bluuebunny/crossref_metadata_2025_split huggingface dataset:
PTBP1 Lactylation Promotes Glioma Stem Cell Maintenance through PFKFB4-Driven Glycolysis
Authors: Zhou Zijian , Yin Xianyong , Sun Hao , Lu Jiaze , Li Yuming , Fan Yang , Lv Peiwen , Han Min , Wu Jing , Li Shengjie , Liu Zihao , Zhao Hongbo , Sun Haohan , Fan Hao , Wang Shan , Xin Tao 
Published: November 2024

Abstract
Long-standing evidence implicates glioma stem cells (GSC) as the major driver for glioma propagation and recurrence. GSCs have a distinctive metabolic landscape characterized by elevated glycolysis. Lactate accumulation resulting from enhanced glycolytic activity can drive lysine lactylation to regulate protein functions, suggesting that elucidating the lactylation landscape in GSCs could provide insights into glioma biology. Herein, we have demonstrated that global lactylation was significantly elevated in GSCs compared with differentiated glioma cells. Polypyrimidine tract–binding protein 1 (PTBP1), a central regulator of RNA processing, was hyperlactylated in GSCs, and SIRT1 induced PTBP1 delactylation. PTBP1-K436 lactylation supported glioma progression and GSC maintenance. Mechanistically, K436 lactylation inhibited PTBP1 proteasomal degradation by attenuating the interaction with TRIM21. Moreover, PTBP1 lactylation enhanced RNA-binding capacity and facilitated PFKFB4 mRNA stabilization, which further increased glycolysis. Together, these findings uncovered a lactylation-mediated mechanism in GSCs driven by metabolic reprogramming that induces aberrant epigenetic modifications to further stimulate glycolysis, resulting in a vicious cycle to exacerbate tumorigenesis.
Significance: Glycolysis-induced lactylation enhances the function of PTBP1 to promote glioma stem cell maintenance, indicating that PTBP1 lactylation could be a potential target for the development of innovative glioma therapies.
Pancreatic CAF-Derived Autotaxin Drives Autocrine CTGF Expression to Modulate Protumorigenic Signaling
Authors: Volat Fanny , Medhi Ragini , Maggs Lauren Z. , Deken Marcel A. , Price Alice , Andrews Lauren , Clark Jonathan , Taylor Diane , Carruthers Alan , Taylor-Smith Ewan , Pacheco Natalia , Rudge Simon A. , Fraser Amy , Lopez-Clavijo Andrea F. , Sousa Bebiana C. , Johnson Zoë , Di Conza Giusy , van der Veen Lars , Shah Pritom , Sandig Hilary , Sharpe Hayley J. , Farrow Stuart 
Published: November 2024

Abstract
Autotaxin (ATX), encoded by ENPP2, is a clinical target in pancreatic ductal adenocarcinoma (PDAC). ATX catalyzes the production of lysophosphatidic acid (LPA), an important regulator within the tumor microenvironment (TME), yet the protumorigenic action of the ATX/LPA axis in PDAC remains unclear. In this study, by interrogating patient samples and cell line datasets, we show that the PDAC TME, rather than cancer cells, is responsible for the majority of ENPP2 expression and highlight a key role for cancer-associated fibroblast (CAF)-derived ATX in autocrine and paracrine protumorigenic signaling. Using the clinical-stage ATX inhibitor, IOA-289, we identified connective tissue growth factor (CTGF), also known as CCN2, as a downstream mediator of ATX signaling in the PDAC CAF-derived cell line, 0082T. Genetic ablation or pharmacologic inhibition of ATX in 0082T CAFs reduced CTGF secretion via modulation of LPA/LPA receptor signaling. Despite the loss of ATX function, extracellular levels of LPA were paradoxically increased, indicating a role for ATX beyond its enzymatic activity and suggesting a role for its LPA chaperone function in the LPA/LPA receptor signaling in CAFs. As CAFs are the main source for CTGF in the PDAC TME, these findings suggest a role for ATX in promoting a protumorigenic microenvironment via modulation of CAF secretion not only via its LPA-producing activity but also via its LPA chaperone function, providing a potential mechanism for the antitumor effects of ATX inhibition.
CD49a Targeting Enhances NK Cell Function and Antitumor Immunity
Authors: Zhang Yu , Li Yangyang , Zhang Zhengfeng , Zheng Xiaodong , Peng Hui , Tian Zhigang , Sun Rui , Sun Haoyu 
Published: November 2024

