bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of DAMP Actions in the Tumoral Microenvironment Using Lactoferrin-Glycyrrhizin Nanoconjugate for Glioblastoma Therapy
Authors: Kim Hyung Shik , Park Seok Chan , Kim Hae Jin , Lee Dong Yun 
Published: February 2023

Abstract
Background
High-mobility group box-1 (HMGB1) released from the tumor microenvironment plays a pivotal role in the tumor progression. HMGB1 serves as a damaged-associated molecular pattern (DAMP) that induces tumor angiogenesis and its development. Glycyrrhizin (GL) is an effective intracellular antagonist of tumor released HMGB1, but its pharmacokinetics (PK) and delivery to tumor site is deficient. To address this shortcoming, we developed lactoferrin-glycyrrhizin (Lf-GL) conjugate.
Methods
Biomolecular interaction between Lf-GL and HMGB1 was evaluated by surface plasmon resonance (SPR) binding affinity assay. Inhibition of tumor angiogenesis and development by Lf-GL attenuating HMGB1 action in the tumor microenvironment was comprehensively evaluated through in vitro, ex vivo, and in vivo. Pharmacokinetic study and anti-tumor effects of Lf-GL were investigated in orthotopic glioblastoma mice model.
Results
Lf-GL interacts with lactoferrin receptor (LfR) expressed on BBB and GBM, therefore, efficiently inhibits HMGB1 in both the cytoplasmic and extracellular regions of tumors. Regarding the tumor microenvironment, Lf-GL inhibits angiogenesis and tumor growth by blocking HMGB1 released from necrotic tumors and preventing recruitment of vascular endothelial cells. In addition, Lf-GL improved the PK properties of GL approximately 10-fold in the GBM mouse model and reduced tumor growth by 32%. Concurrently, various biomarkers for tumor were radically diminished.
Conclusion
Collectively, our study demonstrates a close association between HMGB1 and tumor progression, suggesting Lf-GL as a potential strategy for coping with DAMP-related tumor microenvironment.
Reciprocal Effect between Depressive Symptoms and Adolescent Non-suicidal self-injury before and after COVID-19: A Longitudinal Study
Authors: Hu Rui , Peng Li-li , Du Yu , Feng Yi-wei , Xie Lin-shen , Shi Wei , Jia Peng , Jiang Li-hua , Zhao Li 
Published: February 2023

Abstract
Background
Non-suicidal self-injury (NSSI) is a common psychological and behavioral problem among adolescents and has now become a major public health problem for adolescents. Since the COVID-19 outbreak in 2019, it has caused various mental health problems, such as anxiety, depression, and mental burnout, contributing to a severe mental health crisis globally. Thus far, a few studies recorded the temporal change in adolescents’ psychological status during the COVID-19 pandemic as well as that with the implementation of large-scale public health intervention methods, and this study adds to the evidence.
Methods
Based on the Chengdu Positive Child Development (CPCD) survey, the baseline dataset was collected in December 2019, and the first follow-up of the CPCD was conducted in July 2020. A total of 6,023 adolescents aged 10-19 were recruited from five primary and middle schools. Two independent autoregressive cross-lagged models were used to test the bidirectional relationship between NSSI and depressive symptoms in adolescents; logistic regression analysis was used to explore the predictors of NSSI implementation in adolescents with depressive symptoms, which could provide an entry point for behavioral interventions to NSSI.
Results
The prevalence of depressive symptoms among our participants was 32.69% at baseline, and 34.27% at follow-up. The occurrence rate of NSSI in adolescents who may have depressive symptoms was 44.34%%, and that during the pandemic was 53.44%. The difference was statistically significant (P < 0.05). The results of the binary logistic analysis showed that among adolescents, gender, duration of the online class, depression mood, place of residence, and self-perception of relationship with caregivers were the risk factors for NSSI (or > 1, β> 0), and daily sleep hours positive mood was the protective factor (or < 1, β< 0). The lag effect of adolescent depression on their NSSI behavior is significant, which means that based on controlling the adolescent baseline NSSI, the deeper the adolescent depression degree, the more frequent their NSSI behavior (β=0.26, P<0.01). At the same time, adolescents' NSSI behavior also had a lagging effect on depressive symptoms, and adolescents with self-injury behavior were more likely to be depressed (β=0.02, P<0.01). Depression and NSSI are mutual(β=0.77, P<0.05；β=0.27, P<0.01).
Conclusions
The increased depressive symptoms among adolescents exacerbated their NSSI behaviors and hurt their mental health during COVID-19. Screening for depression should be carried out early to serve as a warning sign in preventing and reducing NSSI in adolescents.
Mechanism of salt tolerance in endangered semi-mangrove plant Barringtonia racemosa: anatomical structure, photosynthetic and fluorescence characteristics
Authors: Hu Ju , Deng Xu , Bai Caihong , Li Lin , Yang Xiuling , Lan Chunxiao , Zhong Haiyan , Tan Xiaohui , Liang Fang 
Published: February 2023

