bluuebunny/crossref_metadata_2025_split huggingface dataset:
A consortia of clinical E. coli strains with distinct in-vitro adherent/invasive properties establish their own co-colonization niche and shape the intestinal microbiota in inflammation-susceptible mice
Authors: Bleich Rachel M. , Li Chuang , Sun Shan , Barlogio Cassandra J. , Broberg Christopher A. , Franks Adrienne R. , Bulik-Sullivan Emily , Dogan Belgin , Simpson Kenneth W. , Carroll Ian M. , Fodor Anthony A. , Arthur Janelle C. 
Published: May 2023

Abstract
Background Inflammatory bowel disease (IBD) patients experience recurrent episodes of intestinal inflammation and often follow an unpredictable disease course. Mucosal colonization with adherent-invasive Escherichia coli (AIEC) are believed to perpetuate intestinal inflammation. However, it remains unclear if the 24-year-old AIEC in-vitro definition fully predicts mucosal colonization in-vivo. To fill this gap, we have developed a novel molecular barcoding approach to distinguish strain variants in the gut and have integrated this approach to explore mucosal colonization of distinct patient-derived E. coli isolates in gnotobiotic mouse models of colitis.Results Germ-free inflammation-susceptible interleukin-10-deficient (Il10−/−) and inflammation-resistant WT mice were colonized with a consortia of AIEC and non-AIEC strains, then given a murine fecal transplant to provide niche competition. E. coli strains isolated from human intestinal tissue were each marked with a unique molecular barcode that permits identification and quantification by barcode-targeted sequencing. 16S rRNA sequencing was used to evaluate the microbiome response to E. coli colonization. Our data reveal that specific AIEC and non-AIEC strains reproducibly colonize the intestinal mucosa of WT and Il10−/− mice. These E. coli expand in Il10−/− mice during inflammation and induce compositional dysbiosis to the microbiome in an inflammation-dependent manner. In turn, specific microbes co-evolve in inflamed mice, potentially diversifying E. coli colonization patterns. We observed no selectivity in E. coli colonization patterns in the fecal contents, indicating minimal selective pressure in this niche from host-microbe and interbacterial interactions. Because select AIEC and non-AIEC strains colonize the mucosa, this suggests the in vitro AIEC definition may not fully predict in vivo colonization potential. Further comparison of seven E. coli genomes pinpointed unique genomic features contained only in highly colonizing strains (two AIEC and two non-AIEC). Those colonization-associated features may convey metabolic advantages (e.g., iron acquisition and carbohydrate consumption) to promote efficient mucosal colonization.Conclusions Our findings establish the in-vivo mucosal colonizer, not necessarily AIEC, as a principal dysbiosis driver through crosstalk with host and associated microbes. Furthermore, we highlight the utility of high-throughput screens to decode the in-vivo colonization dynamics of patient-derived bacteria in murine models.
A New Frontier in Mineral Exploration: Hybrid Machine Learning and Bat Metaheuristic Algorithm for Cu-Au Mineral Prospecting in Sonajil area, E-Azerbaijan
Authors: Mohammadzadeh Mohammadjafar , Mahboubiaghdam Majid , Nasseri Aynur , Jahangiri Moharram 
Published: May 2023

Abstract
Modeling mineral prospectivity is a challenging strategy in characterization of blind ore zones and mineral prospecting. Therefore, the application of advanced spatial modeling techniques and machine learning algorithms is important in exploration pattern recognition. In this study, a combination of a support vector machine (SVM) and the bat algorithm (BA) has been employed to improve the classification and produce an optimal prospectivity map of porphyry copper-gold deposit in the Sonajil area, NW of Iran. In the proposed model, BA was used to optimize the SVM parameters. In data preparation, evidence layers of 10 exploratory features (geological, geochemical, remote sensing and boreholes) were prepared. Then based on 100-meter buffering around boreholes, the data (training and testing) was selected. For mapping mineral prospectivity in the area, the results of two predictive single SVM and hybrid SVM-BA models were compared. Both models were trained by way of predictor maps and then the models performance were evaluated by confusion matrix and receiver operating characteristic (ROC) curve. The results showed that both predictive models had an obvious optimization effect on recognizing the Cu-Au mineralization pattern but the hybrid model had higher accuracy in anomalous zone enhancement, with ROC values more than 0.8, indicating this optimization was successful and the selected optimal model is the best predictor for mineral prospectivity in the area. The delineated targets are also in accordance with the characteristics of the area metallogenic system showing that the established hybrid model is an effective tool in mineral prospectivity mapping.
Affordance and the aesthetic experience of raingardens
Authors: Dobbie Meredith Frances , Farrelly Megan Anne 
Published: May 2023

