bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of the Chinese version non-nutritive sweetener FFQ with urinary biomarker in children and adolescents
Authors: Chu Ying-Yueh , Chen Yue-Hwa , Hsieh Rong-Hong , Hsia Shih-Min , Wu Hung-Tsung , Chen Yang-Ching 
Published: April 2022

AbstractObjective:The purpose of the current study was to develop a validated FFQ to evaluate the intake of non-nutritive sweeteners (NNS) in child and adolescent Asian populations.Design:Intensive and overall market research was performed to create the applicable NNS-FFQ with thirteen food categories and 305 items. Six intense sweeteners, including acesulfame potassium, aspartame, sucralose, glycyrrhizin, steviol glycosides and sorbitol, were investigated. The validity and reproducibility of the NNS-FFQ were evaluated. The validity was further assessed by examining the consistency of reported NNS intake compared with urinary biomarkers using Cohen’s κ analysis.Settings:This work was considered to be relevant in Asian societies.Participants:One hundred and two children and adolescents recruited from several clinics were invited to participate in the current study.Results:High content validity indices and high content validity ratio levels were revealed for each sweetener and food category. Reproducibility among subjects was satisfactory. Significant moderate correlations between estimated steviol glycoside/sucralose consumption and sensitive urinary biomarker levels were demonstrated (κ values were 0·59 and 0·45 for steviol glycosides and sucralose, respectively), indicating that the NNS-FFQ can be used to assess an individual’s NNS intake. The dietary intense sweetener consumption pattern evaluated in this measurement was similar to those observed in other Asian countries but differed from those observed in Western populations with respect to types and amounts of NNS.Conclusions:This validated NNS-FFQ can be an applicable and useful tool to evaluate NNS intake in future epidemiological and clinical studies.
REPRESENTING STRUCTURED SEMIGROUPS ON ÉTALE GROUPOID BUNDLES
Authors: BICE TRISTAN 
Published: April 2022

AbstractWe examine a semigroup analogue of the Kumjian–Renault representation of C*-algebras with Cartan subalgebras on twisted groupoids. Specifically, we represent semigroups with distinguished normal subsemigroups as ‘slice-sections’ of groupoid bundles.
The Challenge of Arctic Sea Ice Thickness Prediction by ECMWF on Subseasonal Time Scales
Authors: Xiu Yongwu , Luo Hao , Yang Qinghua , Tietsche Steffen , Day Jonathan , Chen Dake 
Published: April 2022

AbstractA recent study has provided the first thorough assessment of subseasonal Arctic sea ice edge prediction in operational forecast systems. However, the corresponding assessment of the Arctic sea ice thickness (SIT) is still lacking. Here, the Arctic SIT reforecasts from the European Centre for Medium‐Range Weather Forecasts (ECMWF) on subseasonal time scales are evaluated for the first time using a well‐developed SIT reanalysis data set. The results show that ECMWF forecasts of Arctic SIT are more skillful than persistence forecast (PFs) during the transition seasons for lead times longer than 30 days, indicating the advantages of dynamical prediction. However, ECMWF suffers from large initial SIT errors and has lower skill than a PF, especially from March to June. Thus, subseasonal Arctic SIT predictions still face many challenges, and improving the mean SIT in the model and assimilating satellite‐estimated SIT in the ocean analysis would significantly improve SIT forecasts.
W‐Band 76–81 GHz Millimeter‐Wave Comb‐Line Array for Automotive Short Range Radar
Authors: Ng Mou Kehn Malcolm , Rajo‐Iglesias Eva , Yang Tien‐Chen 
Published: April 2022

AbstractIn this paper, we design a W‐band millimeter‐wave antenna for the band of 76–81 GHz for frequency modulated continuous wave (FMCW) multiple input multiple output radar systems in automotive applications. It exhibits radiation patterns that possess narrow beamwidths with minimal beam squint in the elevation plane within the band for detection of vehicles and pedestrians in the forward direction instead of objects on the pavement and above the horizon, as well as a wide beamwidth in the horizontal plane, all as required by automotive radar antennas. A four‐port array of comb‐line antennas with diagonally tilted stubs is herein designed, the latter feature for mitigation of interruption from oncoming vehicles traveling along the opposite direction. In order to suppress the mutual interference between multiple antennas in the array, an electromagnetic band gap (EBG) structure is designed to enhance the isolation between ports. A prototype of the design was manufactured and tested, yielding results that satisfy the design requirements.
Brain integrity is altered by hepatic APOE ε4 in humanized-liver mice
Authors: Giannisis Andreas , Patra Kalicharan , Edlund Anna K. , Nieto Lur Agirrezabala , Benedicto-Gras Joan , Moussaud Simon , de la Rosa Andrés , Twohig Daniel , Bengtsson Tore , Fu Yuan , Bu Guojun , Bial Greg , Foquet Lander , Hammarstedt Christina , Strom Stephen , Kannisto Kristina , Raber Jacob , Ellis Ewa , Nielsen Henrietta M. 
Published: April 2022