Abstract
Approximately 70% of patients receiving immune checkpoint blockade therapies develop treatment resistance. Thus, there is a need for the identification of additional immunotherapeutic targets. CD49a is a membrane protein expressed on NK cells and T cells. In this study, we found that CD49a was highly expressed on the surface of tumor-infiltrating NK cells in various mouse tumor models and that CD49a+ tumor-infiltrating NK cells were more exhausted than CD49a− tumor-infiltrating NK cells. Furthermore, CD49a or NK-specific CD49a deficiency slowed tumor growth and prolonged survival in several mouse tumor models, primarily through the essential role played by NK cells in antitumor activities. Blockade of CD49a using an mAb suppressed tumor development in mice, and combination treatment with anti–PD-L1 further enhanced antitumor efficacy. Our research reveals CD49a on NK cells as an immunotherapeutic target and highlights the potential clinical applications of CD49a-targeted therapies.
Scholarly and Empirical Considerations on Expanding Access for Non-Governmental Organisations Before the European Court of Human Rights
Authors: Erken Elif 
Published: November 2024

Abstract
Non-governmental organisations (ngo s) have long been considered important actors within the European Convention on Human Rights (echr) system. Yet, their influence as litigants remains limited when a case with a specific individual, rather than a general situation, is put before the European Court of Human Rights (ECtHR or Court). This article evaluates the Court’s standing requirements and in doing so, brings together various perspectives on ngo s and the strategies they pursue. By drawing upon interviews with Court officials, ngo representatives, including those with experience litigating under the collective complaints procedure of the European Social Charter (esc), and experts who sit in the esc Committee, it includes a stakeholder perspective on the need to further allow ngo s to engage strategically before the Court and whether inspiration can be derived from the esc system, with specific focus on formalising greater access for ngo s.
Normative Agency and Cross-Cultural Human Rights in East Asia
Authors: Corrigan Daniel P. , Cokelet Bradford 
Published: November 2024

Abstract
According to James Griffin (2008) human rights should be grounded in an account of human dignity, based on “normative agency” – the human capacity to choose and pursue a conception of a worthwhile life. In this paper we take up Griffin’s insight that key legitimate human rights are designed to respect and protect this basic capacity, but reject his assumption that normative agency should always and everywhere be understood in a Western way. We argue that “normative agency” is an indeterminate concept that can be differently understood in different cultural contexts and that thinking about human rights in East Asia should be guided by a Griffin-style approach coupled with an account of normative agency with East Asian characteristics. In developing this idea, we contrast our account with recent, moralized conceptions of Confucian dignity and respond to Griffin’s tacit worries about how to concretely implement views like ours in institutional practice.
Mechanical degradation of polyacrylamide solutions as a model for flow induced blood damage in artificial organs
Authors: Pohl Manfred , Wendt Max O. , Koch Brigitte , Vlastos George A. 
Published: November 2024

Human or animal blood is normally used as a test fluid for the in vitro evaluation of hemolysis by artificial organs. However, blood has some disadvantages (large biological variability and problems with cleaning the devices). For that reason, we searched for a reproducible technical fluid with blood‐like flow characteristics that exhibits similar shear depending destruction. In this study, a direct comparison between erythrocyte damage of bovine blood and shear‐induced degradation of polyacrylamide solution is given. A uniform shear field was applied to the fluids using a shear device with a plate‐plate geometry. It was shown that similarities exist between erythrocytes disaggregation and breakdown of super molecular structures in polymer solutions, caused by mechanical stress. In both cases steady low shear viscositity was diminished and the elastic component of complex viscosity of blood and polymer solutions has been reduced. There is a correlation between shear‐induced hemolysis of bovine blood and mechanical polymer‐degradation, which depends on the applied shear stresses.
The influence of exercise on the composition of developing equine joints
Authors: van de Lest Chris H.A. , Brama Pieter A.J. , van Weeren P. René 
Published: November 2024

