bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative omics analyses of NCOA4 deficiency reveal an integral role of ferritinophagy in iron homeostasis of hippocampal neuronal HT22 cells
Authors: Bengson Emily F. , Guggisberg Cole A. , Bastian Thomas W. , Georgieff Michael K. , Ryu Moon-Suhn 
Published: January 2023

IntroductionNeurons require iron to support their metabolism, growth, and differentiation, but are also susceptible to iron-induced oxidative stress and cytotoxicity. Ferritin, a cytosolic iron storage unit, mediates cellular adaptation to fluctuations in iron delivery. NCOA4 has been characterized as a selective autophagic cargo receptor facilitating the mobilization of intracellular iron from ferritin. This process named ferritinophagy results in the degradation of ferritin and the consequent release of iron into the cytosol.MethodsHere we demonstrate that NCOA4 is important for the adaptation of the HT22 mouse hippocampal neuronal cell line to cellular iron restriction. Additionally, we determined the pathophysiological implications of impaired ferritinophagy via functional analysis of the omics profile of HT22 cells deficient in NCOA4.ResultsNCOA4 silencing impaired ferritin turnover and was cytotoxic when cells were restricted of iron. Quantitative proteomics identified IRP2 accumulation among the most prominent protein responses produced by NCOA4 depletion in HT22 cells, which is indicative of functional iron deficiency. Additionally, proteins of apoptotic signaling pathway were enriched by those responsive to NCOA4 deficiency. Transcriptome profiles of NCOA4 depletion revealed neuronal cell death, differentiation of neurons, and development of neurons as potential diseases and bio functions affected by impaired ferritinophagy, particularly, when iron was restricted.DiscussionThese findings identify an integral role of NCOA4-mediated ferritinophagy in the maintenance of iron homeostasis by HT22 cells, and its potential implications in controlling genetic pathways of neurodevelopment and neurodegenerative diseases.
The influence of dietary and supplemental omega-3 fatty acids on the omega-3 index: A scoping review
Authors: Dempsey Meghan , Rockwell Michelle S. , Wentz Laurel M. 
Published: January 2023

IntroductionThe majority of the population do not consume adequate omega-3 fatty acids (n-3 FA), leading to global deficiencies, as evidenced by poor omega-3 status. An indicator of overall n-3 FA status, omega3-index (O3i) ≥8% has been associated with reduced risk of chronic disease, most notably cardiovascular disease. Thus, a synthesis of current research summarizing the effects of n-3 FA intake on O3i is warranted to develop and refine clinical recommendations. The purpose of this scoping review was to evaluate the effect of n-3 FA interventions and estimate sufficient n-3 FA intake to improve O3i to meet recommendations.MethodsSearch criteria were human studies published in English from 2004 to 2022 that assessed O3i at baseline and following an n-3 FA intervention.ResultsFifty-eight studies that met inclusion criteria were identified. Protocols included fish consumption, fortified foods, combined eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplements, supplements of single n-3 FA (alpha linolenic acid (ALA), EPA, DHA, etc.), and supplements providing multiple n-3 FA. Dietary supplements varied in chemical composition; the most common were triglycerides or ethyl esters. The lowest supplementation protocol was 100 mg/d, and the largest was 4,400 mg/d EPA and DHA. Supplementation time period ranged from 3 weeks to 1 year. At baseline, three study samples had mean O3i &gt;8%, although many intervention protocols successfully increased O3i.DiscussionGenerally, the lowest doses shown to be effective in raising O3i to recommended levels were &gt;1,000 mg/d of combination DHA plus EPA for 12 weeks or longer. Supplements composed of triglycerides were more bioavailable and thus more effective than other formulas. Based on the data evaluated, practical recommendations to improve O3i to ≥8% are consumption of 1,000–1,500 mg/d EPA plus DHA as triglycerides for at least 12 weeks.
Preoperative prediction of cytokeratin-19 expression for hepatocellular carcinoma using T1 mapping on gadoxetic acid-enhanced MRI combined with diffusion-weighted imaging and clinical indicators
Authors: Zhao Yue , Tan Xiaoliang , Chen Jingmu , Tan Hongweng , Huang Huasheng , Luo Peng , Liang Yongsheng , Jiang Xinqing 
Published: January 2023

