bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneity among tumors with acquired resistance to EGFR tyrosine kinase inhibitors harboring EGFR‐T790M mutation in non‐small cell lung cancer cells
Authors: Katayama Yuki , Yamada Tadaaki , Tokuda Shinsaku , Okura Naoko , Nishioka Naoya , Morimoto Kenji , Tanimura Keiko , Morimoto Yoshie , Iwasaku Masahiro , Horinaka Mano , Sakai Toshiyuki , Kita Kenji , Yano Seiji , Takayama Koichi 
Published: January 2022

AbstractEGFR‐T790M mutation is a major mechanism underlying acquired resistance to first‐ and second‐generation EGFR tyrosine kinase inhibitors (EGFR‐TKIs) in lung cancer with mutated EGFR. However, differences in the biological characteristics of T790M tumors based on treatment regimens with each generation of EGFR‐TKI are not fully understood. We established cell lines with acquired resistance harboring EGFR‐T790M mutation derived from xenograft tumors treated with each generation of EGFR‐TKI and examined their biological characteristics with respect to third‐generation EGFR‐TKI osimertinib sensitivity. Second‐generation EGFR‐TKI dacomitinib‐resistant cells with T790M‐exhibited higher sensitivity to osimertinib than first‐generation EGFR‐TKI gefitinib‐resistant cells with T790M via inhibition of AKT and ERK signaling and promotion of apoptosis. Furthermore, gefitinib‐resistant cells showed enhanced intratumor heterogeneity accompanied by genomic instability and activation of alternative resistance mechanisms compared with dacomitinib‐resistant cells; this suggests that the maintenance of EGFR dependency after acquiring resistance might depend on the type of EGFR‐TKI. Our results demonstrate that the progression of tumor heterogeneity via both genetic and non‐genetic mechanisms might affect osimertinib sensitivity in tumors with acquired resistance harboring EGFR‐T790M mutation.
Pre‐diagnostic levels of sVEGFR2, sTNFR2, sIL‐2Rα and sIL‐6R are associated with glioma risk: A nested case–control study of repeated samples
Authors: Wu Wendy Yi‐Ying , Späth Florentin , Wibom Carl , Björkblom Benny , Dahlin Anna M. , Melin Beatrice 
Published: January 2022

AbstractNo strong aetiological factors have been established for glioma aside from genetic mutations and variants, ionising radiation and an inverse relationship with asthmas and allergies. Our aim was to investigate the association between pre‐diagnostic immune protein levels and glioma risk. We conducted a case–control study nested in the Northern Sweden Health and Disease Study cohort. We analysed 133 glioma cases and 133 control subjects matched by age, sex and date of blood donation. ELISA or Luminex bead‐based multiplex assays were used to measure plasma levels of 19 proteins. Conditional logistic regression models were used to estimate the odds ratios and 95% CIs. To further model the protein trajectories over time, the linear mixed‐effects models were conducted. We found that the levels of sVEGFR2, sTNFR2, sIL‐2Rα and sIL‐6R were associated with glioma risk. After adjusting for the time between blood sample collection and glioma diagnosis, the odds ratios were 1.72 (95% CI = 1.01–2.93), 1.48 (95% CI = 1.01–2.16) and 1.90 (95% CI = 1.14–3.17) for sTNFR2, sIL‐2Rα and sIL‐6R, respectively. The trajectory of sVEGFR2 concentrations over time was different between cases and controls (p‐value = 0.031), increasing for cases (0.8% per year) and constant for controls. Our findings suggest these proteins play important roles in gliomagenesis.
Ultrawide Range and High‐precision Temperature Monitoring based on NiO/Polyimide Hybrid Nanomaterials
Authors: Wu Sicheng , Yu Jiajie , Zhang Ke , Yang Jie , Zhang Shuai , Xing Jian , Liu Changbo , Deng Yuan 
Published: January 2022