An overview is given of the direct and long‐term effects of exercise on the biochemical characteristics of cartilage and subchondral bone, and on the metabolic activity of chondrocytes in the juvenile horse. In the experimental setup 43 foals were reared until weaning at 5 months of age under similar conditions, except for the type and amount of exercise. Fifteen foals remained at pasture (Pasture group and also control group), 14 foals were kept in box stalls (Box group), and 14 foals were kept in the same box stalls but were subjected daily to an increasing number of gallop sprints (Training group). After weaning 8 foals from each group were euthanised. All remaining 19 animals were housed together in a loose box with access to a small paddock to study a possible reversibility of exercise‐induced effects. Post mortem subchondral bone and cartilage samples were collected and analysed for bone morphogenic enzymes, matrix composition, chondrocyte metabolic activity, and bone mineral density. It resulted that lack of exercise leads to a retardation of the normal development of the joint. This is largely compensated for when afterwards a more normal exercise regimen is followed. Most parameters in the Training group approximated those of the pastured foals at age 5 months. However, at age 11 months there were indications for a reduced performance of the investigated tissues in this group. It is concluded that regular, sub‐maximal loading, as occurred in the Pasture group, seems best for an optimal development of the musculoskeletal tissues. The combination of short bouts of heavy exercise superimposed on a basic box rest regimen appears to have adverse effects on long‐term viability of the tissues and may hence lead to an impaired resistance to injury.
Tensile fatigue behaviour of articular cartilage
Authors: Bellucci Giordano , Seedhom Bahaa B. 
Published: November 2024

Although fatigue has been implicated in cartilage failure there are only two studies by the same author, and in both of which cartilage was tested in the direction parallel to the collagen orientation in the surface layer. In the present work articular cartilage was tested also along the perpendicular direction, being the direction in which cartilage possesses lower tensile strength. Specimens were tested under cyclic tensile load. Number of cycles at failure was recorded as well as elongation of the specimen. To date 72 specimens have been tested all from one knee joint. The number of cycles to failure ranged between two and 1.5 million. The surface and deep layers have better fatigue properties whether tested in the parallel or the perpendicular direction, while the middle layer was far weaker. Better fatigue behaviour was observed with specimens tested in parallel than in perpendicular direction to the fibres.
Arterial bends: The development and decay of helical flows
Authors: Blyth M.G. , Mestel A.J. , Zabielski L. 
Published: November 2024

The macrocirculation is modelled by incompressible Newtonian flow through a rigid network of pipes for which possible simplifications are discussed. The common assumptions of two‐dimensionality or axisymmetry can be generalised to helical symmetry, and in the first part of the paper, the three‐dimensionality of arterial bends is considered by varying the curvature and torsion of a section of a helical pipe. The torsion is found to impart a preferential twist to the cross‐sectional flow. This loss of symmetry ensures that flow separation is less severe for a helical bend than for a toroidal bend. The effects of variations in body size are examined using allometric scaling laws. In the second part of the paper, the approach to “fully developed” Dean or Womersley flow is considered in an attempt to quantify the regions of validity of idealised models. A perturbation approach, akin to hydrodynamic stability theory, is used. It is argued that often potential flows are more suitable for describing the rapid interactions between geometry and pulsatility rather than the eventual fully developed state so that, for example, the first 100° of the aortic arch may be considered irrotational. Helical potential flows are found to develop faster than the corresponding toroidal flows, but slower than those in a straight pipe. The presence of vorticity in the core also retards the development of symmetric flows. It is concluded that while idealised flows can occur at some points in the body, in general experimental observation is needed to justify their use. Particular caution is recommended when interpreting calculations with Poiseuille input.
Adhesion of leukocytes under oscillating stagnation point conditions: A numerical study
Authors: Walker P.G. , Alshorman A.A. , Westwood S. , David T. 
Published: November 2024