AbstractLiver-generated plasma apolipoprotein E (apoE) does not enter the brain but nonetheless correlates with Alzheimer’s disease (AD) risk and AD biomarker levels. Carriers of APOEε4, the strongest genetic AD risk factor, exhibit lower plasma apoE and altered brain integrity already at mid-life versus non-APOEε4 carriers. Whether altered plasma liver-derived apoE or specifically an APOEε4 liver phenotype promotes neurodegeneration is unknown. Here we investigated the brains of Fah−/−, Rag2−/−, Il2rg−/− mice on the Non-Obese Diabetic (NOD) background (FRGN) with humanized-livers of an AD risk-associated APOE ε4/ε4 versus an APOE ε2/ε3 genotype. Reduced endogenous mouse apoE levels in the brains of APOE ε4/ε4 liver mice were accompanied by various changes in markers of synaptic integrity, neuroinflammation and insulin signaling. Plasma apoE4 levels were associated with unfavorable changes in several of the assessed markers. These results propose a previously unexplored role of the liver in the APOEε4-associated risk of neurodegenerative disease.
Sulfated alginate oligosaccharide exerts antitumor activity and autophagy induction by inactivating MEK1/ERK/mTOR signaling in a KSR1-dependent manner in osteosarcoma
Authors: Pan Zhen , Wei Xiao-juan , Li Shi-jie , Guo Hua , Li Zhao-hui , Zhang Ke-ke , Lyu Qian-qian , Liu Wei-zhi , Yang Qing-cheng , Cheng Dong-dong 
Published: April 2022

AbstractAlginate oligosaccharide (AOS) has the function to inhibit tumor progression and the sulfated modification can enhance the antitumor activity. To date, the function and mechanism of sulfated AOS (AOS-SO4) in tumors remain largely elusive. We prepared AOS by the enzymatic degradation of alginate, collected AOS-SO4by sulfating following the canonical procedure. Using these materials, in vitro assays showed that both AOS and AOS-SO4elicited antitumor effects in osteosarcoma cells. Sulfated modification significantly enhanced the antitumor activity. In addition, AOS-SO4had obvious effects on cell cycle arrest, apoptosis, and autophagy induction in vitro and in vivo. Mechanistically, we observed that AOS-SO4treatment triggered proapoptotic autophagy by inhibiting MEK1/ERK/mTOR signaling. The ERK activator reversed AOS-SO4-induced autophagy. More importantly, we found that KSR1 interacted with MEK1 and functioned as a positive regulator of MEK1 protein in osteosarcoma cells. High KSR1 expression was significantly associated with poor survival in osteosarcoma patients. Together, these results suggest that AOS-SO4has a better antitumor effect in osteosarcoma by inhibiting MEK1/ERK/mTOR signaling, which is KSR1-dependent; thus, AOS-SO4can be a new potential therapeutic candidate for the treatment of osteosarcoma.
Identifying a confused cell identity for esophageal squamous cell carcinoma
Authors: Pan Xiangyu , Wang Jian , Guo Linjie , Na Feifei , Du Jiajia , Chen Xuelan , Zhong Ailing , Zhao Lei , Zhang Lu , Zhang Mengsha , Wan Xudong , Wang Manli , Liu Hongyu , Dai Siqi , Tan Ping , Chen Jingyao , Liu Yu , Hu Bing , Chen Chong 
Published: April 2022