AbstractThe need for temperature observation appears in all aspects of our lives. With the development of science and technology, higher requirements are put forward for the combination of high‐accuracy and wide detection range of the sensor. In this study, a facile strategy method was developed to prepare a NiO slurry and realize a wide‐range and high‐precision thermistor based on NiO. By dispersing NiO nanoparticles in polyimide (PI) to afford the NiO slurry, a thermistor was obtained by spin coating, thermal curing, and electrode preparation, which can operate in a very wide range from 220 K to 470 K, as well as exhibited an outstanding thermal sensitivity (B) with a value exceeding 5400 K. Moreover, the sensor shows very high detection accuracy and can detect small temperature differences up to 0.05 K. Notably, through brushing the mixture onto the PI substrate or peeling off from the substrate, a flexible, or free‐stand sensor was obtained, which displayed great mechanical properties and stabilities. This allows the sensor to be used on various curved surfaces and other objects with complex shapes, which greatly increases potential applications and the scope of the temperature sensor.
Analytic performance model for parallel overlapping memory‐bound kernels
Authors: Afzal Ayesha , Hager Georg , Wellein Gerhard 
Published: January 2022

AbstractComplex applications running on multicore processors show a rich performance phenomenology. The growing number of cores per ccNUMA domain complicates performance analysis of memory‐bound code since system noise, load imbalance, or task‐based programming models can lead to thread desynchronization. Hence, the simplifying assumption that all cores execute the same loop can not be upheld. Motivated by observations on plain and modified versions of the HPCG benchmark, we construct a performance model of execution of memory‐bound loop kernels. It can predict the memory bandwidth share per kernel on a memory contention domain depending on the number of active cores and which other workload the kernel is paired with. The only code features required are the single‐thread memory request fraction per kernel, which is directly related to the single‐thread memory bandwidth, and its saturated bandwidth. The former can either be measured directly or predicted using the Execution‐Cache‐Memory performance model. The computational intensity of the kernels and the detailed structure of the code is of no significance. We validate our model on Intel Broadwell, Intel Cascade Lake, and AMD Rome processors pairing various streaming and stencil kernels. The error in predicting the bandwidth share per kernel is less than 8%.
Isolation of Transcriptomic‐Quality Total RNA from Mouse Spinal Cords
Authors: Stokes John V. , Nicaise Ashleigh J. , Frodella Christa M. , Varela‐Stokes Andrea S. , Thompson Tom , Kaplan Barbara L. F. 
Published: January 2022

AbstractAssessing cells, proteins, and total RNA in the spinal cord is vital for advancing our understanding of neuroinflammation and neurodegenerative diseases. For instance, immune cells infiltrate the spinal cord in the experimental autoimmune encephalomyelitis (EAE) model, commonly used to study multiple sclerosis. Thus, it is valuable to assess total RNA to determine the neuronal and inflammatory profiles in the spinal cord. Further, RNA profiles are useful for deciphering the effects of drugs or chemicals on neuroinflammation and neurodegenerative diseases such as EAE. The purpose of this protocol and the online video illustrating it is to describe and demonstrate the expulsion of the spinal cord from the mouse spinal column and homogenization of the spinal cord using liquid nitrogen for optimal RNA isolation. Although we present this method with spinal cords from EAE mice, the technique is broadly applicable, including RNA isolation from the spinal cords of healthy mice. Proper performance of these steps is critical to achieving a sufficient yield of transcriptomic‐quality spinal cord RNA when combined with final isolation using commercially available kits. © 2022 Wiley Periodicals LLC.Basic Protocol 1: Isolation of the spinal cord from the spinal columnSupport Protocol: Preparation of blunt‐end needle for spinal cord isolationBasic Protocol 2: Spinal cord homogenization using liquid nitrogenBasic Protocol 3: Assessment of RNA purity, quantification, and integrity
High lysine and high protein‐containing salinity‐tolerant rice grains (Oryza sativa cv IR64)
Authors: Mishra Manjari , Rathore Ray Singh , Singla‐Pareek Sneh L , Pareek Ashwani 
Published: January 2022

