bluuebunny/crossref_metadata_2025_split huggingface dataset:
CCR8 antagonist suppresses liver cancer progression via turning tumor-infiltrating Tregs into less immunosuppressive phenotype
Authors: Wang JianFei , Tian Binle , Wang Zhilong , Cao Mei , Wang Na , Jia Xuebing , Zhang Yuanyuan , Zhou Jingyi , Zhang Wen , Li Zheng , Xue Junli , Fan Guo-Huang , Li Qi 
Published: March 2024

Abstract
Regulatory T cells (Tregs) are main immunosuppressive cells in tumor immune microenvironment (TIME). However, systemic Treg depletion is not favored due to the crucial role of Tregs in the maintenance of immune homeostasis and prevention of autoimmunity. Recently, CCR8 has been identified as a key chemokine receptor expressed on tumor-infiltrating Tregs and targeted blockade exerts anticancer effect in several cancers, but whether this pathway is involved in the progression of hepatocellular carcinoma (HCC) remains unclear. Here we determined CCR8+ Tregs in human TCC tissues and examined the anticancer effect and the underlying molecular mechanisms of CCR8 antagonist antibody, IPG0521m, in murine liver cancer model. Our results demonstrated marked increase of CCR8+ Tregs in human HCC tissues. Treatment of syngeinic liver cancer model with IPG0521m resulted in dramatic inhibition of tumor growth, associated with increased CD8+ T cells in the tumor tissues. Preliminary bulk RNA sequencing analysis indicated that IPG0521m treatment resulted in remarkable increase in antitumor immunity. Furthermore, single-cell RNA sequencing analysis demonstrated that IPG0521m treatment resulted in switch of Tregs from high immunosuppression to low immunosuppression phenotype, associated with elevated CD8+ T and NK cell proliferation and cytotoxicity, and decreased myeloid-derived suppressor cells and tumor-associated macrophages in the tumor tissues. Finally, IPG0521m exerted long-lasting anticancer effect and synergized with PD-1 antibody in tumor inhibition. In conclusion, IPG0521m inhibited liver cancer growth via reducing the immunosuppression of Tregs, thereby boosting anti-cancer immunity. Our study paves the way for the clinical study of CCR8 antagonist in HCC and other cancer therapy.
A two-stage Data Envelopment Analysis Approach Incorporating Global Bounded Adjustment Measure to evaluate the efficiency of medical waste recycling systems with undesirable inputs and outputs
Authors: Song Wen-Jing , Ren Jian-Wei , Chen Chun-Hua , Feng Chen-Xi , Li Lin-Qiang , Ma Chong-Yu 
Published: March 2024

Abstract

With the ever-increasing focus on sustainable development, recycling waste and renewable use of waste products has earned immense consideration from academics and policy-makers. The serious pollution, complex types, and strong infectivity of medical waste (MW) have brought serious challenges to management. Although several researchers have addressed the issue of the MW by optimizing MW management networks and systems, there is still a significant gap in systematically evaluating the efficiency of MW recycling systems. Therefore, this paper proposes a two-stage data envelopment analysis (DEA) approach that combines the virtual frontier and the global bounded adjustment measure (BAM-VF-G), considering both undesirable inputs and outputs. In the first stage, the BAM-G model is used to evaluate the efficiency of MW recycling systems, and the BAM-VF-G model is used to further rank super-efficient MW recycling systems. In the second stage, two types of efficiency decomposition models are proposed. The first type of models decomposes unified efficiency into production efficiency (PE) and environment efficiency (EE). Depending upon the systems structure, the second type of models decomposes unified efficiency into the efficiency of the MW collection and transport subsystem (MWCS) and the efficiency of the MW treatment subsystem (MWTS). The novel approach is used to measure the efficiency of the MW recycling systems in China's new first-tier cities (CNFCs), and we find that: (1) Foshan ranks the highest in efficiency, followed by Qingdao and Dongguan, with efficiency values of 0.3593, 0.1765, and 0.1530, respectively. (2) EE has always been lower than PE and is a critical factor influencing the overall efficiency of MW recycling systems in CNFCs. (3) The MWCS lacks resilience, with an efficiency 0.042 lower than that of the MWTC. Following the outbreak of COVID-19, the efficiency of the MWCS has been decreasing year by year, reaching only 0.762 in 2021, which is a decline of 0.111 compared to 2017.
Strength prediction of LD slag aggregate standard concrete
Authors: Singh Prince , Prasad B. K. , Kumar Virendra 
Published: March 2024

