bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic immune markers in esophageal cancer patients managed with trimodal therapy
Authors: Farrugia Mark K. , Repasky Elizabeth A. , Chen Minhui , Attwood Kristopher , Catalfamo Kayla , Rosenheck Hanna , Yao Song , Mattson David M. , Mukherjee Sarbajit , Kukar Moshim , Witkiewicz Agnieszka K. , Singh Anurag K. 
Published: January 2025

Abstract

Background
Esophageal cancer (ESC) is an aggressive disease which often presents at an advanced stage. Despite trimodal therapy, 40–50% patients can develop metastatic disease by 18 months. Identification of patients at risk for metastatic spread is challenging with need for improved prognostication. We investigated whether the immune landscape of pretreatment tissue was associated with relapse in ESC patients.

Methods
Between April 2010 and October 2018, we identified 25 patients who had undergone trimodal therapy for ESC and had pretreatment biopsies suitable for analyses. We performed high-throughput multispectral immunofluorescence (mIF) analysis on formalin-fixed paraffin embedded biopsy samples. Analysis of 27 unique populations via immune and exhaustion mIF panels was performed and expression was normalized to total cell counts.

Results
Of the 25 patients analyzed, the median follow-up time was 23.9 months, during which 12 (48%) patients suffered a relapse with a median time to progression of 13.1 months. mIF revealed higher expression of HLA-DR (p = 0.019), CD8/LAG3 (p = 0.046), and CD8/CTLA4 (p = 0.027) among patients without relapse. Time to progression (TTP) and disease-specific survival (DSS) were stratified by median expression of each significant subpopulation and formally tested by the log-rank test. Higher than median expression of HLA-DR (p = 0.027), CD8/LAG3 (p = 0.039), and CD8/CTLA4 (p = 0.039) were significantly associated with TTP. Similarly, HLA-DR (p = 0.0069) and CD8/CTLA4 (p = 0.036) were significantly associated with improved DSS, whereas no significant observations were found with CD8/LAG3 (p = 0.11) expression. Stromal, but not tumoral expression of CD163 and CD163/PDL1 were significantly associated with improved TTP and DSS.

Conclusions
High expression of HLA-DR, CD8/CTLA4, and stromal expression of CD163 and CD163/PDL1 within pretreatment biopsy ESC samples was associated with significantly reduced rates of relapse. Increased presence of these markers suggests that an improved immune landscape is associated with less aggressive disease and may provide an opportunity for risk-based treatment strategies.
Spatial expression of fibroblast activation protein-α in clear cell renal cell carcinomas revealed by multiplex immunoprofiling analysis of the tumor microenvironment
Authors: Larrinaga Gorka , Redrado Miriam , Loizaga-Iriarte Ana , Pérez-Fernández Amparo , Santos-Martín Aida , Angulo Javier C. , Fernández José A. , Calvo Alfonso , López José I. 
Published: January 2025

Abstract
Clear cell renal cell carcinoma (ccRCC) is one of the most challenging neoplasms because of its phenotypic variability and intratumoral heterogeneity. Because of its variability, ccRCC is a good test bench for the application of new technological approaches to unveiling its intricacies. Multiplex immunofluorescence (mIF) is an emerging method that enables the simultaneous and detailed assessment of tumor and stromal cell subpopulations in a single tissue section. This novel approach represents a promising step forward for analyzing the microenvironmental cell composition and distribution across the tumor and understanding its possible interactions with tumor cells. This study provides the first characterization of the spatial distribution of fibroblast activation protein-α (FAP)-expressing cancer-associated fibroblasts (FAP + CAFs) in conjunction with lymphoid (CD4 + , CD8 + , CD4 + FOXP3 + , and CD20 +) and myeloid (CD68 +) cells in tissue sections from ccRCC in their early phases of evolution (n = 88). Both the tumor center and periphery were analyzed with mIF. FAP + CAFs and tumor-infiltrating lymphocytes (TILs) were significantly concentrated at the tumor periphery. Additionally, elevated percentages of FAP + CAFs were correlated with larger tumors and synchronous metastases. Increased levels of CD68 +  and CD4 + FOXP3 +  cells (above the 75th percentile) were linked to worse cancer-specific survival (CSS) in patients with ccRCC. Furthermore, significant correlations emerged among FAP + CAFs, TILs, and CD68 +  cells, and the co-occurrence of elevated FAP + CAFs, T-cytotoxic (CD8 +), T-regulatory (CD4 + FOXP3 +) cells, and macrophages (CD68 +) at the tumor center were independently associated with worse CSS. These findings suggest that FAP + CAFs contribute to the aggressiveness of ccRCC, and their role is potentially mediated by their ability to foster an immunosuppressive environment within the renal tumor microenvironment.
Tissue factor targeted near-infrared photoimmunotherapy: a versatile therapeutic approach for malignancies
Authors: Takao Seiichiro , Fukushima Hiroshi , Furusawa Aki , Kato Takuya , Okuyama Shuhei , Kano Makoto , Yamamoto Hiroshi , Suzuki Motofumi , Kano Miyu , Choyke Peter L. , Kobayashi Hisataka 
Published: January 2025