AbstractContext.Raingardens are being retrofitted in cities worldwide to contribute to urban sustainability and resilience. They must function both technically and aesthetically. Although technical design guidelines for raingardens are available, aesthetic design guidelines are limited.Objectives.Understanding how raingardens are aesthetically experienced can inform their design and management to optimise their acceptance when retrofitted into streetscapes. Four types of aesthetic experience of landscapes are described in the literature. Understanding which type applies in raingarden perception can contribute to aesthetic design guidelines.Methods.As part of a broader study into perception of raingardens in Melbourne, Australia, using mixed methods, survey and focus group data were analysed quantitatively and qualitatively to reveal perceptual aesthetic experiences, either directly or by inference.Results.Scenic and ecological aesthetics, aesthetics of care and knowledge, and attachment and identity were identified. A fifth aesthetic, initially considered as affordance, emerged from analysis. As affordance underpins all landscape aesthetic experiences, this fifth aesthetic experience, relating to a person’s ability to function in or use the landscape, is named an aesthetic of function. Design guidelines are proposed to accommodate different aesthetic experiences of streetscapes retrofitted with raingardens to optimise their appreciation and acceptance.Conclusions.Landscape assessment as aesthetic preference has dominated landscape perception literature. This study suggests that perceived affordances drive aesthetic experiences in the perceptible realm. We call on landscape designers and managers to consider design of retrofitted raingardens that does not mimic natural forms but draws attention to nature-based processes within the raingardens and fosters environmental ethics.
Exploration of Serum Metabolic Signature of Erythrodermic Psoriasis Based on High-throughput Ultra-performance Liquid Chromatography Mass Spectrometry
Authors: Guo Lan , Wu Chao , Jin Hong-Zhong 
Published: May 2023

AbstractBackgroundErythrodermic psoriasis (EP) is a rare and life-threatening disease, the pathogenesis of which remains to be largely unknown. The dysregulated metabolites could be tightly associated with the disease pathogenesis.ObjectivesTo explore the distinctive serum metabolic signature of EP.MethodsSerum samples of 20 EP patients and 20 matched healthy controls were collected. Non-targeted metabolomics based on a high-throughput ultra-performance liquid chromatography mass spectrometry (UHPLC-MS) was conducted. Principal components analysis (PCA), partial least squares discriminant analysis (PLS-DA) and pathway analysis were performed.Results65 metabolites of known identity were significantly changed in EP patients compared to controls, including 24 up-regulated metabolites and 41 down-regulated metabolites. EP patients had lower levels of glycerophosphocholines, including lysophosphatidylcholine (LPC), phosphatidylcholine (PC), and lysophosphatidyl ethanolamine (LPE). EP patients had lower levels of bile acids, including 7-ketodeoxycholic, deoxycholic and lithocholic acid. EP patients had lower esculetin and 3-hexenedioic acid levels. The area under the curve (AUC) value of esculetin, 7-ketodeoxycholic acid and 3-hexenedioic acid was higher than 0.90. Dysregulated metabolites were significantly enriched in the glycerophospholipid metabolism pathway.ConclusionsThe serum metabolic signature of EP was discovered. The down-regulated glycerophosphocholines and bile acids might take part in the development of EP. The dysregulated metabolites might be associated with damaged skin barriers and extensive skin inflammation. The metabolite differences help elucidate the development and pathogenesis of EP and they may provide insights for therapeutic interventions.
A phase II study on the efficacy of regorafenib in treating patients with c-KIT-mutated metastatic malignant melanoma that progressed after previous treatment (KCSG-UN-14-13)
Authors: Kim Kyoo Hyun , Jung Minkyu , Lee Hyo Jin , Lee Su Jin , Kim Miso , Ahn Mi Sun , Choi Moon Young , Lee Na-Ri , Shin Sang Joon 
Published: May 2023

