bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of fludarabine and treosulfan on ovarian tumor cells and mesothelin chimeric antigen receptor T cells
Authors: El-Serafi Ibrahim , Micallef Nilsson Isabella , Moter Alina , Duan Zhe , Mattsson Jonas , Magalhaes Isabelle 
Published: July 2024

AbstractIn addition to their immunosuppressive effect, cytostatics conditioning prior to adoptive therapy such as chimeric antigen receptor (CAR) T cells may play a role in debulking and remodeling the tumor microenvironment. We investigated in vitro the killing efficacy and impact of treosulfan and fludarabine on ovarian cancer cells expressing mesothelin (MSLN) and effect on MSLN-targeting CAR T cells. Treosulfan and fludarabine had a synergetic effect on killing of SKOV3 and OVCAR4 cells. Sensitivity to the combination of treosulfan and fludarabine was increased when SKOV3 cells expressed MSLN and when OVCAR4 cells were tested in hypoxia, while MSLN cells surface expression by SKOV3 and OVCAR4 cells was not altered after treosulfan or fludarabine exposure. Exposure to treosulfan or fludarabine (10 µM) neither impacted MSLN-CAR T cells degranulation, cytokines production upon challenge with MSLN + OVCAR3 cells, nor induced mitochondrial defects. Combination of treosulfan and fludarabine decreased MSLN-CAR T cells anti-tumor killing in normoxia but not hypoxia. In conclusion, treosulfan and fludarabine killed MSLN + ovarian cancer cells without altering MSLN-CAR T cells functions (at low cytostatics concentration) even in hypoxic conditions, and our data support the use of treosulfan and fludarabine as conditioning drugs prior to MSLN-CAR T cell therapy.
Identification and validation of tumor-specific T cell receptors from tumor infiltrating lymphocytes using tumor organoid co-cultures
Authors: Li Zhilang , Ma Lisha , Gao Zhaoya , Wang Xiya , Che Xuan , Zhang Pengchong , Li Yixian , Zhang Qianjing , Liu Tianxing , Sun Yuan , Bai Yun , Deng Hongkui 
Published: July 2024

AbstractT cell receptor-engineered T cells (TCR-Ts) therapy is promising for cancer immunotherapy. Most studies have focused on identifying tumor-specific T cell receptors (TCRs) through predicted tumor neoantigens. However, current algorithms for predicting tumor neoantigens are unreliable and many neoantigens are derived from non-coding regions. Thus, the technological platform for identifying tumor-specific TCRs using natural antigens expressed on tumor cells is urgently needed. In this study, tumor organoids-enriched tumor infiltrating lymphocytes (oeT) were obtained by repeatedly stimulation of autologous patient-derived organoids (PDO) in vitro. The oeT cells specifically responded to autologous tumor PDO by detecting CD137 expression and the secretion of IFN-γ using enzyme-linked immunospot assay. The measurement of oeT cell-mediated killing of three-dimensional organoids was conducted using a caspase3/7 flow cytometry assay kit. Subsequently, tumor-specific T cells were isolated based on CD137 expression and their TCRs were identified through single-cell RT-PCR analysis. The specificity cytotoxicity of TCRs were confirmed by transferring to primary peripheral blood T cells. The co-culture system proved highly effective in generating CD8+ tumor-specific oeT cells. These oeT cells effectively induced IFN-γ secretion and exhibited specificity in killing autologous tumor organoids, while not eliciting a cytotoxic response against normal organoids. The analysis conducted by TCRs revealed a significant expansion of T cells within a specific subset of TCRs. Subsequently, the TCRs were cloned and transferred to peripheral blood T cells generation engineered TCR-Ts, which adequately recognized and killed tumor cell in a patient-specific manner. The co-culture system provided an approach to generate tumor-specific TCRs from tumor-infiltrating lymphocytes of patients with colorectal cancer, and tumor-specific TCRs can potentially be used for personalized TCR-T therapy.
Embedding of Markov matrices for $$\varvec{d \leqslant 4}$$
Authors: Baake Michael , Sumner Jeremy 
Published: July 2024

