bluuebunny/crossref_metadata_2025 huggingface dataset:
Job insecurity is associated with presenteeism, but not with absenteeism: A study of 19 720 full-time waged workers in South Korea
Authors: Kim Ji-Hwan , Yoon Jaehong , Bahk Jinwook , Kim Seung-Sup
Published: August 2020

Objective

This study examined whether perceived job insecurity was associated with absenteeism and presenteeism, and how these associations varied when the differential cutoff was applied to define absenteeism and presenteeism.

Methods

We analyzed a nationally representative dataset of 19 720 full-time waged workers from the 4th Korean Working Conditions Survey (2014). As an independent variable, perceived job insecurity was assessed. As dependent variables, absenteeism and presenteeism were measured. Seven differential cutoffs (from “1 day” to “7 days”) were used when defining absenteeism and presenteeism. A Poisson regression model with a robust error variance was applied for the analysis.

Results

When “1 day” was cutoff to define absenteeism and presenteeism, job insecurity was not associated with both absenteeism (PR: 1.07, 95% CI: 0.97, 1.16) and presenteeism (PR: 1.05, 95% CI: 1.00, 1.10). When the higher cutoff was used, the association between job insecurity and absenteeism was attenuated and remained statistically nonsignificant. However, statistically significant associations between job insecurity and presenteeism were observed when the differential cutoff was used: “2 days” (PR: 1.07, 95% CI: 1.01, 1.13), “3 days” (PR: 1.14, 95% CI: 1.06, 1.22), “4 days” (PR: 1.15, 95% CI: 1.05, 1.26), “5 days” (PR: 1.18, 95% CI: 1.06, 1.30), “6 days” (PR: 1.17, 95% CI: 1.02, 1.33), and “7 days” (PR: 1.17, 95% CI: 1.02, 1.34).

Conclusion

This study found that perceived job insecurity was associated with presenteeism, but not absenteeism. Furthermore, the association differed by cutoff applied to define presenteeism among full-time waged workers in South Korea.
Bacterial multi‐solute transporters
Authors: Slotboom Dirk J. , Ettema Thijs W. , Nijland Mark , Thangaratnarajah Chancievan
Published: August 2020

Bacterial membrane proteins of the SbmA/BacA family are multi‐solute transporters that mediate the uptake of structurally diverse hydrophilic molecules, including aminoglycoside antibiotics and antimicrobial peptides. Some family members are full‐length ATP‐binding cassette (ABC) transporters, whereas other members are truncated homologues that lack the nucleotide‐binding domains and thus mediate ATP‐independent transport. A recent cryo‐EM structure of the ABC transporter Rv1819c from Mycobacterium tuberculosis has shed light on the structural basis for multi‐solute transport and has provided insight into the mechanism of transport. Here, we discuss how the protein architecture makes SbmA/BacA family transporters prone to inadvertent import of antibiotics and speculate on the question which physiological processes may benefit from multi‐solute transport.
Adaptive dynamic surface control of stochastic nonstrict‐feedback constrained nonlinear systems with input and state unmodeled dynamics
Authors: Chen Penghao , Zhang Tianping
Published: August 2020

In this paper, the issue of adaptive neural control is discussed for a class of stochastic nonstrict‐feedback constrained nonlinear systems with input and state unmodeled dynamics. A dynamic signal produced by the first‐order auxiliary system is employed to deal with the dynamical uncertain terms. Radial basis function neural networks are used to reconstruct unknown nonlinear continuous functions. With the help of the mean value theorem and Young's inequality, only one learning parameter is adjusted online at recursive each step. Using the hyperbolic tangent function as nonlinear mapping, the output constrained stochastic nonstrict‐feedback system in the presence of unmodeled dynamics is transformed into a novel unconstrained stochastic nonstrict‐feedback system. Based on dynamic surface control technology and the property of Gaussian function, adaptive neural control is developed for the transformed stochastic nonstrict‐feedback system. The output abides by stochastic constraints in probability. By the Lyapunov method, all signals of the closed‐loop control system are proved to be semi‐global uniform ultimate bounded (SGUUB) in probability. The obtained theoretical findings are verified by two numerical examples.
Experimental and Biological Insights from Proteomic Analyses of Extracellular Vesicle Cargos in Normalcy and Disease
Authors: Charest Al
Published: August 2020

Extracellular vesicles (EVs) offer a vehicle for diagnostic and therapeutic utility. EVs carry bioactive cargo and an accrued interest in their characterization has emerged. Efforts at identifying EV‐enriched protein or RNA led to a surprising realization that EVs are excessively heterogeneous in nature. This diversity is originally attributed to vesicle sizes but it is becoming evident that different classes of EVs vehiculate distinct molecular cargos. Therefore, one of the current challenges in EV research is their selective isolation in quantities sufficient for efficient downstream analyses. Many protocols have been developed; however, reproducibility between research groups can be difficult to reach and inter‐studies analyses of data from different isolation protocols are unmanageable. Therefore, there is an unmet need to optimize and standardize methods and protocols for the isolation and purification of EVs. This review focuses on the diverse techniques and protocols used over the years to isolate and purify EVs with a special emphasis on their adequacy for proteomics applications. By combining recent advances in specific isolation methods that yield superior quality of EV preparations and mass spectrometry techniques, the field is now prepared for transformative advancements in establishing distinct categorization and cargo identification of subpopulations based on EV surface markers.
Combating Antibiotic‐Resistant Gram‐Negative Bacteria Strains with Tetracycline‐Conjugated Carbon Nanoparticles
Authors: Kim Tak H. , Raiz Asim , Unni Aradhana Devi , Murhekar Shweta , Donose Bogdan C. , Floetenmeyer Matthias , Cock Ian E. , Brown Christopher L.
Published: August 2020