Abstract
Tissue factor (TF) is a cell surface protein that plays a role in blood clotting but is also commonly expressed in many cancers. Recent research implicated TF in cancer proliferation, metastasis, angiogenesis, and immune escape. Therefore, TF can be considered a viable therapeutic target against cancer. Herein, we developed and tested a TF-targeted near-infrared photoimmunotherapy (NIR-PIT) as a potential treatment for several types of cancer. Tisotumab, a TF antibody, was conjugated to IR700. The efficacy of TF-targeted NIR-PIT was investigated using multiple cancer cell lines (A431; epidermoid carcinoma, HPAF-II; pancreatic adenocarcinoma, HSC-2; oral carcinoma, HT1376-luc; bladder carcinoma, MDAMB231; breast adenocarcinoma, and SKOV3-luc; ovarian serous cystadenocarcinoma) in vitro. In vivo, the efficacy of TF-targeted NIR-PIT was evaluated in HPAF-II and A431 xenograft mouse models. Pathologic changes in these tumors after NIR-PIT were evaluated in these tumor models. All cancer lines demonstrated TF expression in vitro and in vivo. Additionally, TF expression was documented to localize to cancer cells in tumors. In vitro, TF-targeted NIR-PIT caused cell death in a light dose-dependent manner. In vivo, TF-targeted NIR-PIT suppressed tumor growth and improved survival rates compared to controls. Furthermore, in vivo NIR-PIT showed histological signs of cancer cell damage, such as cytoplasmic vacuolation, nuclear dysmorphism, and extracellular leakage of LDHA consistent with cell death. In conclusion, TF-targeted NIR-PIT holds promise as a treatment for multiple cancer models expressing TF, spanning multiple cancer types.
Cell therapies for viral diseases: a new frontier
Authors: Nardo David , Maddox Emileigh G. , Riley James L. 
Published: January 2025

AbstractDespite advances in medicine and antimicrobial research, viral infections continue to pose a major threat to human health. While major strides have been made in generating vaccines and small molecules to combat emerging pathogens, new modalities of treatment are warranted in diseases where there is a lack of treatment options, or where treatment cannot fully eradicate pathogens, as in HIV infection. Cellular therapies, some of which are FDA approved for treating cancer, take advantage of our developing understanding of the immune system, and harness this knowledge to enhance, or direct, immune responses toward infectious agents. As with cancer, viruses that evade immunity, do so by avoiding immune recognition or by redirecting the cellular responses that would eradicate them. As such, infusing virus specific immune cells has the potential to improve patient outcomes and should be investigated as a potential tool in the arsenal to fight infection. The present manuscript summarizes key findings made using cellular therapies for the treatment of viral infections, focusing on the potential that these strategies might have in controlling disease.
Small bowel duplication cyst in the pediatric population—when to operate?
Authors: Dreznik Yael , Almog Anastasia , Paran Maya , Konen Osnat , Kravarusic Dragan 
Published: January 2025

Abstract
Introduction

Aim
The aim of the study is to determine the optimal timing for surgery in patients with small bowel duplications.

Methods
A retrospective cohort study, including all patients younger than 18 years who were diagnosed with small bowel duplications from 2013 until 2024 in a single tertiary medical center, was performed. Patients’ demographics, duplication size and location, pathological results, and clinical outcomes were collected.