AbstractThe embedding problem of Markov matrices in Markov semigroups is a classic problem that regained a lot of impetus and activities through recent needs in phylogeny and population genetics. Here, we give an account for dimensions $$d\leqslant 4$$

d
⩽
4

, including a complete and simplified treatment of the case $$d=3$$

d
=
3

, and derive the results in a systematic fashion, with an eye on the potential applications. Further, we reconsider the setup of the corresponding problem for time-inhomogeneous Markov chains, which is needed for real-world applications because transition rates need not be constant over time. Additional cases of this more general embedding occur for any $$d\geqslant 3$$

d
⩾
3

. We review the known case of $$d=3$$

d
=
3

and describe the setting for future work on $$d=4$$

d
=
4

.
Patients with paradoxical low-flow, low-gradient aortic stenosis gain the least benefit from TAVI among all hemodynamic subtypes
Authors: Puls Miriam , Beuthner Bo Eric , Topci Rodi , Jacob Christoph Friedemann , Steinhaus Kristin Elisabeth , Paul Niels , Beißbarth Tim , Toischer Karl , Jacobshagen Claudius , Hasenfuß Gerd 
Published: July 2024

Abstract
Background
Substantial controversy exists regarding the clinical benefit of patients with severe paradoxical low-flow, low-gradient aortic stenosis (PLF-LG AS) from TAVI. Therefore, we compared post-TAVI benefit by long-term mortality (all-cause, CV and SCD), clinical improvement of heart failure symptoms, and cardiac reverse remodelling in guideline-defined AS subtypes.

Methods
We prospectively included 250 consecutive TAVI patients. TTE, 6mwt, MLHFQ, NYHA status and NT-proBNP were recorded at baseline and 6 months. Long-term mortality and causes of death were assessed.

Results
107 individuals suffered from normal EF, high gradient AS (NEF-HG AS), 36 from low EF, high gradient AS (LEF-HG), 52 from “classic” low-flow, low-gradient AS (LEF-LG AS), and 38 from paradoxical low-flow, low-gradient AS (PLF-LG AS).
TAVI lead to a significant decrease in MLHFQ score and NT-proBNP levels in all subtypes except for PLF-LG. Regarding reverse remodelling, a significant increase in EF and decrease in LVEDV was present only in subtypes with reduced baseline EF, whereas a significant decrease in LVMI and LAVI could be observed in all subtypes except for PLF-LG. During a follow-up of 3–5 years, PLF-LG patients exhibited the poorest survival among all subtypes (HR 4.2, P = 0.0002 for CV mortality; HR 7.3, P = 0.004 for SCD, in comparison with NEF-HG). Importantly, PLF-LG was independently predictive for CV mortality (HR 2.9 [1.3–6.9], P = 0.009).

Conclusions
PLF-LG patients exhibit the highest mortality (particularly CV and SCD), the poorest symptomatic benefit and the least reverse cardiac remodelling after TAVI among all subtypes. Thus, this cohort seems to gain the least benefit.

Graphical abstract
The effects of different levels of sports activity on health-related quality of life and lifestyle habits in high school Italian students
Authors: Lodovica Lazzeri Maria Francesca , Francesca Mastorci , Paolo Piaggi , Gabriele Trivellini , Anselmo Casu , Caleb Devine , Cristina Doveri , Irene Marinaro , Alessandro Pingitore 
Published: July 2024

Abstract
Physical activity (PA) is an important predictor of physical and mental health preventing chronic degenerative diseases. The purpose of this study was to investigate in a group of Italian high school students whether health-related quality of life (HRQoL) and lifestyle habits (diet) are associated with the level of physical activity performed (low, moderate, high). Data were collected from 2819 adolescents (n = 951 males). HRQoL was analyzed using the Italian version of the KIDSCREEN-52. Physical activity level was analyzed using the PAQ-A, while eating habits with KIDMED. Practicing physical activity in general improves HRQoL. Specifically, adolescents practicing moderate or high PA, in single dimensions of HRQoL, showed better mood (p < 0.001), self-perception (p < 0.001), family relationships (p < 0.001), reported a higher perception of socioeconomic status (p < 0.05), relationship with peers (p < 0.001), and social acceptance (p < 0.001). High PA subjects reported increased physical (p < 0.001) and mental health (p < 0.001), increased autonomy (p < 0.001), and school learning (p < 0.001). For lifestyle habits, practicing moderate PA showed higher adherence tox the Mediterranean diet (p < 0.001).
Conclusion: Our results highlighted a positive association between the frequency of PA levels, some dimensions of HRQoL, and risk behaviors. These findings demonstrated the protective role of sports not only as a preventive strategy for the onset of chronic degenerative diseases, but also as an educator of healthy lifestyle habits, thus suggesting the importance and need to implement strategies to promote sports practice.
Monitoring the risk of a tailings dam collapse through spectral analysis of satellite InSAR time-series data
Authors: Das Sourav , Priyadarshana Anuradha , Grebby Stephen 
Published: July 2024