AbstractThe cell identity of malignant cells and how they acquire it are fundamental for our understanding of cancer. Here, we report that esophageal squamous cell carcinoma (ESCC) cells display molecular features equally similar but distinct to all three types of normal esophageal epithelial cells, which we term as confused cell identity (CCI). CCI is an independent prognostic marker associated with poor prognosis in ESCC. Further, we identify tropomyosin 4 (TPM4) as a critical CCI gene that promotes the aggressiveness of ESCC in vitro and in vivo. And TPM4 creates CCI through activating the Jak/STAT-SOX2 pathway. Thus, our study suggests an unrecognized feature of ESCC cells, which might be of value for clinic prognosis and potential interference.
Targeting non-coding RNAs to overcome cancer therapy resistance
Authors: Chen BaoQing , Dragomir Mihnea P. , Yang Chen , Li Qiaoqiao , Horst David , Calin George A. 
Published: April 2022

AbstractIt is now well known that non-coding RNAs (ncRNAs), rather than protein-coding transcripts, are the preponderant RNA transcripts. NcRNAs, particularly microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are widely appreciated as pervasive regulators of multiple cancer hallmarks such as proliferation, apoptosis, invasion, metastasis, and genomic instability. Despite recent discoveries in cancer therapy, resistance to chemotherapy, radiotherapy, targeted therapy, and immunotherapy continue to be a major setback. Recent studies have shown that ncRNAs also play a major role in resistance to different cancer therapies by rewiring essential signaling pathways. In this review, we present the intricate mechanisms through which dysregulated ncRNAs control resistance to the four major types of cancer therapies. We will focus on the current clinical implications of ncRNAs as biomarkers to predict treatment response (intrinsic resistance) and to detect resistance to therapy after the start of treatment (acquired resistance). Furthermore, we will present the potential of targeting ncRNA to overcome cancer treatment resistance, and we will discuss the challenges of ncRNA-targeted therapy—especially the development of delivery systems.
Structural neuroimaging measures and lifetime depression across levels of phenotyping in UK biobank
Authors: Harris Mathew A. , Cox Simon R. , de Nooij Laura , Barbu Miruna C. , Adams Mark J. , Shen Xueyi , Deary Ian J. , Lawrie Stephen M. , McIntosh Andrew M. , Whalley Heather C. 
Published: April 2022

AbstractDepression is assessed in various ways in research, with large population studies often relying on minimal phenotyping. Genetic results suggest clinical diagnoses and self-report measures of depression show some core similarities, but also important differences. It is not yet clear how neuroimaging associations depend on levels of phenotyping. We studied 39,300 UK Biobank imaging participants (20,701 female; aged 44.6 to 82.3 years, M = 64.1, SD = 7.5) with structural neuroimaging and lifetime depression data. Past depression phenotypes included a single-item self-report measure, an intermediate measure of ‘probable’ lifetime depression, derived from multiple questionnaire items relevant to a history of depression, and a retrospective clinical diagnosis according to DSM-IV criteria. We tested (i) associations between brain structural measures and each depression phenotype, and (ii) effects of phenotype on these associations. Depression-brain structure associations were small (β < 0.1) for all phenotypes, but still significant after FDR correction for many regional metrics. Lifetime depression was consistently associated with reduced white matter integrity across phenotypes. Cortical thickness showed negative associations with Self-reported Depression in particular. Phenotype effects were small across most metrics, but significant for cortical thickness in most regions. We report consistent effects of lifetime depression in brain structural measures, including reduced integrity of thalamic radiations and association fibres. We also observed significant differences in associations with cortical thickness across depression phenotypes. Although these results did not relate to level of phenotyping as expected, effects of phenotype definition are still an important consideration for future depression research.
Serum-derived extracellular vesicles facilitate temozolomide resistance in glioblastoma through a HOTAIR-dependent mechanism
Authors: Wang Xiaosong , Yu Xiaojun , Xu Haoran , Wei Kang , Wang Shanxi , Wang Yingguang , Han Junfei 
Published: April 2022

