bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive analysis reveals KLB as a prognostic biomarker in colorectal cancer based on systematic pancancer analysis
Authors: Bi Xiaofei , Zhang Wenjin , Shen Meimei Shen , Wu Guicheng , Fang Chengmei , Gao Jian 
Published: March 2024

Abstract
Background
The incidence of colorectal cancer, a prevalent digestive system tumor, is increasing. Earlier research has demonstrated the significant impact of β-Klotho(KLB) on the development of metabolic disorders. Nonetheless, the function of KLB in tumors, particularly in colorectal cancer(CRC), remains underresearched.
Methods
By employing databases such as the TCGA, GTEx, Human Protein Atlas, UALCAN, and cBioPortal, we gathered information regarding KLB expression levels, its predictive and diagnostic importance, epigenetic characteristics, various immune and molecular subtypes, immune checkpoints, and the extent of immune infiltration. The “clusterProfiler” R package was utilized for enrichment analysis to investigate the possible role of KLB. To determine the optimal prognostic model, multivariate Cox regression and Akaike's information criterion were applied. Additionally, CCK-8 assays, colony formation assays, and cell scratch assays were employed to assess the impact of KLB on the biological activities of CRC cells.
Results
Pancancer studies revealed a decrease in KLB in CRC and various other cancers, but an increase in KLB in liver hepatocellular carcinoma and prostate adenocarcinoma. Consequently, reduced KLB expression correlated with a lower TNM stage and unfavorable clinical outcomes in CRC patients. The nomogram, developed considering KLB, CEA level, and TNM stage, demonstrated enhanced predictive accuracy in CRC. Analysis of immune cell infiltration revealed a correlation between reduced KLB expression and decreased infiltration of immune cells. Experiments involving CCK-8, colony formation, and cell scratch assays revealed that the increased in vitro expression of KLB suppressed the growth, movement, and infiltration of CRC cells.
Conclusion
The expression levels of KLB were lower in CRC tissues than in normal tissues. A notable correlation was found between its reduced expression and a grim outlook. Furthermore, KLB is crucial for the immune response of tumors and the biological actions of CRC cells. Consequently, KLB could be a potential biomarker for prognosis and a target for therapy in CRC patients.
Integrated bioinformatics combined with machine learning to analyze shared biomarkers and pathways in psoriasis and cervical squamous cell carcinoma
Authors: Liu Luyu , Yin Pan , Ruida Yang , Zhang Guanfei , Wu Cong , Zheng Yan , Wu Shaobo , Liu Meng 
Published: March 2024

Abstract

Background:
Psoriasis extends beyond its dermatological inflammatory manifestations, encompassing systemic inflammation. Existing studies have indicated a potential risk of cervical cancer among patients with psoriasis, suggesting a potential mechanism of co-morbidity. This study aims to explore the key genes, pathways, and immune cells that may link psoriasis and cervical squamous cell carcinoma (CESC).
Methods:
The cervical squamous cell carcinoma dataset (GSE63514) was downloaded from the Gene Expression Omnibus (GEO). Two psoriasis-related datasets (GSE13355 and GSE14905) were merged into one comprehensive dataset after removing batch effects. Differentially expressed genes were identified using Limma and co-expression network analysis (WGCNA), and machine learning random forest algorithm (RF) was used to screen the hub genes. We analyzed relevant gene enrichment pathways using GO and KEGG, and immune cell infiltration in psoriasis and squamous cervical cancer samples using CIBERSORT. The miRNA-mRNA and TFs-mRNA regulatory networks were then constructed using Cytoscape, and the biomarkers for psoriasis and CESC were determined. Potential drug targets were obtained from the cMAP database, and biomarker expression levels in hela and psoriatic cell models were quantified by RT-qPCR.
Results:
In this study, we identified 27 key genes associated with psoriasis and cervical squamous cell carcinoma. NCAPH, UHRF1, CDCA2, CENPN and MELK were identified as hub genes using the Random Forest machine learning algorithm. Chromosome mitotic region segregation, nucleotide binding and DNA methylation are the major enrichment pathways for common DEGs in the mitotic cell cycle. Then we analyzed immune cell infiltration in psoriasis and cervical squamous cell carcinoma samples using CIBERSORT. Meanwhile, we used the cMAP database to identify ten small molecule compounds that interact with the central gene as drug candidates for treatment. By analyzing miRNA-mRNA and TFs-mRNA regulatory networks, we identified three miRNAs and nine transcription factors closely associated with five key genes and validated their expression in external validation datasets and clinical samples. Finally, we examined the diagnostic effects with ROC curves, and performed experimental validation in hela and psoriatic cell models.
Conclusions:
We identified five biomarkers, NCAPH, UHRF1, CDCA2, CENPN, and MELK, which may play important roles in the common pathogenesis of psoriasis and cervical squamous cell carcinoma, furthermore predict potential therapeutic agents. These findings open up new perspectives for the diagnosis and treatment of psoriasis and squamous cell carcinoma of the cervix.
Reinforcement Learning for Zero-Day Vulnerability Detection in IoT Devices: A Proactive Approach
Authors: Reddy Bhargavi Peddi , Shaik Shakeel Ahamad , Gaddam Venu Gopal , S Ramakrishna K V S , M Jogendra Kumar 
Published: March 2024