Abstract
Barringtonia racemosa is a rare and endangered semi-mangrove plant with salt tolerance (≤ 25‰ salt). However, mechanisms governing the salt tolerance has not been elucidated. Therefore, biomass, photosynthetic and fluorescent characteristics, and anatomical structure of B. racemosa were studied to investigate the mechanism of salt tolerance. The results showed that stem dry weight decreased under high salt stress (30‰-40‰). Net photosynthetic rate, intercellular CO2 concentration of B. racemosa significantly decreased under 35‰ and 40‰ salt treatments, Fv/Fm decreased significantly under 40‰ salt stress, ΦPSI decreased significantly under 35‰ and 40‰ salt stress. The thickness of epidermis of root significantly increased under 25‰ and 40‰ salt treatments. The outer cortex and stele diameters of root significantly increased, under high salt treatments. The xylem and phloem of stem significantly increased under salt treatments, while the cambium and cortex of stem significantly decreased under salt treatments. The width of the increment or stable palisade tissue and spongy mesophyll. Therefore, stable net photosynthetic rate and intercellular CO2 concentration, increment of Fv/Fm and ΦPSI, the increment or stable palisade tissue and spongy mesophyll of leaf and the increment of epidermis, outer cortex, and stele diameter of root could contribute to salt tolerance of B. racemosa.
Non-driver mutations landscape in different stages of primary myelofibrosis determined ASXL1 mutations play a critical role in disease progression
Authors: Yan Xin , Xu Zefeng , Zhang Peihong , Sun Qi , Jia Yujiao , Qing Tiejun , Qu Shiqiang , Pan Lijuan , Li Zhanqi , Liu Jinqin , Song Zhen , GAO QINGYAN , Jiao Meng , Gong Jingye , Wang Huijun , Li Bing , Xiao Zhijian 
Published: February 2023

Abstract
Except for driver mutations (JAK2, MPL, CALR), primary myelofibrosis (PMF) patients have much more non-driver mutations than polycythemia vera (PV) and essential thrombocythemia (ET) patients. The relationship between disease progression (prefibrotic (Pre) to overtfibrotic (Overt) to accelerate phase/blast phase (AP/BP)) and non-driver mutations is still not very clear. To uncover the effect of these non-driver mutations in the progression of PMF, we retrospectively analyzed 275 samples in different stages (69 Pre-PMF, 161 Overt-PMF and 45 PMF-AP/BP) from 258 consecutive patients. Univariate analysis showed that ASXL1 mutations were closely related to PMF progression with increasing frequency in this process. Multivariate analysis furtherly confirmed that ASXL1 mutations were enriched both in Overt-PMF and in PMF-AP/BP, while U2AF1 mutations were only enriched in Overt-PMF and RUNX1 and NRAS mutations were only enriched in PMF-AP/BP. The data of serial samples from Overt-PMF patients who developed to AP/BP showed that ASXL1 mutations more frequently co-occurred with newly acquired RAS pathway mutations, while RUNX1 mutations were usually freshly acquired with independence on ASXL1 mutations during AP/BP transformation. Collectively, ASXL1 mutations may play a crucial role in the whole course of PMF progression and should be targeted as potential intervention point.
Assessing the genetic relationship between gastroesophageal reflux disease and chronic respiratory diseases: A Mendelian randomization study
Authors: Cheng Xiaoxue , Shi Jiang , Zhang Ding , Li Caichen , He Jianxing , Liang Wenhua 
Published: February 2023

