, a black‐capped squirrel monkey, and a crested macaque
Authors: Swiegers Jordan , Bhagwandin Adhil , Maseko Busisiwe C. , Sherwood Chet C. , Hård Therese , Bertelsen Mads F. , Spocter Muhammad A. , Molnár Zoltán , Manger Paul R.
Published: July 2021

In the current study, we examined the number, distribution, and aspects of the neurochemical identities of infracortical white matter neurons, also termed white matter interstitial cells (WMICs), in the brains of a southern lesser galago (Galago moholi), a black‐capped squirrel monkey (Saimiri boliviensis boliviensis), and a crested macaque (Macaca nigra). Staining for neuronal nuclear marker (NeuN) revealed WMICs throughout the infracortical white matter, these cells being most dense close to inner cortical border, decreasing in density with depth in the white matter. Stereological analysis of NeuN‐immunopositive cells revealed estimates of approximately 1.1, 10.8, and 37.7 million WMICs within the infracortical white matter of the galago, squirrel monkey, and crested macaque, respectively. The total numbers of WMICs form a distinct negative allometric relationship with brain mass and white matter volume when examined in a larger sample of primates where similar measures have been obtained. In all three primates studied, the highest densities of WMICs were in the white matter of the frontal lobe, with the occipital lobe having the lowest. Immunostaining revealed significant subpopulations of WMICs containing neuronal nitric oxide synthase (nNOS) and calretinin, with very few WMICs containing parvalbumin, and none containing calbindin. The nNOS and calretinin immunopositive WMICs represent approximately 21% of the total WMIC population; however, variances in the proportions of these neurochemical phenotypes were noted. Our results indicate that both the squirrel monkey and crested macaque might be informative animal models for the study of WMICs in neurodegenerative and psychiatric disorders in humans.
Kullback chi square and Gustafson Kessel probabilistic neural network based soil fertility prediction
Authors: Rajamanickam Jayalakshmi , Mani Savitha Devi
Published: July 2021

Agriculture plays a significant role in any country's wealth creation, fulfilling food security needs and employment generation thereby contributing immensely to the country's growth and GDP. However, certain characteristics such as climate and environmental changes have extensively become menacing factors in the agriculture output. As soil is an influential specification influencing the prediction of crop yield, soil analysis becomes imperative and can assist farmers in preliminary adaptations towards better crop planning thereby facilitating higher yields. Machine learning algorithms have materialized in soil fertility prediction as an encouraging method for enhancing production. However, the spread and usage of this method are still limited by the lack of clear applicability due to the uncertainties involved and therefore resulting in false predictions by farmers. In this work, we take into account and address both the problems by incorporating uncertainty quantification utilizing the fishers ratio preprocessing model and Kullback divergent chi‐square feature selection for soil fertility prediction. Next, Gustafson‐Kessel probabilistic neural network classification uses the soil fertility predictive model to produce the probability distribution as output and the different types of soil fertility level instead of a single value. We analyze and prove that the new method not only provides uncertainty quantification but also minimizes the processing time and false positive rate with high accuracy than the existing soil fertility prediction methods.
A multi‐objective distance vector‐hop localization algorithm based on differential evolution quantum particle swarm optimization
Authors: Han Dezhi , Wang Jing , Tang Canren , Weng Tien‐Hsiung , Li Kuan‐Ching , Dobre Ciprian
Published: July 2021