AbstractLysine cannot be synthesized by the human body, and it is, therefore, an indispensable amino acid in the human that must be consumed in adequate amounts to prevent disease. Unfortunately, lysine is not abundant in many important food sources such as rice grains. Efforts to fortify rice and other monocotyledonous crops with high lysine have proved to be challenging because of their effects on plant growth. The present study was designed to avoid the problems that are often encountered in engineering lysine metabolism. We generated different over‐expression constructs for the key anabolic enzyme, dihydrodipicolinate synthase (DHDPS and cdapA) and knockdown (KD) constructs for the catabolic enzyme—lysine ketoglutarate reductase/saccharopine dehydrogenase (LKR/SDH), with expression under the control of either the CaMV35S promoter or the endosperm‐specific glutelinD1 promoter. The use of the endosperm‐specific promoter together with the lysine feedback‐insensitive cdapA for over‐expression provides distinct advantages, as does silencing of LKR/SDH under the control of this promoter. Rice plants produced by over‐expressing cdapA together with silencing of LKR/SDH showed a 58% increase in grain lysine content, as well as higher amounts of total seed protein levels. Moreover, the transgenic seedlings were more tolerant to salinity. These results demonstrate that it is possible to generate high lysine stress‐tolerant rice varieties, which have the potential to reduce the need for dietary supplementation.
Omega‐3 polyunsaturated fatty acid encapsulation system: Physical and oxidative stability, and medical applications
Authors: Du Qiwei , Zhou Linhui , Li Minghui , Lyu Fei , Liu Jianhua , Ding Yuting 
Published: January 2022

AbstractThe benefits of omega‐3 (ω‐3) polyunsaturated fatty acids (PUFAs) to human health and the therapeutic properties of diseases have been widely identified. However, due to abundant double bonds, they are sensitive to environmental conditions which cause oxidative deterioration. This is one of the main factors limiting their application. The encapsulation of ω‐3 PUFAs is an effective way to improve their oxidation stability. This review summarizes the recent advances in different forms of ω‐3 encapsulation systems, such as emulsions, liposomes, microcapsules, and liquid crystalline. Particular emphasis is given to the effects of food‐derived biopolymers wall materials (proteins, polysaccharides, and esters) on encapsulation efficiency and oxidation stability of ω‐3 PUFAs encapsulation systems. In addition, the effects of natural antioxidants (polyphenols, carotenoids, flavonoids, plant essential oils, etc.) on the antioxidant enhancement of ω‐3 PUFAs encapsulation system based on food‐derived biopolymers are discussed. Different forms of ω‐3 PUFAs encapsulation systems have been proven to be used as supplements in the medical field. The regulation and improvement of the ω‐3 PUFAs encapsulation system on the diseases of animal and human, which are related to central nervous system, retina, lung, kidney and tissue cell, are systematically discussed.
Pricing vulnerable options under correlated skew Brownian motions
Authors: Guo Che , Wang Xingchun 
Published: January 2022

AbstractIn this paper, we consider vulnerable options in a pricing model with correlated skew Brownian motions. In the proposed pricing model, both the underlying asset and option issuer's assets are exposed to endogenous and exogenous risks. We deduct a new pricing formula of vulnerable European options, and then use it to illustrate the effect of the skewness parameters on vulnerable option prices. An interesting finding is that vulnerable option prices are higher when the variance of the logarithm of option issuer's assets is larger in some cases.
The digital transformation of hepatology: The patient is logged in
Authors: Wu Tiffany , Simonetto Douglas A. , Halamka John D. , Shah Vijay H. 
Published: January 2022

Abstract
The rise in innovative digital health technologies has led a paradigm shift in health care toward personalized, patient‐centric medicine that is reaching beyond traditional brick‐and‐mortar facilities into patients’ homes and everyday lives. Digital solutions can monitor and detect early changes in physiological data, predict disease progression and health‐related outcomes based on individual risk factors, and manage disease intervention with a range of accessible telemedicine and mobile health options. In this review, we discuss the unique transformation underway in the care of patients with liver disease, specifically examining the digital transformation of diagnostics, prediction and clinical decision‐making, and management. Additionally, we discuss the general considerations needed to confirm validity and oversight of new technologies, usability and acceptability of digital solutions, and equity and inclusivity of vulnerable populations.
Fetal alcohol spectrum disorder resources for educators: A scoping review
Authors: Lees Briana , Riches Julia , Mewton Louise , Elliott Elizabeth J. , Allsop Steve , Newton Nicola , Thomas Sue , Rice Lauren J. , Nepal Smriti , Teesson Maree , Stapinski Lexine A. 
Published: January 2022

