bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bias polarity dependent low-frequency noise in ultra-thin AlOx-based magnetic tunnel junctions
Authors: Chen Chun-Yen , Gonzalez-Ruano César , Martinez Isidoro , Aliev Farkhad G. , Ling Dah-Chin , Tang Yu-Hui , Hong Jhen-Yong 
Published: June 2024

AbstractWe exploit bias polarity dependent low-frequency noise (LFN) spectroscopy to investigate charge transport dynamics in ultra-thin AlOx-based magnetic tunnel junctions (MTJs) with bipolar resistive switching (RS). By measuring the noise characteristics across the entire bias voltage range of bipolar RS, we find that the voltage noise level exhibits an bias polarity dependence. This distinct feature is intimately correlated with reconfiguring of the inherently existing oxygen vacancies ($${V}_{O}^{..}$$

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) in as-grown MTJ devices during the SET and RESET switching processes. In addition, we observe two-level random telegraph noise (RTN) with a longer and shorter tunneling length in the high resistance state (HRS) and low resistance state (LRS) at a low bias voltage. The intrinsic voltage fluctuations of RTN arise from the dynamics of electron trapping/de-trapping processes at the $${V}_{O}^{..}$$

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-related trap sites. Notably, the RTN magnitude is similar in LRS but nonidentical in that of HRS for different bias polarity. These findings strongly suggest that the inherent $${V}_{O}^{..}$$

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are distributed near the top CoFe/AlOx interface in the HRS; in contrast, they are expanded to the middle region of the AlOx in the LRS. More importantly, we demonstrate that the location and distribution of the inherent $${V}_{O}^{..}$$

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can be electrically tuned, which plays an essential role in the charge transport dynamics in the ultra-thin AlOx-based MTJs and have significant implications for developing emergent memory and logic devices.
Disulfidptosis-related genes serve as potential prognostic biomarkers and indicate tumor microenvironment characteristics and immunotherapy response in prostate cancer
Authors: Zhou Rongbin , Lu Dingjin , Mi Junhao , Wang Chengbang , Lu Wenhao , Wang Zuheng , Li Xiao , Wei Chunmeng , Zhang Huiyong , Ji Jin , Zhang Yifeng , Zhang Duobing , Wang Fubo 
Published: June 2024

AbstractDisulfidptosis, a newly identified programmed cell death pathway in prostate cancer (PCa), is closely associated with intracellular disulfide stress and glycolysis. This study aims to elucidate the roles of disulfidptosis-related genes (DRGs) in the pathogenesis and progression of PCa, with the goal of improving diagnostic and therapeutic approaches. We analyzed PCa datasets and normal tissue transcriptome data from TCGA, GEO, and MSKCC. Using consensus clustering analysis and LASSO regression, we developed a risk scoring model, which was validated in an independent cohort. The model's predictive accuracy was confirmed through Kaplan–Meier curves, receiver operating characteristic (ROC) curves, and nomograms. Additionally, we explored the relationship between the risk score and immune cell infiltration, and examined the tumor microenvironment and somatic mutations across different risk groups. We also investigated responses to immunotherapy and drug sensitivity. Our analysis identified two disulfidosis subtypes with significant differences in survival, immune environments, and treatment responses. According to our risk score, the high-risk group exhibited poorer progression-free survival (PFS) and higher tumor mutational burden (TMB), associated with increased immune suppression. Functional enrichment analysis linked high-risk features to key cancer pathways, including the IL-17 signaling pathway. Moreover, drug sensitivity analysis revealed varied responses to chemotherapy, suggesting the potential for disulfidosis-based personalized treatment strategies. Notably, we identified PROK1 as a crucial prognostic marker in PCa, with its reduced expression correlating with disease progression. In summary, our study comprehensively assessed the clinical implications of DRGs in PCa progression and prognosis, offering vital insights for tailored precision medicine approaches.
Identification of 8 candidate microsatellite instability loci in colorectal cancer and validation of the ACVR2A mechanism in the tumor progression
Authors: Wang Jingyu , Zhang Zhe , Liu Hui , Liu Nian , Hu Yucheng , Guo Wenjuan , Li Xiangzhao 
Published: June 2024