Nontoxic carbon nanoparticle samples prepared by both bottom‐up and top‐down approaches do not inhibit Gram‐negative bacterial growth, indicating excellent biocompatibilities. However, cell growth inhibitory efficacies increase considerably when the carbon nanoparticles are conjugated with the antibiotic tetracycline. In tetracycline‐resistant bacteria, these efficacies can approach tenfold higher activities when compared to tetracycline alone. No structural abnormality such as membrane disruptions is evident in the tested bacterial strains; this is in contrast with other nanocarbon systems such as graphene oxides, carbon nanotubes, and amine‐functionalized carbon nanoparticles which do exhibit membrane disruptions. In comparison, the tetracycline‐conjugated carbon nanoparticles induce membrane perturbations (but not membrane disruptions), inhibiting bacterial efflux mechanisms. It is proposed that when tetracycline is conjugated to the surface of carbon nanoparticles, it functions to direct the nanoparticles to membrane‐associated tetracycline efflux pumps, thereby blocking and subsequently inhibiting their function. The conjugation between biocompatible carbon nanoparticles and subtherapeutic but well‐established antibiotic molecules may provide hybrid antibiotic assembly strategies resulting in effective multidrug efflux inhibition for combating antibiotic resistance.
Self‐Propelling Janus Particles for Hemostasis in Perforating and Irregular Wounds with Massive Hemorrhage
Authors: Li Qing , Hu Enling , Yu Kun , Xie Ruiqi , Lu Fei , Lu Bitao , Bao Rong , Zhao Tianfu , Dai Fangyin , Lan Guangqian
Published: August 2020

Achieving rapid and safe control of perforating and irregular hemorrhage, defined as bleeding wounds with irregular external and internal wound shape, located deep within complex and covert hemorrhage sites, is vital to decrease the risk of mortality during prehospital treatments and surgical procedures. However, current hemostatic materials do not control hemorrhage effectively as their ability to access the bleeding source and coagulate blood is limited. Here, a biphasic Janus self‐propelled hemostatic particle (MSS@CaCO3) is prepared via uniaxial growth of flower‐like calcium carbonate crystal (CaCO3) on negatively‐modified‐microporous starch (MSS). The as‐synthesized hemostatic particle (MSS@CaCO3T) is loaded with thrombin and powered by the internal component CaCO3, with the collaborative use of protonated tranexamic acid. These particles are capable of traveling against the blood flow allowing them to access deep bleeding sites, inducing synergistic blood coagulation effects to effectively halt hemorrhaging. The self‐propelling Janus hemostatic particle is sufficiently available in the deep bleeding sites of liver and femoral artery hemorrhage models, wherein the hemorrhage is rapidly controlled in ≈50 s and ≈3 min, respectively. To the authors’ knowledge, this is the first attempt of controlling hemorrhage using Janus hemostatic particles with a self‐propelling property.
Atomically Thin Hexagonal Boron Nitride and Its Heterostructures
Authors: Zhang Jia , Tan Biying , Zhang Xin , Gao Feng , Hu Yunxia , Wang Lifeng , Duan Xiaoming , Yang Zhihua , Hu PingAn
Published: August 2020

Atomically thin hexagonal boron nitride (h‐BN) is an emerging star of 2D materials. It is taken as an optimal substrate for other 2D‐material‐based devices owing to its atomical flatness, absence of dangling bonds, and excellent stability. Specifically, h‐BN is found to be a natural hyperbolic material in the mid‐infrared range, as well as a piezoelectric material. All the unique properties are beneficial for novel applications in optoelectronics and electronics. Currently, most of these applications are merely based on exfoliated h‐BN flakes at their proof‐of‐concept stages. Chemical vapor deposition (CVD) is considered as the most promising approach for producing large‐scale, high‐quality, atomically thin h‐BN films and heterostructures. Herein, CVD synthesis of atomically thin h‐BN is the focus. Also, the growth kinetics are systematically investigated to point out general strategies for controllable and scalable preparation of single‐crystal h‐BN film. Meanwhile, epitaxial growth of 2D materials onto h‐BN and at its edge to construct heterostructures is summarized, emphasizing that the specific orientation of constituent parts in heterostructures can introduce novel properties. Finally, recent applications of atomically thin h‐BN and its heterostructures in optoelectronics and electronics are summarized.
Desolvation‐Triggered Versatile Transfer‐Printing of Pure BN Films with Thermal–Optical Dual Functionality
Authors: Han Yujin , Han Hyeuk Jin , Rah Yoonhyuk , Kim Cheolgyu , Kim Moohyum , Lim Hunhee , Ahn Kwang Ho , Jang Hanhwi , Yu Kyoungsik , Kim Taek‐Soo , Cho Eugene N. , Jung Yeon Sik
Published: August 2020

Although hexagonal boron nitride (BN) nanostructures have recently received significant attention due to their unique physical and chemical properties, their applications have been limited by a lack of processability and poor film quality. In this study, a versatile method to transfer‐print high‐quality BN films composed of densely stacked BN nanosheets based on a desolvation‐induced adhesion switching (DIAS) mechanism is developed. It is shown that edge functionalization of BN sheets and rational selection of membrane surface energy combined with systematic control of solvation and desolvation status enable extensive tunability of interfacial interactions at BN–BN, BN–membrane, and BN–substrate boundaries. Therefore, without incorporating any additives in the BN film and applying any surface treatment on target substrates, DIAS achieves a near 100% transfer yield of pure BN films on diverse substrates, including substrates containing significant surface irregularities. The printed BNs demonstrate high optical transparency (>90%) and excellent thermal conductivity (>167 W m−1 K−1) for few‐micrometer‐thick films due to their dense and well‐ordered microstructures. In addition to outstanding heat dissipation capability, substantial optical enhancement effects are confirmed for light‐emitting, photoluminescent, and photovoltaic devices, demonstrating their remarkable promise for next‐generation optoelectronic device platforms.
Tumor‐Activated Size‐Enlargeable Bioinspired Lipoproteins Access Cancer Cells in Tumor to Elicit Anti‐Tumor Immune Responses
Authors: Li Jie , Wang Hong , Wang Yuqi , Gong Xiang , Xu Xiaoxuan , Sha Xianyi , Zhang Ao , Zhang Zhiwen , Li Yaping
Published: August 2020