AbstractChildren with foetal alcohol spectrum disorder (FASD) can experience neurodevelopmental, physical, psychological and behavioural impairments that can result in a disrupted school experience. However, educators often have limited knowledge or experience in the identification and support of students with FASD, and there is a critical need for effective tools and resources to ensure students with FASD are supported in their ongoing learning and development. This scoping review aimed to identify and evaluate publicly available educator resources that aid in the identification, and support of students with FASD in primary/elementary school. In addition, educators and FASD experts were consulted to obtain feedback on currently available resources, and key issues and priorities for FASD resources. In total, 124 resources were identified by searching peer‐reviewed and grey literature databases, app stores, podcast services and contacting FASD experts. Information was found on identification (23 resources) and support of students with FASD (119 resources). No resources provided information on the referral. Most resources were average (40%) to good (33%) quality, as measured by a composite tool based on adaptions of the NHMRC FORM Framework and iCAHE Guideline Quality Checklist. A minority of resources had been formally evaluated (7%). Review findings and consultations with experts and educators indicate a critical need for referral guides, evidence‐based short‐format resources and centralised access for school communities to high‐quality resources. Taken together, this study has identified key areas for future resource development and research to better support primary school students with FASD.
Significance of the lncRNAs MALAT1 and ANRIL in occurrence and development of glaucoma
Authors: Huang Guoqiang , Liang Dong , Luo Lidan , Lan Chenghong , Luo Chengfeng , Xu Hongwang , Lai Jiangfeng 
Published: January 2022

AbstractBackgroundPrimary open‐angle glaucoma (POAG) is the commonest form of glaucoma which is estimated to cause bilaterally blind within 11.1 million people by 2020. Therefore, the primary objectives of this study were to investigate the clinical significance of single‐nucleotide polymorphisms (SNPs) in the lncRNAs MALAT1 and ANRIL in a Chinese Han POAG cohort.MethodsThree hundred and forty‐six glaucoma patients and 263 healthy controls were recruited, and totally 14 SNPs in MALAT1 and ANRIL were genotyped between the two populations.ResultsThe MALAT1 SNPs rs619586 (A>G), rs3200401 (C>T), and rs664589 (C>G) were associated with POAG risk, and the ANRIL SNPs rs2383207 (A>G), rs564398 (A>G), rs2157719 (A>G), rs7865618 (G>A), and rs4977574 (A>G) were associated with POAG (p < 0.05). The MALAT1 haplotypes ACG and ATC, comprised rs619586, rs3200401, and rs664589, increased POAG risk, and the ANRIL haplotype AAGAA, made up of rs2383207, rs7865618, rs4977574, rs564398, and rs2157719, show a significantly increased risk of POAG. In addition, rs619586 (A>G) of MALAT1 and rs564398/rs2157719 of ANRIL were associated with a smaller vertical cup‐to‐disc ratio, while rs619586 of MALAT1 and rs2383207/rs4977574 of ANRIL were associated with higher intraocular pressure in the POAG population.ConclusionSingle‐nucleotide polymorphisms and haplotypes in ANRIL and MALAT1 were associated with POAG onset in our study population, which provide more possibilities to POAG diagnosis and treatment.
Immunomodulatory potential of natural products from herbal medicines as immune checkpoints inhibitors: Helping to fight against cancer via multiple targets
Authors: Zhong Zhangfeng , Vong Chi Teng , Chen Feiyu , Tan Horyue , Zhang Cheng , Wang Ning , Cui Liao , Wang Yitao , Feng Yibin 
Published: January 2022

AbstractImmunotherapy sheds new light to cancer treatment and is satisfied by cancer patients. However, immunotoxicity, single‐source antibodies, and single‐targeting stratege are potential challenges to the success of cancer immunotherapy. A huge number of promising lead compounds for cancer treatment are of natural origin from herbal medicines. The application of natural products from herbal medicines that have immunomodulatory properties could alter the landscape of immunotherapy drastically. The present study summarizes current medication for cancer immunotherapy and discusses the potential chemicals from herbal medicines as immune checkpoint inhibitors that have a broad range of immunomodulatory effects. Therefore, this review provides valuable insights into the efficacy and mechanism of actions of cancer immunotherapies, including natural products and combined treatment with immune checkpoint inhibitors, which could confer an improved clinical outcome for cancer treatment.
Chinese nurses' self‐expression media image during COVID‐19 pandemic: A qualitative media image analysis
Authors: Cao Huili , Chen Yangjie , He Xingyue , Song Yejun , Wang Qiaohong , Yang Hui 
Published: January 2022