AbstractExtracellular vesicle (EV)-mediated transfer of long non-coding RNAs (lncRNAs) has been reported to regulate chemoresistance in various cancers. We herein investigate the therapeutic potential of bioinformatically identified HOTAIR transferred by serum-derived EVs (serum-EVs) in temozolomide (TMZ) resistance of glioblastoma (GBM) and the downstream mechanisms. EVs were isolated from the serum of GBM patients. Expression of HOTAIR was examined in the clinical tissue samples and serum-EVs of GBM patients. The downstream miRNAs of HOTAIR and its target genes were predicted in silico. The effects of the HOTAIR transmitted by serum-EVs in malignant phenotypes, tumor growth, and TMZ resistance were assessed in vitro and in vivo. HOTAIR expression was upregulated in clinical tissues, cells, and serum-EVs of GBM. Co-culture data showed that GBM-serum-EVs facilitated GBM cell proliferative and invasive phenotypes and TMZ resistance by elevating HOTAIR. In GBM cells, HOTAIR competitively bound to miR-526b-3p and weakened miR-526b-3p’s binding ability to EVA1, thus increasing the expression of EVA1. Furthermore, HOTAIR carried by serum-EVs promoted tumor growth and TMZ resistance in vivo by suppressing miR-526b-3p-mediated EVA1 inhibition. GBM-serum-EV-enclosed HOTAIR may augment GBM progression and chemoresistance through miR-526b-3p downregulation and EVA1 upregulation. These results provide a strategy to reduce TMZ resistance in GBM treatment.
Generation of resolving memory neutrophils through pharmacological training with 4-PBA or genetic deletion of TRAM
Authors: Lin RuiCi , Yi Ziyue , Wang Jing , Geng Shuo , Li Liwu 
Published: April 2022

AbstractNeutrophils are the dominant leukocytes in circulation and the first responders to infection and inflammatory cues. While the roles of neutrophils in driving inflammation have been widely recognized, the contribution of neutrophils in facilitating inflammation resolution is under-studied. Here, through single-cell RNA sequencing analysis, we identified a subpopulation of neutrophils exhibiting pro-resolving characteristics with greater Cd200r and Cd86 expression at the resting state. We further discovered that 4-PBA, a peroxisomal stress-reducing agent, can potently train neutrophils into the resolving state with enhanced expression of CD200R, CD86, as well as soluble pro-resolving mediators Resolvin D1 and SerpinB1. Resolving neutrophils trained by 4-PBA manifest enhanced phagocytosis and bacterial-killing functions. Mechanistically, the generation of resolving neutrophils is mediated by the PPARγ/LMO4/STAT3 signaling circuit modulated by TLR4 adaptor molecule TRAM. We further demonstrated that genetic deletion of TRAM renders the constitutive expansion of resolving neutrophils, with an enhanced signaling circuitry of PPARγ/LMO4/STAT3. These findings may have profound implications for the effective training of resolving neutrophils with therapeutic potential in the treatment of both acute infection as well as chronic inflammatory diseases.
Structure of the active pharmaceutical ingredient bismuth subsalicylate
Authors: Svensson Grape Erik , Rooth Victoria , Nero Mathias , Willhammar Tom , Inge A. Ken 
Published: April 2022

AbstractStructure determination of pharmaceutical compounds is invaluable for drug development but remains challenging for those that form as small crystals with defects. Bismuth subsalicylate, among the most commercially significant bismuth compounds, is an active ingredient in over-the-counter medications such as Pepto-Bismol, used to treat dyspepsia and H. pylori infections. Despite its century-long history, the structure of bismuth subsalicylate is still under debate. Here we show that advanced electron microscopy techniques, namely three-dimensional electron diffraction and scanning transmission electron microscopy, can give insight into the structure of active pharmaceutical ingredients that are difficult to characterize using conventional methods due to their small size or intricate structural features. Hierarchical clustering analysis of three-dimensional electron diffraction data from ordered crystals of bismuth subsalicylate revealed a layered structure. A detailed investigation using high-resolution scanning transmission electron microscopy showed variations in the stacking of layers, the presence of which has likely hindered structure solution by other means. Together, these modern electron crystallography techniques provide a toolbox for structure determination of active pharmaceutical ingredients and drug discovery, demonstrated by this study of bismuth subsalicylate.
Protection following BNT162b2 booster in adolescents substantially exceeds that of a fresh 2-dose vaccine
Authors: Amir Ofra , Goldberg Yair , Mandel Micha , Bar-On Yinon M. , Bodenheimer Omri , Ash Nachman , Alroy-Preis Sharon , Huppert Amit , Milo Ron 
Published: April 2022