Abstract
Zero - Day vulnerabilities pose a significant threat to the security of IoT devices, as they remain undetected and unpatched by vendors. In this research paper, we propose a novel approach to Zero-Day Vulnerability Detection in IoT devices using reinforcement learning for conjecture generation. Our model leverages real-time telemetry data from IoT devices and metadata about the network to generate potential conjectures about Zero-Day vulnerabilities. The agent is trained with a deep reinforcement learning architecture and benefits from a human-in-the-loop to incorporate domain expertise. We evaluate the performance of the model on a real-world IoT testbed and compare it with existing approaches, demonstrating its proactive and efficient nature in detecting Zero-Day vulnerabilities.
Keywords: Zero-Day Vulnerabilities, IoT Devices, Reinforcement Learning, Conjecture Generation Vulnerability Detection
Integrated proteomics and metabolomics analysis reveals new insight into the synergistic antitumor effect of valproic acid plus simvastatin in prostate cancer xenograft model associated with downmodulation of YAP/TAZ signaling
Authors: Iannelli Federica , Lombardi Rita , Costantini Susan , Roca Maria Serena , Addi Laura , Bruzzese Francesca , Gennaro Elena Di , Budillon Alfredo , Pucci Biagio 
Published: March 2024

Abstract

Background: Despite advancements in therapeutic approaches, including taxane-based chemotherapy and androgen receptor targeting agents, metastatic castration-resistant prostate cancer (mCRPC) remains an incurable tumour, underlying the need of novel strategies that can target the complexities of this disease and bypass the development of drug-resistance mechanisms. We previously demonstrated the synergistic antitumor interaction of the antiepileptic with histone deacetylase inhibitory activity valproic acid (VPA), and the lipid-lowering drug simvastatin (SIM). This combination sensitizes mCRPC cells to docetaxel treatment, both in vitro and in vivo models, by targeting cancer stem cells compartment via mevalonate pathway/YAP axis modulation.
Methods Here, by a combined proteomic and metabolomic/lipidomic approach we characterized tumor samples derived from 22Rv1 mCRPC cells xenografted mice, treated or not with VPA/SIM combination, coupled with an in deep bioinformatics analysis.
Results We confirmed a specific impact of VPA/SIM on Hippo-YAP signaling pathway, functionally related with modulation of cancer-related extracellular matrix biology and metabolic reprogramming, providing further insights into the molecular mechanism of the VPA/SIM antitumor effect.
Conclusions In the current study, we present an in-depth exploration of the potential to repurpose in mCRPC treatment two generic and safe drugs, valproic acid (VPA) and simvastatin (SIM), that already showcased anti-tumor efficacy in combination, primarily affecting cancer stem cell compartment via MVP/YAP axis modulation. Bioinformatics analysis of LC-MS/MS proteomics and of 1H-NMR metabolomics/lipidomics results, confirmed a specific impact of VPA/SIM on Hippo-YAP
Reduction in mitochondrial ATP synthesis depolarizes neurons from the subpostremal nucleus of the solitary tract of rats
Authors: Zarpellon Patrik Saul , Murat Cahuê , Leão Ricardo Mauricio 
Published: March 2024

