bluuebunny/crossref_metadata_2025_split huggingface dataset:
ENSO coupling to the equatorial Atlantic: Analysis with an extended improved recharge oscillator model
Authors: Crespo-Miguel Rodrigo , Polo Irene , Mechoso Carlos R. , Rodríguez-Fonseca Belén , Cao-García Francisco J. 
Published: January 2023

IntroductionObservational and modeling studies have examined the interactions between El Niño-Southern Oscillation (ENSO) and the equatorial Atlantic variability as incorporated into the classical charge-recharge oscillator model of ENSO. These studies included the role of the Atlantic in the predictability of ENSO but assumed stationarity in the relationships, i.e., that models’ coefficients do not change over time. A recent work by the authors has challenged the stationarity assumption in the ENSO framework but without considering the equatorial Atlantic influence on ENSO.MethodsThe present paper addresses the changing relationship between ENSO and the Atlantic El Niño using an extended version of the recharge oscillator model. The classical two-variable model of ENSO is extended by adding a linear coupling on the SST anomalies in the equatorial Atlantic. The model’s coefficients are computed for different periods. This calculation is done using two methods to fit the model to the data: (1) the traditional method (ReOsc), and (2) a novel method (ReOsc+) based on fitting the Fisher’s Z transform of the auto and cross-correlation functions.ResultsWe show that, during the 20th century, the characteristic damping rate of the SST and thermocline depth anomalies in the Pacific have decreased in time by a factor of 2 and 3, respectively. Moreover, the damping time of the ENSO fluctuations has doubled from 10 to 20 months, and the oscillation period of ENSO has decreased from 60-70 months before the 1960s to 50 months afterward. These two changes have contributed to enhancing ENSO amplitude. The results also show that correlations between ENSO and the Atlantic SST strengthened after the 70s and the way in which the impact of the equatorial Atlantic is added to the internal ENSO variability.ConclusionsThe remote effects of the equatorial Atlantic on ENSO must be considered in studies of ENSO dynamics and predictability during specific time-periods. Our results provide further insight into the evolution of the ENSO dynamics and its coupling to the equatorial Atlantic, as well as an improved tool to study the coupling of climatic and ecological variables.
Feature preserving mesh network for semantic segmentation of retinal vasculature to support ophthalmic disease analysis
Authors: Imran Syed Muhammad Ali , Saleem Muhammad Waqas , Hameed Muhammad Talha , Hussain Abida , Naqvi Rizwan Ali , Lee Seung Won 
Published: January 2023

IntroductionOphthalmic diseases are approaching an alarming count across the globe. Typically, ophthalmologists depend on manual methods for the analysis of different ophthalmic diseases such as glaucoma, Sickle cell retinopathy (SCR), diabetic retinopathy, and hypertensive retinopathy. All these manual assessments are not reliable, time-consuming, tedious, and prone to error. Therefore, automatic methods are desirable to replace conventional approaches. The accuracy of this segmentation of these vessels using automated approaches directly depends on the quality of fundus images. Retinal vessels are assumed as a potential biomarker for the diagnosis of many ophthalmic diseases. Mostly newly developed ophthalmic diseases contain minor changes in vasculature which is a critical job for the early detection and analysis of disease.MethodSeveral artificial intelligence-based methods suggested intelligent solutions for automated retinal vessel detection. However, existing methods exhibited significant limitations in segmentation performance, complexity, and computational efficiency. Specifically, most of the existing methods failed in detecting small vessels owing to vanishing gradient problems. To overcome the stated problems, an intelligence-based automated shallow network with high performance and low cost is designed named Feature Preserving Mesh Network (FPM-Net) for the accurate segmentation of retinal vessels. FPM-Net employs a feature-preserving block that preserves the spatial features and helps in maintaining a better segmentation performance. Similarly, FPM-Net architecture uses a series of feature concatenation that also boosts the overall segmentation performance. Finally, preserved features, low-level input image information, and up-sampled spatial features are aggregated at the final concatenation stage for improved pixel prediction accuracy. The technique is reliable since it performs better on the DRIVE database, CHASE-DB1 database, and STARE dataset.Results and discussionExperimental outcomes confirm that FPM-Net outperforms state-of-the-art techniques with superior computational efficiency. In addition, presented results are achieved without using any preprocessing or postprocessing scheme. Our proposed method FPM-Net gives improvement results which can be observed with DRIVE datasets, it gives Se, Sp, and Acc as 0.8285, 0.98270, 0.92920, for CHASE-DB1 dataset 0.8219, 0.9840, 0.9728 and STARE datasets it produces 0.8618, 0.9819 and 0.9727 respectively. Which is a remarkable difference and enhancement as compared to the conventional methods using only 2.45 million trainable parameters.
Analysis of ferroptosis-associated genes in Crohn’s disease based on bioinformatics
Authors: Ji Xingyu , Ma Su , Sun Xiaomei , Yu Dan , Song Ye , Li Rui 
Published: January 2023