Abstract
Background c-KIT mutations are found in approximately 15% of the patients with malignant melanoma; agents such as imatinib have previously shown high response rates. Regorafenib, an oral multikinase inhibitor, acts against wild-type and mutant KIT. This multi-institutional phase II single-arm study aimed to evaluate the efficacy of regorafenib against metastatic malignant melanoma harboring the c-KIT mutation.Methods Patients with recurrent/metastatic melanoma positive for c-KIT mutations, whose disease progressed after at least one line of systemic treatment, were eligible. The patients received oral regorafenib 160 mg once daily for 3 weeks (4-week cycle). The primary endpoint was the disease control rate (DCR), and the secondary endpoints were safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS).Results In all, 153 patients were screened for c-KIT mutations and 23 patients were enrolled (December 2014–January 2022). c-KIT mutations were frequently reported in exon 11 (14/23, 60.9%), followed by exons 13, 17, and 9 in 5 (21.7%), 5 (21.7%), and 2 (8.7%) patients, respectively. The DCR at 8 weeks was 73.9%, with 2 patients (8.7%) achieving CR, 5 (21.7%) achieving PR, and 10 (43.5%) showing stable disease. The ORR was 30.4% (7/23). The median follow-up period was 15.2 months (95% confidence interval [CI], 10.0–21.5), and median OS and PFS were 21.5 months (95% CI, 15.1–27.9) and 7.1 months (95% CI, 5.0–9.2), respectively. Circulating tumor DNA (ctDNA) analysis in selected patients showed high c-KIT correlation (85.7%) with tissue-based tumor mutational profiles. Skin reactions, including Palmar-plantar erythrodysesthesia (52.2%) and skin rash (30.4%) were the most common adverse events (AEs). Grade 3 AEs, including infection, rash, mucositis, and marrow suppression, occurred in 9 patients (39.1%).Conclusion Regorafenib in second- or later-line settings demonstrated significant activity in patients with metastatic melanoma harboring c-KIT mutations, with an ORR of 30.4% and DCR of 73.9%.Trial registration ClinicalTrials.gov NCT02501551, registered Jul 17, 2015.
STAT3-mediated ferroptosis is involved in α-synuclein pathology
Authors: Zhang Han , Jing Xiuna , Zhang Jieli , Huang Kaixun , Chen Ying , Shen Qingyu , Tao Enxiang , Lin Danyu 
Published: May 2023

AbstractBackgroundOligomeric α-synuclein (α-syn) can activate microglia to drive the early stages of Parkinson's disease (PD) pathogenesis. Our previous studies have found a significant expression difference between the lncRNA IL6ST-AS and its antisense RNA IL6ST in the cerebrospinal fluid of PD patients. Furthermore, in α-syn-induced HMC3 cells, a decline in IL6ST and its downstream target JAK2/STAT3 were also observed. Accumulating investigations have illustrated that STAT3 regulates the expression of ferroptosis-related genes and further influences the proliferation of cells.MethodsThe role and mechanisms of IL6ST/JAK2/STAT3 axis in α-syn induced HMC3 cells and PD mouse models were explored by Western blot or immunohistochemistry. Transcriptome sequencing of HMC3 cells exposed to α-syn oligomers and PD mouse models were performed. The STAT3 activator and the STAT3 inhibitor were used to regulate the expression of STAT3. qPCR was used to detect the expression of ferroptosis regulation genes (FRG) in HMC3 cells induced by α-syn or STAT3 inhibitor. ROS, lipid peroxidation and iron levels were measured by flow cytometry.ResultsWe found that α-syn could impair cell activity and stalely inhibit the IL6ST/ STAT3/HIF-1α pathway in α-syn-induced HMC3 cells. Besides, we performed transcriptomic analysis for α-syn-induced HMC3 cells and in α-syn-induced PD mouse models and GSEA indicated an association with ferroptosis. The reduction in P-STAT3 resulted in the lower expression of HIF-1α and the transcriptional activation of ferroptosis positive regulation (FPR) genes. P-STAT3 mediated ferroptotic cell death in α-syn-induced HMC3 cells by modulating lipid peroxidation and iron metabolism levels. An in vivo study revealed that the IL6ST/JAK2/STAT3/HIF-1α pathway was upregulated in PD mouse models.ConclusionsSTAT3 was an important factor that regulates ferroptosis in α-syn pathology via the JAK2/STAT3/HIF-1α axis. Our research illustrated the relationship of the JAK2/STAT3/HIF-1α axis and ferroptosis in the pathological process of α-syn both in vitro and in vivo, providing new topics of interest regarding the inflammation damage hypothesis and pathogenesis in PD.
A Fuzzy Colored Petri-Net Approach for Hybrid Intrusion Prediction
Authors: Jemili Farah 
Published: May 2023

