bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual-Nuclide Biodistribution and Therapeutic Evaluation of a Novel Antibody-Based Radiopharmaceutical in Anaplastic Thyroid Cancer Xenografts
Authors: Lundgren Mortensen Anja Charlotte. , Berglund Hanna , Jha Preeti , Stenman Adam , Selvaraju Ram Kumar , Lundqvist Hans , Hofström Camilla , Persson Helena , Juhlin C. Christofer , Zedenius Jan , Frejd Fredrik Y. , Nestor Marika 
Published: February 2025

Abstract
Anaplastic thyroid cancer (ATC) is a rare but severe form of thyroid cancer responsible for approximately 50% of thyroid cancer deaths. Consequently, the identification of innovative therapies remains crucial for the effective treatment of ATC. Molecular radiotherapy is a rapidly growing field within oncology and the cell surface antigen CD44v6, which is overexpressed in several cancers, is a plausible target for molecular radiotherapy of ATC. Immunohistochemistry (IHC) of 39 ATC patient samples were evaluated for CD44v6 expression. Biodistribution and dosimetry of 125I/177Lu-labeled UU-40, a CD44v6 specific antibody, followed by in vivo efficacy in two ATC xenograft models with varying target expression levels (ACT-1 and BHT-101) accompanied by SPECT-imaging evaluated radiolabeled UU-40 for therapeutic efficiency in ATC xenografts. The IHC revealed CD44v6 immunoreactivity in 46% of ATC patient samples. The biodistribution favored 177LuUU-40 over the 125I-labeled antibody and confirmed in vivo specificity of both radioconjugates. The in vivo efficacy and accompanied SPECT imaging of a moderate CD44v6-expressing xenograft model (BHT-101) verified the tumor specificity as well as the target-specific effect of 177Lu -UU-40 on tumor growth and survival. A 100% complete response rate was demonstrated as a result of therapy using a single dose of 16 MBq 177Lu -UU-40 in a high CD44v6-expressing xenograft model (ACT-1), and SPECT-imaging revealed excellent tumor uptake of the radioconjugate at 14 days post-injection. This study verifies the expression of CD44v6 in ATC and cements the superiority and promise of 177Lu -UU-40 over 131I-UU-40 for antibody-based molecular radiotherapy of CD44v6-positive ATC.
A checkpoint reversal receptor mediates bipartite activation and enhances
CAR T-cell function
Authors: Landi Daniel , Navai Shoba A. , Brock Rebecca M. , Fousek Kristen , Nawas Zeid , Sanber Khaled , Chauvin-Fleurence Cynthia , Bhat Raksha R. , Xu Shuo , Krishnamurthy Purna , Choe Michelle , Campbell Matthew , Morris Jessica S. , Gad Ahmed Z. , Shree Ankita , Echeandia Alesandra , Saadeldin Amr , Matthew Pretty R. , Mullikin Dolores , Bielamowicz Kevin , Kurenbekova Lyazat , Major Angela M. , Salsman Vita S. , Byrd Tiara T. , Hicks M. John , Zhang Yi Jonathan. , Yustein Jason , Carisey Alexandre F. , Joseph Sujith K. , Ahmed Nabil , Hegde Meenakshi 
Published: February 2025

Abstract
The efficacy of CAR T-cells (CART) in solid tumors is limited by immune inhibition. In our study, we observed that effector cytokines mediated the upregulation of the PD-L1 immune-checkpoint in primary glioblastoma (GBM). To offset the PD-L1 inhibitory signal, we engineered PD-1 checkpoint reversal receptors (CPR) with a CD28 or 41BB co-stimulatory endodomain and co-expressed them with a first-generation or a CD28-containing second-generation HER2-specific CAR (CPR/CART) using bicistronic vectors. We found that bipartite T-cell activation, by CAR-generated signal 1 and CPR co-stimulation (signal 2), fine-tuned pro-inflammatory cytokine release and sustained antitumor activity. While both CPR28 and CPR41BB effectively counteracted the PD-1 signal in vitro, CPR41BB, when co-expressed with a first-generation CAR (CARζ/CPR41BB), promoted central memory differentiation following repeat antigenic stimulation. CARζ/CPR41BB T-cells formed a robust immune synapse with tumor targets, similar to a 4-1BB-containing second-generation CART, maintained the favorable metabolic parameters associated with 4-1BB co-stimulation, and demonstrated superior antitumor function after adoptive transfer in xenograft models of GBM and metastatic osteosarcoma. Thus, a CPR molecule with 4-1BB co-stimulation that curtails PD-1 inhibition and complements CAR signaling to optimize T-cell activation could enhance CART efficacy against solid tumors.
TRPV4 Promotes Vascular Calcification by Directly Associating With and Activating β-Catenin
Authors: Yuan Menglu , Li Qi , Wang Zhiwei , Liu Liangju , Wen Chengyuan , Liu Guizhu , Yu Fan , Feng Lei , Yang Liu 
Published: February 2025