Abstract
Background
Although the association between gastroesophageal reflux disease (GERD) and chronic respiratory diseases was found in previous observational studies, it remains uncertain whether GERD causally influences them. Herein, we aimed to estimate the causal associations between GERD and 5 chronic respiratory diseases.
Methods
88 GERD-associated single nucleotide polymorphisms (SNPs) identified by the latest genome-wide association study were included as instrumental variables. Individual-level genetic summary data of participants were obtained from corresponding studies and the FinnGen consortium. We applied the inverse-variance weighted method to estimate the causality between genetically predicted GERD and 5 chronic respiratory diseases. Furthermore, the associations between GERD and common risk factors were investigated, and mediation analyses were conducted using multivariable MR. Various sensitivity analyses were also performed to verify the robustness of the findings.
Results
This study demonstrated that genetically predicted GERD was causally associated with an increased risk of asthma (OR 1.39, 95%CI 1.25–1.56, P < 0.001), idiopathic pulmonary fibrosis (IPF) (OR 1.43, 95%CI 1.05–1.95, P = 0.022), chronic obstructive disease (COPD) (OR 1.64, 95%CI 1.41–1.93, P < 0.001), chronic bronchitis (OR 1.77, 95%CI 1.15–2.74, P = 0.009), while no correlation was observed for bronchiectasis (OR 0.93, 95%CI 0.68–1.27, P = 0.645). Additionally, GERD was associated with 10 common risk factors for chronic respiratory diseases. Nevertheless, no significant mediators were discovered.
Conclusions
Our study indicated that GERD was a causal factor in the development of asthma, IPF, COPD and chronic bronchitis, suggesting that GERD-associated micro-aspiration of gastric contents process might play a role in the development of pulmonary fibrosis in these diseases.
The effect of interaction between selenium and other elements on the cognitive function of rural elderly Chinese
Authors: Duan Lidan , Su Liqin , He Xiaohong , Du Yegang , Duan Yanying , Xu Ning , Wu Rangpeng , Zhu Yunfeng , Shao Ranqi , Unverzagt Frederick W , Hake Ann M , Jin Yinlong , Gao Sujuan 
Published: February 2023

Abstract
Purpose
To evaluate the association between combined exposure of selenium (Se) and other elements and cognitive function in older adults.
Methods
A cross-sectional study involving 416 rural older adults aged 60 or older was conducted in four areas with different soil Se levels in Enshi county, China. Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine whole blood Se, copper (Cu), iron (Fe), zinc (Zn), calcium (Ca), magnesium (Mg), cadmium (Cd), arsenic (As) and lead (Pb) concentration. Nine standard cognitive tests were applied to assess cognitive function. Analysis of covariance (ANCOVA) and generalized linear models (GLM) were used to determine the association between elements exposure and cognitive function.
Results
The results of Lasso regression show that Se, Cu, Fe, Zn, Ca and Pb were independently identified to be associated with cognition. ANCOVA and GLM consistently indicated that Se and Ca were related to cognitive function. The multi-element model incorporating these selected six elements showed higher composite Z scores of 0.32 (95%CI: 0.087 to 0.533) for log-transformed Se (p < 0.05), 0.75 (95%CI: 0.007 to 1.493) for log-transformed Cu (p = 0.048) and a lower score of 0.67 (95%CI: -1.263 to -0.083) for log-transformed Ca (p < 0.05). Moreover, Se can antagonize the negative effect of Ca on cognitive function (p for interaction = 0.031).
Conclusion
Our findings suggested that higher Se and Cu level were associated with better cognitive function in the elderly, and blood Se can antagonize the cognitive damage of blood Ca.
New mathematical statements about the cardinality and the intersection of P problems, NP problems and NP-Hard problems
Authors: Louiz Akram 
Published: February 2023

Abstract
Thanks to my short studies about informatics, I present to you this mathematical proof that deals with the sets of P problems, NP-Complete problems and NP-Hard problems in order to prove new formulas about the cardinality of each group of problems and about the intersection of each one of these sets. This work ends with a theoremabout the complexity ofproblems that allows us to identify NP problems even if their algorithms have infinite time of execution. Hence, I invite all the readers to use and develop the formulas of this article and to present their opinions about them.
Serum inflammatory biomarkers are associated with increased choroidal thickness in Keratoconus
Authors: Pinheiro-Costa João , Lima-Fontes Mario , Luís Carla , Martins Sandra , Soares Raquel , Madeira Dulce , Falcão-Reis Fernando , Carneiro Angela 
Published: February 2023