ObjectivesTo explore the value of T1 mapping on gadoxetic acid-enhanced magnetic resonance imaging (MRI) in preoperative predicting cytokeratin 19 (CK19) expression for hepatocellular carcinoma (HCC).MethodsThis retrospective study included 158 patients from two institutions with surgically resected treatment-native solitary HCC who underwent preoperative T1 mapping on gadoxetic acid-enhanced MRI. Patients from institution I (n = 102) and institution II (n = 56) were assigned to training and test sets, respectively. univariable and multivariable logistic regression analyses were performed to investigate the association of clinicoradiological variables with CK19. The receiver operating characteristic (ROC) curve and precision-recall (PR) curve were used to evaluate the performance for CK19 prediction. Then, a prediction nomogram was developed for CK19 expression. The performance of the prediction nomogram was evaluated by its discrimination, calibration, and clinical utility.ResultsMultivariable logistic regression analysis showed that AFP&gt;400ng/ml (OR=4.607, 95%CI: 1.098-19.326; p=0.037), relative apparent diffusion coefficient (rADC)≤0.71 (OR=3.450, 95%CI: 1.126-10.567; p=0.030), T1 relaxation time in the 20-minute hepatobiliary phase (T1rt-HBP)&gt;797msec (OR=4.509, 95%CI: 1.301-15.626; p=0.018) were significant independent predictors of CK19 expression. The clinical-quantitative model (CQ-Model) constructed based on these significant variables had the best predictive performance with an area under the ROC curve of 0.844, an area under the PR curve of 0.785 and an F1 score of 0.778. The nomogram constructed based on CQ-Model demonstrated satisfactory performance with C index of 0.844 (95%CI: 0.759-0.908) and 0.818 (95%CI: 0.693-0.902) in the training and test sets, respectively.ConclusionsT1 mapping on gadoxetic acid-enhanced MRI has good predictive efficacy for preoperative prediction of CK19 expression in HCC, which can promote the individualized risk stratification and further treatment decision of HCC patients.
Combined iodine-125 seed strand, portal vein stent, transarterial chemoembolization, lenvatinib and anti-PD-1 antibodies therapy for hepatocellular carcinoma and Vp4 portal vein tumor thrombus: A propensity-score analysis
Authors: Zhang Zi-Han , Hou Si-Nan , Yu Jia-Ze , Zhang Wen , Ma Jing-Qin , Yang Min-Jie , Liu Qing-Xin , Liu Ling-Xiao , Luo Jian-Jun , Qu Xu-Dong , Yan Zhi-Ping 
Published: January 2023

ObjectiveTo evaluate the safety and efficacy of interventional therapy (iodine-125[125I] seed strand and portal vein stent [PVS] implantation plus transarterial chemoembolization [TACE]) combined with systemic therapy (lenvatinib plus anti-PD-1 antibody) as first-line treatment for hepatocellular carcinoma (HCC) patients with Vp4 portal vein tumor thrombus (PVTT).Patients and methodsFrom December 2018 to October 2021, 87 HCC patients with Vp4 PVTT were included in this single-center retrospective study. Forty-seven patients underwent interventional therapy combined with lenvatinib and anti-PD-1 antibody (group A), while 40 cases underwent interventional therapy combined with lenvatinib only (group B). Overall response rate (ORR), stent occlusion rates (SOR), median overall survival (OS), median progression-free survival (PFS) and median stent patency time (SPT) were compared between the 2 groups.ResultsThe mean intended dose (r = 10 mm; z = 0; 240 days) was 64.9 ± 1.0 Gy and 64.5 ± 1.1 Gy in group A and B, respectively (p = 0.133). ORR and SOR were significantly different between group A and B (ORR, 55.3% vs 17.5%, p &lt; 0.001; SOR, 12.8% vs 35.0%, p = 0.014). In the propensity-score matching (PSM) cohort, the median OS, median PFS and median SPT were significantly longer in group A compared with group B (32 PSM pairs; OS, 17.7 ± 1.7 vs 12.0 ± 0.8 months, p = 0.010; PFS, 17.0 ± 4.3 vs 8.0 ± 0.7 months, p &lt; 0.001; SPT, not-reached vs 12.5 ± 1.1 months, p = 0.028).ConclusionThis interventional therapy combined with lenvatinib and anti-PD-1 antibody is safe and effective for HCC patients with Vp4 PVTT.
Population pharmacokinetics of buprenorphine and naloxone sublingual combination in Chinese healthy volunteers and patients with opioid use disorder: Model-based dose optimization
Authors: Gu Meng , Li Anning , Mak Wenyao , Dong Fang , Xu Nuo , Zhang Jingye , Shi Yufei , Zheng Nan , Tang Zhijia , He Qingfeng , Ruan Canjun , Guo Wei , Xiang Xiaoqiang , Wang Chuanyue , Han Bing , Zhu Xiao 
Published: January 2023