Abstract

Neurons of the subpostremal nucleus of the solitary tract (NTS) respond to changes in extracellular glucose with alterations in membrane potential with both depolarization and hyperpolarization. From 5 mM glucose, a rapid shift to 0.5 mM glucose produces a membrane depolarization by an unknown mechanism in most neurons from juvenile rats. However, the mechanism involved in this response needs to be known. Here, we investigated if the low glucose-induced depolarization could be mimicked by reducing ATP synthesis and possible mediators of this effect. We showed that applying the mitochondrial uncoupler CCCP (1 µM) reproduced the effects of low glucose depolarizing the membrane, generating an inward current, and decreasing membrane resistance. On the other hand, activation of AMPK did not alter these parameters. To test if low glucose and CCCP could depolarize the membrane by affecting the ionic gradient, we inhibited the electrogenic Na/K pump with 10 µM of ouabain. We observed a similar membrane depolarization but not a decrease in membrane resistance. We conclude that perfusion of neurons of the subpostremal NTS with a low glucose solution depolarizes the membrane by probably reducing intracellular ATP, but not by activating AMPK or decreasing the ionic gradient across the membrane.
Unveiling the Antifungal Mechanisms of CTP, a New Copper(II)- Theophylline/1,10-Phenanthroline Complex, on Drug-Resistant Non-albicans Candida Species
Authors: Frota Heloisa F. , Barbosa Pedro F. , Lorentino Carolline M. A. , Affonso Lorena R. F. , Ramos Lívia S. , Oliveira Simone S.C. , Souza Lucieri O.P. , Abosede Olufunso O. , Ogunlaja Adeniyi S. , Branquinha Marta H. , Santos André L. S. 
Published: March 2024

Abstract

Candida species are the commonest opportunistic human fungal pathogens worldwide, with Candida albicans serving as the primary representative. However, non-albicans Candida species (NACs) have been on the rise in terms of incidence, and they are associated with outbreaks and instances of antifungal resistance. The search for new strategies to combat antifungal-resistant Candida strains is of paramount importance. Recently, our group reported the anti-Candida activity of a coordination compound containing copper(II) complexed with theophylline (theo) and 1,10-phenanthroline (phen), known as “CTP” – Cu(theo)2phen(H2O).5H2O. In the present work, we investigated the mechanisms of action of CTP against six medically relevant, antifungal-resistant NACs, including C. auris, C. glabrata, C. haemulonii, C. krusei, C. parapsilosis and C. tropicalis. CTP effectively inhibited the activity of mitochondrial dehydrogenases, leading to an increase in intracellular reactive oxygen species production. CTP treatment resulted in significant damage to the plasma membrane, as evidenced by the passive incorporation of propidium iodide, and DNA fragmentation as evidenced by the TUNEL assay. Scanning electron microscopy images confirmed that the fungal surface underwent substantial alterations due to CTP treatment, including the formation of invaginations that led to cavitations and lysis. These surface modifications significantly impacted the ability of Candida cells to adhere to the polystyrene surface and form a robust biofilm structure. Moreover, CTP was effective in disassembling mature biofilms formed by these NACs. CTP represents a promising avenue for the development of novel antifungals with innovative mechanisms of action against clinically relevant NACs that are resistant to antifungals commonly used in clinical settings.
Effect of Mn on selective catalytic reduction of NOx by NH3 from Rare earth tailings and mechanistic analysis
Authors: Lu Linbo , Gao Hongmin , Wu Wenfei , Hou Limin 
Published: March 2024

Abstract
In order to obtain good performance of low temperature denitration catalyst, we modified manganese on rare earth tailings by impregnation method, and investigated the effect of manganese modification on the denitrification performance of rare earth tailings by X-ray diffraction, Brunauer-Emmett-Teller, Temperature program reduction, Temperature-programmed desorption of ammoniaand X-ray photoelectron spectroscopy characterisation methods. The results showed: The optimum amount of manganese-modified rare earth tailings was 5 mass fraction, and the denitrification efficiency reached up to 78 percent at 200 degrees centigrade. The addition of manganese resulted in the appearance of uniformly dispersed MnOx on the catalyst surface, and the new component interacted with iron and cerium in the minerals to promote the redox cycle and greatly enhance the redox capacity of the catalyst. It also increased the content of Fe3+ and adsorbed oxygen on the surface, which led to the increase of Brønsted acid sites and the generation of more Mn3+ and Mn4+, which promoted the selective catalytic reduction reaction, but the strong oxidizing ability of manganese resulted in the low selectivity of N2. From the in situ IR results, NO in the Mn-modified catalyst mainly participates in the reaction as monodentate nitrate to promote the SCR reaction, following the L-H mechanism.
Evaluation of extracellular alkaline proteases from Bacillus amyloliquefaciens, B. siamensis, B. subtilis, and B. velezensis
Authors: Prabmark Kanoknart , Saeng-kla Kanphorn , Boonyapakron Katewadee , Aiewviriyasakul Katesuda , Sritus Wipawee , Bunterngsook Benjarat , Poncheewin Wasin , Kanokratana Pattanop , Champreda Verawat , Laothanachareon Thanaporn 
Published: March 2024

