bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamical control of nanoscale electron density in atomically thin n-type semiconductors via nano-electric pulse generator
Authors: Kim Sujeong , Lee Hyeongwoo , Eom Seonhye , Ji Gangseon , Choi Soo Ho , Joo Huitae , Bae Jinhyuk , Kim Ki Kang , Park Hyeong-Ryeol , Park Kyoung-Duck
Published: November 2024

Controlling electron density in two-dimensional semiconductors is crucial for both comprehensive understanding of fundamental material properties and their technological applications. However, conventional electrostatic doping methods exhibit limitations, particularly in addressing electric field–induced drift and subsequent diffusion of electrons, which restrict nanoscale doping. Here, we present a tip-induced nanospectroscopic electric pulse modulator to dynamically control nanoscale electron density, thereby facilitating precise measurement of nano-optoelectronic behaviors within a MoS
2
monolayer. The tip-induced electric pulse enables nanoscale modulation of electron distribution as a function of electric pulse width. We simultaneously investigate spatially altering photoluminescence quantum yield at the nanoscale region. We model the extent of electron depletion region, confirming a minimum doping region with a radius of ∼265 nanometers for a 30-nanosecond pulse width. Our approach paves the way for engineering local electron density and in situ nano-optical characterization in two-dimensional materials, enabling an in-depth understanding of doping-dependent nano-optoelectronic phenomena.
Robust generation of intrinsic C points with magneto-optical bound states in the continuum
Authors: Lv Wenjing , Qin Haoye , Su Zengping , Zhang Chengzhi , Huang Jiongpeng , Shi Yuzhi , Li Bo , Genevet Patrice , Song Qinghua
Published: November 2024

C points, circular polarization in momentum space, play crucial roles in chiral wave manipulations. However, conventional approaches of achieving intrinsic C points using photonic crystals with broken symmetries suffer from a low
Q
factor and high sensitivity to structural geometry, rendering them fragile and susceptible to perturbations and disorders. We report magneto-optical (MO) bound states in the continuum (BICs) with a symmetry-preserved planar photonic crystal. We achieve intrinsic C points at Γ point that are robust against variation in both structural geometry and external magnetic field. MO coupling between two modes induces Zeeman splitting, leading to MO BICs and quasi-BICs with circular eigenstates for high-
Q
chiral responses. Furthermore, switchable C point handedness and circular dichroism are enabled by reversing the magnetic field. These findings unveil BICs and quasi-BICs with circular eigenstates and on-demand control of C points, paving the way for advanced chiral wave manipulation with enhanced light-matter interaction.
1-Deoxynojirimycin affects high glucose-induced pancreatic beta-cell dysfunction through regulating CEBPA expression and AMPK pathway
Authors: Li Xiaoying , Liu Shenggui , Wang Siqi , Ai Xinghui , Wei Lin
Published: November 2024

This study aims to explore the role of 1-deoxynojirimycin (DNJ) in high glucose-induced β-cells and to further explore the molecular mechanism of DNJ effect on β-cells through network pharmacology. In the study, high glucose treatment of mouse INS-1 cells inhibited cell proliferation and insulin secretion, decreased the expression of Bcl-2 protein and Ins1 and Ins2 genes, promoted apoptosis, and increased cleaved caspase-3 and cleaved caspase-9 expression levels as well as intracellular reactive oxygen species production. DNJ treatment significantly restored the dysfunction of INS-1 cells induced by high glucose, and DNJ showed no toxicity to normal INS-1 cells. Silencing CEBPA promoted, while overexpression of CEBPA relieved the dysfunction of pancreatic β-cells induced by high glucose. DNJ treatment partially restored the pancreatic β-cell dysfunction caused by silencing CEBPA. In conclusion, DNJ can inhibit high glucose-induced pancreatic β-cell dysfunction by promoting the expression of CEBPA.
Reconstruction of Langevin dynamics using the second-order approximation of Kramers–Moyal conditional moments and its application to model price fluctuations
Authors: Movahed Ali Asghar , Noshad Houshyar
Published: November 2024

The reconstruction of stochastic evolution equations from time-series data in terms of the Langevin equation and the corresponding Fokker–Planck equation is often challenged by the inevitably finite temporal sampling of time-series data. With the aim of improving the reconstruction of stochastic evolution equations from empirical time-series data, one can use a finite sampling [Formula: see text] expansion of the Kramers–Moyal (KM) conditional moments. Depending on the number of terms used from such expansion one obtains different orders of approximation of the KM coefficients. In this paper, we derive and employ the second-order approximation [Formula: see text] of the KM conditional moments for the Langevin dynamics and demonstrate that its use leads to the modification of the diffusion coefficient. To demonstrate the substantial potential for practical applications, we utilize data-driven techniques to estimate fluctuations in synthetic time series generated from both linear and nonlinear diffusive processes. Furthermore, we show that when Langevin dynamics is specifically used to model asset prices (here gold price), the use of the second-order approximation of the KM coefficients leads to more accurate prices simulation and prediction that have not been observed in similar work by others.
Comprehensive review on computational modeling of rheological behavior of various food with esophageal disorders: A mechanical perspective and diet modification
Authors: Mishra Abhishek , Kalyan Kumar Erukala , Mishra Sriharsha , Pal Ankit , Chaudhury Kaustav , Panda Subrata Kumar
Published: November 2024