The sublingual combination of buprenorphine (BUP) and naloxone (NLX) is a new treatment option for opioid use disorder (OUD) and is effective in preventing drug abuse. This study aimed to explore rational dosing regimen for OUD patients in China via a model-based dose optimization approach. BUP, norbuprenorphine (norBUP), and NLX plasma concentrations of 34 healthy volunteers and 12 OUD subjects after single or repeated dosing were included. A parent-metabolite population pharmacokinetics (popPK) model with transit compartments for absorption was implemented to describe the pharmacokinetic profile of BUP-norBUP. In addition, NLX concentrations were well captured by a one-compartment popPK model. Covariate analysis showed that every additional swallow after the administration within the observed range (0–12) resulted in a 3.5% reduction in BUP bioavailability. This provides a possible reason for the less-than-dose proportionality of BUP. There were no differences in the pharmacokinetic characteristics between BUP or NLX in healthy volunteers and OUD subjects. Ethnic sensitivity analysis demonstrated that the dose-normalized peak concentration and area-under-the-curve of BUP in Chinese were about half of Puerto Ricans, which was consistent with a higher clearance observed in Chinese (166 L/h vs. 270 L/h). Furthermore, Monte Carlo simulations showed that an 8 mg three-times daily dose was the optimized regimen for Chinese OUD subjects. This regimen ensured that opioid receptor occupancy remained at a maximum (70%) in more than 95% of subjects, at the same time, with NLX plasma concentrations below the withdrawal reaction threshold (4.6 ng/mL).
Machine learning-aided detection of heart failure (LVEF ≤ 49%) by using ballistocardiography and respiratory effort signals
Authors: Feng Shen , Wu Xianda , Bao Andong , Lin Guanyang , Sun Pengtao , Cen Huan , Chen Sinan , Liu Yuexia , He Wenning , Pang Zhiqiang , Zhang Han 
Published: January 2023

Purpose: Under the influence of COVID-19 and the in-hospital cost, the in-home detection of cardiovascular disease with smart sensing devices is becoming more popular recently. In the presence of the qualified signals, ballistocardiography (BCG) can not only reflect the cardiac mechanical movements, but also detect the HF in a non-contact manner. However, for the potential HF patients, the additional quality assessment with ECG-aided requires more procedures and brings the inconvenience to their in-home HF diagnosis. To enable the HF detection in many real applications, we proposed a machine learning-aided scheme for the HF detection in this paper, where the BCG signals recorded from the force sensor were employed without the heartbeat location, and the respiratory effort signals separated from force sensors provided more HF features due to the connection between the heart and the lung systems. Finally, the effectiveness of the proposed HF detection scheme was verified in comparative experiments.Methods: First, a piezoelectric sensor was used to record a signal sequences of the two-dimensional vital sign, which includes the BCG and the respiratory effort. Then, the linear and the non-linear features w.r.t. BCG and respiratory effort signals were extracted to serve the HF detection. Finally, the improved HF detection performance was verified through the LOO and the LOSO cross-validation settings with different machine learning classifiers.Results: The proposed machine learning-aided scheme achieved the robust performance in the HF detection by using 4 different classifiers, and yielded an accuracy of 94.97% and 87.00% in the LOO and the LOSO experiments, respectively. In addition, experimental results demonstrated that the designed respiratory and cardiopulmonary features are beneficial to the HF detection (LVEF ≤49%).Conclusion: This study proposed a machine learning-aided HF diagnostic scheme. Experimental results demonstrated that the proposed scheme can fully exploit the relationship between the heart and the lung systems to potentially improve the in-home HF detection performance by using both the BCG, the respiratory and the cardiopulmonary-related features.
Abscisic acid agonists suitable for optimizing plant water use
Authors: Roeder Jan , Liu Jinghui , Doch Isabel , Ruschhaupt Moritz , Christmann Alexander , Grill Erwin , Helmke Hendrik , Hohmann Sabine , Lehr Stefan , Frackenpohl Jens , Yang Zhenyu 
Published: January 2023