Wireless sensor networks (WSNs) have actively been considered in vast amount of applications in fields of science and engineering. The node location technology is one of the most critical technologies of WSNs. Aiming at the problem of distance vector‐hop (DV‐HOP) algorithm's excessive estimation error, we propose in this article a multi‐objective DV‐HOP localization algorithm based on differential evolution quantum particle swarm optimization (DQPSO‐DV‐HOP). First, the set of anchor nodes generated during the deployment phase that would cause large errors is eliminated, and a correction factor is introduced to modify the average hop distance to reflect the actual situation of the network better. In the node localization phase, the objective function we propose is optimized under a combination of the DE and QPSO algorithms, so the estimated results of unknown nodes are optimized and modified by using the QPSO algorithm of fast convergence, which is easy to converge to the optimal global value. Simulation results show that the localization stability, accuracy, and convergence given by the proposed DQPSO‐DV‐HOP algorithm are better than other schemes. High precision positioning algorithm can improve the accuracy of energy consumption monitoring and provide more accurate data for energy saving management.
Family history of diabetes and risk of SARS‐COV‐2 in UK Biobank: A prospective cohort study
Authors: Jani Bhautesh Dinesh , Nicholl Barbara I. , Hanlon Peter , Mair Frances S. , Gill Jason MR. , Gray Stuart R. , Celis‐Morales Carlos A. , Ho Frederick K. , Lyall Donald M. , Anderson Jana J. , Hastie Claire E. , Bailey Mark ES. , Foster Hamish , Pell Jill P. , Welsh Paul , Sattar Naveed
Published: July 2021

Introduction

The aim of this study was to determine risk of being SARS‐CoV‐2 positive and severe infection (associated with hospitalization/mortality) in those with family history of diabetes.

Methods

We used UK Biobank, an observational cohort recruited between 2006 and 2010. We compared the risk of being SARS‐CoV‐2 positive and severe infection for those with family history of diabetes (mother/father/sibling) against those without.

Results

Of 401,268 participants in total, 13,331 tested positive for SARS‐CoV‐2 and 2282 had severe infection by end of January 2021. In unadjusted models, participants with ≥2 family members with diabetes were more likely to be SARS‐CoV‐2 positive (risk ratio‐RR 1.35; 95% confidence interval‐CI 1.24–1.47) and severe infection (RR 1.30; 95% CI 1.04–1.59), compared to those without. The excess risk of being tested positive for SARS‐CoV‐2 was attenuated but significant after adjusting for demographics, lifestyle factors, multimorbidity and presence of cardiometabolic conditions. The excess risk for severe infection was no longer significant after adjusting for demographics, lifestyle factors, multimorbidity and presence of cardiometabolic conditions, and was absent when excluding incident diabetes.

Conclusion

The totality of the results suggests that good lifestyle and not developing incident diabetes may lessen risks of severe infections in people with a strong family of diabetes.
Influence of carbon nanoparticle geometry on the fire resistance and anti‐aging properties of intumescent fire‐retardant coatings
Authors: Xu Zhisheng , Xie Xiaojiang , Yan Long , Zhou Huan
Published: July 2021

Three types of carbon nanoparticles, namely layered graphene (GN), tubular carbon nanotubes (CNTs), and spherical carbon black (CB), were applied in the intumescent fire‐retardant coatings. The influence of carbon nanoparticle geometry on the fire‐resistant and anti‐aging properties of the intumescent coatings was investigated. The fire protection and smoke density tests show that both spherical CB and tubular CNTs can effectively improve the fire resistance and smoke suppression properties of the coatings, which is attributed to the fact that the addition of either CB or CNTs can promote the swelling process of coating and produce a positive effect on improving the compactness and thickness of char residues. Especially, the coating containing 0.1 wt% CB acquires the lowest flame spread rating (FSR) value of 6.5, smoke density rating (SDR) value of 17.6%, and equilibrium backside temperature of 169.2°C at 900 seconds, showing superior fire resistance and smoke suppression performance. However, the layered GN shows a negative effect on the fire resistance and smoke suppression properties of the coating, which is ascribed to the fact that GN platelets inhibit the intumescent process of coating, resulting in the decrease of barrier effect. The results of accelerated aging test show that the incorporation of either CNTs or CB can weaken the blistering and powdering phenomenon, thus imparting superior durability of integrity and fire resistance to the intumescent coatings.
Tracking accuracy of strategic intelligence forecasts: Findings from a long‐term Canadian study
Authors: Mandel David R. , Irwin Daniel
Published: July 2021