AbstractSlope failures possess destructive power that can cause significant damage to both life and infrastructure. Monitoring slopes prone to instabilities is therefore critical in mitigating the risk posed by their failure. The purpose of slope monitoring is to detect precursory signs of stability issues, such as changes in the rate of displacement with which a slope is deforming. This information can then be used to predict the timing or probability of an imminent failure in order to provide an early warning. Most approaches to predicting slope failures, such as the inverse velocity method, focus on predicting the timing of a potential failure. However, such approaches are deterministic and require some subjective analysis of displacement monitoring data to generate reliable timing predictions. In this study, a more objective, probabilistic-learning algorithm is proposed to detect and characterise the risk of a slope failure, based on spectral analysis of serially correlated displacement time-series data. The algorithm is applied to satellite-based interferometric synthetic radar (InSAR) displacement time-series data to retrospectively analyse the risk of the 2019 Brumadinho tailings dam collapse in Brazil. Two potential risk milestones are identified and signs of a definitive but emergent risk (27 February 2018-26 August 2018) and imminent risk of collapse of the tailings dam (27 June 2018-24 December 2018) are detected by the algorithm as the empirical points of inflection and maximum on a risk trajectory, respectively. Importantly, this precursory indication of risk of failure is detected as early as at least five months prior to the dam collapse on 25 January 2019. The results of this study demonstrate that the combination of spectral methods and second order statistical properties of InSAR displacement time-series data can reveal signs of a transition into an unstable deformation regime, and that this algorithm can provide sufficient early-warning that could help mitigate catastrophic slope failures.
Lyapunov-guided representation of recurrent neural network performance
Authors: Vogt Ryan , Zheng Yang , Shlizerman Eli 
Published: July 2024

AbstractRecurrent neural networks (RNN) are ubiquitous computing systems for sequences and multivariate time-series data. While several robust RNN architectures are known, it is unclear how to relate RNN initialization, architecture, and other hyperparameters with accuracy for a given task. In this work, we propose treating RNN as dynamical systems and correlating hyperparameters with accuracy through Lyapunov spectral analysis, a methodology designed explicitly for nonlinear dynamical systems. To address the fact that RNN features go beyond the existing Lyapunov spectral analysis, we propose to infer relevant features from the Lyapunov spectrum with an Autoencoder and an embedding of its Latent representation (AeLLE). Our studies of various RNN architectures show that AeLLE successfully correlates RNN Lyapunov spectrum with accuracy. Furthermore, the Latent representation learned by AeLLE is generalizable to novel inputs from the same task and is formed early in the process of RNN training. The latter property allows for predicting the accuracy to which RNN would converge when training is complete. We conclude that the representation of RNN through the Lyapunov spectrum, along with AeLLE, provides a novel method for the organization and interpretation of variants of RNN architectures.
Electron Spin Resonance Spectroscopy on Magnetic van der Waals Compounds
Authors: Kataev Vladislav , Büchner Bernd , Alfonsov Alexey 
Published: July 2024

