bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design and development of dual targeting CAR protein for the development of CAR T-cell therapy against KRAS mutated pancreatic ductal adenocarcinoma using computational approaches
Authors: Ramalingam Prasanna Srinivasan , Premkumar T. , Sundararajan Vino , Hussain Md Sadique , Arumugam Sivakumar 
Published: October 2024

AbstractMutant KRAS promotes the proliferation, metastasis, and aggressiveness of various cancers including pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), and colorectal adenocarcinoma (CRC) respectively. Mutant KRAS therapeutics are limited, while Sotorasib and Adagrasib were the only FDA-approved drugs for the treatment of KRASG12C mutated NSCLC. Chimeric antigen receptor (CAR) T-cell therapy has been emerged as an effective strategy against hematological malignancies and being extended towards solid cancers including PDAC. mesothelin (MSLN) and Carcinoembryonic Antigen (CEA) were reported to be highly overexpressed in KRAS-mutated PDAC. Meanwhile, in clinical trials, several CAR T-cell therapy studies are mainly focused towards these two cancer antigens in PDAC, however, the dual targeting of these two neoantigens is not reported. In the present study, we have designed and developed a novel dual-targeting CAR protein by employing various bioinformatics approaches such as functional analysis (antigenicity, allergenicity, antigen binding sites & signalling cascades), qualitative analysis (physicochemical, prediction, refinement & validation of 2D and 3D structures), molecular docking, and in silico cloning. Our results revealed that the designed CAR protein specifically binds with both MSLN & CEA with significant binding affinities, and was predicted to be stable & non-allergenic. Additionally, the protein–protein interaction network reveals the T-cell mediated antitumor responses of each domain in the designed CAR. Conclusively, we have designed and developed a dual targeting (MSLN & CEA) CAR protein towards KRAS-mutated PDAC using computational approaches. Alongside, we further recommend to engineer this designed CAR in T-cells and evaluating their therapeutic efficiency in in vitro and in vivo studies in the near future.
Surgically Treated Clear Cell Sarcomas — What Influences Outcomes?
Authors: Tadala Harsha S. S. , Gulia Ashish , Puri Ajay , Rekhi Bharat , Laskar Siddhartha 
Published: October 2024

AbstractClear cell sarcoma (CCS) also called as melanoma of soft parts is a rare malignant soft-tissue tumor with melanocytic differentiation, primarily located in deep soft tissue and has preference for lymph node and pulmonary metastasis. Metastatic patients have poor oncologic prognosis and so far, no adjuvant treatment seems to be effective in these cases. All cases were retrieved from our prospectively maintained surgical database. Twenty-nine patients (14 males,15 females) with a mean age of 34 years (13–69 years) were operated between 2004 and 2020. Overall survival and recurrence free survival were evaluated. At mean follow-up of 45 months, out of 29 cases, 2 lost to follow-up, 6 patients had nodal metastasis, 3 had lung metastasis, one had both at presentation, 15 patients had died due to disease and 12 are alive. Nodal metastasis rate was 24% (7/29). Positive margin is observed in 6 (19%). 24 patients had recurrence of which 6 had both local and distant. The 5-year OS, LRFS, DRFS were 53%, 56%, 35% respectively at 5 years. Survival rates were significantly poor in patients with metastasis at presentation, 66% vs. 25% (p = 0.016). CCS is an aggressive soft tissue malignancy with high propensity for metastasis. The overall survival of CCS is poor. Metastasis at presentation negatively impacts on survival. Distant recurrences, especially nodal recurrences are not uncommon and complete surgical resection of all recurrences if possible is advisable. Research to develop new chemotherapeutic agents and targeted therapies may help improve the prognosis of CCS.
Lateral Shear Stress Calculation Model Based on Flow Velocity Field Distribution from Experimental Debris Flows
Authors: Yan Yan , Wang Renhe , Xiong Guanglin , Feng Hanlu , Xiang Bin , Hu Sheng , Wang Xinglu , Lei Yu 
Published: October 2024