The limited lymphocytes infiltration and immunosuppression in tumor are the major challenges of cancer immunotherapy. The use of immunogenic cell death (ICD)‐inducing agents has potential to potentiate antitumor immune responses, but is tremendously hampered by the poor delivery efficiency. Herein, a tumor‐activated size‐enlargeable bioinspired lipoprotein of oxaliplatin (TA‐OBL) is designed to access cancer cells and boost the ICD‐induced antitumor immunity for synergizing immune‐checkpoint blockades (ICBs)‐mediated immunotherapy. TA‐OBL is constructed by integrating a legumain‐sensitive melittin conjugate for improving intratumoral permeation and cancer cell accessibility, a pH‐sensitive phospholipid for triggering size‐enlargement and drug release in intracellular acidic environments, a nitroreductase‐sensitive hydrophobic oxaliplatin prodrug (N‐OXP) for eliciting antitumor immunity into the bioinspired nano‐sized lipoprotein system. TA‐OBL treatment produced robust antitumor immune responses and its combination with ICBs demonstrates strong therapeutic benefits with delayed tumor growth and extended survival rate, making it a promising delivery nanoplatform to elicit antitumor immunity for cancer immunotherapy.
Electron Beam Lithography of Magnetic Skyrmions
Authors: Guang Yao , Peng Yong , Yan Zhengren , Liu Yizhou , Zhang Junwei , Zeng Xue , Zhang Senfu , Zhang Shilei , Burn David M. , Jaouen Nicolas , Wei Jinwu , Xu Hongjun , Feng Jiafeng , Fang Chi , van der Laan Gerrit , Hesjedal Thorsten , Cui Baoshan , Zhang Xixiang , Yu Guoqiang , Han Xiufeng
Published: August 2020

The emergence of magnetic skyrmions, topological spin textures, has aroused tremendous interest in studying the rich physics related to their topology. While skyrmions promise high‐density and energy‐efficient magnetic memory devices for information technology, the manifestation of their nontrivial topology through single skyrmions and ordered and disordered skyrmion lattices could also give rise to many fascinating physical phenomena, such as chiral magnon and skyrmion glass states. Therefore, generating skyrmions at designated locations on a large scale, while controlling the skyrmion patterns, is the key to advancing topological magnetism. Here, a new, yet general, approach to the “printing” of skyrmions with zero‐field stability in arbitrary patterns on a massive scale in exchange‐biased magnetic multilayers is presented. By exploiting the fact that the antiferromagnetic order can be reconfigured by local thermal excitations, a focused electron beam with a graphic pattern generator to “print” skyrmions is used, which is referred to as skyrmion lithography. This work provides a route to design arbitrary skyrmion patterns, thereby establishing the foundation for further exploration of topological magnetism.
T‐Cell‐Mimicking Nanoparticles for Cancer Immunotherapy
Authors: Kang Mikyung , Hong Jihye , Jung Mungyo , Kwon Sung Pil , Song Seuk Young , Kim Han Young , Lee Ju‐Ro , Kang Seokyung , Han Jin , Koo Ja‐Hyun , Ryu Ju Hee , Lim Songhyun , Sohn Hee Su , Choi Je‐Min , Doh Junsang , Kim Byung‐Soo
Published: August 2020

Cancer immunotherapies, including adoptive T cell transfer and immune checkpoint blockades, have recently shown considerable success in cancer treatment. Nevertheless, transferred T cells often become exhausted because of the immunosuppressive tumor microenvironment. Immune checkpoint blockades, in contrast, can reinvigorate the exhausted T cells; however, the therapeutic efficacy is modest in 70–80% of patients. To address some of the challenges faced by the current cancer treatments, here T‐cell‐membrane‐coated nanoparticles (TCMNPs) are developed for cancer immunotherapy. Similar to cytotoxic T cells, TCMNPs can be targeted at tumors via T‐cell‐membrane‐originated proteins and kill cancer cells by releasing anticancer molecules and inducing Fas‐ligand‐mediated apoptosis. Unlike cytotoxic T cells, TCMNPs are resistant to immunosuppressive molecules (e.g., transforming growth factor‐β1 (TGF‐β1)) and programmed death‐ligand 1 (PD‐L1) of cancer cells by scavenging TGF‐β1 and PD‐L1. Indeed, TCMNPs exhibit higher therapeutic efficacy than an immune checkpoint blockade in melanoma treatment. Furthermore, the anti‐tumoral actions of TCMNPs are also demonstrated in the treatment of lung cancer in an antigen‐nonspecific manner. Taken together, TCMNPs have a potential to improve the current cancer immunotherapy.
Electrohydrodynamic and Hydroelectric Effects at the Water–Solid Interface: from Fundamentals to Applications
Authors: Xu Wanghuai , Song Yuxin , Xu Ronald X. , Wang Zuankai
Published: August 2020