Abstract
Inflammation may play a significant role in Keratoconus (KC), but the relationship between inflammatory markers and choroidal thickness (CT) is unknown. The purpose of this study was to evaluate serum inflammatory markers and correlate them with the choroidal profile of KC patients and control subjects. Forty patients with KC and 26 age-matched control subjects were enrolled in a cross-sectional case-control study. Choroidal profile was studied with a Spectralis Heidelberg apparatus and venous blood samples were collected. Neutrophil/lymphocyte ratio (NLR), monocyte/HDL ratio (MHR), platelet/lymphocyte ratio (PLR) and systemic immune inflammation index (SII) were calculated. Serum inflammatory biomarkers IL-1, IL-6 and TNF-alfa were also analyzed. KC group presented thicker choroids in each evaluated point when compared to the control group (subfoveal CT 417.38 ± 79.79 vs 299.61 ± 76.13, p < 0.001 for all measured locations). Mean values of NLR, PLR and SII were significantly higher in patients with KC (NLR p = 0.001; PLR p = 0.042; SII p = 0.007). Although KC patients presented higher mean levels of MHR, IL-1, IL-6 and TNF-α than control group, no significant differences were achieved. Positive correlations were found between subfoveal CT and NLR and SII (0.408, p = 0.001 and 0.288, p = 0.019 respectively). The results presented are in favor of a relationship between the increased CT and inflammatory mechanisms in KC patients. The elevated serum inflammatory indices NLR, SII and PLR provide additional evidence of a role for systemic inflammation in the pathophysiology of KC.
Alterations in Dynamic Functional Connectivity in Patients with Cerebral small vessel disease
Authors: Chen Futao , Chen Qian , Zhu Yajing , Long Cong , Lu Jiaming , Jiang Yaoxian , Zhang Xin , Zhang Bing 
Published: February 2023

Abstract
Background: Cerebral small vessel disease (CSVD) is a common disease that seriously endangers people's health, and is easily overlooked by both patients and clinicians due to its near-silent onset. Dynamic functional connectivity (DFC) is a new concept focusing on the dynamic features and patterns of brain networks, that represents a powerful tool for gaining novel insight into neurological diseases.
Purpose: To assess alterations in DFC in CSVD patients, and the correlation of DFC with cognitive function.
Methods: We enrolled 35 CSVD patients and 31 normal control subjects (NC). Resting-state functional MRI with a sliding-window approach and k-means clustering based on independent component analysis (ICA) was used to evaluate DFC. The temporal properties of fractional windows and the mean dwell time in each state, as well as the number of transitions between each pair of DFC states, were calculated. Additionally, we assessed the strength of the dynamic states and the associations of altered neuroimaging measures with cognitive performance.
Results: A dynamic analysis of all included subjects suggested four distinct functional connectivity states. Compared with the NC group, the CSVD group had more fractional windows and longer mean dwell times in state 4 characterized by sparse functional connections both within and between networks. Additionally, the CSVD group had a reduced number of windows and reduced dwell times compared to the NC group in state 3 characterized by highly positive FC between the somatomotor and visual networks, and negative FC in the basal ganglia and somatomotor and visual networks. The number of transitions between state2 and state3, and between state3 and state4 was significantly reduced in the CSVD group compared to the NC group. Moreover, there was a statistically significant difference in the connection strength between the two groups, and the altered temporal properties of DFC were significantly related to cognitive performance.
Conclusion: Our study indicated that CSVD is characterized by altered temporal properties in DFC that may be sensitive neuroimaging biomarkers for early disease identification. Further study of DFC changes could help us to better understand the progressive dysfunction of networks in CSVD states.
Machine learning-based prognostic modeling of lysosome-related genes for predicting prognosis and immune status of patients with hepatocellular carcinoma
Authors: Li Wenhua , Wang Qianwen , Lu Junxia , Zhao Bin , Geng Yuqing , Wu Xiangwei , Chen Xueling 
Published: February 2023