AbstractDebris flows continuously erode the channel downward and sideways during formation and development, which changes channel topography, enlarges debris flow extent, and increases the potential for downstream damage. Previous studies have focused on debris flow channel bed erosion, with relatively little research on lateral erosion, which greatly limits understanding of flow generation mechanisms and compromises calibration of engineering parameters for prevention and control. Sidewall resistance and sidewall shear stress are key to the study of lateral erosion, and the distribution of the flow field directly reflects sidewall resistance characteristics. Therefore, this study has focused on three aspects: flow field distribution, sidewall resistance, and sidewall shear stress. First, the flow velocity distribution and sidewall resistance were characterized using laboratory debris flow experiments, then a debris flow velocity distribution model was established, and a method for calculating sidewall resistance was developed based on models of flow velocity distribution and rheology. A calculation method for the sidewall shear stress of debris flow was then developed using the quantitative relationship between sidewall shear stress and sidewall resistance. Finally, the experiment was validated and supplemented through numerical simulations, enhancing the reliability and scientific validity of the research results. The study provides a theoretical basis for the calculation of the lateral erosion rate of debris flows.
Recent developments in mathematical aspects of relativistic fluids
Authors: Disconzi Marcelo 
Published: October 2024

AbstractWe review some recent developments in mathematical aspects of relativistic fluids. The goal is to provide a quick entry point to some research topics of current interest that is accessible to graduate students and researchers from adjacent fields, as well as to researches working on broader aspects of relativistic fluid dynamics interested in its mathematical formalism. Instead of complete proofs, which can be found in the published literature, here we focus on the proofs’ main ideas and key concepts. After an introduction to the relativistic Euler equations, we cover the following topics: a new wave-transport formulation of the relativistic Euler equations tailored to applications; the problem of shock formation for relativistic Euler; rough (i.e., low-regularity) solutions to the relativistic Euler equations; the relativistic Euler equations with a physical vacuum boundary; relativistic fluids with viscosity. We finish with a discussion of open problems and future directions of research.
Evaluating and Predicting Meteorological Drought Using Different Climate Reanalysis Datasets over New South Wales, Australia
Authors: Pradhan Biswajeet , Elias Pratik J. , Almazroui Mansour 
Published: October 2024

AbstractDroughts are one of the most disastrous natural hazards, primarily due to their persistence and spatial distribution. Drought prediction is one of the key challenges for effective drought management and to do so, studies often involve the use of station-based data which are effective only in regions with high-gauge density. Therefore, there is growing interest in the use of interpolated climatic grids to predict droughts. In recent decades, drought conditions have been aggravated by climate change and for that reason the use of climatic variables is important to accurately predict droughts. The analysis of any aspect of drought can be affected by the choice of data and drought index. Therefore, this study aims to identify the most suitable dataset and drought index for the New South Wales (NSW) region of Australia. The present study evaluates various precipitation datasets (Climate Research Unit (CRU), ERA-5, and Scientific Information for Land Owners (SILO)) and their corresponding variations on the Standardised Precipitation Index (SPI) at different time scales. Based on the findings, CRU was used to predict meteorological drought using machine learning techniques. The different machine learning models are Support Vector Regression, Random Forest and Artificial Neural Networks. The results suggest SVM to be the best performing model among these models for predicting SPI at short time scales (1 month and 3 month) and ANN to be the best performing model for long-term scales (6 months and 12 months). Such findings depict the capabilities of different models in examining drought characteristics and confirming the use of interpolated climatic grids thereby assisting in regional drought management.
Intravenous administration of gold nanoparticles in rats exhibit alterations in sphingomyelins, bile acids, sphingolipids, and cholesterol esters levels
Authors: Al-Sulaiti Haya , Ismail Roua , Anwardeen Najeha , Al-Saei Aisha Nasser J M , Alkilany Alaaldin , Elrayess Mohamed A. , Rachid Ousama 
Published: October 2024