Electrohydrodynamic and hydroelectric effects at the water–solid interface are of fundamental importance and also underpin many important applications ranging from the controlled liquid transport by applying an external electric field to the power generation from moving liquid. Also, recent advances in micro/nanofabrication and nanomaterials provide additional dimension and flexibility in controlling electrohydrodynamic and hydroelectric effects at the water–solid interface to achieve preferred functions. Despite extensive progress, the cohesive and unified review of these two largely opposite effects is currently lacking. This review first discusses the important common foundations underpinning these two effects such as contact electrification and electric double layer (EDL), then takes a parallel approach to elaborate the electrohydrodynamic processes such as electrically induced liquid flow, wetting, and droplet motion, as well as the hydroelectricity resulting from their opposite processes. The practical applications and the unsolved challenges related to these two interfacial effects are also highlighted.
Rare‐Earth Metal Ions Doped Graphene Quantum Dots for Near‐IR In Vitro/In Vivo/Ex Vivo Imaging Applications
Authors: Hasan Md. Tanvir , Gonzalez‐Rodriguez Roberto , Lin Ching‐Wei , Campbell Elizabeth , Vasireddy Satvik , Tsedev Uyanga , Belcher Angela M. , Naumov Anton V.
Published: August 2020

Near‐infrared (NIR) emitting biocompatible nanomaterials are desired in biotechnology as higher penetration depth fluorescence imaging probes. In this work, novel NIR‐emissive Nd3+‐doped or Tm3+‐doped biocompatible graphene quantum dots (GQDs) are developed via scalable, single‐step bottom‐up synthesis. Water‐soluble Nd‐GQDs/Tm‐GQDs with average diameters of 5.6–8.2 nm possess crystalline graphene lattice with <1 atomic percent of Nd/Tm and exhibit NIR fluorescence at ≈1060/≈925 nm attributed to the intrinsic transitions of Nd3+/Tm3+. High biocompatibility with >80% cell viability at 1 mg mL−1 for Nd‐GQDs and 0.25 mg mL−1 for Tm‐GQDs makes them well‐suited for bioimaging. In vitro, both GQD types exhibit efficient internalization with their intracellular emission maximized at 6 h. The pH‐dependence of this emission can serve as plethora of diagnostic applications. GQDs enable in vivo NIR imaging in live sedated NCr nude mice with IV administration: their NIR emission maximized at 6 h post‐injection is primarily detected in intestine, kidneys, liver, and spleen, however, diminishing to none at 48 h. Ex vivo organ/slice imaging shows significant Tm‐GQD fluorescence signatures in the aforementioned organs/slices. This capability of NIR fluorescence imaging in cells, tissues, and real‐time detection in live animals makes biocompatible rare‐earth metal‐doped GQDs an attractive new candidate for in vitro/in vivo/ex vivo theranostics.
Lead‐Free Cs3Sb2Br9 Single Crystals for High Performance Narrowband Photodetector
Authors: Liu Ping , Liu Yuan , Zhang Siwei , Li Jingzhou , Wang Chunyun , Zhao Cong , Nie Pengbo , Dong Yuhan , Zhang Xuan , Zhao Shixi , Wei Guodan
Published: August 2020

Lead‐free single crystal perovskite materials exhibit impressive characteristics, such as high carrier mobility, low trap density, and long diffusion length. Herein, the high‐performance blue light photodetectors are reported based on lead‐free all‐inorganic Cs3Sb2Br9 perovskite single crystals. These millimeter‐sized Cs3Sb2Br9 single crystals have small thermal activation energy of 56.8 meV estimated by temperature‐dependent photoluminescence study. There is no obvious structural phase transition of the as‐obtained Cs3Sb2Br9 single crystals since no Raman peak shift is observed with temperature increasing from 80 to 300 K. The as‐constructed high quality Cs3Sb2Br9 single crystals photodetectors have an excellent performance of a responsivity of 2.29 A W−1, a sharp detectivity of 3.77 × 1012 Jones, and an external quantum efficiency (EQE) peak of 1.8 × 103%. Moreover, the photodetectors exhibit a fast response time (<0.2 ms) and the full width at half maximum (FWHM) of the sharp EQE peak is as narrow as 15 nm. This work provides a promising strategy in the design of lead‐free, stable, and high‐performance perovskites for photodetector devices.
Targeting Glioblastoma: Advances in Drug Delivery and Novel Therapeutic Approaches
Authors: Yeini Eilam , Ofek Paula , Albeck Nitzan , Rodriguez Ajamil Daniel , Neufeld Lena , Eldar‐Boock Anat , Kleiner Ron , Vaskovich Daniella , Koshrovski‐Michael Shani , Dangoor Sahar Israeli , Krivitsky Adva , Burgos Luna Christian , Shenbach‐Koltin Gal , Goldenfeld Miki , Hadad Ori , Tiram Galia , Satchi‐Fainaro Ronit
Published: August 2020

Glioblastoma (GB) is the most lethal type of primary tumor in the central nervous system. Current treatments include surgical resection followed by chemotherapy and radiotherapy. With this therapeutic regimen, the median survival is less than two years. However, these treatments do not much improve the overall survival of GB patients. GBs are highly angiogenic and invasive tumors and often acquire resistance to therapy. The invasive nature of the disease limits the ability to achieve complete resection of the tumor and the majority of GB patients will experience disease relapse. Moreover, GB is highly heterogeneous, harboring different mutations and presenting different phenotypes. As the brain is considered to be an immune‐privileged tissue, GB is defined as a cold tumor for which current immunotherapies have not yet been demonstrated to improve survival. On top of these challenges, the blood brain barrier (BBB) restricts the uptake of drugs by the brain, thus limiting the therapeutic options. Therefore, enormous efforts are being dedicated to the development of novel nanomedicines, which will be able to cross the BBB and specifically target the cancer cells. Here, the current achievements in drug delivery and novel therapeutic approaches for GB therapy are discussed.
The Evolution of Flexible Electronics: From Nature, Beyond Nature, and To Nature
Authors: Wang Panpan , Hu Mengmeng , Wang Hua , Chen Zhe , Feng Yuping , Wang Jiaqi , Ling Wei , Huang Yan
Published: August 2020