Results
Sixteen patients (nine boys, seven girls) underwent laparoscopic-assisted resection of small bowel duplication at an average age of 3 years. A prenatal diagnosis was made in 11 patients, 10 (91%) of whom underwent elective surgery at a median age of 1.3 years. Overall, six patients required semi-elective or urgent surgery due to bowel obstruction, abdominal discomfort, or symptomatic anemia, with most (83%) lacking prenatal evaluation. Elective surgery patients had significantly smaller duplications (13 cm3 vs. 135 cm3). Post-operative recovery was satisfactory in all patients, with an average hospital stay of 6 days.

Conclusion
In conclusion, asymptomatic, small duplication cysts in the small bowel of pediatric patients can be managed expectantly and can be operated after the first year of age. This approach is safe and allows for laparoscopic exploration in older infants, yielding satisfactory outcomes.
Bandgap characteristics analysis and graded design of a novel metamaterial for flexural wave suppression
Authors: Yang Fan , Ma Zhaoyang , Guo Xingming 
Published: January 2025

AbstractA novel elastic metamaterial is proposed with the aim of achieving low-frequency broad bandgaps and bandgap regulation. The band structure of the proposed metamaterial is calculated based on the Floquet-Bloch theorem, and the boundary modes of each bandgap are analyzed to understand the effects of each component of the unit cell on the bandgap formation. It is found that the metamaterials with a low elastic modulus of ligaments can generate flexural wave bandgaps below 300 Hz. Multi-frequency vibrations can be suppressed through the selective manipulation of bandgaps. The dual-graded design of metamaterials that can significantly improve the bandgap width is proposed based on parametric studies. A new way that can regulate the bandgap is revealed by studying the graded elastic modulus in the substrate. The results demonstrate that the nonlinear gradient of the elastic modulus in the substrate offers better bandgap performance. Based on these analyses, the proposed elastic metamaterials can pave the way for multi-frequency vibration control, low-frequency bandgap broadening, and bandgap tuning.
Spatiotemporal analysis of land surface temperature and land cover changes in Prešov city using downscaling approach and machine learning algorithms
Authors: Uhrin Anton , Onačillová Katarína 
Published: January 2025

Abstract
In recent decades, global climate change and rapid urbanization have aggravated the urban heat island (UHI) effect, affecting the well-being of urban citizens. Although this significant phenomenon is more pronounced in larger metropolitan areas due to extensive impervious surfaces, small- and medium-sized cities also experience UHI effects, yet research on UHI in these cities is rare, emphasizing the importance of land surface temperature (LST) as a key parameter for studying UHI dynamics. Therefore, this paper focuses on the evaluation of LST and land cover (LC) changes in the city of Prešov, Slovakia, a typical medium-sized European city that has recently undergone significant LC changes. In this study, we use the relationship between Landsat-8/Landsat-9-derived LST and spectral indices Normalized Difference Built-Up Index (NDBI), Normalized Difference Vegetation Index (NDVI), Normalized Difference Water Index (NDWI) derived from Landsat-8/Landsat-9 and Sentinel-2 to downscale LST to 10 m. Two machine learning (ML) algorithms, support vector machine (SVM) and random forest (RF), are used to assess image classification and identify how different types and LC changes in selected years 2017, 2019, and 2023 affect the pattern of LST. The results show that several decisions made during the last decade, such as the construction of new urban fabrics and roads, caused the increase in LST. The LC change evaluation, based on the RF classification algorithm, achieved overall accuracies of 93.2% in 2017, 89.6% in 2019, and 91.5% in 2023, outperforming SVM by 0.8% in 2017 and 4.3% in 2023. This approach identifies UHI-prone areas with higher spatial resolution, helping urban planning mitigate the negative effects of increasing urban LSTs.
Understanding the spatial distribution of tiny house villages for the homeless and the contextual factors underlying their establishment in the United States
Authors: Kpeebi Yetimoni , Evans Krista 
Published: January 2025