Abstract
Reducing the impact of computer attacks is crucial, and Intrusion Detection Systems (IDS) are an important tool in achieving this goal. However, IDSs have limitations and are unable to detect all attacks or anticipate future ones. To address this issue, we propose a new approach called a hybrid intrusion prediction system (IPS) that not only detects attacks but also predicts potential intrusions. By simulating the behavior of intruders on internal machines, our system provides network administrators with a comprehensive overview, enabling them to identify possible future intrusions and minimize the impact of attacks. Our study aims to predict future attacks based on the behavioral patterns of previously detected intrusions. We describe the architecture and implementation of our proposed system in this paper. Our experiments using real-world datasets demonstrate that the system is highly effective, achieving a high rate of accurate predictions.
Acceptance and use of a clinical decision support system in musculoskeletal pain disorders – The SupportPrim Project
Authors: Granviken Fredrik , Meisingset Ingebrigt , Vasseljen Ottar , Bach Kerstin , Bones Anita Formo , Klevanger Nina Elisabeth 
Published: May 2023

Abstract
Background We have developed a clinical decision support system (CDSS) based on methods from artificial intelligence to support physiotherapists and patients in the decision-making process of managing musculoskeletal (MSK) pain disorders in primary care. The CDSS finds the most similar successful patients from the past to give treatment recommendations for a new patient. Using previous similar patients with successful outcomes to advise treatment moves management of MSK pain patients from one-size fits all recommendations to more individually tailored treatment. This study aimed to describe the development and explore the acceptance and use of the CDSS for MSK pain patients.Methods This mixed-methods study was carried out in the Norwegian physiotherapy primary healthcare sector between October and November 2020, ahead of a randomised controlled trial. We included four physiotherapists and three of their patients, in total 12 patients, with musculoskeletal pain in the neck, shoulder, back, hip, knee or complex pain. We conducted semi-structured telephone interviews with all participants. The interviews were analysed using the Framework Method. In addition, physiotherapists answered the 10-item System Usability Scale.Results Overall, both the physiotherapists and patients found the system acceptable and usable. Important findings from the analysis of the interviews were that the CDSS was valued as a preparatory and exploratory tool, facilitating the therapeutic relationship. However, the physiotherapists used the system mainly to support their previous and current practice rather than involving patients to a greater extent in decisions and learning from previous successful patients.Conclusions The CDSS was acceptable and usable to both the patients and physiotherapists. However, the system appeared not to considerably influence the physiotherapists' clinical reasoning and choice of treatment based on information from most similar successful patients. This could be due to a smaller than optimal number of previous patients in the CDSS or insufficient clinical implementation. Extensive training of physiotherapists should not be underestimated to build understanding and trust in CDSSs.
The Importance of Development and Application of Subtyping Models for Breast Cancer on the Same Platform
Authors: Li Xiangnan , Hu Zixin 
Published: May 2023