Abstract

Alkaline proteases have several applications in various industries. In this study, alkaline proteases from Bacillus amyloliquefaciens TBRC 2902, B. siamensis TBRC 1180, B. subtilis TBRC 6663, and B. velezensis TBRC 7773 were characterized. The production of extracellular protease activity was optimal using tapioca starch as the carbon source for TBRC 2902 and TBRC 1180, and soluble starch for TBRC 7773, whereas both carbon sources were optimal for TBRC 6663. Yeast extract was the optimal organic nitrogen source for all the strains. Skim milk was an equally effective alternative organic nitrogen source for TBRC 2902, TBRC 1180, and TBRC 7773, whereas soytone was as effective as yeast extract for TBRC 6663. To enhance the alkaline protease activity by 10-20%, inorganic nitrogen sources are essential for certain strains including TBRC 2902 and TBRC 1180, which require diammonium hydrogen phosphate and potassium nitrate, respectively. The B. siamensis TBRC 1180 alkaline protease exhibited optimal pH and temperature values of 9.0 and 60°C, respectively, whereas the enzymes from the other strains showed lower optimal pH and temperature values of 8.0 and 50°C, respectively. All enzymes exhibited tolerance to non-ionic surfactants, with more than 40% relative activity remaining when exposed to Triton X-100, Tween-20, and Tween-80 for 24 hours, indicating the potential application of these enzymes as detergent additives.
Two-Dimensional Confined Topological Modes in All Dielectric Guided Mode Resonance Structure Through Surface Features
Authors: Ramachandra Swathy , Menezes Maclean Paul , Tumuluru Vamsi Krishna , Kulkarni Raghavendra G , Sinha Rajat K , Bhowmick Kaustav 
Published: March 2024

Abstract
Guided mode resonance (GMR) structures offer simplicity and have spectral resonance capabilities such as narrowband resonance, high Q-factor, whereas topological surface features offer spatial light control. In this paper, we explore the integration of the GMR structures with topological photonics to achieve extreme two-dimensional (2D) spatial confinement of light. With this integration, we propose a novel design that leverages discontinuous surface features (crosscut) to excite Jackiw - Rebbi (JR) solution, which describes relationship between Dirac equation and topological insulators. Finite element modelling, considering various structural and material parameters, demonstrate a 40% improvement in light confinement, with a calculated full width half maximum (FWHM) of approximately ~ 18 ± 3nm, compared to benchmark GMR structures with topological photonics. This significant enhancement showcases the potential of our approach for applications demanding ultra- precise spatial resolution. Furthermore, tolerance studies reveal good robustness to variations in the dimensions of the crosscut and angle of polarization, ensuring practical feasibility. The proposed structure exhibited good tolerance of up to ~ ± 10%. This work paves the way for highly confined 2D light manipulation within all- dielectric platforms, opening exciting avenues for nanophotonic devices and applications requiring light localization.
Genome-wide analysis of Rice OsDHSRP gene family and their Expression profiles under different Abiotic Stresses
Authors: Kanathala Anjana Priyadarshani , Bollempally Prashanth , Kyasarapu Prathik , Singam Prashant , Kethavath Srinivas Naik 
Published: March 2024

Abstract

Rice serves as a principal food class globally and the crop have been gradually impeded by environmental constraints such as drought, floods, salinity, heat, and cold. Plants adapt their physiological operations in response to external stimuli via signal transduction, thereby modulates gene expression and triggers a range of cellular responses. To feed the current population expansion, it is necessary to develop crops which are able to withstand climate change is highly desirable. OsDHSRP1 is an E3-ubiquitin ligase whose expression is highly stimulated by salinity, heat, and drought conditions, and it acts as a negative modulator by boosting ROS production. The genome-wide comprehensive and expression analysis of OsDHSRP1 in rice have still not been reported. In the current research, we are providing genome wide prediction, structural, evolutionary characterization, and expression analysis of OsDHSRP gene family of Oryza under diverse abiotic stresses. A total of 15 OsDHSRP genes were discovered in Oryza genome, which contains C3HC4 zinc finger conserved domain. The elucidation of Intron/Exon and motif patterns provide structural aspects of these genes. Cis-regulatory analysis and Transcription factor prediction studies revealed their roles and interaction with genes involved in multiple abiotic variables. Expression evaluation of OsDHSRP genes by q-RT PCR revealed that OsDHSRP1 exhibited strong expression trends in leaflets during cold stress followed by drought and salt stress conditions, suggests the role of OsDHSRP1 under diverse abiotic stress circumstances in Oryza. This study provides further insights into regulation of expression of OsDHSRP genes for developing climate resilient crops.
Early Initiation of Ceftaroline-Based Combination Therapy for Methicillin-resistant Staphylococcus aureus Bacteremia
Authors: Hicks Addison S. , Dolan Mackenzie A. , Shah Megan D. , Elwood Sarah E. , Platts-Mills James A. , Madden Gregory R. , Elliott Zachary S. , Eby Joshua C. 
Published: March 2024