Disorders and diseases present considerable challenges to human society, and among them, dysphagia stands out as a frequently observed disorder, notably affecting both the elderly and pediatric populations. Addressing this issue has been the focus of numerous clinical and medical research efforts. However, a comprehensive approach that investigates both the mechanical and biological aspects of dysphagia holds promise for proposing and implementing more effective solutions. By exploring the mechanobiology of the human digestive system, particularly focusing on swallowing and esophageal peristalsis, a deeper understanding of dysphagia can be gained. Studying the rheological behavior of food during the digestion process becomes crucial, allowing for the customization of food diets for individuals affected by this disorder. This review provides an overview of various mathematical and finite element analysis (FEA) models that have been proposed to address dysphagia. Additionally, it explores the rheological properties of the food bolus, offering acumens that can contribute to a more nuanced understanding of the disorder. This multidimensional approach holds the potential to improve both the diagnosis and treatment of dysphagia, ultimately enhancing the quality of life for individuals affected by this condition.
Shade quandle presentations for oriented links
Authors: Ishii Atsushi , Kawamura Kengo , Oshiro Kanako , Taniguchi Yuta
Published: November 2024

The purpose of this paper is to introduce an enriched presentation, called a shade quandle presentation, containing information that can be used to normalize Alexander type invariants. We also introduce transformations on shade quandle presentations and show that two shade quandle presentations of an oriented link are related by the transformations. We see that the transformations are finer than the strong Tietze transformations to normalize Alexander type invariants.
Black hole solutions surrounded by anisotropic fluid in f(𝕋,𝒯) gravity
Authors: da Silva Franciele M. , Santos Luis C. N. , Bezerra V. B.
Published: November 2024

In this work, we investigate some extensions of the Kiselev black hole solutions in the context of [Formula: see text] gravity. By mapping the components of the Kiselev energy–momentum tensor into the anisotropic energy–momentum tensor and assuming a particular form of [Formula: see text], we obtain exact solutions for the field equations in this theory that carries dependence on the coupling constant and on the parameter of the equation of state of the fluid. We show that in this scenario of modified gravity some new structure is added to the geometry of spacetime as compared to the Kiselev black hole. We analyze the energy conditions, mass, horizons and the Hawking temperature considering particular values for the parameter of the equation of state.
Low-energy incomplete fusion: A systematic study of entrance channel parameters
Authors: Jashwal Anuj Kumar , Agarwal Avinash , Kumar Munish , Vardhan Harsh , Khan Mohd. Faizan , Rizvi I. A. , Chaubey A. K. , Kumar K. , Dutt S.
Published: November 2024

Research into heavy-ion fusion, a key area of modern nuclear reaction physics, has flourished in recent decades pursuant to developments in accelerator technology. The primary goal of studying heavy-ion reactions is to gain knowledge about the underlying processes and how they are affected by entrance channel parameters, such as beam energy, angular momentum and mass asymmetry. The fusion mechanism of non-[Formula: see text]-cluster projectiles, such [Formula: see text]N and [Formula: see text]F, has been studied in the low-energy zone. It has been challenging to analyze the contributing degrees of freedom in such reactions due to the absence of experimental data. The present study reports the measurement of residual cross-sections from the [Formula: see text]F induced reaction on [Formula: see text]Nb within the energy range of 3–6 MeV/A. The stack foil activation technique followed by offline [Formula: see text] spectroscopy was employed to measure the cross-sections of residues populated in the reaction. The experimental data were compared with theoretical predictions from statistical model code PACE4 to probe the underlying reaction dynamics. The imitation of xn and pxn channel data grossly by model code suggests the production of residues via the complete fusion (CF) mode, while the enhancement observation in [Formula: see text]-channel cross-sections hints at the signatures of incomplete fusion (ICF) in addition to the dominant CF. Thus, the ICF strength fraction ([Formula: see text]) was calculated. Moreover, the estimated incomplete fusion fraction has been used to study the effect of several entrance channel parameters on incomplete fusion reaction dynamics. The present analysis shows the presence of strong clustering in the [Formula: see text]F projectile as [Formula: see text] and [Formula: see text]N.
Improving the Solution Procedure of Incremental Harmonic Balance Method for Multi-Degree-of-Freedom Self-Excited Vibration Systems
Authors: Wu Qianjing , Wang Yilong , Cao Dengqing
Published: November 2024

When applying the Incremental Harmonic Balance (IHB) method to solve the limit cycle in a self-excited system, the practice of fixing one of the harmonic coefficients effectively solves the problem that there are more unknowns than algebraic equations due to the presence of unknown angular frequencies in the periodic response. However, an inappropriate value for this fixed harmonic coefficient can significantly affect the convergence of subsequent Newton–Poisson iterations. To address this issue, we propose a technique that dynamically adjusts the value of the fixed harmonic coefficient, effectively improving the convergence and stability of the traditional IHB method and providing an efficient solution for the parametric study of self-excited systems. The efficiency and performance of our method in accurately predicting periodic solutions are demonstrated by its application to Van der Pol oscillators and predicting vortex-induced vibrations in cable-stayed structures. Numerical simulations show that the results obtained by the proposed method are very close to those obtained by the Runge–Kutta method. This study opens up a robust and efficient approach for analyzing and studying the dynamic behavior of complex self-excited systems.
Emergent Simplicities in the Living Histories of Individual Cells
Authors: Wright Charles S. , Joshi Kunaal , Biswas Rudro R. , Iyer-Biswas Srividya
Published: November 2024