The flourishing development of multifunctional flexible electronics cannot leave the beneficial role of nature, which provides continuous inspiration in their material, structural, and functional designs. During the evolution of flexible electronics, some originated from nature, some were even beyond nature, and others were implantable or biodegradable eventually to nature. Therefore, the relationship between flexible electronics and nature is undoubtedly vital since harmony between nature and technology evolution would promote the sustainable development. Herein, materials selection and functionality design for flexible electronics that are mostly inspired from nature are first introduced with certain functionality even beyond nature. Then, frontier advances on flexible electronics including the main individual components (i.e., energy (the power source) and the sensor (the electric load)) are presented from nature, beyond nature, and to nature with the aim of enlightening the harmonious relationship between the modern electronics technology and nature. Finally, critical issues in next‐generation flexible electronics are discussed to provide possible solutions and new insights in prospective exploration directions.
TRADES: Targeted RNA Demethylation by SunTag System
Authors: Mo Jing , Chen Zonggui , Qin Shanshan , Li Shu , Liu Chuangang , Zhang Lu , Ran Ruoxi , Kong Ying , Wang Fang , Liu Songmei , Zhou Yu , Zhang Xiaolian , Weng Xiaocheng , Zhou Xiang
Published: August 2020

N6‐methyladenosine (m6A) is rapidly being studied and uncovered to play a significant role in various biological processes as well as in RNA fate and functions, while the effects of defined m6A sites are rarely characterized for the lack of convenient tools. To provide an applicable method to remove m6A modification at specific loci, an m6A editing system called “targeted RNA demethylation by SunTag system (TRADES)” is engineered. In this system, the targeting element dCas13b is fused to ten copies of GCN4 peptides which can recruit multiple scFv‐fusion RNA demethylase to demethylate the target m6A site. Owing to this design, TRADES is more flexible to the indistinct m6A sites for its wide editing window. By site‐specific demethylation of messenger RNA (mRNA) SON A2699, the lifetime of SON RNA is successfully prolonged in HeLa cells. Meanwhile, TRADES negligibly influences the lifetime of other non‐targeted transcripts. TRADES also can regulate the gene expression of target transcript in an m6A‐dependent manner. Moreover, the interference occuring for HBV and HIV replications demonstrates that the TRADES system holds potential in viral life cycle regulation and clinical applications.
Dual‐Isolation and Profiling of Circulating Tumor Cells and Cancer Exosomes from Blood Samples with Melanoma Using Immunoaffinity‐Based Microfluidic Interfaces
Authors: Kang Yoon‐Tae , Hadlock Thomas , Lo Ting‐Wen , Purcell Emma , Mutukuri Anusha , Fouladdel Shamileh , Raguera Monica De Silva , Fairbairn Heather , Murlidhar Vasudha , Durham Alison , McLean Scott A. , Nagrath Sunitha
Published: August 2020

Melanoma is among the most aggressive cancers, and its rate of incidence continues to grow. Early detection of melanoma has been hampered due to the lack of promising markers for testing. Recent advances in liquid biopsy have proposed noninvasive alternatives for cancer diagnosis and monitoring. Circulating tumor cells (CTCs) and cancer‐exosomes are gaining influence as promising biomarkers because of their cancer‐associated molecular markers and signatures. However, technologies that offer the dual‐isolation of CTCs and exosomes using a single sample have not been thoroughly developed. The dual‐utilization OncoBean (DUO) device is conjugated with melanoma specific antibodies, MCAM and MCSP, enabling simultaneous CTC and exosome isolations. Using blood samples from patients, CTCs and exosomes are specifically isolated from a single sample and then undergo molecular profiling for comprehensive study. Melanoma patients have 0–17CTCs mL−1 and 299 µg exosomal protein mL−1 while healthy donors display fewer than 2CTCs and 75.6 µg of exosomes mL−1, respectively. It is also demonstrated that both markers express melanoma‐associated genes using multiplex qRT‐PCR to test for expression pattern of a 96 gene panel. The dual isolation and molecular characterization will allow for further research into melanoma to identify viable markers for disease progression and treatment efficacy.
Nidogen 1‐Enriched Extracellular Vesicles Facilitate Extrahepatic Metastasis of Liver Cancer by Activating Pulmonary Fibroblasts to Secrete Tumor Necrosis Factor Receptor 1
Authors: Mao Xiaowen , Tey Sze Keong , Yeung Cherlie Lot Sum , Kwong Ernest Man Lok , Fung Yi Man Eva , Chung Clive Yik Sham , Mak Lung‐Yi , Wong Danny Ka Ho , Yuen Man‐Fung , Ho James Chung Man , Pang Herbert , Wong Maria Pik , Leung Carmen Oi‐Ning , Lee Terence Kin Wah , Ma Victor , Cho William Chi‐Shing , Cao Peihua , Xu Xiaoping , Gao Yi , Yam Judy Wai Ping
Published: August 2020

In hepatocellular carcinoma (HCC) patients with extrahepatic metastasis, the lung is the most frequent site of metastasis. However, how the lung microenvironment favors disseminated cells remains unclear. Here, it is found that nidogen 1 (NID1) in metastatic HCC cell‐derived extracellular vesicles (EVs) promotes pre‐metastatic niche formation in the lung by enhancing angiogenesis and pulmonary endothelial permeability to facilitate colonization of tumor cells and extrahepatic metastasis. EV‐NID1 also activates fibroblasts, which secrete tumor necrosis factor receptor 1 (TNFR1), facilitate lung colonization of tumor cells, and augment HCC cell growth and motility. Administration of anti‐TNFR1 antibody effectively diminishes lung metastasis induced by the metastatic HCC cell‐derived EVs in mice. In the clinical perspective, analysis of serum EV‐NID1 and TNFR1 in HCC patients reveals their positive correlation and association with tumor stages suggesting the potential of these molecules as noninvasive biomarkers for the early detection of HCC. In conclusion, these results demonstrate the interplay of HCC EVs and activated fibroblasts in pre‐metastatic niche formation and how blockage of their functions inhibits distant metastasis to the lungs. This study offers promise for the new direction of HCC treatment by targeting oncogenic EV components and their mediated pathways.
Nonvolatile Memory and Artificial Synaptic Characteristics in Thin‐Film Transistors with Atomic Layer Deposited HfOx Gate Insulator and ZnO Channel Layer
Authors: Lee Hyerin , Beom Keonwon , Kim Minju , Kang Chi Jung , Yoon Tae‐Sik
Published: August 2020