AbstractThe field of research on magnetic van der Waals compounds—a special subclass of quasi-two-dimensional materials—is currently rapidly expanding due to the relevance of these compounds to fundamental research where they serve as a playground for the investigation of different models of quantum magnetism and also in view of their unique magneto-electronic and magneto-optical properties pertinent to novel technological applications. The electron spin resonance (ESR) spectroscopy plays an important role in the exploration of the rich magnetic behavior of van der Waals compounds due to its high sensitivity to magnetic anisotropies and unprecedentedly high energy resolution that altogether enable one to obtain thorough insights into the details of the spin structure in the magnetically ordered state and the low-energy spin dynamics in the ordered and paramagnetic phases. This article provides an overview of the recent achievements in this field made by the ESR spectroscopic techniques encompassing representatives of antiferro- and ferromagnetic van der Waals compounds of different crystal structures and chemical composition as well as of a special category of these materials termed magnetic topological insulators.
Performance of ChatGPT in classifying periodontitis according to the 2018 classification of periodontal diseases
Authors: Tastan Eroglu Zeynep , Babayigit Osman , Ozkan Sen Dilek , Ucan Yarkac Fatma 
Published: July 2024

Abstract
Objectives
This study assessed the ability of ChatGPT, an artificial intelligence(AI) language model, to determine the stage, grade, and extent of periodontitis based on the 2018 classification.

Materials and methods
This study used baseline digital data of 200 untreated periodontitis patients to compare standardized reference diagnoses (RDs) with ChatGPT findings and determine the best criteria for assessing stage and grade. RDs were provided by four experts who examined each case. Standardized texts containing the relevant information for each situation were constructed to query ChatGPT. RDs were compared to ChatGPT's responses. Variables influencing the responses of ChatGPT were evaluated.

Results
ChatGPT successfully identified the periodontitis stage, grade, and extent in 59.5%, 50.5%, and 84.0% of cases, respectively. Cohen’s kappa values for stage, grade and extent were respectively 0.447, 0.284, and 0.652. A multiple correspondence analysis showed high variance between ChatGPT’s staging and the variables affecting the stage (64.08%) and low variance between ChatGPT’s grading and the variables affecting the grade (42.71%).

Conclusions
The present performance of ChatGPT in the classification of periodontitis exhibited a reasonable level. However, it is expected that additional improvements would increase its effectiveness and broaden its range of functionalities (NCT05926999).

Clinical relevance
Despite ChatGPT's current limitations in accurately classifying periodontitis, it is important to note that the model has not been specifically trained for this task. However, it is expected that with additional improvements, the effectiveness and capabilities of ChatGPT might be enhanced.
An approach for the design of dewatering systems: the case of an excavation for the construction of the assembly shaft of a tunnel boring machine
Authors: Pujades-Garnes Estanislao , Badiella Guillem , Jurado Anna , Carrera Jesus , Vazquez-Suñe Enric 
Published: July 2024

AbstractRobust approaches are needed for designing efficient dewatering systems of deep excavations below the water table to avoid unforeseen incidents (e.g., bottom instabilities in deep excavations and flooding, among others). This paper proposes a methodology, which integrates existing experiences, that was adopted to design the dewatering system of an excavation in the city of Barcelona (Spain). The approach consists of combining: (i) detailed geological and hydrogeological characterizations, (ii) numerical modelling for parameter estimation and drawdown predictions, and (iii) analytical assessment for stability evaluation and soil deformation predictions. The idea is that by combining a set of relatively easy to apply methods, it is possible to successfully solve a complex and risky problem. The methodology allows designing efficient dewatering systems, increasing safety and mitigating potential impacts of groundwater pumping. The most significant conclusion is that the most important step of the proposed approach is the hydrogeological characterization because it allows building realistic and representative numerical models to address most of the challenges associated to dewatering.
Innovation in coastal governance: management and expectations of the UK’s first sandscaping scheme
Authors: Lorenzoni Irene , Day Sophie A. , Mahony Martin , Tolhurst Trevor J. , Bark Rosalind H. 
Published: July 2024