Organisms maintain the status quo, holding key physiological variables constant to within an acceptable tolerance, and yet adapt with precision and plasticity to dynamic changes in externalities. What organizational principles ensure such exquisite yet robust control of systems-level “state variables” in complex systems with an extraordinary number of moving parts and fluctuating variables? Here, we focus on these issues in the specific context of intra- and intergenerational life histories of individual bacterial cells, whose biographies are precisely charted via high-precision dynamic experiments using the SChemostat technology. We highlight intra- and intergenerational scaling laws and other “emergent simplicities” revealed by these high-precision data. In turn, these facilitate a principled route to dimensional reduction of the problem and serve as essential building blocks for phenomenological and mechanistic theory. Parameter-free data-theory matches for multiple organisms validate theory frameworks and explicate the systems physics of stochastic homeostasis and adaptation.
Moral Decision-Making in Organizations
Authors: Kouchaki Maryam , Smith Isaac H.
Published: November 2024

Research on moral decision-making in organizations has expanded significantly over the past few decades. In this review, we build on prior comprehensive reviews on the topic to provide an updated view of the field, based on the latest findings. We first provide a brief historical overview of influential theories of moral decision-making and then describe the individual characteristics, interpersonal factors, and organizational factors that have been shown to influence people's morally relevant choices, as well as the cognitive, affective, and even physiological processes at play. We then provide a more critical view of the field and focus on what we do not know, suggesting several avenues for future research. Specifically, we call for more research that incorporates the temporal dynamics of moral decision-making in organizations and that better accounts for the nature of the real-world moral issues people face at work. We conclude with some practical implications.
Simulation-Based Investigation on Thermal Propagation in Li-ion Battery Modules with Regard to the Thermal Management System
Authors: Weber Niklas , Michel Christian , Schuhmann Sebastian , Tübke Jens , Nirschl Hermann
Published: November 2024

Thermal propagation in Li-ion battery systems is affected by a wide range of influencing factors including chemical cell properties as well as thermal transport phenomena. Due to the dependence on thermal surroundings it is crucial to regard the entire battery system including peripheral components when assessing thermal runaway and propagation risks. This study proposes a simulation-based approach to support design and dimensioning of potential safety measures. It is based on a chemical model for the thermal runaway decomposition reactions combined with 3D thermal simulations. This is applied on exemplary ten cell battery pack in order to investigate on effects on heat transfer during thermal propagation. Insulation and cooling systems are included in the simulation environment for that purpose. It is found that propagation behavior significantly depends on their positioning within in pack and on thermal boundary conditions. Placing too many barriers may exacerbate hazardous situations instead of mitigating them due to heat accumulation effects. Cooling systems are shown to be able to support thermal runaway mitigation strategies but their effectiveness is limited by thermal transport inside the battery cells.
Method—Research on Multi-Scale Signal Processing and Efficient Model Construction Strategies in Lithium-Ion Battery State Prediction
Authors: Gao Zhijun , Dai Rui , Ning Yi , Guo Xifeng
Published: November 2024

To tackle the question of limited generalization and inefficiency in predicting state of health (SOH) and state of charge (SOC) in lithium-ion batteries across diverse sequence lengths, a novel hybrid model is developed. This model integrates multivariate variational mode decomposition (MVMD), informer, and long short-term Memory (LSTM) networks. Initially, battery health features are extracted from the charge and discharge curves, which are then validated for their relevance to SOH and SOC via correlation analysis and random forest algorithms. These features undergo multi-scale decomposition using MVMD, thereby encapsulating the intricate dynamics of battery state changes across various time scales. This decomposition enhances the model’s adaptability to different sequence lengths, bolstering its generalization capability. Subsequently, the informer model is utilized to identify temporal patterns within the decomposed features. Finally, LSTM exploits its capacity to capture temporal dependencies for further refinement of the predictions. This hybrid strategy yields substantial enhancements in both efficiency and accuracy. Compared to the transformer model, the proposed hybrid model demonstrates a 30% reduction in SOH prediction error and a 22% decrease in SOC prediction error, concurrently slashing training time significantly. Spanning diverse sequence lengths and battery types, demonstrates the model’s strong generalization capabilities.
High‐Risk Chronic Lymphocytic Leukemia Complicating the Course of Imatinib‐Treated Chronic Myeloid Leukemia: Successful Disease Management With Dual Tyrosine Kinase Inhibition
Authors: James Daniel , Green Simone , Molica Stefano , Allsup David
Published: November 2024

The coexistence of chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL) in the same patient is exceedingly rare, with only a few cases reported in the literature. Here, we report a patient with CML who, having achieved a major molecular response with imatinib, subsequently developed CLL, which necessitated the concomitant administration of ibrutinib.
ViT‐AMD: A New Deep Learning Model for Age‐Related Macular Degeneration Diagnosis From Fundus Images
Authors: Le Ngoc Thien , Le Truong Thanh , Deelertpaiboon Sunchai , Srisiri Wattanasak , Pongsachareonnont Pear Ferreira , Suwajanakorn Disorn , Mavichak Apivat , Itthipanichpong Rath , Asdornwised Widhyakorn , Benjapolakul Watit , Chaitusaney Surachai , Kaewplung Pasu
Published: November 2024