AbstractThis study probes the utility of biomarkers for microsatellite instability (MSI) detection and elucidates the molecular dynamics propelling colorectal cancer (CRC) progression. We synthesized a primer panel targeting 725 MSI loci, informed by The Cancer Genome Atlas (TCGA) and ancillary databases, to construct an amplicon library for next-generation sequencing (NGS). K-means clustering facilitated the distillation of 8 prime MSI loci, including activin A receptor type 2A (ACVR2A). Subsequently, we explored ACVR2A’s influence on CRC advancement through in vivo tumor experiments and hematoxylin–eosin (HE) staining. Transwell assays gauged ACVR2A’s role in CRC cell migration and invasion, while colony formation assays appraised cell proliferation. Western blotting illuminated the impact of ACVR2A suppression on CRC’s PI3K/AKT/mTOR pathway protein expressions under hypoxia. Additionally, ACVR2A’s influence on CRC-induced angiogenesis was quantified via angiogenesis assays. K-means clustering of NGS data pinpointed 32 MSI loci specific to tumor and DNA mismatch repair deficiency (dMMR) tissues. ACVR2A emerged as a pivotal biomarker, discerning MSI-H tissues with 90.97% sensitivity. A curated 8-loci set demonstrated 100% sensitivity and specificity for MSI-H detection in CRC. In vitro analyses corroborated ACVR2A’s critical role, revealing its suppression of CRC proliferation, migration, and invasion. Moreover, ACVR2A inhibition under CRC-induced hypoxia markedly escalated MMP3, CyclinA, CyclinD1, and HIF1α protein expressions, alongside angiogenesis, by triggering the PI3K/AKT/mTOR cascade. The 8-loci ensemble stands as the optimal marker for MSI-H identification in CRC. ACVR2A, a central element within this group, deters CRC progression, while its suppression amplifies PI3K/AKT/mTOR signaling and angiogenesis under hypoxic stress.
Low-molecular-weight heparin in the prevention of unexplained recurrent miscarriage: a systematic review and meta-analysis
Authors: Scarrone Margherita , Salmeri Noemi , Buzzaccarini Giovanni , Canti Valentina , Pasi Federica , Papaleo Enrico , Rovere-Querini Patrizia , Candiani Massimo , Alteri Alessandra , Busnelli Andrea , Vanni Valeria Stella 
Published: June 2024

AbstractThe etiology of recurrent pregnancy loss (RPL) is complex and multifactorial and in half of patients it remains unexplained (U-RPL). Recently, low-molecular-weight heparin (LMWH) has gained increasing relevance for its therapeutic potential. On this regard, the aim of this systematic review and meta-analysis is to analyze the efficacy of low molecular weight heparin (LMWH) from the beginning of pregnancy in terms of live birth rates (LBR) in U-RPL. Registered randomized controlled trials (RCTs) were included. We stratified findings based on relevant clinical factors including number of previous miscarriages, treatment type and control type. Intervention or exposure was defined as the administration of LMWH alone or in combination with low-dose aspirin (LDA). A total of 6 studies involving 1016 patients were included. The meta-analysis results showed that LMWH used in the treatment of U-RPL was not associated with an increase in LBR with a pooled OR of 1.01, a medium heterogeneity (26.42%) and no publication bias. Results of other sub-analyses according to country, treatment type, and control type showed no significant effect of LMWH on LBR in all subgroups, with a high heterogeneity. The results highlight a non-significant effect of LMWH in U-RPL on LBR based on moderate quality evidence.Registration number: PROSPERO: (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022326433).
Compact coherent perfect absorbers using topological guided-mode resonances
Authors: Park Chan Young , Lee Ki Young , Choi Yu Sung , Yoon Jae Woong 
Published: June 2024

AbstractWe propose a topological coherent perfect absorber that enables almost ideal performance with remarkably compact device footprint and tight incident beams. The proposed structure is based on a topological junction of two guided-mode-resonance gratings. The structure provides robust systematic ways of remarkably tight lateral confinement of the absorbing resonance mode and near-perfect mode-match to arbitrary incident beams, which are unavailable with the conventional approaches. We demonstrate an exemplary amorphous Si thin-film structure that enables near-perfect absorptance modulation between 1.7 and 99% with device footprint width of 30-μm and 10-μm-wide incident Gaussian beams. Therefore, our proposed approach greatly improves practicality of guided-mode-resonance coherent perfect absorbers.
The risk factors in diabetic foot ulcers and predictive value of prognosis of wound tissue vascular endothelium growth factor
Authors: Xu Jing , Gao Jian , Li Hui , Zhu Zhoujun , Liu Junliang , Gao Chong 
Published: June 2024