Forecasting plays a vital role in intelligence assessment and contributes to national security decision‐making by improving strategic foresight. Remarkably, most intelligence organizations do not proactively track their forecasting accuracy and, therefore, do not know how accurate their forecasts are or what types of biases intelligence analysts (or organizations) might exhibit. We review research on geopolitical forecasting and a roughly decade‐long program of research to assess the accuracy of strategic intelligence forecasts produced by and for the Government of Canada. This research is described in three phases corresponding to previously published research, following which novel analyses (drawing from the data used in the earlier phases) are reported. The findings reveal a high degree of forecasting accuracy as well as significant underconfidence. These results were evident regardless of whether analysts assigned numeric probabilities to their forecasts. However, the novel analyses clarified that there is a substantial cost to accuracy if end‐users rely on their own interpretations of verbal probability terms used in the forecasts. We recommend that intelligence organizations proactively track forecasting accuracy as a means of supporting accountability and organizational learning. We further recommend that intelligence organizations use numeric probabilities in their forecasts to support better comprehension of these estimates by end‐users.
Characterization and functional properties of conjugates of rice protein with exopolysaccharides from Arthrobacter ps‐5 by Maillard reaction
Authors: Zhao Yuguang , Ye Shuhong , Wan Huiping , Zhang Xingxing , Sun Mingqi
Published: July 2021

The study examined the potential nutritive value of rice protein (RP) through Maillard reaction. Structures and properties of synthetic conjugates of RP and exopolysaccharide (EPS) from Arthrobacter ps‐5 were investigated systematically. Fluorescence characteristics and high molecular weight compounds appeared in Maillard reaction products (MRPs). Moreover, EPS or its degradation products in the form of covalent bond cross‐linked with RP were identified, where –NH2 disappeared and C=O, C=N and C–N increased. Determination of free –SH residues suggested mutual conversion between disulfide bonds and sulfhydryl groups occurred during Maillard reaction. HPLC analysis identified conjugates with different molecular weight, where melanoprotein was formed by covalent bonds. As RP conjugated with EPS, the molecules spread out and changed the spatial structure. Functional properties of MRPs, including solubility, foaming activity, emulsifying ability and resistance to oxidation, were greatly improved. The study has discovered an efficient method for increasing the application value of plant protein.
The effects of health spending on the propagation of infectious diseases
Authors: Castro Marcelo , Mattos Enlinson , Patriota Fernanda
Published: July 2021

We explore the discontinuity in the allocation of the main federal grant to Brazilian municipalities to identify the local effects of health spending and the spillovers into the bordering jurisdictions. Fiscal reactions are asymmetric: small neighbors reduce health spending, while we do not find a significant budgetary response in the largest neighbor. Our results suggest a reduction in the spread of infectious diseases in the neighbors, with fewer residents hospitalized with gastrointestinal infections. In addition, the elderly demand less hospitalization in the largest bordering jurisdictions due to respiratory infectious diseases. Finally, we find a direct and significant reduction in infant mortality, consistent with the observed pediatricians' increase, while the spillover effects on neighbors' mortality rates are not conclusive.
Developing COVID‐19 emergency response centres in geographically challenged areas of Pakistan: A case study of the Aga Khan Development Network
Authors: Jan Rafat , Uddin Miraj , Ullah Ihsan , Bibi Mubarek , Nawaz Sardar , Rehmani Mehnaz , Meherali Salima
Published: July 2021

The inevitable COVID‐19 global pandemic has severely affected Pakistan’s fragile healthcare system. The system was already facing a significant burden of noncommunicable and other infectious diseases, and the pandemic further exacerbated the disease and the healthcare burden in Pakistan. In such a situation, people who live in geographically challenged areas with limited healthcare infrastructure and resources are more vulnerable to the impacts of a pandemic. The authors share the experience of the development of emergency response centres (ERCs) in the rural remote mountainous regions of Pakistan–Chitral, an initiative that the Government of Pakistan and Aga Khan Health Service Pakistan (AKHSP) implemented to manage the increasing rates of COVID‐19 cases in these areas. The authors outline the processes that need to be undertaken to develop such healthcare facilities in a short period of time and discusses the challenges of establishing and operating these centres and the lessons learnt during and after the development of these centres in the remote mountainous regions of Pakistan.