Age‐related macular degeneration (AMD) diagnosis using fundus images is one of the critical missions of the eye‐care screening program in many countries. Various proposed deep learning models have been studied for this research interest, which aim to achieve the mission and outperform human‐based approaches. However, research efforts are still required for the improvement of model classification accuracy, sensitivity, and specificity values. In this study, we proposed the model named as ViT‐AMD, which is based on the latest Vision Transformer (ViT) structure, to diagnosis a fundus image as normal, dry AMD, or wet AMD types. Unlike convolution neural network models, ViT consists of the attention map layers, which show more effective performance for image classification task. Our training process is based on the 5‐fold cross‐validation and transfer learning techniques using Chula‐AMD dataset at the Department of Ophthalmology, the King Chulalongkorn Memorial Hospital, Bangkok. Furthermore, we also test the performance of trained model using an independent image datasets. The results showed that for the 3‐classes AMD classification (normal vs. dry AMD vs. wet AMD) on the Chula‐AMD dataset, the averaged accuracy, precision, sensitivity, and specificity of our trained model are about 93.40%, 92.15%, 91.27%, and 96.57%, respectively. For result testing on independent datasets, the averaged accuracy, precision, sensitivity, and specificity of trained model are about 74, 20%, 75.35%, 74.13%, and 87.07%, respectively. Compared with the results from the baseline CNN‐based model (DenseNet201), the trained ViT‐AMD model has outperformed significantly. In conclusion, the ViT‐AMD model have proved their usefulness to assist the ophthalmologist to diagnosis the AMD disease.
Behavioral Determinants of Childhood Obesity in the United States: An Exploratory Study
Authors: Palit Soumitra , Sufyani Tahia , Inungu Joseph N. , Cheng Chin-I. , Nartey Emmanuel
Published: November 2024

Childhood obesity is a complex and multifactorial phenomenon. Understanding these factors is crucial in developing effective interventions to prevent and treat childhood obesity. The purpose of this study is to provide an update on factors related to childhood obesity in the United States. This cross‐sectional study analyzed data from the 2021 Youth Risk Behavior Surveillance System (YRBSS) survey to assess factors associated with childhood obesity among US children aged 12 to 17 years. Logistic regression analysis was used to identify the sociodemographic factors associated with overweight and obesity. Data were analyzed using R studio (4.3.2). A total of 12,836 respondents were enrolled in this study. Among them, the prevalence of overweight, obesity, and morbid obesity was found to be 17.66%, 11.21%, and 1.76%, respectively. Respondents with a BMI over 25 were mostly male (17.63%) and of White race (32.77%). The main sociodemographic factors associated with overweight and obesity were being 14 or 15 years old, male, non‐White, having a history of alcohol or marijuana consumption, and not practicing physical activity. These findings can inform targeted interventions for prevention and management. This research sheds light on critical sociodemographic factors related to childhood obesity in the U.S., highlighting its complexity. The findings emphasize the influence of age, gender, ethnicity, and lifestyle behaviors, such as substance use and physical inactivity, on obesity rates among youth. These insights are crucial for developing targeted interventions. Addressing these factors offers a real chance to enhance future health outcomes, and underscoring the need for comprehensive strategies that include both health education and broader community support to instill healthy habits early on. In addition, unexpected results concerning vegetable consumption and the omission of genetic and familial data suggest areas for further research.
The Effect of Children’s Phubbing on Parents’ Psychological Wellbeing: A Moderated Mediation Analysis
Authors: Al-Saggaf Yeslam , Hogg Rachel
Published: November 2024

Attending to the phone while interacting face‐to‐face with another person, a behaviour known as phubbing, can be detrimental to the phubbed person’s psychological wellbeing. Recent research revealed that phubbing friends and partners indirectly affected the phubbed individual’s wellbeing. The aim of this study was to investigate the effect of children’s phubbing on parents’ psychological wellbeing; not the effect of parents’ phubbing on children’s psychological wellbeing, which has been the focus of most of current research. Two hundred and sixty six (266) parents of smartphone users participated in a web survey. The questionnaire measured parents’ experience of being phubbed by their children, psychological wellbeing, relationship satisfaction, loneliness, and self‐esteem. The analysis showed a significant indirect effect of children’s phubbing on parents’ psychological wellbeing through the mediating roles of relationship satisfaction and loneliness. Children’s phubbing increased parents’ feelings of loneliness, and this rise in levels of loneliness worsened parents’ psychological wellbeing. Similarly, children’s phubbing decreased parents’ relationship satisfaction with their children, and this decrease in feelings of relationship satisfaction worsened parents’ psychological wellbeing. Additionally, children’s phubbing affected parents’ psychological wellbeing through the mediating roles of relationship satisfaction and loneliness in sequence (chain effect). As children’s phubbing increased parents’ feelings of loneliness, parents’ relationship satisfaction with their children dropped. The lowering of feelings of relationship satisfaction worsened parents’ psychological wellbeing. A moderated mediation analysis revealed that children’s phubbing decreased parents’ relationship satisfaction with their children, especially for parents who are low on self‐esteem. This study is one of the first that offers insights into how children’s phubbing and parents’ psychological wellbeing are related.
The Effect of Grouper Bone Nano‐Calcium (GBN) and Medium‐Chain Triglyceride (MCT) Supplementation on the Ovariectomized Rats
Authors: Kusumawati Pipin , Pranoto Yudi , Triwitono Priyanto , Latief Fourier Dzar Eljabbar
Published: November 2024

The objective of this research was to investigate the calcium bioavailability and the influence of substituting synthetic calcium carbonate (CaCO3) with grouper bone nano‐calcium (GBN), and medium‐chain triglyceride (MCT) with long‐chain triglyceride (LCT) in the diet of ovariectomized rats maintained for 8 weeks. Twenty rats were randomly divided into four distinct groups: (1) The OX‐C group: AIN‐93M standard + synthetic CaCO3; (2) the OX‐D group: AIN‐93M standard + no calcium; (3) the OX‐1 group: AIN‐93M standard + GBN; and (4) the OX‐2 group: AIN‐93M with MCT as lipid source + GBN. The test parameters conducted encompassed the evaluation of the rat’s body weight, levels of calcium, phosphorus, and alkaline phosphatase in rat blood serum, examination of the microstructure of rat tibiae by histomorphometry and femora bones by means of 3D micro‐CT image analysis, and assessment of the strength of rat femora bones by the three‐point bending. The results indicated that the GBN calcium diet groups (OX‐1 and OX‐2) were successful substitutes for synthetic CaCO3 of the OX‐C group. GBN calcium diet groups have shown superiority in terms of trabeculae thickness (Tb.Th), bone volume (BV/TV), bone mineral density (BMD), and particularly in bone strength evaluations. The GBN calcium diet groups exhibited serum calcium, serum phosphorus, and alkaline phosphatase levels that were comparable to those of synthetic CaCO3 calcium. As the calcium‐deficient group, OX‐D revealed a much lower and distinct performance than other groups. This research demonstrated that MCT exhibit comparable performance to LCT; however, it did not establish that substituting LCT for MCT was superior.
Cluster of Speaking‐Up Behavior in Clinical Nurses and Its Association With Nursing Organizational Culture, Teamwork, and Working Condition: A Cross‐Sectional Study
Authors: Lee Eunhee , Kwon Hyunjeong
Published: November 2024