AbstractDiabetic foot ulcer (DFU) is a leading cause of high-level amputation in DM patients, with a low wound healing rate and a high incidence of infection. Vascular endothelial growth factor (VEGF) plays an important role in diabetes mellitus (DM) related complications. This study aims to explore the VEGF expression and its predictive value for prognosis in DFU, in order to provide basis for the prevention of DFU related adverse events. We analyzed 502 patients, with 328 in healing group and 174 in non-healing/recurrent group. The general clinical data and laboratory indicators of patients were compared through Spearman correlation analysis, ROC analysis and logistic regression analysis. Finally, the independent risk factors for adverse prognosis in DFU patients were confirmed. Spearman analysis reveals a positive correlation between the DFU healing rate and ABI, VEGF in wound tissue, and positive rate of VEGF expression, and a negative correlation with DM duration, FPG, HbA1c, TC, Scr, BUN, and serum VEGF. Further logistic regression analysis finds that the DM duration, FPG, HbA1c, ABI, serum VEGF, VEGF in wound tissue, and positive rate of VEGF expression are the independent risk factors for adverse prognosis in DFU (p < 0.05). DM duration, FPG, HbA1c, ABI, serum VEGF, VEGF in wound tissue, and positive rate of VEGF expression are the independent risk factors for prognosis in DFU patients. Patients with these risk factors should be screened in time, which is of great significance to prevent DFU related adverse events and improve outcomes.
Physiological platelet aggregation assay to mitigate drug-induced thrombocytopenia using a microphysiological system
Authors: Harada Kosuke , Wenlong Wang , Shinozawa Tadahiro 
Published: June 2024

AbstractDeveloping a reliable method to predict thrombocytopenia is imperative in drug discovery. Here, we establish an assay using a microphysiological system (MPS) to recapitulate the in-vivo mechanisms of platelet aggregation and adhesion. This assay highlights the role of shear stress on platelet aggregation and their interactions with vascular endothelial cells. Platelet aggregation induced by soluble collagen was detected under agitated, but not static, conditions using a plate shaker and gravity-driven flow using MPS. Notably, aggregates adhered on vascular endothelial cells under gravity-driven flow in the MPS, and this incident increased in a concentration-dependent manner. Upon comparing the soluble collagen-induced aggregation activity in platelet-rich plasma (PRP) and whole blood, remarkable platelet aggregate formation was observed at concentrations of 30 µg/mL and 3 µg/mL in PRP and whole blood, respectively. Moreover, ODN2395, an oligonucleotide, induced platelet aggregation and adhesion to vascular endothelial cells. SYK inhibition, which mediated thrombogenic activity via glycoprotein VI on platelets, ameliorated platelet aggregation in the system, demonstrating that the mechanism of platelet aggregation was induced by soluble collagen and oligonucleotide. Our evaluation system partially recapitulated the aggregation mechanisms in blood vessels and can contribute to the discovery of safe drugs to mitigate the risk of thrombocytopenia.
Study on deformation and failure characteristics of oblique-cut locked rock slope under rainfall conditions
Authors: Wang Hu , Yuan Guangxiang , Huang Zhiquan , Dong Jun , Wei Yi 
Published: June 2024