AbstractNanoparticles (NP) have gained significant attention in biomedical research due to their unique properties and potential applications in drug delivery, imaging, and diagnostics. Gold (AuNPs) and silver (AgNPs) NPs are among the important nanoplatforms that received extensive attention recently for various biomedical applications. Understanding the complex interaction of these NP in biological systems is essential to unveil their pharmacological, Pharmacokinetic and toxicological attributes. Metabolomics has proven invaluable in providing detailed insights into NP’s biodistribution, metabolic effects, and potential toxicity. This study aims to investigate the underlying metabolic pathways affected by in vivo exposure to NP using a robust metabolomics approach. In this work, spherical polyethylene glycol (PEG) modified AuNPs (13 nm, diameter) or AgNPs (20 nm, diameter) were synthesized and dosed into rats via intravenous route to study the associated metabolic changes. Rats (n = 14) were divided into three groups: control (n = 2), AuNPs (n = 6) and AgNPs (n = 6), to mimic potential biomedical exposure scenarios. Duplicate serum samples were collected 24 h post-dosing, and comprehensive metabolite profiling was performed using liquid chromatography-mass spectrometry (LC-MS/MS) and flow injection analysis-mass spectrometry (FIA-MS/MS). Metabolite extraction followed the MxP Quant 500 Kit protocol, with chromatographic separation using the Xevo TQS system. Metabolite identification and quantification were conducted with isotopically labelled internal standards and multiple reaction monitoring (MRM), utilizing optimized conditions under mass spectrometry (MS) as provided by Biocrates. Annotation of metabolites was determined by retention times and specific MRMs for each compound. Results indicate that AuNPs treatment significantly impacted several metabolic pathways. Notably, there was an increase in sphingomyelin (SM 34:2) levels (estimate 0.23, p ≤ 0.001), which are critical for cell membrane structure and signalling. Additionally, a decrease in glycochenodeoxycholic acid levels was also triggered by treatment with AuNPs, suggesting modulation of bile acid metabolism with potential effects on lipid homeostasis. Furthermore, treatment with AuNPs caused significant alterations in cholesterol ester levels, essential for lipid storage and transport, indicating disruptions in these mechanisms. These metabolic changes suggest that gold nanoparticles can disrupt fatty acid metabolism, pyrimidine/purine metabolism, and amino acid synthesis. These findings contribute to the growing understanding of nanoparticle toxicity profile and underscore the need for further research to ensure the safe application of nanoparticles in biomedical and other fields.
Split Hopkinson bar and flash X-ray characterization of ultra high performance concrete reinforced by steel fibers subjected to dynamic compression
Authors: Krčmářová Nela , Šleichrt Jan , Falta Jan , Koudelka Petr , Kytýř Daniel , Čítek David , Fíla Tomáš 
Published: October 2024

AbstractExcellent mechanical properties of ultra high performance concrete make it suitable for use in special applications, where the material is subjected to dynamic phenomena such as impacts, explosions, or earthquakes. This paper presents a novel experimental approach that integrates a Split Hopkinson Pressure Bar with a flash X-ray system and high-speed optical imaging to investigate the dynamic behavior of steel fiber reinforced UHPC under high strain rate uni-axial compression. In-situ Flash X-ray radiography emerges as a particularly effective tool, providing clear visualization of deformation response and overcoming challenges associated with flying debris encountered in optical inspection. Moreover, computed tomography and scanning electron microscopy appear as a vital technique for analyzing micro-structure and fiber distribution and orientation. The combined approach offers a promising method to study the dynamic behavior of steel fiber reinforced ultra high performance concrete and also holds promise for analyzing more complex modes of deformation and material interactions, providing valuable insights for enhancing the design and performance of critical infrastructure subjected to dynamic loading events.
Rhizomatoflavonoid D and Other Flavonoids from the Twigs of Ochna Rhizomatosa as a Potential Inhibitor of HIV-1
Authors: Messi Angélique Nicolas , Tsakem Bienvenu , Akongwi Mirabel , Bodede Olusola , Moyo Phanankosi , Mbanga Baleba Roger Moise , Tsimi Essomba Marcelle Alida , Poka Madan , Demana Patrick Hulisani , Maharaj Vinesh , Urda Lorena , Klimkait Thomas , Siwe Noundou Xavier , Ngo Mbing Joséphine , Pegnyemb Dieudonné Emmanuel 
Published: October 2024