Climate change and overexploitation of groundwater resources cause constraints on water demand for agriculture, thus threatening crop productivity. For future food security, there is an urgent need for crops of high water use efficiency combined with high crop productivity, i.e. having high water productivity. High water productivity means efficient biomass accumulation at reduced transpiration. Recent studies show that plants are able to optimize carbon uptake per water transpired with little or no trade-off in yield. The phytohormone abscisic acid (ABA) plays a pivotal role in minimizing leaf transpiration and mediating enhanced water productivity. Hence, ABA and more chemically stable ABA agonists have the potential to improve crop water productivity. Synthesis, screening, and identification of suitable ABA agonists are major efforts currently undertaken. In this study, we used yeast expressing the plant ABA signal pathway to prescreen ABA-related cyano cyclopropyl compounds (CCPs). The yeast analysis allowed testing the ABA agonists for general toxicity, efficient uptake, and specificity in regulating different ABA receptor complexes. Subsequently, promising ABA-mimics were analyzed in vitro for ligand-receptor interaction complemented by physiological analyses. Several CCPs activated ABA signaling in yeast and plant cells. CCP1, CCP2, and CCP5 were by an order of magnitude more efficient than ABA in minimizing transpiration of Arabidopsis plants. In a progressive drought experiment, CCP2 mediated an increase in water use efficiency superior to ABA without trade-offs in biomass accumulation.
Functional genomic analysis of K+ related salt-responsive transporters in tolerant and sensitive genotypes of rice
Authors: Haque Umme Sabrina , Elias Sabrina M. , Jahan Israt , Seraj Zeba I. 
Published: January 2023

IntroductionSalinity is a complex environmental stress that affects the growth and production of rice worldwide. But there are some rice landraces in coastal regions that can survive in presence of highly saline conditions. An understanding of the molecular attributes contributing to the salinity tolerance of these genotypes is important for developing salt-tolerant high yielding modern genotypes to ensure food security. Therefore, we investigated the role and functional differences of two K+ salt-responsive transporters. These are OsTPKa or Vacuolar two-pore potassium channel and OsHAK_like or a hypothetical protein of the HAK family. These transporters were selected from previously identified QTLs from the tolerant rice landrace genotype (Horkuch) and sensitive genotype (IR29).MethodsIn silico comparative sequence analysis of the promoter sequences of two these genes between Horkuch and IR29 was done. Real-Time expression of the selected genes in leaves and roots of IR29 (salt-sensitive), I-14 and I-71 (Recombinant Inbred Lines of IR29(♀)× Horkuch), Horkuch and Pokkali (salt-tolerant) under salt-stress at different time points was analyzed. For further insight, OsTPKa and OsHAK_like were chosen for loss-of-function genomic analysis in Horkuch using the CRISPR/Cas9 tool. Furthermore, OsTPKa was chosen for cloning into a sensitive variety by Gateway technology to observe the effect of gain-of-function.ResultsThe promoter sequences of the OsTPKa and OsHAK_like genes showed some significant differences in promoter sequences which may give a survival advantage to Horkuch under salt-stress. These two genes were also found to be overexpressed in tolerant varieties (Horkuch and Pokkali). Moreover, a coordinated expression pattern between these two genes was observed in tolerant Horkuch under salt-stress. Independently transformed plants where the expression of these genes was significantly lowered, performed poorly in physiological tests for salinity tolerance. On the other hand, positively transformed T0 plants with the OsTPKa gene from Horkuch consistently showed growth advantage under both control and salt stress.DiscussionThe poor performance of the transgenic plants with the down-regulated genes OsTPKa and OsHAK_like under salt stress supports the assumption that OsTPKa and OsHAK_like play important roles in defending the rice landrace Horkuch against salt stress, minimizing salt injury, and maintaining plant growth. Moreover, the growth advantage provided by overexpression of the vacuolar OsTPKa K+ transporter, particularly under salt stress reconfirms its important role in providing salt tolerance. The QTL locus from Horkuch containing these two transporters maybe bred into commercial rice to produce high-yielding salt tolerant rice.
Skeleton extraction and pruning point identification of jujube tree for dormant pruning using space colonization algorithm
Authors: Fu Yuxing , Xia Yuyang , Zhang Huiming , Fu Meng , Wang Yong , Fu Wei , Shen Congju 
Published: January 2023