BackgroundFerroptosis, a novel mode of apoptosis has recently been shown to be associated with fibrosis, tumor, cardiovascular, and other diseases. In this study, using bioinformatic analysis, we identified ferroptosis genes associated with Crohn’s disease (CD) and performed biological function analysis, identified potential drug targets, and provided new directions for the future treatment of CD.MethodsDifferential expression analysis was performed using the GSE186582 dataset from the Gene Expression Omnibus (GEO) database. Ferroptosis-associated genes were downloaded from the FerrDB database, and overlapping genes associated with CD and ferroptosis were extracted. Then, we performed functional enrichment analysis, constructed a protein-protein interaction network (PPI), identified the correlation between hub genes and immune infiltration, performed external validation using a second and third dataset (GSE102133, GSE95095), and identified potential therapeutic agents. Finally, we validated the protein expression levels of the identified hub genes by immunohistochemical staining in the colon tissues from CD and healthy participants.ResultsA total of 28 ferroptosis-associated genes associated with CD were identified in our analysis, which included 22 up-regulated and 6 down-regulated genes. Gene Ontology (GO) analysis showed that these genes are essential for the apical plasma membrane and amide transport, and Metascape analysis showed that these genes mainly act on IL-4 and IL-13 signaling pathways. Five hub genes, PTGS2, IL6, IL1B, NOS2, and IDO1, were identified by a protein interaction network, and external validation of these hub genes showed statistically significant differences in expression between the CD patients and normal participants (p &lt; 0.05), and all AUC values were greater than 0.8. Further, we predicted the top 10 drugs used to treat CD. Immune infiltration results suggest that Hub gene is related to T cells, macrophages, dendritic cells, and other immune cells. Finally, the results of immunohistochemical experiments showed that the protein expression of the hub gene was higher in CD colon tissue than in normal subjects (p &lt; 0.05).ConclusionBioinformatics analysis showed that ferroptosis is closely related to the development of CD, and the prediction of potential drugs provides new targets for the treatment of CD. Moreover, five hub genes identified are potentially new and effective markers for the diagnosis of CD.
Cryptotanshinone attenuates LPS-induced acute lung injury by regulating metabolic reprogramming of macrophage
Authors: Ye Zesen , Wang Panxia , Feng Guodong , Wang Quan , Liu Cui , Lu Jing , Chen Jianwen , Liu Peiqing 
Published: January 2023

BackgroundAcute lung injury (ALI) is a life-threatening inflammatory disease without effective therapeutic regimen. Macrophage polarization plays a key role in the initiation and resolution of pulmonary inflammation. Therefore, modulating macrophage phenotype is a potentially effective way for acute lung injury. Cryptotanshinone (CTS) is a lipophilic bioactive compound extracted from the root of Salvia miltiorrhiza with a variety of pharmacological effects, especially the anti-inflammatory role. In this study, we investigated the therapeutic and immunomodulatory effects of CTS on ALI.Materials and methodsThe rat model of ALI was established by intratracheal instillation of LPS (5 mg/kg) to evaluate the lung protective effect of CTS in vivo and to explore the regulation of CTS on the phenotype of lung macrophage polarization. LPS (1 μg/mL) was used to stimulate RAW264.7 macrophages in vitro to further explore the effect of CTS on the polarization and metabolic reprogramming of RAW264.7 macrophages and to clarify the potential mechanism of CTS anti-ALI.ResultsCTS significantly improved lung function, reduced pulmonary edema, effectively inhibited pulmonary inflammatory infiltration, and alleviated ALI. Both in vivo and in vitro results revealed that CTS inhibited the differentiation of macrophage into the M1 phenotype and promoted polarization into M2 phenotype during ALI. Further in vitro studies indicated that CTS significantly suppressed LPS-induced metabolic transition from aerobic oxidation to glycolysis in macrophages. Mechanistically, CTS blocked LPS-induced metabolic transformation of macrophages by activating AMPK.ConclusionThese findings demonstrated that CTS regulates macrophage metabolism by activating AMPK, and then induced M1-type macrophages to transform into M2-type macrophages, thereby alleviating the inflammatory response of ALI, suggesting that CTS might be a potential anti-ALI agent.
Effects of growth stage on the fermentation quality, microbial community, and metabolomic properties of Italian ryegrass (Lolium multiflorum Lam.) silage
Authors: Fu Zhihui , Sun Lin , Wang Zhijun , Liu Jingyi , Hou Meiling , Lu Qiang , Hao Junfeng , Jia Yushan , Ge Gentu 
Published: January 2023