Abstract
Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide, and lysosomes play an important role in cancer progression as organelles that break down biomolecules such as proteins, nucleic acids, and polysaccharides; however, the molecular mechanisms of lysosome-related genes in hepatocellular carcinoma are not fully understood.
Methods：We downloaded hepatocellular carcinoma datasets from the Cancer Genome Atlas(TCGA) and the Gene Expression Omnibus (GEO) as well as lysosome-related gene sets from AIMGO .After univariate Cox screening of the set of lysosome-associated genes differentially expressed in hepatocellular carcinoma and normal tissues, risk models were built by machine learning. Model effects were then assessed using the concordance index (C-index), Kaplan-Meier (K-M) and receiver operating characteristic curves (ROC), and the “GSVA” package was used to explore the biological function and immune microenvironment between the high- and low-risk groups, and the “IMvigor210CoreBiologies” package was used to analyse the response of the high- and low-risk groups to immunotherapy responsiveness, the “pRRophetic”package was used to explore the sensitivity of the high and low-risk groups to chemotherapeutic agents and finally the function of a key gene (RAMP3) was explored at the cellular level.
Results ：univariate Cox yielded 46 differentially and prognostically significant lysosome-related genes and risk models were constructed using eight genes (RAMP3,GPLD1,FABP5,CD68,CSPG4,SORT1,CSPG5,CSF3R) derived from machine learning. The C-index and ROC showed that the risk model was a better predictor of clinical outcomes, with the K-M values indicating that the higher risk group had worse clinical outcomes. There were significant differences in biological function, immune microenvironment and responsiveness to immunotherapy and drug sensitivity between the high and low-risk groups. Finally, we found that RAMP3 inhibited the proliferation, migration and invasion of hepatocellular carcinoma cells and correlated with the sensitivity of hepatocellular carcinoma cells to Idarubicin.
Conclusion：Lysosome-associated gene risk models built by machine learning can effectively predict patient prognosis and offer new prospects for chemotherapy and immunotherapy in HCC. In addition, cellular-level experiments suggest that RAMP3 may be a new target for the treatment of hepatocellular carcinoma.
Characteristics Study of Mechanical and Tribological Behaviour of Gr/Sn Dispersed Al-7Si Alloy Matrix Composite Processed Through Bottom Pouring Stir Casting Technique
Authors: ajay C. Veera , Mohammed K. Thoufiq , Hariharasakthisudhan P. , Kumar V. Nantha , Vishnu R. 
Published: February 2023

Abstract
Among numerous techniques to manufacture Aluminium metal matrix composites, the stir-casting route is employed for mass production because of less expensive. In this work, Al-7Si alloy-based composites reinforced with 10wt% graphite and x wt% of tin (x = 0, 2.5, 5, 7.5 and 10) microparticles are manufactured through the bottom pouring casting route. This study deals with the various effect of the mechanical properties, and wear resistance of Gr, and Sn particulates reinforced Al-7Si alloy matrix composite. The added Sn metal powder up to 7.5 wt.% was diffused in the lattice of hypo eutectic Al-7Si alloy and formed a solid solution. The hybridization of Sn with graphite in Al-7Si alloy matrix brought significant enhancement in the tribological and mechanical properties of the composites. The ductile mode of fracture in all the composites with tear ridges and dimples was noted. The wear rate and the coefficient of friction of the composites were decreased with the addition of Sn metal powder in the material system. The Sn metal powder surfaced during the wear process and formed a thin mechanically mixed tribo layer and reduced the friction. The thin mechanically mixed tribo layer at the interface restricted the direct contact of asperities in the mating surface and reduced the wear loss. Adhesive wear was found to be active in the composites with Sn metal powder.
Multi-criteria decision process to identify groundwater potential zones using geospatial tools in the Arghandab river basin, Afghanistan
Authors: Farahmand Asadullah , Hussaini Mohammad Salem , Jawadi Hussain Ali , Abrunhosa Manuel , Thomas Brian F. 
Published: February 2023

Abstract
This study used remote sensing (RS) and geographic information system (GIS) techniques to assess groundwater potential areas by applying two multi-criteria decision-making analyses in the Arghandab river basin. Twelve influencing parameters summarizing basin characteristics were gathered and generated using geospatial RS and GIS tools. The analytical hierarchy process (AHP) and analytical network process (ANP) were examined to weigh, ranking, and reclassify raster to produce groundwater potential maps. Two multi-criteria decision models were applied to compare results and suitability in the study area. The results of the AHP analysis delineate five groundwater potential zones (GWPZs) classified as very poor (29%), poor (22%), moderate (17%), high (19%), and very high (14%). On the other hand, the results of the ANP analysis classified GWPZs as very poor (25%), poor (9%), moderate (25%), high (30%), and very high (11%). To validate generated GWPZs maps, a total of 270 well locations data were utilized in the receiver operating characteristic (ROC) curve analysis. ROC model accuracy in training and validation stages is marginally higher for the ANP model (0.810 and 0.823) as compared to the AHP model (0.749 and 0.742). The groundwater potential map delineated in this study offers a preliminary assessment to scientists, public authorities, and policymakers for sustainable management of groundwater resources in the study area.