Abstract
Background Intrinsic subtypes have played an important role in breast cancer research. The accuracy of breast cancer research findings depends on the accuracy of intrinsic subtype classification of breast cancer samples. Popular intrinsic subtype models, such as PAM50 and AIMS, were mainly developed on Microarray but are widely used in other platforms. The transferability of these models to RNA-seq and other platforms has rarely been studied. We aim to assess the effectiveness of popular intrinsic subtype models on RNA-seq data and improve the accuracy of breast cancer subtyping on this platform.Methods Assuming that one breast cancer sample only belongs to one subtype irrespective of the expression measuring platform, we assessed the consistency of subtype predictions of PAM50 and AIMS for TCGA Microarray and RNA-seq data from the same samples using Kappa statistic. We also built 12 models using common and intrinsic genes on both Microarray and RNA-seq data, and evaluated their performance under the same assumption.Results Both PAM50 and AIMS failed to produce consistent predictions for Microarray and RNA-seq data from the same samples, with Kappa values of 0.33 and 0.21, respectively. Data normalization improved prediction consistency but introduced false classification. Microarray-developed models showed low prediction consistency when applied to both Microarray and RNA-seq profiles of the same samples. However, prediction consistency between predictions of RNA-seq developed model predicting RNA-seq data and Microarray developed model predicting Microarray data was high with most Kappa values above 0.85.Conclusion Great caution should be taken when using PAM50 and AIMS for the subtyping of breast cancer RNA-seq data. Breast cancer subtyping models should be developed and applied on the same platform, using unnormalized expression data for accurate subtype prediction purpose.
Cirrhotic-extracellular matrix attenuates aPD-1 treatment response by initiating immunosuppressive neutrophil extracellular traps formation in hepatocellular carcinoma
Authors: Shen Xiao-Tian , Xie Sun-Zhe , Zou Tian-Tian , Hu Bei-Yuan , Xu Jing , Zhen Xin , Xu Yun-Feng , Wang Xu-Feng , Wang Hao , Wang Shun , Zhu Le , Yu Kang-Kang , Zhu Wen-Wei , Lu Lu , Zhang Ju-Bo , Chen Jin-Hong , Dong Qiong-Zhu , Yang Lu-Yu , Qin Lun-Xiu 
Published: May 2023

Abstract
Background Hepatocellular carcinoma (HCC) is closely associated with chronic liver diseases, particularly liver cirrhosis, which has an altered extracellular matrix (ECM) composition. The influence and its mechanism of the cirrhotic-ECM on the response of HCC to immune checkpoint inhibitor (ICI) remains less clarified.Methods In silico, proteomic and IHC assessment of alteration of cirrhotic-ECM were applied in clinical cohort. Multiple pre-clinical models with ECM manipulation were used to evaluate cirrhotic-ECM’s effect on ICI treatment. In silico, flow cytometry and IHC were applied to explore how cirrhotic-ECM affect HCC microenvironment. In vitro and in vivo experiments were carried out to identify the mechanism of how cirrhotic-ECM undermined ICI treatment.Results We defined “a pro-tumor cirrhotic-ECM” which was featured as the up-regulation of Col1. Cirrhotic-ECM/Col1 was closely related to impaired T cell function and limited aPD-1 response of HCC patients from the TCGA pan cancer cohort and the authors’ institution, as well as in multiple pre-clinical models. Mechanically, cirrhotic-ECM/Col1 orchestrated an immunosuppressive microenvironment (TME) by triggering Col1-DDR1-NFκB-CXCL8 axis, which initiated neutrophil extracellular traps (NETs) formation to shield HCC cells from attacking T cells and impede approaching T cells. Nilotinib, an inhibitor of DDR1, reversed the neutrophils/NETs dominant TME and efficiently enhanced the response of HCC to aPD-1.Conclusions cirrhotic-ECM modulated a NETs enriched TME in HCC, produced an immune suppressive TME and weakened ICI efficiency. Col1 receptor DDR1 could be a potential target synergically used with ICI to overcome ECM mediated ICI resistance. These provide a mechanical insight and novel strategy to overcome the ICI resistance of HCC.
An Improved DQN Algorithm for Automated Guided Vehicle Pathfinding Problem in Port Environment
Authors: Leibing Xiao , Wei Xinchao , Xu Yuelei , Xu Xin , Li Huafeng 
Published: May 2023

Abstract
This paper introduces the D* Hindsight Deep Q-learning (DH-DQN) algorithm, which combines the D* algorithm and is applied to the port AGV path planning problem. To address the drawbacks of long decision times and large storage space of the D* algorithm, this paper proposes an improved DQN algorithm for a single AGV path planning problem. The Hindsight experience replay algorithm is used to alleviate the problem of slow or non-convergence due to sparse reward space. By selecting the actions planned by the D* algorithm with a certain probability, the DH-DQN algorithm's convergence speed and stability are improved, and its decision time is shorter than the classical D* algorithm. The DH-DQN algorithm is used to control an AGV to perform different tasks in different layouts. Experimental results show that the DH-DQN algorithm not only avoids non-convergence in four different layouts but also converges faster than the classical DQN algorithm. Furthermore, the DH-DQN and DQN algorithms' decision-making process's time comparison under the four layouts reveals that DH-DQN saves 24.91\% of the time in the large-scale environment and 28.08\% in the small-scale environment. Therefore, the DH-DQN algorithm performs well in solving the port AGV path planning problem.