AbstractCurrently, HIV morbidity and mortality in sub-Saharan Africa remain a huge concern and awaiting interventions. Even though the combination antiretroviral therapy (cART) has recorded significant success, drug resistance and limited access to available therapeutics are major factors responsible for the low impact of cART in several African communities. Herein, as part of our continuous effort on the investigation of bioactive metabolites ofOchna rhizomatosa, we report the isolation of a new flavonoid; Rhizomatoflavonoid D (1), alongside with four known ones (2–5). The structures of these compounds were elucidated by using spectroscopic techniques (1H NMR,13C NMR, HSQC, HMBC,1H-1H COSY, and ROESY) and mass spectrometry. The antiviral activity of the resulting compounds was assessed using deCIPhR assay run in parallel with the Alamar Blue based cytotoxicity assay. This assay revealed a moderate activity for compound4(72% inhibition at 2.5 µg/mL) while compound1had minimal activity (36% inhibition at 2.5 µg/mL). The prominent inhibitory effect on HIV-1 was showed by compound4(IC50 = 3.1 µM). Unfortunately, compound4proved to be non-selective as it demonstrated also a CC50 = 5.2 µg/mL (Selectivity index of 1.7). The prominent inhibitory effect on HIV-1 showed by compound4(IC50 = 3.1 µM) could be due the presence of a methoxy group at C-7, since this group enhances the lipophilicity of biflavonoids, thereby improving its incorporation into cells.
The connection between social capital and Chinese public health: an analysis of six Chinese general social surveys
Authors: Hao Feng 
Published: October 2024

AbstractThis study examines the connection between social capital and the perceived health status for the Chinese public. Extending from previous research that uses unrepresentative samples, the current project analyzes nationally representative samples of approximately 60,000 respondents. The data are drawn from six waves of the Chinese General Social Survey conducted in 2010, 2012, 2013, 2015, 2017, and 2018, respectively. The multilevel regression approach is used for statistical estimation. Findings show a consistent pattern that social capital, encompassing social network and generalized trust, is positively related to one’s perceived health status across these years. In addition, the moderating impact of personal capital on the link between social capital and perceived health status is identified. Social capital has a greater health impact on those with lower personal capital than those with higher personal capital. This study complements current literature and has implications for public health policies.
Designing TiB2/Cr multilayer coatings on Ti6Al4V substrate for optimized wear resistance
Authors: Wu Bi , Gao Siyang , Xue Weihai , Yang Shuai , Li Shu , Duan Deli 
Published: October 2024

AbstractThe difference in mechanical properties between the TiB2 coating and the Ti6Al4V substrate can deteriorate the wear resistance of the TiB2 coating. To enhance the TiB2-based coating’s ability to deform in coordination with the ductile Ti6Al4V substrate and improve its tribological performance, the TiB2/Cr multilayer coatings were designed and deposited on Ti6Al4V substrates by magnetron sputtering. Results reveal that the FEM stress distribution of the TiB2/Cr multilayer coatings was optimized by varying the ceramic–metal thickness ratio (Q). As Q decreased from 1.0 to 0.5, the fracture toughness and adhesion strength of the coatings improved. The multilayer coating with Q = 0.5 exhibited the best toughness, crack propagation resistance (CPRs), and the smallest equivalent stress area, leading to a threefold enhancement in wear resistance compared to the TiB2 monolayer coating. However, further reduction of Q to 0.3 diminished wear resistance due to low hardness and significant stress concentration. Thus, there is an optimal balance between hardness, toughness, and stress distribution for achieving improved wear resistance in the multilayer design. Moreover, a notable correlation was observed between CPRs and the wear resistance of TiB2/Cr multilayer coatings.
Longitudinale Begleitung hausärztlicher Patient*innen im Medizinstudium: Chancen und Herausforderungen
Authors: Afshar Kambiz , Höft Lea-Mareen , Schneider Nils , Muth Christiane , Hesse Anja , Leeuw Bettina 
Published: October 2024

Zusammenfassung

Hintergrund
In Deutschland gibt es an mehreren Hochschulstandorten allgemeinmedizinische Lehrformate zur longitudinalen Begleitung von Patient*innen. Das Lehrformat weist einige Besonderheiten in Bezug auf die Entwicklung und Durchführung auf.