Nonvolatile memory and synaptic characteristics in thin‐film transistors (TFTs) with HfOx gate insulator and ZnO channel are investigated for the application to nonvolatile memory and artificial synapse in neuromorphic systems. Nonvolatile change of drain current induced by modulated gate stack properties is demonstrated to be applicable to nonvolatile memory operation. It also emulates synaptic weight change for learning and memory functions in artificial synapses. The TFTs with HfOx and ZnO layers deposited by sputtering or atomic layer deposition (ALD) at low temperatures exhibit tunable drain current upon applying gate pulses, featuring analog, reversible, nonvolatile changes with respect to pulse amplitude, width, interval, and repetition number. However, the TFTs with HfOx and ZnO by ALD at high temperatures show negligible change. The structural and chemical analyses reveal similarities in defective nature of sputter‐deposited and low‐temperature ALD HfOx and ZnO layers, leading to analogous drain current modulation. Also, the results of temperature‐ and voltage polarity‐dependent drain current changes and capacitance changes verify that the drain current modulation is driven by oxygen ion migration associated with defective states of HfOx and ZnO layers. It demonstrates feasibility of application of ALD‐HfOx/ZnO TFTs to nonvolatile memory and artificial synapses using modulated gate stack properties.
Controllable p‐to‐n Type Conductance Transition in Top‐Gated Graphene Field Effect Transistor by Interface Trap Engineering
Authors: Peng Songang , Jin Zhi , Yao Yao , Huang Xinnan , Zhang Dayong , Niu Jiebin , Shi Jingyuan , Zhang Yanhui , Yu Guanghui
Published: August 2020

Modulating the electronic property of graphene by doping is essential for its device and circuit applications. Unfortunately, controllable p‐ and n‐type doping in top‐gated graphene field effect transistor (GFET) is reported. Here, the O3‐based atomic layer deposited Al2O3 layer as top gate dielectric is chosen. The epoxide functional group formed in the O3 process serves as effective interface trap sites. As the sweeping range of top gate voltage increases, the Dirac point position of GFET moves from positive voltage to negative voltage. The shift of the Dirac point voltage indicates the doping transition of graphene from p‐type to n‐type. The gate voltage dependent doping can be attributed to the charge exchange between graphene and interface trap sites. Furthermore, a trap‐dependent charge model is proposed to explain the transport mechanism in the doping process. This approach is promising to produce the complementary p‐ and n‐type top‐gated GFET for multiple applications.
Residency Leadership Lessons From the Epicenter of the COVID‐19 Surge
Authors: Rabin Elaine , Willis James , Alexander Dorian , Steinberg Eric , Chung Arlene , Kulkarni Miriam , He Chen , Parikh Saumil
Published: August 2020

Emergency medicine residency program directors (PDs) in areas hit hardest by the initial U.S. COVID‐19 pandemic surge faced novel and rapidly evolving organizational, educational, and resident wellness challenges. Despite variations in residency size, hospital setting, and patient population, PDs from eight residencies in “the epicenter” found uniformity in many of the lessons learned. Here we present those lessons and suggestions for high‐yield preparation for running a residency during a surge. Of particular importance were frequent, transparent communication and stepwise staffing plans. Illness of residents and other staff occurred early and were substantially reduced as personal protective equipment protocols tightened. Wellness was compromised by anxiety and illness, with varying timelines. New, rich educational opportunities emerged. All programs declared ACGME pandemic status but remained able to maintain some educational offerings. Planning ahead for future surges can significantly reduce the real‐time burden for residency leadership, which is particularly important as clinical demands on leadership may also increase with a surge.
Daratumumab‐lenalidomide‐dexamethasone vs standard‐of‐care regimens: Efficacy in transplant‐ineligible untreated myeloma
Authors: Durie Brian G. M. , Kumar Shaji K. , Usmani Saad Z. , Nonyane Bareng A. S. , Ammann Eric M. , Lam Annette , Kobos Rachel , Maiese Eric M. , Facon Thierry
Published: August 2020

Daratumumab in combination with lenalidomide‐dexamethasone (D‐Rd) recently received FDA approval for the treatment of transplant‐ineligible patients with newly diagnosed multiple myeloma (NDMM). The present PEGASUS study compared progression‐free survival (PFS) in patients treated with D‐Rd in the MAIA trial and patients treated with common standard‐of‐care regimens from the Flatiron Health electronic health record‐derived deidentified database, which has data from patients treated primarily at community‐based oncology practices in the United States. Individual‐level patient data from both data sources were used to perform an anchored indirect treatment comparison (ITC) of D‐Rd to bortezomib‐lenalidomide‐dexamethasone (VRd) and bortezomib‐dexamethasone (Vd); lenalidomide‐dexamethasone (Rd) was the common anchor for the ITC. Hazard ratios (HRs) reflecting direct comparisons of PFS within MAIA (D‐Rd vs Rd) and Flatiron Health (VRd vs Rd; Vd vs Rd) were used to make ITCs for D‐Rd vs VRd and Vd, respectively. After application of MAIA inclusion/exclusion criteria and propensity‐score weighting, the Flatiron Health patients resembled the MAIA trial population on measured baseline characteristics. Based on the direct comparison within MAIA, treatment with D‐Rd was associated with a significantly lower risk of progression or death compared to Rd (HR 0.54; 95% CI 0.42, 0.71). Based on the ITCs, D‐Rd was associated with a significantly lower risk of progression or death compared to VRd (HR 0.68; 95% CI 0.48, 0.98) and Vd (HR 0.48; 95% CI 0.33, 0.69). In the absence of head‐to‐head trials comparing D‐Rd to VRd or Vd, the present ITC may help inform treatment selection in transplant‐ineligible patients with NDMM.
Cutaneous B‐cell lymphomas: 2021 update on diagnosis, risk‐stratification, and management
Authors: Hristov Alexandra C. , Tejasvi Trilokraj , Wilcox Ryan A.
Published: August 2020