Abstract
The purpose of this study is to investigate how, incorporating Linz-Donawitz slag (LD slag) as a partial replacement for natural fine and coarse aggregates, affects the compressive strength of concrete. The study also aims to compare the performance of these LD slag-based concretes with conventional concrete. The research involves substituting the natural fine and coarse aggregates typically used in concrete with LD slag aggregates. This replacement is done by weight and is carried out incrementally at 20%, reaching up to 100%. To conduct the experiments, concrete of grade M35 is cast into standard cube, cylinder, and prism specimens using both the natural aggregates and the LD slag aggregates. These specimens are then cured underwater and subjected to testing to evaluate their compressive strength, split tensile strength, and flexural strength. The experimental results show that the concrete made with LD slag aggregates exhibits a higher density compared to the reference concrete. Also the LD slag aggregate concretes (LDSAC) exhibited better performance under compressive, split tensile and flexural loading as compared to the conventional concrete, particularly when the replacement of aggregates fell within the range of 40–80%. Furthermore, the study employs a machine learning technique called Random Forest (RF) to predict the compressive, split tensile and flexural strengths of the concrete.
Clinical, functional and radiological outcome after osteosynthesis of ankle fractures using a specific provocation test
Authors: Zimmermann Julian , Zingg Liv , Frey Walter , Schläppi Michel , Babians Arby , Zingg Urs 
Published: March 2024

Abstract

Background
Ankle fractures are frequent and despite numerous publications on its treatment and outcome, there is a lack of precise data on the functional results in young, healthy and sportive patients. We hypothesized that patients after open reduction and internal fixation (ORIF) of a simple ankle fracture would have a similar function compared to a healthy control group, whereas patients with complex fractures will have significant functional deficits. Furthermore, we postulate that there is a discrepancy between the radiological and the functional outcomes.
Methods
Therefore, a specific provocation test has been developed to evaluate the postoperative possibilities of weight bearing, stop-and-go activities and range of motion during extremes of movements. In combination with three questionnaires and a radiographic evaluation the true functional outcome and the possibility of participating in sportive activities has been investigated and compared with an age and sex matched control group.
Results
A clear impairment even in unilateral and simple ankle fractures has been found. Impairment increased in tests including stop-and-go activities in combination with load bearing and with the complexity of the fractures. Concerning the subjective outcome there was a significant impairment in daily activities without any difference in preoperative and postoperative sportive activity between the groups. No difference was found in the radiological assessment.
Conclusions
The study shows the need of more complex functional evaluation in young and sportive patients after open reduction and internal fixation of an ankle fracture.
Trial registration:
BASEC-Nr. 2018 − 01124
Out of Model Zoo: Towards Selecting the Best Deep Neural Network with Cognitive Analysis
Authors: Yang Ying , Lv Xiao 
Published: March 2024

Abstract
Deep neural networks have achieved impressive performance on a huge amount of tasks and many model zoos are available that provide pre-trained models for free download. Despite the convenience, it is still difficult for the resource-constrained companies, especially startups, to select the best model from many candidates for their own tasks. Due to the lack of training data, the main challenges are to (1) evaluate the robustness of models with a test dataset and (2) optimize the prediction to maximize the usage of the model zoo. To address these challenges, we propose a robust model selector, Miss DL, which incorporates cognitive analysis and a series of criteria to select robust models from a given model zoo. We first propose a systemic method to simulate the distortions of new data points and calculate the dominant labels of the new data points. Then, we propose a metric to measure the robustness of models and select the best model. Motivated by the low confidence scores of the selected model on certain data points, we select a complementary model for each class for optimization. We evaluate the proposed Miss DL on popular deep neural networks and image datasets, including CIFAR-10, CIFAR-100, and ImageNet. Extensive experiments are performed to show the robustness and efficiency of Miss DL in different settings.
Pembrolizumab-axitinib versus nivolumab-cabozantinib as first-line therapy in patients with metastatic renal cell carcinoma: a retrospective real-world comparison (ARON-1)
Authors: Santoni Matteo , Roviello Giandomenico , Grande Enrique , Giorgi Ugo , Fiala Ondrej , Seront Emmanuel , Molina-Cerrillo Javier , Pichler Renate , Myint Zin W. , Kucharz Jakub , Kanesvaran Ravindran , Büttner Thomas , Pichler Martin , Basso Umberto , Kopecky Jindrich , Bourlon Maria T. , Cerbone Linda , Buchler Tomas , Pinto Alvaro , Liaño Alfonso Gómez , Gianni Caterina , Zgura Anca , Rescigno Pasquale , Ansari Jawaher , Caffo Orazio , Küronya Zsófia , Vitale Maria Giuseppa , Bhuva Dipen , Catalano Martina , Vau Nuno , Kopp Ray Manneh , Buti Sebastiano , Bamias Aristotelis , Porta Camillo , Sunela Kaisa , Massari Francesco 
Published: March 2024