IntroductionThis study aimed to investigate the effects of different growth stages (booting period-SYK; initial flowering-SCK; full flowering-SSK) on the fermentation quality, microbial community, metabolic pathways and metabolomic characteristics of Italian ryegrass silage.MethodsSingle molecule real-time (SMRT) sequencing and ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) were used to analyze bacterial communities and metabolites, respectively.ResultsAfter 60 d of fermentation, SYK had the lowest pH and the highest lactic acid content, which were significantly different from the other groups. The bacteria with the highest abundance in SYK, SCK and SSK groups were Lactiplantibacillus plantarum (63.98%), Weissella minor (28.82%) and Levilactobacillus brevis (64.81%), respectively. In addition, among the main differential metabolites in different growth stages, the number of amino acids was the most, and the corresponding metabolic pathways were mainly amino acid metabolic pathways. The biosynthesis of phenylalanine, tyrosine and tryptophan was significantly enriched (p&lt;0.01) at booting stage and full flowering stage. Purine metabolism and ABC transporter pathway were significantly enriched at the initial flowering (p&lt;0.001). Lactiplantibacillus plantarum had a negative correlation with xanthine and ganoderic acid F. Weissella minor had a positive correlation with D-Mannose and ganoderic acid F. Levilactobacillus brevis had a positive correlation with xanthine, and Latilactobacillus sakei had a positive correlation with cinnamic acid, D-Mannose, 2-Hydroxycinnamic acid and uridine.DiscussionIn conclusion, this study reveals the interaction mechanisms between ryegrass raw materials at different growth stages and epiphytic microorganisms during ensiling fermentation, providing new ideas for screening functional lactic acid bacteria, and laying a theoretical foundation for the production of safe and high-quality silage.
ELOVL5 and IGFBP6 genes modulate sensitivity of breast cancer cells to ferroptosis
Authors: Nikulin Sergey , Razumovskaya Alexandra , Poloznikov Andrey , Zakharova Galina , Alekseev Boris , Tonevitsky Alexander 
Published: January 2023

Introduction: Relapse of breast cancer is one of the key obstacles to successful treatment. Previously we have shown that low expression of ELOVL5 and IGFBP6 genes in breast cancer tissue corresponded to poor prognosis. ELOVL5 participates directly in the elongation of polyunsaturated fatty acids (PUFAs) that are considered to play an important role in cancer cell metabolism. Thus, in this work we studied the changes in lipid metabolism in breast cancer cells with reduced expression of either ELOVL5 or IGFBP6 gene.Methods: MDA-MB-231 cells with a stable knockdown of either ELOVL5 or IGFBP6 gene were used in this study. Transcriptomic and proteomic analysis as well as RT-PCR were utilized to assess gene expression. Content of individual fatty acids in the cells was measured with HPLC-MS. HPLC was used for analysis of the kinetics of PUFAs uptake. Cell viability was measured with MTS assay. Flow cytometry was used to measure activation of apoptosis. Fluorescent microscopy was utilized to assess accumulation of ROS and formation of lipid droplets. Glutathione peroxidase activity was measured with a colorimetric assay.Results: We found that the knockdown of IGFBP6 gene led to significant changes in the profile of fatty acids in the cells and in the expression of many genes associated with lipid metabolism. As some PUFAs are known to inhibit proliferation and cause death of cancer cells, we also tested the response of the cells to single PUFAs and to combinations of docosahexaenoic acid (DHA, a n-3 PUFA) with standard chemotherapeutic drugs. Our data suggest that external PUFAs cause cell death by activation of ferroptosis, an iron-dependent mechanism of cell death with excessive lipid peroxidation. Moreover, both knockdowns increased cells’ sensitivity to ferroptosis, probably due to a significant decrease in the activity of the antioxidant enzyme GPX4. Addition of DHA to commonly used chemotherapeutic drugs enhanced their effect significantly, especially for the cells with low expression of IGFBP6 gene.Discussion: The results of this study suggest that addition of PUFAs to the treatment regimen for the patients with low expression of IGFBP6 and ELOVL5 genes can be potentially beneficial and is worth testing in a clinically relevant setting.
Association between cognitive frailty and falls among older community dwellers in China: A Chinese longitudinal healthy longevity survey-based study
Authors: Chen Huihe , Huang Lanhui , Xiang Wei , Liu Yu , Xu Jian-Wen 
Published: January 2023