Disease Overview

Approximately one‐fourth of primary cutaneous lymphomas are B‐cell derived and are generally classified into three distinct subgroups: primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous marginal zone lymphoma (PCMZL), and primary cutaneous diffuse large B‐cell lymphoma, leg type (PCDLBCL, LT).

Diagnosis

Diagnosis and disease classification is based on histopathologic review and immunohistochemical staining of an appropriate skin biopsy. Pathologic review and an appropriate staging evaluation are necessary to distinguish primary cutaneous B‐cell lymphomas from systemic B‐cell lymphomas with secondary skin involvement.

Risk‐Stratification

Disease histopathology remains the most important prognostic determinant in primary cutaneous B‐cell lymphomas. Both PCFCL and PCMZL are indolent lymphomas that infrequently disseminate to extracutaneous sites and are associated with 5‐year survival rates that exceed 95%. In contrast, PCDLBCL, LT is an aggressive lymphoma with an inferior prognosis.

Risk‐Adapted Therapy

Both PCFCL and PCMZL patients with solitary or relatively few skin lesions may be effectively managed with local radiation therapy. While single‐agent rituximab may be employed for patients with more widespread skin involvement, multi‐agent chemotherapy is rarely appropriate. In contrast, management of patients with PCDLBCL, LT is comparable to the management of patients with systemic DLBCL.
The deregulation of NOTCH pathway, inflammatory cytokines, and keratinization genes in two Dowling–Degos disease patients with hidradenitis suppurativa
Authors: Cortez Cardoso Penha Ricardo , Cortez de Almeida Rita Fernanda , Câmara Mariz Juliana , Brewer Lisboa Lilian , do Nascimento Barbosa Lívia , Souto da Silva Roberto
Published: August 2020

Dowling–Degos disease (DDD) is a rare autosomal‐dominant genodermatosis and it has been associated with hidradenitis suppurativa (HS). Deregulation of NOTCH pathway has been linked to the development of HS in DDD context (DDD‐HS). However, molecular alterations in DDD‐HS, including altered gene expression of NOTCH and downstream effectors that are involved in the follicular differentiation and inflammatory response, are poorly defined. We report two cases of patients diagnosed with DDD‐HS, one of those, under Adalimumab treatment. Our results have shown downregulation of NOTCH1/NCSTN pathway, distinct molecular profiles of inflammatory cytokines (IL23A and TNF), and a novel aberrant upregulation of genes involved in the cornified envelope (CE) formation (SPRR1B, SPRR2D, SPRR3, and IVL) in paired HS lesions of two DDD patients.
Adult phenotype of the homozygous missense mutation c.655G>A, p.Gly219Arg in SLC13A5: A case report
Authors: Arvio Maria , Lähdetie Jaana
Published: August 2020

Homozygous recessive or compound heterozygous mutations in SLC13A5‐gene as a cause of Early Infantile Epileptic Encephalopathy subtype 25 (OMIM 615905) were published in 2014. Previous clinical reports describe young patients, aged <34 years. We describe 54‐ and 56‐year‐old siblings and show that the disorder linked to SLC13A5 is not just a pediatric problem but may affect the patient for decades resulting in profound intellectual disability, severe motor handicap, and abnormal electroencephalography without active epilepsy. Other diagnostic hints in adults are small size, spasticity and severe abrasion due to amelogenesis imperfecta of the hypoplastic type.
Genetic feedback for psychiatric conditions: Where are we now and where are we going
Authors: Driver Morgan N. , Kuo Sally I‐Chun , Dick Danielle M.
Published: August 2020

Genome‐wide association studies are rapidly advancing our understanding of the genetic architecture of complex disorders, including many psychiatric conditions such as major depression, schizophrenia, and substance use disorders. One common goal of genome‐wide association studies is to use findings for enhanced clinical prediction in the future, which can aid in identifying at‐risk individuals to enable more effective prevention screening and treatment strategies. In order to achieve this goal, we first need to gain a better understanding of the issues surrounding the return of complex genetic results. In this article, we summarize the current literature on: (a) genetic literacy in the general population, (b) the public's interest in receiving genetic test results for psychiatric conditions, (c) how individuals react to and interpret their genotypic information for specific psychiatric conditions, and (d) gaps in our knowledge that will be critical to address as we move toward returning genotypic information for psychiatric conditions in both research and clinical settings. By reviewing extant studies, we aim to increase awareness of the potential benefits and consequences of returning genotypic information for psychiatric conditions.
Insertion sites in manual proximal phalanges of African apes and modern humans
Authors: Bucchi Ana , Luengo Javier , Del Bove Antonietta , Lorenzo Carlos
Published: August 2020

Objectives

The primary aim of this study was to describe the insertion sites of the ligaments holding theflexor digitorum profundusandsuperficialismuscles (flexor ridges) in proximal phalanges 2–5 of African apes and modern humans. To interpret differences in flexor ridge size based on general behavioral differences among taxa.