Abstract
Background
The optimal first-line therapy for metastatic renal cell carcinoma (mRCC) remains uncertain, despite recent advancements in immune-based combinations. This retrospective study compares the effectiveness of pembrolizumab plus axitinib (PA) and nivolumab plus cabozantinib (NC) as first-line treatments for mRCC in a real-world setting.
Methods
Patient data were collected from 55 centres across 16 countries, encompassing individuals diagnosed with mRCC receiving first-line treatment with PA or NC between January 2016 and October 2023. Clinical and tumour features and treatment responses were recorded. The primary endpoints were overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and time to second progression. Statistical analyses included Kaplan-Meier survival estimates, Cox proportional hazard models, and chi-square tests.
Results
A total of 760 patients with a median age of 64 years (range, 29–88) were included. Of them, 607 received PA, and only 153 NC. Median OS was 55.7 months and not reached (NR) for PA and NC, respectively (P = .51), while median PFS was longer with NC (27.6 months) than for PA (16.2 months, P = .003). Subgroup analysis suggested a PFS benefits for NC in male, younger patients, intermediate-risk group, clear cell histology, and lung involvement, as well as ORR favoured NC in good risk patients. Multivariate analysis identified first-line therapy as a significant factor associated with PFS.
Conclusions
In this certainly biased retrospective comparison, NC demonstrated superior ORR and longer PFS compared to PA in mRCC. These findings underscore the importance of considering individual patient characteristics and risk profiles when selecting first-line therapy for mRCC.
Vicia faba Fungal diseases: Could nanostructures drug delivery systems be a novel paradigm for therapy?
Authors: Hasaneen Mohammed N. A. , Helal Sara H. , El-Zayat Mustafa M. , Abdel-Aziz Heba M. M. 
Published: March 2024

Abstract
New drug delivery strategies have become a pioneer and novel approach in controlling plant diseases in application research nowadays. In this paper, we investigate the delivery of chitosan nanoparticles (CSNPs), carbon nanotubes (CNTs) and solid lipid nanoparticles (SLNPs) loaded with nystatin (NYS) and fluconazole (FLZ) antifungal antibiotics for diseased Vicia faba plants by foliar uptake. CSNPs-NYS or FLZ, CNTs-NYS or FLZ and SLNPs-NYS or FLZ were easily applied to leaf surfaces and enter the stomata via gas uptake, avoiding direct interaction with soil systems. The uptake, translocation and biosafety of nano-drug delivery systems inside Vicia faba plants was investigated by transmission electron microscopy. The results obtained revealed that all different nanoparticles were taken up and transported through phloem tissues, in particular, sieve tubes of either healthy, infected or recovered Vicia faba plants. On the other hand, growth and yield developmental parameters in the present study including shoot length, number of pods per plants, weight of pod, number of seeds per pod, weight of seed, seed yield per plant, harvest index, crop index and mobilization index of healthy and recovered Vicia fabaplants showed, in general, significant increases. The net results indicate the possibility of these formulation to protect plant from the disease with a sequence of: solid lipid nanoparticles-FLZ; 346 %> CSNPs+FLZ; 315 %> CNTs+FLZ; 274%
Unlocking the Mysteries of Long COVID in Children and Young People: Insights from a Policy Review and Social Media Analysis in the UK
Authors: Chepo Macarena , Martin Sam , Déom Noémie , Khalid Ahmad Firas , Vindrola-Padros Cecilia 
Published: March 2024