BackgroundThe combined effect of cognitive impairment (CoI) and frailty on falls is controversial. This study aimed to explore whether older adults with cognitive frailty (CF) were at a higher risk of falls than those with only CoI or frailty and to present a fall prediction model based on CF.MethodsA total of 4,067 adults aged ≥ 60 years were included from the Chinese Longitudinal Healthy Longevity Survey through face-to-face interviews. Cognitive function and frailty were assessed using the mini-mental state examination scale and frailty index, respectively. Logistic regression was used to determine fall-associated risk factors and develop a fall prediction model. A nomogram was then plotted. The model performance was evaluated using the area under the curve (AUC), concordance index (C-index), and calibration curve. All analyses were performed using SPSS and R statistical packages.ResultsThe prevalence of CF and falls were 1.4 and 19.4%, respectively. After adjusting for covariates, the odds ratio of CF, frailty only, and CoI only for falls were 2.27 (95% CI: 1.29–3.97), 1.41 (95% CI: 1.16–1.73), and 0.99 (95% CI: 0.43–2.29), respectively. CF, sex, age, hearing difficulty, depression, anxiety, disability in instrumental activities of daily living, and serious illness in the past 2 years were independently associated with falls. A prediction model based on these factors yielded an AUC of 0.646 and a C-index of 0.641.ConclusionCognitive frailty (CF) exerted a cumulative effect on falls than did CoI or frailty alone. Joint assessments of cognitive function and frailty status may be beneficial for fall risk screening in community. A prediction model using CF as a factor could be helpful for this process.
Association between glaucoma and risk of stroke: A systematic review and meta-analysis
Authors: Wang Meng , Chen Ni , Sun Bai-chao , Guo Chun-Bao , Zhang Shuang , Huang Ming-Jie , Zhou Ben-Gang , Wang Xiang-yu , Huang Zheng-Biao 
Published: January 2023

Background/objectivesRecently, several studies explored the association between glaucoma and the risk of stroke, but these results were inconsistent. Therefore, we conducted a meta-analysis to examine this possible association.MethodsWe conducted a systematic literature search of PubMed, Embase, and Web of Science from inception until February 28, 2022. Random-effects meta-analysis was conducted by generic inverse variance method. Sensitivity and subgroup analyses were performed. The review protocol has been registered with PROSPERO (CRD42022312797).ResultsSeven studies (involving 362,267 participants) have been published from 2004 to 2017 and included in the meta-analysis. These studies included four retrospective cohort studies, two cross-sectional studies, and one case–control study. Meta-analysis of these data has shown that glaucoma was associated with an increased risk of stroke (OR = 1.94, 95% CI = 1.45–2.59). Most of the subgroup analyses demonstrated similar results. These findings were stable in sensitivity analyses.ConclusionsWe found that glaucoma was associated with an increased risk of stroke. The result suggests that patients with glaucoma need to be assessed the risk of stroke to reduce the incidence of stroke. To better explore the nature of any association, prospective studies that consider the stroke subtypes, sample size, district, and other confounding factors are needed.
Elevated concentrations of macrophage migration inhibitory factor in serum and cerebral microdialysate are associated with delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage
Authors: Neumaier Felix , Stoppe Christian , Stoykova Anzhela , Weiss Miriam , Veldeman Michael , Höllig Anke , Hamou Hussam Aldin , Temel Yasin , Conzen Catharina , Schmidt Tobias Philip , Dogan Rabia , Wiesmann Martin , Clusmann Hans , Schubert Gerrit Alexander , Haeren Roel Hubert Louis , Albanna Walid 
Published: January 2023