Introduction: Nurses, as frontline healthcare professionals, play a crucial role in ensuring patient safety, making their ability to speak up imperative. However, there are limited studies categorizing nurses based on their speaking‐up behaviors and comparing their organizational characteristics. This study aimed to identify patterns of nurses’ speaking‐up behaviors and examine differences in organizational cultures, teamwork climates, and working conditions according to these patterns.

Methods: A cross‐sectional survey was conducted, involving 597 nurses directly participating in nursing care in Korean hospitals. The Speaking Up about Patient Safety Questionnaire (SUPS‐Q), Nursing Organizational Culture Questionnaire, and Safety Attitude Questionnaire‐Korean version (SAQ‐K) were employed to measure nurses’ speaking‐up‐related behaviors, organizational culture, teamwork climate, and working conditions. Cluster analysis was used to identify clusters of nurses based on their speaking‐up‐related behavior. Differences in nursing organizational culture, teamwork climate, and working conditions among clusters were analyzed using one‐way analyses of variance.

Results: Three clusters of nurses were identified based on their speaking‐up‐related behaviors. Cluster 1 (35%) showed high perceived concerns, moderate withholding, and speaking up, while Cluster 2 (37%) had moderate concerns, low withholding, and high speaking up. Cluster 3 (28%) had moderate concerns but low withholding and speaking up. Clinical experience significantly differed among clusters, with less experienced nurses predominantly in Cluster 1. Cluster 2 had the most collaborative culture, best teamwork climate, and working conditions.

Conclusion: Ensuring patient safety requires nurses to speak up about patient safety concerns. Creating safe working environments and fostering an organizational culture that prioritizes patient safety are essential steps in promoting nurses’ willingness to speak up about patient safety.
Identification of a Novel Mesenchymal Stem Cell–Related Signature for Predicting the Prognosis and Therapeutic Responses of Bladder Cancer
Authors: Yang Enguang , Ji Luhua , Zhang Xinyu , Jing Suoshi , Li Pan , Wang Hanzhang , Zhang Luyang , Zhang Yuanfeng , Yang Li , Tian Junqiang , Wang Zhiping
Published: November 2024

Background: Mesenchymal stem cells (MSCs) have been identified to have a unique migratory pattern toward tumor sites across diverse cancer types, playing a crucial role in cancer progression, treatment resistance, and immunosuppression. This study aims to formulate a prognostic model focused on MSC‐associated markers to efficiently predict the clinical outcomes and responses to therapy in individuals with bladder cancer (BC).

Methods: Clinical and transcriptome profiling data were extracted from The Cancer Genome Atlas Urothelial Bladder Carcinoma (TCGA‐BLCA) and GSE31684 databases. Systematic quantification of MSC prevalences and stromal indices was undertaken, culminating in the discernment of genes correlated with stromal MSCs following a thorough application of weighted gene coexpression network analysis techniques. Subsequently, an exhaustive risk signature pertinent to MSC was formulated by amalgamating methods from univariate and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression models. Drugs targeting genes associated with MSCs were screened using molecular docking.

Results: The prognostic model for MSC incorporated five critical genes: ZNF165, matrix remodeling‐associated 7 (MXRA7), CEMIP, ADP‐ribosylation factor‐like 4C (ARL4C), and cerebral endothelial cell adhesion molecule (CERCAM). In the case of BC patients, stratification was performed into discrete risk categories, utilizing the median MSC risk score as a criterion. It was striking that those classified within the high‐MSC‐risk bracket demonstrated correlations with unfavorable prognostic implications. Enhanced responsiveness to immunotherapy in low‐MSC‐risk patients was delineated compared to their high‐MSC‐risk counterparts. A heightened receptivity was noted toward particular chemotherapy drugs, encompassing gemcitabine, vincristine, paclitaxel, gefitinib, and sorafenib, within this high‐risk group. Conversely, a superior reaction to cisplatin was distinctly evident among those marked by low MSC scores. The results of molecular docking demonstrated that kaempferol exhibited favorable docking with ZNF165, quercetin exhibited favorable docking with MXRA7, mairin exhibited favorable docking with CEMIP, and limonin diosphenol exhibited favorable docking with ARL4C.