Abstract
There is still much unknown about the long-term consequences of COVID-19, otherwise known as post-acute sequelae of COVID (PASC). The challenge of defining the manifestation of Long COVID in children and young people (CYP) was specifically identified as a research subject by the National Institute for Health and care Research (NIHR). The lack of data relating to this age group and the impact the symptoms of PASC may have on the well-being and development of children have made research on this topic especially pressing. This healthcare policy study focuses on the applicability of Thompson et al.'s and Campbell and Carnevale’s frameworks in understanding the formulation and implementation of Long COVID healthcare policies. The analysis uses the ‘LISTEN’ method, applying a mixed method analysis of policy data and social media discourse analysis. Overall, the findings of this review of Long COVID policy guidelines for CYP and adults between 2020 and 2022, highlight increased public concern around the ethical aspects of policy-making, with high focus on Accountability and Responsiveness. The review concludes with several policy recommendations such as enhancing accountability through regular audits, promoting inclusiveness by incorporating CYP perspectives, ensuring transparency via regular updates, and maintaining equity in policy impact. Clinical policies should provide clear guidelines for healthcare providers, support mental health services for CYP and healthcare workers, and clarify school policies regarding Long COVID. Policymakers should also consider a health equity perspective in their Long COVID recovery policies.
Plataformas digitales y prácticas pedagógicas de docentes: promesas no cumplidas
Authors: Barragán-Giraldo Diego Fernando , Pirela Morillo Johann Enrique , Riaño-Diaz John Agustin , Munevar Vargas Sandro Leonardo 
Published: March 2024

Las plataformas digitales como escenarios de prácticas pedagógicas de docentes tienen alta potencialidad para la gestión del conocimiento, del aprendizaje, en el marco de principios democráticos y de construcción de ciudadanía. Pero alrededor de estas ha prevalecido un discurso teórico y práctico que privilegia nociones optimistas y triunfalistas que han postergado los procesos de reflexión sobre las repercusiones y tensiones que se generan en escenarios donde interactúan los agentes educativos. Se utilizó como método la Revisión Sistemática de Literatura, utilizando la fuente de datos Dimensions, de lo cual se evidenciaron vacíos en relación con posturas críticas sobre las plataformas y prácticas pedagógicas de docentes, lo cual deberá ser superado para ampliar la mirada analítica y proponer estrategias que permitan una apropiación más sistémica, situada y ética que tome en cuenta las zonas de oportunidad, pero también de opacidad. La alfabetización crítica en el uso de las plataformas sigue siendo un asunto pendiente para que se cumplan las promesas que se plantearon en relación con las plataformas digitales y su impacto en una educación que potencie el pensamiento crítico, la participación y la democratización del conocimiento.
Laboratorios digitales y plataformas de acceso abierto: retos y propuestas para la democratización del aprendizaje.
Authors: Espinoza Castro Karla Esther , Apolo Buenaño Diego Eduardo , Sánchez Barrera Ruth Nohemí , Bravo Guzhñay Byron Florencio 
Published: March 2024

Las transformaciones en relación con el uso de tecnologías en espacios educativos se han acelerado; pero ello también, ha traído consigo implicancias que pueden pasar desapercibidas por los usuarios. Por ello, el presente estudio tiene como objetivo analizar cómo el uso de laboratorios digitales podría aportar a la democratización del conocimiento. Para ello se recurrió a un enfoque cualitativo de alcance descriptivo exploratorio que mediante entrevistas a autoridades de una institución educativa pública y expertos de Ecuador, México y Colombia permitió aproximarse a la comprensión del fenómeno. Como principales resultados se puede mencionar que existen retos importantes a tomar en cuenta como: que los recortes presupuestarios afectan a la educación pública; además que el acceso a plataformas de pago es restringido. Cabe mencionar también que el uso de estos espacios puede aportar al proceso de enseñanza-aprendizaje pero que en su mayoría los recursos son brindados por instituciones privadas que tienen costo. Pese a ello, también emergen posibilidades para que puedan existir iniciativas que desarrollen laboratorios virtuales de libre acceso, contextualizados y que recurran a diferentes recursos como la realidad virtual para motivar el aprendizaje.
Presentación sección especial: Plataformas digitales y datificación en el sistema educativo. Posibilidades y desafíos
Authors: Rivera-Vargas Pablo , Jacovkis Judith , Raffaghelli Juliana 
Published: March 2024