Ziel der Arbeit
Neben der exemplarischen Beschreibung der Lehrformate an den Hochschulstandorten Bielefeld und Hannover stellen wir die Ergebnisse eines Workshops zur Entwicklung dieses Lehrformats vor.

Material und Methoden
Am 18.11.2023 führten wir im Rahmen der Tagung der Gesellschaft für Hochschullehre in der Allgemeinmedizin (GHA) in Bielefeld einen 90-minütigen Workshop durch. Die Teilnehmenden erarbeiteten in Kleingruppen Kriterien für geeignete Patient*innen, Lernziele und Inhalte für die longitudinale Patient*innenbegleitung. Nach einem Erfahrungsbericht bestehender Konzepte diskutierten sie Chancen und Herausforderungen dieses Lehrformats.

Ergebnisse
Die insgesamt 17 Teilnehmenden sahen als Auswahlkriterien für geeignete Patient*innen das Vorliegen einer häufigen chronischen Erkrankung ohne hohe Krankheitslast, eine Lebenserwartung von mehr als 2 Jahren und Persönlichkeitsmerkmale wie Flexibilität und Offenheit an. Als Chancen erachteten sie u. a. das Erfassen komplexer Krankheitsverläufe, den longitudinalen Aspekt in der Betreuung sowie die Reflexion der eigenen ärztlichen Rolle. Als Herausforderungen identifizierten sie u. a. die Auswahl geeigneter Patient*innen, den Aufwand für alle Beteiligten sowie die Gefahr einer Überforderung der Studierenden.

Diskussion
Der Workshop ermöglicht in kurzer Zeit eine erste Reflexion, einen Abgleich mit bestehenden Konzepten und konkrete erste Schritte für die Umsetzung eines derartigen Formats am eigenen Standort. Die Ergebnisse dienen der Weiterentwicklung bestehender Lehrkonzepte.
Clustering of listed stock exchange companies active in the cement using the FPC clustering algorithm
Authors: Safari-monjeghtapeh Leila , Esmaeilpour Mansour 
Published: October 2024

Abstract
Data mining and techniques for analyzing big data play a crucial role in various practical fields, including financial markets. However, only a few quantitative studies have been focused on predicting daily stock market returns. The data mining methods used in previous studies are either incomplete or inefficient. This study used the FPC clustering algorithm and prominent clustering algorithms such as K-means, IPC, FDPC, and GOPC for clustering stock market data. The stock market data utilized in this study comprise data from cement companies listed on the Tehran Stock Exchange. These data concerning capital returns and price fluctuations will be examined and analyzed to guide investment decisions. The analysis process involves extracting the stock market data of these companies over the past two years. Subsequently, these companies are categorized based on two criteria: profitability percentage and short-term and long-term price fluctuations, using the FPC clustering algorithm and the classification above algorithms. Then, the results of these clustering analyses are compared against each other using standard and recognized evaluation criteria to assess the quality of the clustering analysis. The findings of this investigation indicate that the FPC algorithm provides more favorable results than other algorithms. Based on the results, companies demonstrating profitability, stability, and loss within short-term (weekly and monthly) and long-term (three-month, six-month, and one-year) time frames will be placed within their respective clusters and introduced accordingly.
Prehospital Point-of-Care Ultrasound to Guide Life Saving Damage Control Interventions and Priority Transport in Resource Scarce Environments
Authors: Ryder Jessica A 
Published: October 2024

Abstract

Point-of-care ultrasound is a proven life-saving diagnostic tool that can be easily utilized in remote and austere settings with ever-improving portability. The utility of point-of-care ultrasound in prehospital care as a feasible and valuable tool to assist in prioritizing patients for damage control resuscitation and transport from the field will be highlighted with a focus on resource-limited environments and conflict settings. The session will conclude with a discussion around the successes, challenges, and lessons-learned after the implementation of a point-of-care ultrasound for trauma training program that was deployed to Ukraine in the fall of 2022.

Learning Objectives
Understand the role that point-of-care ultrasound can play in prehospital patient management.
Identify the benefits and pitfalls of point-of-care ultrasound utilization in the prehospital and resource-scarce environment.
Outline successful strategies and identify potential challenges for implementing a point-of-care ultrasound for trauma training program in complex environments.