AbstractBased on the disaster-pregnant environment and development characteristics of landslide disasters in the western region of Henan Province, a generalized model was established by taking the “oblique-cut” locking rock slope in the layered rock slope as the research object. The numerical simulation method was used to analyze the deformation and failure mechanism and stability influence law of the oblique-cut locking rock slope in western Henan under rainfall conditions. The results show that the inclination angle of the weak interlayer directly affects the deformation and failure characteristics of the slope rock mass. With the increase of the geometric parameters of the slope and the inclination angle of the weak interlayer, the failure mechanism is manifested as the slip shear failure along the level at the foot of the slope → the slip shear failure along the level at the foot of the slope (the sliding surface moves upward) → the shear failure in the middle of the slope surface → the slip shear failure along the level at the foot of the slope (the sliding surface moves downward) → the uplift shear failure at the lower edge of the rock layer. When the dip angle of the weak interlayer is constant, the slope stability decreases gradually with the increase in slope gradient and slope height, and the geometric factors of the slope control the overall change trend of the slope stability coefficient. When the slope is greater than 55° and the slope height is greater than 55 m, the shear stress of the slope locking section exceeds its shear strength, and the probability of landslide instability is greatly increased.
Chemical improvement of soluble rocks: Foundation of Mosul Dam as case study
Authors: Aziz Aram , Soroush Abbas , Fattahi Seyed Mohammad , Imam Seyed Mohammad Reza , Ghahremani Mehrdad 
Published: June 2024

AbstractThe dissolution of soluble rocks (gypsum/anhydrite) beneath the Mosul Dam by water seepage has been observed upon the initial impoundment; consequently, several sinkholes have been manifested in the vicinity of the dam site. Traditional grouting has been envisaged as a potential remedy; however this measure has not eradicated the problem. The main purpose of this study is to overcome the solubility of the gypsum/anhydrite rocks using chemical grouts. Rock samples were acquired from the Fatha Formation outcrop and problematic layers of brecciated gypsum situated at varying depths beneath the Mosul Dam. Two commercially available liquid polymers, polyurethane (PU) and a mixture of acrylic and cement (ARC) were used to investigate their sealing performance in halting of the solubility of the rocks (gypsum/anhydrite). To simulate the dissolution phenomenon under the influence of artificial hydraulic pressure of the dam and the water flow in its abutments, two distinct laboratory models were devised. The outcomes from the experimental study on both untreated and treated samples revealed that the acrylic-cement composite (ARC) and polyurethane (PU) are influential polymers in halting the solubility of the gypsum rock samples under both factors of water pressure and high-velocity water flow.
Eribulin induces micronuclei and enhances the nuclear localization of cGAS in triple-negative breast cancer cells
Authors: Yamada Hideyuki , Takada Mamoru , Ghone Dhaval , Yu Muhan , Nagashima Takeshi , Fujimoto Hiroshi , Sakakibara Junta , Hasegawa Yoshie , Takao Shintaro , Yamada Akimitsu , Narui Kazutaka , Ishikawa Takashi , Suzuki Aussie , Otsuka Masayuki 
Published: June 2024

AbstractEribulin (ERI), clinically utilized for locally advanced or metastatic breast tumors, has shown potential links to the immune system. Notably, the cGAS-STING pathway, a key component of innate immunity, has gained prominence. Yet, limited reports explore ERI's effects on the cGAS-STING pathway. Additionally, the nuclear presence of cGAS remains poorly understood. This study uniquely delves into ERI’s impact on both the cytosolic cGAS-STING pathway and nuclear cGAS. ERI enhances nuclear localization of cGAS, resulting in hyper-activation of the cGAS-STING pathway in triple-negative breast cancer cells. Reduction of cGAS heightened both cell proliferation and ERI sensitivity. In clinical data using ERI in a neo-adjuvant setting, patients with low cGAS cases exhibited reduced likelihood of achieving pathological complete response after ERI treatment. These findings illuminate the potential of cGAS and IFNβ as predictive biomarkers for ERI sensitivity, providing valuable insights for personalized breast cancer treatment strategies.
RNASeq highlights ATF6 pathway regulators for CHO cell engineering with different impacts of ATF6β and WFS1 knockdown on fed-batch production of IgG1
Authors: Rives Dyllan , Peak Caroline , Blenner Mark A. 
Published: June 2024