Conclusions: The five‐gene MSC prognostic model demonstrates substantial efficacy in prognosticating clinical outcomes and gauging responsiveness to chemotherapy and immunotherapy regimens. The genes ZNF165, MXRA7, CEMIP, ARL4C, and CERCAM are underscored as promising candidates warranting further exploration for anti‐MSC therapeutic strategies, thereby offering novel insights for personalized treatment approaches in BC.
Data from Galectin-9 Mediates the Functions of Microglia in the Hypoxic Brain Tumor Microenvironment
Authors: Lee Chanju , Yu Dahee , Kim Hyung-Seok , Kim Ki Sun , Chang Chi Young , Yoon Hee Jung , Won Su Bin , Kim Dae Yeon , Goh Eun Ah , Lee Yong Sun , Park Jong-Bae , Kim Sang Soo , Park Eun Jung
Published: November 2024

Abstract
Galectin-9 (Gal-9) is a multifaceted regulator of various pathophysiologic processes that exerts positive or negative effects in a context-dependent manner. In this study, we elucidated the distinctive functional properties of Gal-9 on myeloid cells within the brain tumor microenvironment (TME). Gal-9–expressing cells were abundant at the hypoxic tumor edge in the tumor-bearing ipsilateral hemisphere compared with the contralateral hemisphere in an intracranial mouse brain tumor model. Gal-9 was highly expressed in microglia and macrophages in tumor-infiltrating cells. In primary glia, both the expression and secretion of Gal-9 were influenced by tumors. Analysis of a human glioblastoma bulk RNA sequencing dataset and a single-cell RNA sequencing dataset from a murine glioma model revealed a correlation between Gal-9 expression and glial cell activation. Notably, the Gal-9high microglial subset was functionally distinct from the Gal-9neg/low subset in the brain TME. Gal-9high microglia exhibited properties of inflammatory activation and higher rates of cell death, whereas Gal-9neg/low microglia displayed a superior phagocytic ability against brain tumor cells. Blockade of Gal-9 suppressed tumor growth and altered the activity of glial and T cells in a mouse glioma model. Additionally, glial Gal-9 expression was regulated by hypoxia-inducible factor-2α in the hypoxic brain TME. Myeloid-specific hypoxia-inducible factor-2α deficiency led to attenuated tumor progression. Together, these findings reveal that Gal-9 on myeloid cells is an immunoregulator and putative therapeutic target in brain tumors.

Significance: Galectin-9 serves as an immune checkpoint molecule that modulates the functional properties of microglia in the brain tumor microenvironment and could potentially be targeted to effectively treat brain tumors.
Data from YAP1 Inhibition Induces Phenotype Switching of Cancer-Associated Fibroblasts to Tumor Suppressive in Prostate Cancer
Authors: Song Hongtao , Lu Tong , Han Donghui , Zhang Jiayu , Gan Lunbiao , Xu Chao , Liu Shaojie , Li Peng , Zhang Keying , Hu Zhihao , Li Hongji , Li Yu , Zhao Xiaolong , Zhang Jingliang , Xing Nianzeng , Shi Changhong , Wen Weihong , Yang Fa , Qin Weijun
Published: November 2024

Abstract
Prostate cancer rarely responds to immune-checkpoint blockade (ICB) therapies. Cancer-associated fibroblasts (CAF) are critical components of the immunologically “cold” tumor microenvironment and are considered a promising target to enhance the immunotherapy response. In this study, we aimed to reveal the mechanisms regulating CAF plasticity to identify potential strategies to switch CAFs from protumorigenic to antitumor phenotypes and to enhance ICB efficacy in prostate cancer. Integration of four prostate cancer single-cell RNA sequencing datasets defined protumorigenic and antitumor CAFs, and RNA-seq, flow cytometry, and a prostate cancer organoid model demonstrated the functions of two CAF subtypes. Extracellular matrix–associated CAFs (ECM-CAF) promoted collagen deposition and cancer cell progression, and lymphocyte-associated CAFs (Lym-CAF) exhibited an antitumor phenotype and induced the infiltration and activation of CD8+ T cells. YAP1 activity regulated the ECM-CAF phenotype, and YAP1 silencing promoted switching to Lym-CAFs. NF-κB p65 was the core transcription factor in the Lym-CAF subset, and YAP1 inhibited nuclear translocation of p65. Selective depletion of YAP1 in ECM-CAFs in vivo promoted CD8+ T-cell infiltration and activation and enhanced the therapeutic effects of anti-PD-1 treatment on prostate cancer. Overall, this study revealed a mechanism regulating CAF identity in prostate cancer and highlighted a therapeutic strategy for altering the CAF subtype to suppress tumor growth and increase sensitivity to ICB.

Significance: YAP1 regulates cancer-associated fibroblast phenotypes and can be targeted to switch cancer-associated fibroblasts from a protumorigenic subtype that promotes extracellular matrix deposition to a tumor-suppressive subtype that stimulates antitumor immunity and immunotherapy efficacy.
Data from Targeting Galectin-1 Overcomes Paclitaxel Resistance in Esophageal Squamous Cell Carcinoma
Authors: Zhou Liting , Tian Jie , Wang Keke , Ma Yijie , Chen Xiaojie , Luo Hui , Lu Bingbing , Wang Nan , Wang Penglei , Liu Xuejiao , Zhao Ran , Zhao Simin , Wang Jiutao , Nie Wenna , Ge Hong , Liu Wenting , Gu Tingxuan , Liu Kangdong , Lee Mee-Hyun , Li Xiang , Dong Zigang
Published: November 2024

Abstract
Resistance to paclitaxel poses a major obstacle in esophageal squamous cell carcinoma (ESCC) treatment. A better understanding of the mechanisms underlying paclitaxel resistance could help identify prognostic biomarkers and improved therapeutic strategies. In this study, we established a patient-derived xenograft model of acquired paclitaxel resistance and used RNA sequencing to identify galectin-1, encoded by LGALS1, as a key mediator of resistance. Integrative analysis of clinical data and physiological studies indicated that serum galectin-1 levels were elevated in resistant patients and correlated with treatment outcomes before and during taxane therapy. Importantly, exposing cells to serum from resistant patients resulted in increased paclitaxel resistance compared to serum from sensitive patients, which was closely associated with galectin-1 concentrations in the serum. The specific clearance of galectin-1 from resistant patient serum significantly restored paclitaxel sensitivity, and inhibiting galectin-1, through knockdown or the pharmacologic inhibitor OTX008, increased sensitivity to paclitaxel. Galectin-1 inhibition reduced the activity of β-catenin, thereby inhibiting stem cell properties induced by the Wnt/β-catenin pathway. Furthermore, galectin-1 regulated MDR1 transcription through increased nuclear accumulation of β-catenin, thus increasing resistance to paclitaxel. Combining OTX008 with clinical taxane formulations effectively reversed paclitaxel resistance in vitro and in vivo. Elevated galectin-1 levels thus serve as an indicator of response to paclitaxel therapy in ESCC, offering a therapeutic intervention strategy to overcome drug resistance.