Abstract

Purpose:
Monotherapy with vancomycin or daptomycin remains guideline-based care for methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B) despite concerns regarding efficacy. Limited data support potential benefit of combination therapy with ceftaroline as initial therapy. We present an assessment of outcomes of patients initiated on early combination therapy for MRSA-B.
Methods:
This was a single-center, retrospective study of adult patients admitted with MRSA-B between July 1, 2017 and April 31, 2023. During this period, there was a change in institutional practice from routine administration of monotherapy to initial combination therapy for most patients with MRSA-B. Combination therapy included vancomycin or daptomycin plus ceftaroline within 72 hours of index blood culture and monotherapy was vancomycin or daptomycin alone. The primary outcome was a composite of persistent bacteremia, 30-day all-cause mortality, and 30-day bacteremia recurrence. Time to microbiological cure and safety outcomes were assessed. All outcomes were assessed using propensity score-weighted logistic regression.
Results:
Of 213 patients included, 118 received monotherapy (115 vancomycin, 3 daptomycin) and 95 received combination therapy with ceftaroline (76 vancomycin, 19 daptomycin). The mean time from MRSA-positive molecular diagnostic blood culture result to combination therapy was 12.1 hours. There was no difference between groups for the primary composite outcome (OR 1.58, 95% CI 0.60, 4.18). Time to microbiological cure was longer with combination therapy (mean difference 1.50 days, 95% CI 0.60, 2.41). Adverse event rates were similar in both groups.
Conclusions:
Early initiation of ceftaroline-based combination therapy did not improve outcomes for patients with MRSA-B in comparison to monotherapy therapy.
A complicated case of diaphragmatic hernia combined with pyothorax
Authors: liu gaohua , yao yi , Wang Juan 
Published: March 2024

Abstract
We report a case of an elderly female who was admitted to the hospital with left-sided chest pain and an out-of-hospital diagnosis of left-sided pleural effusion. After admission, she was diagnosed with left-sided pyothorax after computed tomography (CT) examination and puncture and tube placement, and diaphragmatic hernia with pyothorax was considered after surgical treatment. This kind of case is rarely reported at present, and the clinical diagnostic ability was further improved through the reflection of this case.
Automated Gait Detection in Older Adults during Daily-Living using Self-Supervised Learning of Wrist- Worn Accelerometer Data: Development and Validation of ElderNet
Authors: Brand Yonatan E. , Kluge Felix , Palmerini Luca , Paraschiv-Ionescu Anisoara , Becker Clemens , Cereatti Andrea , Maetzler Walter , Sharrack Basil , Vereijken Beatrix , Yarnall Alison J. , Rochester Lynn , Din Silvia Del , Muller Arne , Buchman Aron S. , Hausdorff Jeffrey M. , Perlman Or 
Published: March 2024

Abstract

Progressive gait impairment is common in aging adults. Remote phenotyping of gait during daily living has the potential to quantify gait alterations and evaluate the effects of interventions that may prevent disability in the aging population. Here, we developed ElderNet, a self-supervised learning model for gait detection from wrist-worn accelerometer data. Validation involved two diverse cohorts, including over 1,000 participants without gait labels, as well as 83 participants with labeled data: older adults with Parkinson's disease, proximal femoral fracture, chronic obstructive pulmonary disease, congestive heart failure, and healthy adults. ElderNet presented high accuracy (96.43 ± 2.27), specificity (98.87 ± 2.15), recall (82.32 ± 11.37), precision (86.69 ± 17.61), and F1 score (82.92 ± 13.39). The suggested method yielded superior performance compared to two state-of-the-art gait detection algorithms, with improved accuracy and F1 score (p < 0.05). In an initial evaluation of construct validity, ElderNet identified differences in estimated daily walking durations across cohorts with different clinical characteristics, such as mobility disability (p < 0.001) and parkinsonism (p < 0.001). The proposed self-supervised gait detection method has the potential to serve as a valuable tool for remote phenotyping of gait function during daily living in aging adults.