Materials and methods

We analyzed 3D models of manual proximal phalanges 2–5 from 29 gorillas (Gorilla beringeiandGorilla gorilla), 30 chimpanzees (Pan troglodytes)and 36 recent modern humans. Flexor ridges (mm2) were compared within and across genera.

Results

Gorillas and chimpanzees had larger flexor ridges for phalanges 2–4 than humans and this difference subsists when controlling for body size. Each genus had a unique insertion size pattern across the digits, with the most heterogeneous pattern found in chimpanzees, followed by humans, and lastly gorillas. These patterns corresponded strongly to the differences in the size of the phalanges within each genus, except for phalanx 5 in humans, which had a larger flexor ridge than expected.

Discussion

When comparing these genera, the flexor ridges signal differences between taxa that use their hands for manipulation and locomotion (gorillas and chimpanzees) and taxa that use them exclusively for manipulation (humans). This functional signal was also apparent in the PP5 of humans, whose larger FR may be indicating the high recruitment of this digit during forceful precision grip characteristic of humans.
Exposure to interpersonal racism and avoidance behaviours reported by Aboriginal and Torres Strait Islander people with a disability
Authors: Temple Jeromey B. , Wong Heather , Ferdinand Angeline , Avery Scott , Paradies Yin , Kelaher Margaret
Published: August 2020

Using the National Aboriginal and Torres Strait Islander Social Survey, this paper examines exposure to interpersonal racism and avoidance reported by Aboriginal and Torres Strait Islander people with disabilities. We find that in 2014–2015, 32 per cent of people aged 15–64 without a disability experienced racism compared with 42 per cent of those with a disability. Half of those living with an intellectual or psychological disability reported racism, and about 20 per cent of those with any disability avoided settings such as healthcare, education or the general public due to past instances of racism, relative to 11 per cent of those without a disability. After adjusting for confounding factors and complex survey design, presence of a disability was associated with a 1.6–1.8 odds increase in exposure to racism, more frequent racist exposure and avoidance. Disability was further associated with an approximate doubling of the odds of reporting multi‐context avoidance and the likelihood of reporting both racism and avoidance in tandem. Severity of disability, higher numbers of disabling conditions and specific disability types were associated with increased odds of racism and avoidance. Independent of these effects, removal from one's natural family and identifying with homelands was strongly associated with racism and avoidance.
Does phenotypic expression of bitter taste receptor T2R38 show association with COVID‐19 severity?
Authors: Barham Henry P. , Taha Mohamed A. , Hall Christian A.
Published: August 2020

Background

Severe acute respiratory syndrome‒associated coronavirus‐2 (SARS‐CoV‐2) has been identified as the pathogen causing the outbreak of coronavirus disease‐2019 (COVID‐19) commencing in Wuhan, China, in December 2019. Multiple reports have shown subjective loss of taste and smell as an early and hallmark symptom for COVID‐19.

Methods

A retrospective study was performed in our clinical practice during July 2020 on patients positive for SARS‐CoV‐2 via polymerase chain reaction. All patients were categorized into 3 groups (supertasters, tasters, and nontasters) via taste sensitivity to phenylthiocarbamide, thiourea, and sodium benzoate with taste strip testing. The results of the taste strip tests were correlated with clinical course.

Results

A total of 100 patients (mean, 51 [range, 24‐82] years of age; 44 [44%] women) were assessed. We found that 21 of 100 (21%) were nontasters, 79 of 100 (79%) were tasters, and 0 of 100 (0%) were supertasters (p < 0.001). Twenty‐one of 21 (100%) (p < 0.001) of the patients requiring inpatient admission were classified as nontasters. All 79 (100%) (p < 0.001) of the patients who displayed mild to moderate symptoms not requiring admission were classified as tasters.

Conclusion

Our results show objective data that taste disturbance, specifically global loss of taste, appears to correlate with the clinical course specific to each individual, because 100% of the patients requiring inpatient admission were classified as nontasters.
Validation of chief complaints, medical history, medications, and physician diagnoses structured with an integrated emergency department information system in Japan: the Next Stage ER system
Authors: Goto Tadahiro , Hara Konan , Hashimoto Katsuhiko , Soeno Shoko , Shirakawa Toru , Sonoo Tomohiro , Nakamura Kensuke
Published: August 2020

Aim

Emergency department information systems (EDIS) facilitate free‐text data use for clinical research; however, no study has validated whether the Next Stage ER system (NSER), an EDIS used in Japan, accurately translates electronic medical records (EMRs) into structured data.

Methods

This is a retrospective cohort study using data from the emergency department (ED) of a tertiary care hospital from 2018 to 2019. We used EMRs of 500 random samples from 27,000 ED visits during the study period. Through the NSER system, chief complaints were translated into 231 chief complaint categories based on the Japan Triage and Acuity Scale. Medical history and physician’s diagnoses were encoded using the International Classification of Diseases, 10th Revision; medications were encoded as Anatomical Therapeutic Chemical Classification System codes. Two reviewers independently reviewed 20 items (e.g., presence of fever) for each study component (e.g., chief complaints). We calculated association measures of the structured data by the NSER system, using the chart review results as the gold standard.

Results

Sensitivities were very high (>90%) in 17 chief complaints. Positive predictive values were high for 14 chief complaints (≥80%). Negative predictive values were ≥96% for all chief complaints. For medical history and medications, most of the association measures were very high (>90%). For physicians’ ED diagnoses, sensitivities were very high (>93%) in 16 diagnoses; specificities and negative predictive values were very high (>97%).

Conclusions

Chief complaints, medical history, medications, and physician’s ED diagnoses in EMRs were well‐translated into existing categories or coding by the NSER system.