Como consecuencia de las transformaciones iniciadas en los últimos años, y que se han acelerado en el contexto de la pandemia del COVID-19, se ha intensificado la penetración de nuevas infraestructuras, plataformas digitales y herramientas de uso intensivo de datos en los sistemas educativos nacionales (Suárez et al., 2023; Williamson & Hogan, 2020; Pangrazio et al. 2022). Este fenómeno está transformando rápidamente los procesos de enseñanza-aprendizaje y afectando a dimensiones como la justicia escolar, la privacidad y el derecho a la educación.
En parte, esto se debe a la creciente importancia de las corporaciones BigTech, que tienen una influencia cada vez mayor en el diseño de la política educativa y en la creación de nuevos mercados educativos a través de la venta y distribución de dispositivos y plataformas digitales comerciales a los gobiernos y sus sistemas educativos (Sancho et al., 2020; Saura et al., 2022; Parcerisa et al., 2022).
Beyond Conventional Therapies: Molecular Dynamics of Alzheimer's
Treatment through CLOCK/BMAL1 Interactions
Authors: Haskologlu Ismail Celil , Erdag Emine , Sehirli Ahmet Ozer , Uludag Orhan , Abacioglu Nurettin 
Published: March 2024

Background:
Alzheimer's Disease (AD) represents a neurodegenerative disorder characterized
by cognitive and behavioral impairments significantly hindering social and occupational
functioning. Melatonin, a hormone pivotal in regulating the body's intrinsic circadian rhythm, also
acts as a catalyst in the breakdown of beta-amyloid deposits, offering a promising therapeutic approach
for AD. The upregulation of Brain and Muscle ARNT-Like 1 (Bmal1) gene expression, stimulated
by melatonin, emerges as a potential contributor to AD intervention. Current pharmacological
interventions, such as FDA-approved cholinesterase inhibitors and the recently authorized
monoclonal antibody, Lecanemab, are utilized in AD management. However, the connection between
these medications and Bmal1 remains insufficiently explored.

Objective:
This study aims to investigate the molecular effects of FDA-endorsed drugs on the
CLOCK: Bmal1 dimer. Furthermore, considering the interactions between melatonin and Bmal1,
this research explores the potential synergistic efficacy of combining these pharmaceutical agents
with melatonin for AD treatment.

Methods:
Using molecular docking and MM/PBSA methodologies, this research determines the
binding affinities of drugs within the Bmal1 binding site, constructing interaction profiles.

Results:
The findings reveal that, among FDA-approved drugs, galanthamine and donepezil demonstrate
notably similar binding energy values to melatonin, interacting within the Bmal1 binding
site through analogous amino acid residues and functional groups.

Conclusion:
A novel therapeutic approach emerges, suggesting the combination of melatonin
with Lecanemab as a monoclonal antibody therapy. Importantly, prior research has not explored
the effects of FDA-approved drugs on Bmal1 expression or their potential for synergistic effects.
Exploring Squalene's Impact on Epidermal Thickening and Collagen
Production: Molecular Docking Insights
Authors: Safaei Mohsen , Goodarzi Arash , Noori Fariba , Farmani Ahmad Reza , Kouhpayeh Seyed Amin , Abpeikar Zahra 
Published: March 2024

Background::
Aging is a progressive deterioration characterized by the gradual buildup
of physiological alterations as time passes. The aging phenomenon encompasses various interconnected
systems within the body, such as the skin, bones, cartilage, and hair.

Objective and Methods:
In this study, based on the appropriate properties of squalene, including
antioxidant, anti-inflammatory, and skin repair properties, a molecular docking study was designed
for the drug squalene and proteins related to the dermis and epidermis pathway and collagen
production (including Col3A1, Col1A2, FBN1, Decorin, and HAS2).

Results and Discussion::
The docking results indicated that the interaction of squalene with hyaluronan
synthetase 2 (HAS2) possessed the highest negative binding free energy value of -10.90
KCal/mol, followed by decorin with a value of -9.99 KCal/mol. Also, the inhibition constant values
of squalene- HAS2 and squalene-decorin complexes were equal to 1.61 and 7.51 μM, respectively.
It has been stated that decorin (as a small proteoglycan) and HAS2 are involved in controlling
the assembly of skin fibrils and the biosynthesis of glucosaminoglycans, respectively.

Conclusion::
Considering that proteoglycans and glucosaminoglycans play a role in the skin aging
process, squalene may be used as an anti-aging agent to induce these pathways and for different
purposes. Squalene may be used as a potential agent alone or in combination with other
compounds in tissue engineering scaffolds for cosmetic, anti-aging, wound healing, and tissue
repair applications.