AbstractSecretion levels required of industrial Chinese hamster ovary (CHO) cell lines can challenge endoplasmic reticulum (ER) homeostasis, and ER stress caused by accumulation of misfolded proteins can be a bottleneck in biomanufacturing. The unfolded protein response (UPR) is initiated to restore homeostasis in response to ER stress, and optimization of the UPR can improve CHO cell production of therapeutic proteins. We compared the fed-batch growth, production characteristics, and transcriptomic response of an immunoglobulin G1 (IgG1) producer to its parental, non-producing host cell line. We conducted differential gene expression analysis using high throughput RNA sequencing (RNASeq) and quantitative polymerase chain reaction (qPCR) to study the ER stress response of each cell line during fed-batch culture. The UPR was activated in the IgG1 producer compared to the host cell line and our analysis of differential expression profiles indicated transient upregulation of ATF6α target mRNAs in the IgG1 producer, suggesting two upstream regulators of the ATF6 arm of the UPR, ATF6β and WFS1, are rational engineering targets. Although both ATF6β and WFS1 have been reported to negatively regulate ATF6α, this study shows knockdown of either target elicits different effects in an IgG1-producing CHO cell line. Stable knockdown of ATF6β decreased cell growth without decreasing titer; however, knockdown of WFS1 decreased titer without affecting growth. Relative expression measured by qPCR indicated no direct relationship between ATF6β and WFS1 expression, but upregulation of WFS1 in one pool was correlated with decreased growth and upregulation of ER chaperone mRNAs. While knockdown of WFS1 had negative impacts on UPR activation and product mRNA expression, knockdown of ATF6β improved the UPR specifically later in fed-batch leading to increased overall productivity.
A microphysiological system reveals neutrophil contact-dependent attenuation of pancreatic tumor progression by CXCR2 inhibition-based immunotherapy
Authors: Shao Shuai , Delk Nikki A. , Jones Caroline N. 
Published: June 2024

AbstractCancer cells recruit neutrophils from the bloodstream into the tumor tissue, where these immune cells promote the progression of numerous solid tumors. Studies in mice suggest that blocking neutrophil recruitment to tumors by inhibition of neutrophil chemokine receptor CXCR2 could be a potential immunotherapy for pancreatic cancer. Yet, the mechanisms by which neutrophils promote tumor progression in humans, as well as how CXCR2 inhibition could potentially serve as a cancer therapy, remain elusive. In this study, we developed a human cell-based microphysiological system to quantify neutrophil-tumor spheroid interactions in both “separated” and “contact” scenarios. We found that neutrophils promote the invasion of tumor spheroids through the secretion of soluble factors and direct contact with cancer cells. However, they promote the proliferation of tumor spheroids solely through direct contact. Interestingly, treatment with AZD-5069, a CXCR2 inhibitor, attenuates invasion and proliferation of tumor spheroids by blocking direct contact with neutrophils. Our findings also show that CXCR2 inhibition reduces neutrophil migration toward tumor spheroids. These results shed new light on the tumor-promoting mechanisms of human neutrophils and the tumor-suppressive mechanisms of CXCR2 inhibition in pancreatic cancer and may aid in the design and optimization of novel immunotherapeutic strategies based on neutrophils.
Addressing data limitations in seizure prediction through transfer learning
Authors: Lopes Fábio , Pinto Mauro F. , Dourado António , Schulze-Bonhage Andreas , Dümpelmann Matthias , Teixeira César 
Published: June 2024

AbstractAccording to the literature, seizure prediction models should be developed following a patient-specific approach. However, seizures are usually very rare events, meaning the number of events that may be used to optimise seizure prediction approaches is limited. To overcome such constraint, we analysed the possibility of using data from patients from an external database to improve patient-specific seizure prediction models. We present seizure prediction models trained using a transfer learning procedure. We trained a deep convolutional autoencoder using electroencephalogram data from 41 patients collected from the EPILEPSIAE database. Then, a bidirectional long short-term memory and a classifier layers were added on the top of the encoder part and were optimised for 24 patients from the Universitätsklinikum Freiburg individually. The encoder was used as a feature extraction module. Therefore, its weights were not changed during the patient-specific training. Experimental results showed that seizure prediction models optimised using pretrained weights present about four times fewer false alarms while maintaining the same ability to predict seizures and achieved more 13% validated patients. Therefore, results evidenced that the optimisation using transfer learning was more stable and faster, saving computational resources. In summary, adopting transfer learning for seizure prediction models represents a significant advancement. It addresses the data limitation seen in the seizure prediction field and offers more efficient and stable training, conserving computational resources. Additionally, despite the compact size, transfer learning allows to easily share data knowledge due to fewer ethical restrictions and lower storage requirements. The convolutional autoencoder developed in this study will be shared with the scientific community, promoting further research.