AbstractIsrael began administering a BNT162b2 booster dose to restore protection following the waning of the 2-dose vaccine. Biological studies have shown that a “fresh” booster dose leads to increased antibody levels compared to a fresh 2-dose vaccine, which may suggest increased effectiveness. To compare the real-world effectiveness of a fresh (up to 60 days) booster dose with that of a fresh 2-dose vaccine, we took advantage of a quasi-experimental study that compares populations that were eligible to receive the vaccine at different times due to age-dependent policies. Specifically, we compared the confirmed infection rates in adolescents aged 12–14 (215,653 individuals) who received the 2-dose vaccine and in adolescents aged 16–18 (103,454 individuals) who received the booster dose. Our analysis shows that the confirmed infection rate was lower by a factor of 3.7 (95% CI: 2.7 to 5.2) in the booster group.
The nuclear receptor ERR cooperates with the cardiogenic factor GATA4 to orchestrate cardiomyocyte maturation
Authors: Sakamoto Tomoya , Batmanov Kirill , Wan Shibiao , Guo Yuanjun , Lai Ling , Vega Rick B. , Kelly Daniel P. 
Published: April 2022

AbstractEstrogen-related receptors (ERR) α and γ were shown recently to serve as regulators of cardiac maturation, yet the underlying mechanisms have not been delineated. Herein, we find that ERR signaling is necessary for induction of genes involved in mitochondrial and cardiac-specific contractile processes during human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) differentiation. Genomic interrogation studies demonstrate that ERRγ occupies many cardiomyocyte enhancers/super-enhancers, often co-localizing with the cardiogenic factor GATA4. ERRγ interacts with GATA4 to cooperatively activate transcription of targets involved in cardiomyocyte-specific processes such as contractile function, whereas ERRγ-mediated control of metabolic genes occurs independent of GATA4. Both mechanisms require the transcriptional coregulator PGC-1α. A disease-causing GATA4 mutation is shown to diminish PGC-1α/ERR/GATA4 cooperativity and expression of ERR target genes are downregulated in human heart failure samples suggesting that dysregulation of this circuitry may contribute to congenital and acquired forms of heart failure.
Super-resolving microscopy images of Li-ion electrodes for fine-feature quantification using generative adversarial networks
Authors: Furat Orkun , Finegan Donal P. , Yang Zhenzhen , Kirstein Tom , Smith Kandler , Schmidt Volker 
Published: April 2022

AbstractFor a deeper understanding of the functional behavior of energy materials, it is necessary to investigate their microstructure, e.g., via imaging techniques like scanning electron microscopy (SEM). However, active materials are often heterogeneous, necessitating quantification of features over large volumes to achieve representativity which often requires reduced resolution for large fields of view. Cracks within Li-ion electrode particles are an example of fine features, representative quantification of which requires large volumes of tens of particles. To overcome the trade-off between the imaged volume of the material and the resolution achieved, we deploy generative adversarial networks (GAN), namely SRGANs, to super-resolve SEM images of cracked cathode materials. A quantitative analysis indicates that SRGANs outperform various other networks for crack detection within aged cathode particles. This makes GANs viable for performing super-resolution on microscopy images for mitigating the trade-off between resolution and field of view, thus enabling representative quantification of fine features.
A compact polymer–inorganic hybrid gas barrier nanolayer for flexible organic light-emitting diode displays
Authors: Kim Seung Hun , Song Seung Yong , Kim Soo Youn , Chang Moon Won , Kwon Hyo Jeong , Yoon Kwan Hyuck , Sung Woo Yong , Sung Myung Mo , Chu Hye Yong 
Published: April 2022

AbstractAtomic layer infiltration technology allows the formation of a nanometer-thick polymer-inorganic hybrid barrier layer in polymer material for flexible organic light-emitting diode (OLED) displays. In this study, according to transmission electron microscopy and secondary-ion mass spectrometry analysis results under various process conditions, a compact polymer-inorganic hybrid nanolayer was successfully formed in a polymer and good barrier performance was revealed with a low water vapor transmission rate under optimal process conditions. Additionally, through gas chromatography-mass spectrometry measurements after ultra-violet radiation testing, polymer out-gassing decreased compared to bare polymers. Based on barrier properties, the polymer with a polymer-inorganic hybrid barrier nanolayer was applied to a flexible OLED display as a substrate. During storage tests and folding tests, the flexible OLED display exhibits good reliability and better flexibility compared to those with an inorganic barrier layer. These results confirm that the polymer-inorganic hybrid nanolayer is suitable for barrier layer formation in flexible OLED displays.