Significance: Galectin-1 is a key mediator of paclitaxel resistance in esophageal squamous cell carcinoma that can be targeted to improve taxane efficacy, suggesting broad therapeutic potential for treating various cancer types.
Data from Hypoxia Stimulates PYGB Enzymatic Activity to Promote Glycogen Metabolism and Cholangiocarcinoma Progression
Authors: Pan Yani , Zhou Yue , Shen Yonghua , Xu Lei , Liu Hongwen , Zhang Nannan , Huang Tianlu , Meng Kui , Liu Yu , Wang Lishan , Bai Ge , Chen Qi , Zhu Yun , Zou Xiaoping , Wang Siliang , Wang Zhangding , Wang Lei
Published: November 2024

Abstract
Cholangiocarcinoma (CCA) displays enhanced glycolysis, pivotal for fulfilling the heightened energy demands intrinsic to its malignant progression. Recent research has indicated that endogenous glycogen rather than exogenous glucose acts as the major carbon source for glycolysis, highlighting the need to better understand the regulation of glycogen homeostasis in CCA. Here, through comprehensive integrative analysis, we identified that glycogen phosphorylase brain form (PYGB), the main enzyme involved in glycogen homeostasis, was markedly upregulated in CCA tissues, serving as an independent prognostic indicator for human patients with CCA. Moreover, elevated PYGB expression potentiated cholangiocarcinogenesis and augmented CCA cell proliferation in both organoid and xenograft models. Hypoxia stimulated PYGB activity in a phosphoglycerate kinase 1–dependent manner, leading to glycogenolysis and the subsequent release of glucose-6-phosphate (G6P) and thereby facilitating aerobic glycolysis. Notably, a virtual screening pinpointed the β-blocker carvedilol as a potent pharmacologic inhibitor of PYGB that could attenuate CCA progression. Collectively, these findings position PYGB as a promising prognostic biomarker and therapeutic target for CCA.

 Significance: Cholangiocarcinoma cells exhibit high glycogen phosphorylase activity under hypoxic conditions that mediates metabolic reprograming to promote glycolysis and support tumor development.
Supplementary Table S5 from Hepatocellular Carcinoma Immune Microenvironment Analysis: A Comprehensive Assessment with Computational and Classical Pathology
Authors: Ercan Caner , Renne Salvatore Lorenzo , Di Tommaso Luca , Ng Charlotte K.Y. , Piscuoglio Salvatore , Terracciano Luigi M.
Published: November 2024

Supplementary Table S5. Performance Metrics of Automatic TIME Phenotype Assessment Algorithm.
Supplementary Table S1 from High Mechanical Conditioning by Tumor Extracellular Matrix Stiffness Is a Predictive Biomarker for Antifibrotic Therapy in HER2-Negative Breast Cancer
Authors: Quintela-Fandino Miguel , Bermejo Begoña , Zamora Esther , Moreno Fernando , García-Saenz José Ángel , Pernas Sonia , Martínez-Jañez Noelia , Jiménez Desirée , Adrover Encarna , de Andrés Raquel , Mourón Silvana , Bueno Maria J. , Manso Luis , Viñas Gemma , Alba Emilio , Llombart-Cussac Antonio , Cortés Javier , Tebar Cristina , Roe Denise J. , Grant Adam , Watson Adam , Colomer Ramon , Mouneimne Ghassan
Published: November 2024

Concordance between MeCo and 21-gene recurrence scores
Supplementary Figure 6 from GDF-15 Predicts Epithelioid Hemangioendothelioma Aggressiveness and Is Downregulated by Sirolimus through ATF4/ATF5 Suppression
Authors: Stacchiotti Silvia , Martini Silvia , Pasquali Sandro , Frezza Anna M. , Beretta Alessia , Percio Stefano , Lecchi Mara , Tortoreto Monica , Barisella Marta , Collini Paola , Dagrada Gian Paolo , Merlini Alessandra , Huang Paul H. , Jenks Andrew , Jones Robin L. , Tap William D. , Ingrosso Matilde , Morosi Carlo , Brich Silvia , Giani Claudia , Verderio Paolo , Casali Paolo G. , Leonard Hugh , Gronchi Alessandro , Zuco Valentina , Zaffaroni Nadia
Published: November 2024

Supplementary Figure 6. Time-course analysis of siRNA-mediated down regulation of GDF-15 in EHE cell line.
Supplementary Figure S2 from A Phase I First-in-Human Study of ABBV-011, a Seizure-Related Homolog Protein 6–Targeting Antibody–Drug Conjugate, in Patients with Small Cell Lung Cancer
Authors: Morgensztern Daniel , Ready Neal , Johnson Melissa L. , Dowlati Afshin , Choudhury Noura , Carbone David P. , Schaefer Eric , Arnold Susanne M. , Puri Sonam , Piotrowska Zofia , Hegde Aparna , Chiang Anne C. , Iams Wade , Tolcher Anthony , Nosaki Kaname , Kozuki Toshiyuki , Li Tianhong , Santana-Davila Rafael , Akamatsu Hiroaki , Murakami Haruyasu , Yokouchi Hiroshi , Wang Song , Zha Jiuhong , Li Rui , Robinson Randy R. , Hingorani Pooja , Jeng Edwin E. , Furqan Muhammad
Published: November 2024