Leukocyte recruitment from blood to the endothelium plays an important role in atherosclerotic plaque formation. Cells show a primary and secondary adhesive process with primary bonds responsible for capture and rolling and secondary bonds for arrest. Our objective was to investigate the role played by this process on the adhesion of leukocytes in complex flow. Cells were modelled as rigid spheres with spring like adhesion molecules which formed bonds with endothelial receptors. Models of bond kinetics and Newton's laws of motion were solved numerically to determine cell motion. Fluid force was obtained from the local shear rate obtained from a CFD simulation of the flow over a backward facing step. In stagnation point flow the shear rate near the stagnation point has a large gradient such that adherent cells in this region roll to a high shear region preventing permanent adhesion. This is enhanced if a small time dependent perturbation is imposed upon the stagnation point. For lower shear rates the cell rolling velocity may be such that secondary bonds have time to form. These bonds resist the lower fluid forces and consequently there is a relatively large permanent adhesion region.
Tensile properties of fibroblasts and vascular smooth muscle cells
Authors: Miyazaki Hiroshi , Hayashi Kozaburo , Hasegawa Yoshitaka 
Published: November 2024

Tensile properties of fibroblasts (FBs) and vascular smooth muscle cells (VSMCs) of synthetic and contractile phenotypes were studied using a newly developed micro‐tensile tester. FBs were obtained from the rabbit patellar tendon. Synthetic and contractile VSMCs were isolated from the rabbit thoracic aorta with an explant and an enzymatic digestion method, respectively. Each cell was attached to the fine tips of a pair of micropipettes with a cell adhesive and, then, stretched at the speed of 6 μm/sec. Load and length were obtained using a cantilever‐type load cell and a VDA, respectively. FBs were broken at the load of 0.9 μN and the elongation to failure of 86 μm, and had the stiffness of 0.02 N/m. VSMCs were not broken even at 2.4 μN. The stiffness of synthetic and contractile VSMCs were 0.09 and 0.17 N/m, respectively. Such large different tensile properties among the three cells are attributable to the differences in components and cytoskeletal structures.
Induced changes of leukocyte slow rolling in an in flow pharmacological model of adhesion to endothelial cells
Authors: Renard M. , Heutte F. , Boutherin‐Falson O. , Finet M. , Boisseau M.R. 
Published: November 2024

Background: Rolling of leukocytes at the surface of the vascular endothelium is a prerequisite for a subsequent firm adhesion, particularly the slow rolling appearing on ELAM CD62E. Therefore, it may be considered that increasing the rolling velocities should be a precise therapeutic target in clinical situations where leukocytes accumulate, mainly venous and arterial ischaemia. Methods: Human neutrophils were allowed to flow on endothelial HUVECs, with and without 4 hours interleukin‐1α activation, the cells having or not been incubated with INO5042 anti‐inflammatory drug. Under a mean shear‐stress of 2 dyn/cm2, rollers and stickers were identified and quantified, using a video‐camera and picture analysing software. Results: When the drug had been added to endothelial cells a shift of velocities was observed towards fast speeds (from 3–5 to 7–11 μm/sec). The same results was significantly found when neutrophils, alone or along with endothelium, had been submitted to the drug, the number of stickers and rollers beeing reduced as well. Finally, such a precise pharmacological method proved efficient to detect the exact mechanism of INO5042 on white cell adhesion.
The use of rice husk ash as a potential filler in formulations of elastomeric compositions for rubber-metal vibration isolators
Authors: Bobrova Valeria , Kasperovich Andrei , Efremov Sergey , Nechipurenko Sergey , Lezhnev Sergey , Panin Evgeniy 
Published: November 2024

This study focused on the use of rice husk ash obtained by carbonation in a pyrolysis furnace at a temperature of 550 °C–600 °C to develop a formulation of an elastomeric composition intended for the manufacture of a rubber-metal vibration isolator with reduced environmental impact and a satisfactory set of operational properties. Nine compositions were prepared, comprising different dosages of rice husk ash. These were used as partial and/or complete replacements for N772 carbon black (10, 20, 30 and 40 wt%) and as additional fillers (5, 10, 15 and 20 wt%). Our results show that fully replacing carbon black with rice husk ash improves the technological characteristics of rubber compounds, which can contribute to a reduction in the energy intensity of the manufacturing process of products derived from them. The strength, hardness, and tear resistance of rubbers when replacing N772 with ash in a dosage of up to 20 wt% permit the production of compositions with a satisfactory set of strength properties. An increase in the dosage of ash in excess of 10 wt% when combined with N772 results in a deterioration in the basic physical and mechanical properties of rubbers. As the loading of rice husk ash in place of carbon black is increased, the resistance of the studied compositions to ozone is enhanced, as is the elastic recovery after a given deformation. This will lead to an increase in the service life of the finished product.
Training to Improve Instruction and Outcomes for Children With Cortical Visual Impairment
Authors: Wall Emerson Robert , Anderson Dawn , Steffer Stephanie 
Published: November 2024