The dormant pruning of jujube is a labor-intensive and time-consuming activity in the production and management of jujube orchards, which mainly depends on manual operation. Automatic pruning using robots could be a better way to solve the shortage of skilled labor and improve efficiency. In order to realize automatic pruning of jujube trees, a method of pruning point identification based on skeleton information is presented. This study used an RGB-D camera to collect multi-view information on jujube trees and built a complete point cloud information model of jujube trees. The space colonization algorithm acts on the global point cloud to generate the skeleton of jujube trees. The iterative relationship between skeleton points was represented by constructing a directed graph. The proposed skeleton analysis algorithm marked the skeleton as the trunk, the primary branches, and the lateral branches and identified the pruning points under the guidance of pruning rules. Finally, the visual model of the pruned jujube tree was established through the skeleton information. The results showed that the registration errors of individual jujube trees were less than 0.91 cm, and the average registration error was 0.66 cm, which provided a favorable database for skeleton extraction. The skeleton structure extracted by the space colonization algorithm had a high degree of coincidence with jujube trees, and the identified pruning points were all located on the primary branches of jujube trees. The study provides a method to identify the pruning points of jujube trees and successfully verifies the validity of the pruning points, which can provide a reference for the location of the pruning points and visual research basis for automatic pruning.
Exploring the relationships between visuospatial working memory, math, letter-sound knowledge, motor competence, and gender in first grade children: A correlational study
Authors: Eriksen Adrian Dybfest , Olsen Alexander , Sigmundsson Hermundur 
Published: January 2023

IntroductionDevelopment of crucial skills accelerates at the start of formal schooling, although, more knowledge is needed about the relationships between such skills. The current study explored the relationships between visuospatial working memory, letter-sound knowledge, math competence and motor competence, as well as potential effects of gender.Materials and methodsThe sample consisted of 85 (42 girls) 6 to 7 years old first grade children, and was measured with a test battery consisting of tests designed for each skill domain.ResultsResults demonstrated weak to moderate statistically significant correlations between visuospatial working memory, letter-sound knowledge, math competence, with no statistically significant gender differences. Two motor tasks measuring manual dexterity, placing bricks and building bricks, showed a weak statistically significant correlation.DiscussionWe argue that the findings demonstrate the relationships between these skills are low to moderate in first grade. Furthermore, we argue that these skills ought to be trained deliberately. The potential role of visuospatial working memory in procurement of novel skills in early childhood ought to be explored further in future studies.
Prediction of transition to psychosis from an at-risk mental state using structural neuroimaging, genetic, and environmental data
Authors: Tavares Vânia , Vassos Evangelos , Marquand Andre , Stone James , Valli Isabel , Barker Gareth J. , Ferreira Hugo , Prata Diana 
Published: January 2023

IntroductionPsychosis is usually preceded by a prodromal phase in which patients are clinically identified as being at in an “At Risk Mental State” (ARMS). A few studies have demonstrated the feasibility of predicting psychosis transition from an ARMS using structural magnetic resonance imaging (sMRI) data and machine learning (ML) methods. However, the reliability of these findings is unclear due to possible sampling bias. Moreover, the value of genetic and environmental data in predicting transition to psychosis from an ARMS is yet to be explored.MethodsIn this study we aimed to predict transition to psychosis from an ARMS using a combination of ML, sMRI, genome-wide genotypes, and environmental risk factors as predictors, in a sample drawn from a pool of 246 ARMS subjects (60 of whom later transitioned to psychosis). First, the modality-specific values in predicting transition to psychosis were evaluated using several: (a) feature types; (b) feature manipulation strategies; (c) ML algorithms; (d) cross-validation strategies, as well as sample balancing and bootstrapping. Subsequently, the modalities whose at least 60% of the classification models showed an balanced accuracy (BAC) statistically better than chance level were included in a multimodal classification model.Results and discussionResults showed that none of the modalities alone, i.e., neuroimaging, genetic or environmental data, could predict psychosis from an ARMS statistically better than chance and, as such, no multimodal classification model was trained/tested. These results suggest that the value of structural MRI data and genome-wide genotypes in predicting psychosis from an ARMS, which has been fostered by previous evidence, should be reconsidered.