Mean (± SD) preliminary ABBV-011 ADC concentration-time profiles following IV infusion of ABBV-011 (0.3 to 2.0 mg/kg) in cycle 1
Supplementary Figure S2 from Predictive and Dynamic Signature for Antiangiogenics in Combination with a PD1 Inhibitor in Soft-Tissue Sarcoma: Correlative Studies Linked to the IMMUNOSARC Trial
Authors: Moura David S. , Lopez-Marti Jesus M. , Benesova Iva , de Andrea Carlos , di Lernia Davide , Lacerenza Serena , Mondaza-Hernandez Jose L. , Martin-Ruiz Marta , Ramirez-Calvo Marta , Grignani Giovanni , Martinez-Trufero Javier , Redondo Andres , Valverde Claudia , Stacchiotti Silvia , Lopez-Pousa Antonio , Lopez-Guerrero José A. , Gutierrez Antonio , Encinas-Tobajas Victor , Hindi Nadia , Sangiolo Dario , Lopez-Martin Jose A. , Strizova Zuzana Ozaniak , Martin-Broto Javier
Published: November 2024

Supplementary Figure S2. Correlation between progression-free survival (PFS) and the dynamic increase in cytologic markers. A) CD3; B) CD4; C) CD8; D) CD20; E) CD66b; F) CD68 and G) CD138. PFS cut-off was defined as 9.4 months and calculated by MAXSTAT. Significance was defined as p<0.05 and calculated by Wilcoxon paired test.
Supplementary Figure S7 from Epigenome Reprogramming Through H3K27 and H3K4 Trimethylation as a Resistance Mechanism to DNA Methylation Inhibition in BRAFV600E-Mutated Colorectal Cancer
Authors: Lee Hey Min , Saw Ajay Kumar , Morris Van K. , Napolitano Stefania , Bristow Christopher , Srinivasan Sanjana , Peoples Micheal , Sorokin Alexey , Kanikarla Marie Preeti , Schulz Jonathan , Singh Anand K. , Terranova Christopher , Coker Oluwadara , Jain Abhinav , Kopetz Scott , Rai Kunal
Published: November 2024

Graphical representation of adaptive epigenome reprogramming upon 5-azacitidine treatment in BRAFV600E CRC
Supplemental Figure S1 from Androgen Deprivation Therapy Drives a Distinct Immune Phenotype in Localized Prostate Cancer
Authors: Dallos Matthew C. , Obradovic Aleksandar Z. , McCann Patrick , Chowdhury Nivedita , Pratapa Aditya , Aggen David H. , Gaffney Christopher , Autio Karen A. , Virk Renu K. , De Marzo Angelo M. , Antonarakis Emmanuel S. , Scher Howard I. , Drake Charles G. , Rathkopf Dana E.
Published: November 2024

Supplemental Figure S1. Sample clustering by RNAseq and top differentially expressed genes by treatment group.
Data from TAK1 Promotes an Immunosuppressive Tumor Microenvironment through Cancer-Associated Fibroblast Phenotypic Conversion in Pancreatic Ductal Adenocarcinoma
Authors: Sheng Nan , Shindo Koji , Ohuchida Kenoki , Shinkawa Tomohiko , Zhang Bo , Feng Haimin , Yamamoto Takeo , Moriyama Taiki , Ikenaga Naoki , Nakata Kohei , Oda Yoshinao , Nakamura Masafumi
Published: November 2024

AbstractPurpose:
We aim to clarify the precise function of TGFβ1-activated kinase 1 (TAK1) in cancer-associated fibroblasts (CAF) within human pancreatic ductal adenocarcinoma (PDAC) by investigating its role in cytokine-mediated signaling pathways.
Experimental Design:
The expression of TAK1 in pancreatic cancer was confirmed by The Cancer Genome Atlas data and human pancreatic cancer specimens. CAFs from freshly resected PDAC specimens were cultured and used in a three-dimensional model for direct and indirect coculture with PDAC tumors to investigate TAK1 function. Additionally, organoids from [LSL-KrasG12D/+, LSL-Trp53R172H/+, Pdx1-Cre (KPC)] mice were mixed with CAFs and injected subcutaneously into C57BL/6 mice to explore in vivo functional interactions of TAK1.
Results:
The Cancer Genome Atlas data revealed significant upregulation of TAK1 in PDAC, associating with a positive correlation with the T-cell exhaustion signature. Knockdown of TAK1 in CAFs decreased the inflammatory CAF signature and increased the myofibroblastic CAF signature both in vitro and in vivo. The absence of TAK1 hindered CAF proliferation, blocked several inflammatory factors via multiple pathways associated with immunosuppression, and hindered epithelial–mesenchymal transition and outgrowth in vitro in spheroid cocultures with PDAC cells. Additionally, TAK1 inhibitor restrained tumor growth, increased CD4+ and CD8+ T-cell abundance, and reduced immunosuppressive cells present in vivo.
Conclusions:
Blocking the TAK1+ CAF phenotype leads to the conversion of protumorigenic CAFs to antitumorigenic CAFs. This highlights TAK1 as a potential therapeutic target, particularly in CAFs, and represents a novel avenue for combined immunotherapy in PDAC.