Introduction This study investigated a training regimen for teachers of children with visual impairments (TVIs) who need to assess, plan instruction for, and teach students with cortical visual impairment (CVI), as well as the effect of these strategies on the visual behaviors of these students. Method TVIs learned CVI content knowledge and knowledge of a specific app-based system called CViConnect through a group workshop, seven asynchronous modules, and a year of mentorship from a TVI certified in CVI. When using the CViConnect system on iPads, data are captured during the instructional session, and the looking and touching behaviors of students are automatically saved to a remote server. Results TVIs with and without specific training used Phase I activities the most, but untrained TVIs used Phase II and III activities more than trained TVIs. Sessions conducted by trained TVIs averaged three times longer than those done by untrained TVIs. Students taught by TVIs without specific training touched items that were not meant to be selected (i.e., sprites and backgrounds) much more than students with trained TVIs, but students taught by trained TVIs looked at the screen more often— M = 0.08 looks/s versus M = 0.07 looks/s, t(3317) = 2.59, p = .005, d = 0.09—had longer sustained looks— M = 34.08 s versus M = 6.67 s, t(3317) = 10.11, p < .001, d = 0.35—and spent more time looking at the screen than students with untrained TVIs: M = 9.51 s versus M = 3.21 s, t(3317) = 4.12, p < .001, d = 0.14. Discussion Training led TVIs to be able to identify appropriate activities for their students with CVI, thus encouraging the children to use looking behaviors instead of becoming visually overwhelmed and randomly tapping on the screen. Implications for Practitioners These data seem to show that the training regimen in this project leads TVIs to choose activities of an appropriate level for their students with CVI and to use the CViConnect system to increase looking behaviors in their students.
Development of a nomogram based on whole-tumor multiparametric MRI histogram analysis to predict deep myometrial invasion in stage I endometrioid endometrial carcinoma preoperatively
Authors: Deng Ying , Zhao Tingting , Zhang Jun , Dai Qiang , Yan Bin 
Published: November 2024

Background The depth of myometrial invasion determines whether International Federation of Gynecology and Obstetrics stage I endometrioid endometrial carcinoma (EEC) patients undergo lymph node dissection. However, subjective evaluation results relying on magnetic resonance imaging (MRI) are not always satisfactory. Purpose To develop a nomogram based on whole-volume tumor MRI histogram parameters to preoperatively predict deep myometrial invasion (DMI) in patients with stage I EEC. Material and Methods This retrospective analysis included 131 EEC patients and a training/validation cohort of 92/39 patients at a 7:3 ratio. The histogram parameters were obtained from multiple sequences (ADC mapping and T2-weighted imaging) within volumes of interest. Univariate analysis, least absolute shrinkage and selection operator (LASSO) regression, and multivariate logistic regression were used for feature selection. The performance of clinical model, histogram model, and histogram nomogram was evaluated by calculating the area under the receiver operating characteristic curve (AUC). Results Age and two morphological features (maximum anteroposterior tumor diameter on sagittal T2-weighted images [APsag] and the tumor area ratio [TAR]) were selected to construct the clinical model. Five histogram parameters were selected for the creation of the histogram model. The nomogram, which combines the histogram parameters, age, APsag, and TAR, achieved the highest AUCs in both the training and validation cohorts (nomogram vs. histogram vs. clinical model: 0.973 vs. 0.871 vs. 0.934 [training] and 0.972 vs. 0.870 vs. 0.928 [validation]). Conclusion The MR histogram nomogram can help predict the DMI of patients with stage I EEC preoperatively, assisting physicians in the development of personalized treatment strategies.