ObjectiveInflammation is increasingly recognized to be involved in the pathophysiology of aneurysmal subarachnoid hemorrhage (aSAH) and may increase the susceptibility to delayed cerebral ischemia (DCI). Macrophage migration inhibitory factor (MIF) has been shown to be elevated in serum and cerebrospinal fluid (CSF) after aSAH. Here, we determined MIF levels in serum, CSF and cerebral microdialysate (MD) at different time-points after aSAH and evaluated their clinical implications.MethodsMIF levels were measured in serum, CSF and MD obtained from 30 aSAH patients during early (EPd1−4), critical (CPd5−15) and late (LPd16−21) phase after hemorrhage. For subgroup analyses, patients were stratified based on demographic and clinical data.ResultsMIF levels in serum increased during CPd5−15 and decreased again during LPd16−21, while CSF levels showed little changes over time. MD levels peaked during EPd1−4, decreased during CPd5−15 and increased again during LPd16−21. Subgroup analyses revealed significantly higher serum levels in patients with aneurysms located in the anterior vs. posterior circulation during CPd5−15 (17.3 [15.1–21.1] vs. 10.0 [8.4–11.5] ng/ml, p = 0.009) and in patients with DCI vs. no DCI during CPd5−15 (17.9 [15.1–22.7] vs. 11.9 [8.9–15.9] ng/ml, p = 0.026) and LPd16−21 (17.4 [11.7–27.9] vs. 11.3 [9.2–12.2] ng/ml, p = 0.021). In addition, MIF levels in MD during CPd5−15 were significantly higher in patients with DCI vs. no DCI (3.6 [1.8–10.7] vs. 0.2 [0.1–0.7] ng/ml, p = 0.026), while CSF levels during the whole observation period were similar in all subgroups.ConclusionOur findings in a small cohort of aSAH patients provide preliminary data on systemic, global cerebral and local cerebral MIF levels after aSAH and their clinical implications.Clinical trial registrationClinicalTrials.gov, identifier: NCT02142166.
Symptoms and patterns of symptom propagation in incipient ischemic stroke and migraine aura
Authors: Scutelnic Adrian , Bracher Jacqueline , Kreis Lukas A. , Beyeler Morin , Fischer Urs , Arnold Marcel , Mattle Heinrich P. , Jung Simon , Schankin Christoph J. 
Published: January 2023

Background and objectivesTaking a detailed history of symptoms is important for differentiating incipient ischemic stroke and migraine aura. The aim of our study is to describe in detail symptom type and temporal pattern of symptom evolution (i.e., symptom succession and the time lapse between symptoms) and to identify differentiating clinical features in patients with ischemic stroke and migraine with aura.MethodsConsecutive patients with ischemic stroke and migraine with aura were interviewed using a structured questionnaire. Stroke diagnosis was confirmed by imaging and migraine with aura was diagnosed according to the current criteria of the International Headache Society. Wake-up strokes and patients with severe cognitive deficits were excluded.ResultsIn stroke patients and migraine patients, respectively, 50/78 (64%) vs. 123/326 (37%) had one, 18 (23%) vs. 127 (38%) had two, 5 (6%) vs. 69 (21%) had three, 2 (2%) vs. 4 (1%) had four, and 3 (3%) vs. 3 (1%) had five visual symptoms. In respect of sensory symptoms, 76/145 (52.4%) vs. 116/175 (66%) reported paresthesia and 92/145 (63.4%) vs. 132 (75%) numbness. Looking at the beginning, visual symptoms were the first symptom more often in migraine aura than in ischemic stroke (72.1 vs 18.8%, P &lt; 0.001; PPV 86.8%). Sensory (29 vs 13.9%, P = 0.001; PPV 54.8%) and motor symptoms (20.5 vs 1.4%, P &lt; 0.001; PPV 88.9%) were the first symptom more frequently in ischemic stroke. Of patients with consecutive symptoms, 39 of 201 (19%) compared to 34 of 117 (29%) (P = 0.02; PPV 46.6%) reported at least two simultaneous symptoms. A time lapse between symptoms of &lt; 1 min (18.6 vs 6.3%, P &lt; 0.001; PPV 57.1%) and &gt; 360 min (15.8 vs 0%, χ2 = 39.61, P &lt; 0.001; PPV 100%) was more frequent in stroke whereas a time lapse between 5 and 60 min was more frequent in migraine aura (41.1 vs 68.7%, χ2 = 23.52, P &lt; 0.001; PPV 78.7%).ConclusionThere is a significant overlap in the clinical presentation of stroke and migraine aura. In particular, a substantial proportion of patients in one group had symptoms that are traditionally attributed to the other group. This study highlights the similarities and differences between symptoms of ischemic stroke and migraine aura and challenges our reasoning in daily clinical practice.