AbstractThe increase in homelessness in the US has prompted several responses, including the development of tiny house villages. Initial efforts were made in 2019 to establish a national database of these villages. While the geographical locations, physical and social characteristics of these villages have been well documented, there remains a gap in understanding the spatial distribution of these villages, and the contextual factors that underly their establishment. Building on the 2019 database, this study developed a more user-friendly interactive online map to facilitate public contribution and enhance data collection on tiny house villages for the homeless. The study also employed a density-based clustering tool using ArcGIS to analyze the spatial distribution of tiny house villages across the US. A pronounced clustering was found along the West Coast, especially in states like Washington, California, and Oregon. In terms of political leanings, Blue (Democratic) states were found to have a higher clustering of these villages compared to Red (Republican) states. The study recommends fostering stronger partnerships to address regulatory barriers and ensure the equitable distribution of tiny house villages, particularly in regions with high homelessness rates but fewer resources for affordable housing solutions.
A Review of Unmanned Vehicle Control with Adaptive Dynamic Programming Implementations
Authors: Liu Hao , Yi Xinning , Liu Deyuan , Valavanis Kimon P. 
Published: January 2025

AbstractIn this review, the optimal control designs via adaptive dynamic programming (ADP) of unmanned vehicles are investigated. Various complex tasks in unmanned systems are addressed as fundamental optimal regulation and tracking control problems related to the position and attitude of vehicles. The optimal control can be obtained by solving the Hamilton-Jacobi-Bellman equation using ADP-based control methods. Neural network implementations and policy iterative ADP algorithms are common approaches in ADP-based control methods, enabling online updates and partially model-free control for unmanned vehicles with various structures. For complexities and uncertain disturbances in unmanned vehicle dynamics, robust ADP-based control methods are proposed, including robust ADP control for matched and unmatched uncertainties, robust guaranteed cost control with ADP, and ADP-based $$H_\infty $$

H
∞

control. In order to reduce communication and computational costs in unmanned vehicle operations, a preliminary discussion on event-triggered optimal control using ADP-based control methods is presented.
Physics-Preserving IMPES Based Multiscale Methods for Immiscible Two-Phase Flow in Highly Heterogeneous Porous Media
Authors: Wang Yiran , Chung Eric , Sun Shuyu 
Published: January 2025

Abstract
In this paper, we introduce a novel physics-preserving multiscale approach to tackle the challenge of immiscible two-phase flow problems. These are typically described as a coupled system comprising Darcy’s law and mass conservation equations. Physics-preserving IMplicit Pressure Explicit Saturation (P-IMPES) scheme, is designed to uphold local mass conservation for both phases while remaining unbiased. Notably, when the time step is kept below a certain threshold, the P-IMPES scheme ensures bounds-preserving saturation for both phases. For velocity updates, we employ the mixed generalized multiscale finite element method (MGMsFEM), a highly efficient solver that operates on a coarse grid to compute unknowns. We adopt an operation splitting technique to manage the complexities of two-phase flow, utilizing an upwind strategy for explicit saturation iteration, while employing the MGMsFEM to compute velocity via a decoupled system on a coarse mesh. To validate the effectiveness and robustness of our proposed method, we conduct a series of comprehensive experiments. Additionally, we provide a rigorous analysis to establish the theoretical underpinnings of the method, which are corroborated by our numerical findings. Both simulations and analysis demonstrate that our approach strikes a favorable balance between accuracy and computational efficiency.
Development and Validation of a Neurosurgical Phantom for Simulating External Ventricular Drain Placement
Authors: van Doormaal Jesse A. M. , Fick Tim , Boskovic Ernest , Hoving Eelco W. , Robe Pierre A. J. T. , van Doormaal Tristan P. C. 
Published: January 2025