AbstractAimTo explore and describe nurses' self‐expression media image during COVID‐19 pandemic in China.BackgroundNurses play an important role in COVID‐19 pandemic. Although nurses were widely reported by the media, which included praise for nurses and nursing work, the researches on how nurses expressed their self‐images were limited.DesignQualitative media analysis.MethodsQualitative media analysis was conducted from January to April 2020, the researchers collected images and texts of 16 Chinese nurses who take care of COVID‐19 patients. These images and texts were published on WeChat Moments by themselves. After analysed each image and text, researchers identified the denotative and connotative elements in each image and summarized each image in narrative way.FindingsThis study analysed 219 pictures and 15 short videos of 16 nurses' self‐expression in WeChat moments. In this study, the media image self‐expression of nurses were mostly positive. The images expressed by nurses in this study included care image; hero image; soldier image; female image; hope image and team image. Nurses rarely showed negative images in the media; The negative nurses image were expressed in hidden way, which included exhausted nurses image and fragile nurses image. Moreover, the nurse self‐expression media image emphasized the nursing professionalism, but less showed the nursing connotation.ConclusionsThe positive media image self‐expression of nurses should be encouraged. Nurse Managers should pay attention to the deficiency of nursing image expression and guide nurses to show the essence and connotation of nursing.
Probing protein nanopores with poly(ethylene glycol)s
Authors: Liu Wenxing , Nestorovich Ekaterina M. 
Published: January 2022

AbstractNeutral water‐soluble poly(ethylene glycol)s (PEGs) have been extensively explored in protein nanopore research for the past several decades. The principal use of PEGs is to investigate the membrane protein ion channel physical characteristics and transport properties. In addition, protein nanopores are used to study polymer–protein interactions and polymer physicochemical properties. In this review, we focus on the biophysical studies on probing protein ion channels with PEGs, specifically on nanopore sizing by PEG partitioning. We discuss the fluctuation analysis of ion channel currents in response to the PEGs moving within their confined geometries. The advantages, limitations, and recent developments of the approach are also addressed.
Tools and techniques for solution‐phase structural understanding of SmI2–additive complexes
Authors: Maity Sandeepan 
Published: January 2022

AbstractSmI2 is a versatile reducing agent for organic synthesis. Additive‐induced tailoring of reaction mechanisms and products is one of the most promising aspects of this multifaceted reagent. In most instances, additives form a coordination complex with SmI2. Insight on the solution‐phase structure of SmI2 in the presence of additives is significant to decipher possible reaction mechanisms and predict reactivity of SmI2 in the presence of an entirely new additive. A series of experimental and computational tools are used to unravel the solution‐phase structure of SmI2–additive complex. This review aims to provide a comprehensive overview of how different analytic tools are employed, and data are analyzed to arrive at a possible solution‐phase structure of SmI2–additive complex. Understanding of SmI2–additive solution‐phase structure in predicting SmI2 reactivity and plausible reaction mechanism is also discussed.
Quantitative systems pharmacology model for Alzheimer’s disease to predict the effect of aducanumab on brain amyloid
Authors: Lin Lin , Hua Fei , Salinas Cristian , Young Carissa , Bussiere Thierry , Apgar Joshua F. , Burke John M. , Kandadi Muralidharan Kumar , Rajagovindan Rajasimhan , Nestorov Ivan 
Published: January 2022

AbstractAlzheimer's disease (AD) is an irreversible, progressive brain disorder that impairs memory and cognitive function. Dysregulation of the amyloid‐β (Aβ) pathway and amyloid plaque accumulation in the brain are hallmarks of AD. Aducanumab is a human, immunoglobulin gamma 1 monoclonal antibody targeting aggregated forms of Aβ. In phase Ib and phase III studies, aducanumab reduced Aβ plaques in a dose dependent manner, as measured by standard uptake value ratio of amyloid positron emission tomography imaging. The goal of this work was to develop a quantitative systems pharmacology model describing the production, aggregation, clearance, and transport of Aβ as well as the mechanism of action for the drug to understand the relationship between aducanumab dosing regimens and changes of different Aβ species, particularly plaques in the brain. The model was used to better understand the pharmacodynamic effects observed in the clinical trials of aducanumab and assist in the clinical development of future Aβ therapies.