AbstractMany coastal places around the UK face change, with impacts on communities, livelihoods, and landscapes. A tidal surge in 2013 caused significant erosion and flooding on the east coast of England (UK). This was the catalyst for the innovative Bacton to Walcott Coastal Management Scheme, also known as the Sandscaping Scheme, implemented in summer 2019. It is a one-off, large-scale beach nourishment scheme with a design prediction of 15–20 years functional life, the first of its kind in the UK and worldwide outside of the Netherlands. Through stakeholder interviews and a household questionnaire survey, this paper examines the institutional and political challenges, expectations, and hopes associated with this Scheme just before its implementation. The findings indicate that a combination of factors enabled technical and institutional experimentation and innovation at this location: critical erosion risk at a site of strategic infrastructure adjacent to two highly vulnerable villages, extensive stakeholder collaboration across scales, resolute leadership, and recognition of co-benefits. Although most interviewees and local residents foresaw significant benefit from the Scheme—not least respite from the deep anxiety caused by the threat of flooding and erosion risk—tensions were expressed around uncertainty beyond the Scheme’s lifetime and the need to start effective conversations about future adaptation options for the area. This study provides reflections for similar nature-based coastal management schemes elsewhere. It highlights the fundamental challenges facing the governance of natural and social coastal systems for adapting to current and future coastal change and the importance of articulating local and sometimes intangible understandings and expectations of adaptive coastal management interventions.
Incidence of anastomotic leakage using powered circular staplers versus manual circular staplers for left colorectal anastomosis: a cost-effectiveness analysis
Authors: Pla-Martí V. , Martín-Arévalo J. , Moro-Valdezate D. , García-Botello S. , Pérez-Santiago L. , Barrachina-Martinez I. , González-de-Julián S. , Vivas-Consuelo D. , Espí-Macías A. 
Published: July 2024

Abstract
Background
Colorectal anastomotic leakage causes severe consequences for patients and healthcare system as it will lead to increased consumption of hospital resources and costs. Technological improvements in anastomotic devices could reduce the incidence of leakage and its economic impact. The aim of the present study was to assess if the use of a new powered circular stapler is cost-effective.

Method
This observational study included patients undergoing left-sided circular stapled colorectal anastomosis between January 2018 and December 2021. Propensity score matching was carried out to create two comparable groups depending on whether the anastomosis was performed using a manual or powered circular device. The rate of anastomotic leakage, its severity, the consumption of hospital resources, and its cost were the main outcome measures. A cost-effectiveness analysis comparing the powered circular stapler versus manual circular staplers was performed.

Results
A total of 330 patients were included in the study, 165 in each group. Anastomotic leakage rates were significantly different (p = 0.012): 22 patients (13.3%) in the manual group versus 8 patients (4.8%) in the powered group. The effectiveness of the powered stapler and manual stapler was 98.27% and 93.69%, respectively. The average cost per patient in the powered group was €6238.38, compared with €9700.12 in the manual group. The incremental cost-effectiveness ratio was − €74,915.28 per patient without anastomotic complications.

Conclusion
The incremental cost of powered circular stapler compared with manual devices was offset by the savings from lowered incidence and cost of management of anastomotic leaks.
Targeting S100A12 to Improve Angiogenesis and Accelerate Diabetic Wound Healing
Authors: Qin Shitian , Bie Fan , Chen Shuying , Xu Yingbin , Chen Lei , Shu Bin , Yang Fan , Lu Yangzhou , Li Jialin , Zhao Jingling 
Published: July 2024

Abstract
Long-term inflammation and impaired angiogenesis are thought to be the causes of delayed healing or nonhealing of diabetic wounds. S100A12 is an essential pro-inflammatory factor involved in inflammatory reactions and serves as a biomarker for various inflammatory diseases. However, whether high level of S100A12 exists in and affects the healing of diabetic wounds, as well as the underlying molecular mechanisms, remain unclear. In this study, we found that the serum concentration of S100A12 is significantly elevated in patients with type 2 diabetes. Exposure of stratified epidermal cells to high glucose environment led to increased expression and secretion of S100A12, resulting in impaired endothelial function by binding to the advanced glycation endproducts (RAGE) or Toll-like receptor 4 (TLR4) on endothelial cell. The transcription factor Krüpple-like Factor 5 (KLF5) is highly expressed in the epidermis under high glucose conditions, activating the transcriptional activity of the S100A12 and boost its expression. By establishing diabetic wounds model in alloxan-induced diabetic rabbit, we found that local inhibition of S100A12 significantly accelerated diabetic wound healing by promoting angiogenesis. Our results illustrated the novel endothelial-specific injury function of S100A12 in diabetic wounds and suggest that S100A12 is a potential target for the treatment of diabetic wounds.