AbstractThis study aimed to develop and validate a cost-effective, customizable patient-specific phantom for simulating external ventricular drain placement, combining image segmentation, 3-D printing and molding techniques. Two variations of the phantom were created based on patient MRI data, integrating a realistic skin layer with anatomical landmarks, a 3-D printed skull, an agarose polysaccharide gel brain, and a ventricular cavity. To validate the phantom, 15 neurosurgeons, residents, and physician assistants performed 30 EVD placements. The effectiveness of the phantom as a training tool was assessed through a standardized user experience questionnaire, which evaluated the physical attributes, realism, and overall satisfaction. The mechanical properties of the phantom brain were quantified by measuring catheter insertion forces using a linear force tester to compare them to those experienced in real brain tissue. The study participants successfully completed EVD placements with a 76.7% optimal placement rate, which aligns with rates observed in clinical practice. Feedback highlighted the anatomical accuracy of the phantom and its value in enhancing surgical skills, though it also identified areas for improvement, particularly in the realism of the skin layer. Mechanical testing demonstrated that the insertion forces required were comparable to those encountered in actual brain tissue. The developed phantom offers a realistic, low-cost, and adaptable model for EVD simulation. This tool is particularly beneficial for both training and research, with future enhancements planned to improve the realism of the skin and incorporate more anatomical features to increase the fidelity of the simulation.
Perception of Civil Society on the Curricular Integration of Media Competence: Challenges and Opportunities in Latin America
Authors: Rojas-Estrada Elizabeth-Guadalupe , García-Ruiz Rosa , Aguaded Ignacio 
Published: January 2025

AbstractMedia Competence (MC) enables citizens to efficiently utilize information and communication technologies, for both consuming and producing content, in order to participate in digital society in a responsible and reflective manner. Its integration in the curriculum requires inter-sectorial collaboration, which includes not only education authorities, but also key actors such as Civil Society Organizations (CSO). The present study examines the perception of CSO with regard to the integration of MC in the curriculum of basic education in Latin American countries. For this, a survey was designed that was stored in a digital platform. It was completed by 63 CSO from fourteen different countries. The main findings indicate that: a) the CSO recognize the importance of teaching MC and the associated challenges, such as the digital divide, the lack of political will, and the lack of understanding of the concept by the population in general; and b) they contribute through the creation of education resources and the teaching of classes for teachers and other vulnerable groups; however, it is crucial to strengthen the network of collaboration with other groups of interest, prioritize MC in their agendas, and ensure that CSO receive training in this area.
Does public funding reduce financial constraints of young firms in Germany?
Authors: Weuschek Nadine 
Published: January 2025

Abstract
This paper examines the financing situation of young firms in Germany after receiving public funding. I find that, on average, public funding is associated with a significant reduction in the future probability of experiencing financial constraints. While grant tend to improve relationships with equity investors, subsidized loans or loan guarantees tend to improve relationships with external providers of both equity and debt capital. Additionally, I show that the effect of public funding is stronger for more financially constrained firms when provided as a subsidized loan or loan guarantee, and heterogeneous across entrepreneurs and startups. Furthermore, my results suggest that public funding is positively related to real outcomes, and that grants also help firms by stabilizing their economic position.
Influence of Neighborhood Socioeconomic Deprivation on Effectiveness of an Intensive Lifestyle Intervention
Authors: Sy Mamadou , Pilla Scott , Bennett Wendy , Yeh Hsin-Chieh , Baptiste-Roberts Kesha , Gary-Webb Tiffany L. , Vaidya Dhananjay , Clark Jeanne M. 
Published: January 2025

Abstract
Objective
To assess the influence of neighborhood socioeconomic deprivation on the effectiveness of an intensive lifestyle intervention (ILI) in the Look AHEAD trial.

Research Design and Methods
Look AHEAD randomized adults with overweight/obesity and type 2 diabetes to ILI for weight loss, or Diabetes Support and Education (DSE). We linked participant data from four study sites to the 2000 United States Census to generate a neighborhood socioeconomic deprivation score. We analyzed the effect of neighborhood deprivation in tertiles on various clinical outcomes including weight and HbA1c changes over 4 years using a mixed-effects linear model with random intercept and an interaction term between deprivation tertile and study arm over 4 years.

Results
Among 1213 participants at baseline, the mean age was 60 years, 41% were male, and 65% identified as White, 26% as Black, and 4% as Hispanic. Most participants had a college degree (84%) and reported an annual income over $40,000 (75%). The deprivation score ranged from −12.04 to −2.61 in the most deprived tertile and 2.01 to 18.69 in the least deprived tertile (the lower the score, the higher the deprivation). There were no statistically significant treatment differences by deprivation score in weight or HbA1c changes over the 4-year period.

Conclusions
In this clinical trial population, an intensive lifestyle intervention was equally effective across levels of neighborhood socioeconomic deprivation. However, these findings may not extend to individuals with the lowest income and educational attainment who are not typically represented in clinical trials and for whom more research is needed.