BACKGROUND:

Vascular calcification contributes to increased cardiovascular morbidity and mortality in patients with chronic kidney disease, diabetes, and atherosclerosis. Currently, there are no effective therapeutic strategies to prevent or reverse vascular calcification. TRPV4 (transient receptor potential channel V4), a key Ca
2+
-permeable channel, plays an important role in various diseases. However, the role and mechanism of TRPV4 in vascular calcification have not yet been elucidated.

METHODS:
The effects of TRPV4 on vascular calcification were explored in vitro and in vivo. TRPV4 interactome assessment and molecular docking were performed to investigate the mechanism and specific therapeutic strategy for vascular calcification.

RESULTS:

TRPV4 was substantially upregulated in high inorganic phosphate–induced calcified vascular smooth muscle cells (SMCs) and calcified aortas from cholecalciferol (vitamin D3)-overloaded mice. TRPV4 overexpression increased the expression of the osteochondrogenic markers Runx2 (runt-related transcription factor 2), Msx2 (Msh homeobox 2), and Sox9 (SRY-box transcription factor 9) and exacerbated high inorganic phosphate–induced vascular SMC calcification in a Ca
2+
influx–dependent manner. In contrast, TRPV4 deficiency or inactivation significantly inhibited vascular SMC calcification under high inorganic phosphate conditions. Moreover, compared with that in control littermates, SMC-specific TRPV4 deficiency in mice alleviated vitamin D3–induced and 5/6 nephrectomy–induced vascular calcification. Mechanistically, TRPV4 interacted with β-catenin and activated β-catenin/TCF (T-cell factor) transcriptional activity via Ca
2+
/ASK1 (apoptosis signal regulating kinase 1)/p38 signaling. β-Catenin knockdown abolished the effects of TRPV4 overexpression on vascular SMC calcification. TRPV4/β-catenin interaction is pivotal for maintaining TRPV4/Ca
2+
-induced ASK1/p38/β-catenin activation. Hesperidin, a natural product found in citrus fruits, effectively disrupted TRPV4/β-catenin interaction, thereby inhibiting ASK1/p38/β-catenin activity and preventing vascular calcification.

CONCLUSIONS:
Our study identified TRPV4 as a new pathogenic factor for vascular calcification that directly associates with and activates β-catenin. Blocking the TRPV4/β-catenin interaction through hesperidin suppressed the progression of vascular calcification and may be an effective precision strategy to address vascular calcification.
SRSF4-Associated ca-circFOXP1 Regulates Hypoxia-Induced PASMC Proliferation by the Formation of R Loop With Host Gene
Authors: Song Xinyue , Xu Ya , Li Mengnan , Guan Xiaoyu , Liu Huiyu , Zhang Jingya , Sun Hanliang , Ma Cui , Zhang Lixin , Zhao Xijuan , Zheng Xiaodong , Zhu Daling 
Published: February 2025

BACKGROUND:
Pulmonary hypertension (PH) is a rare and fatal disease, the pathological changes of which include pulmonary arterial smooth muscle cell (PASMC) proliferation, which is the pathological basis of pulmonary vascular remodeling. Studies have demonstrated that chromatin-associated circRNA can regulate a variety of biological processes, including PASMC proliferation in patients with hypoxic PH. However, the role of chromatin-associated circRNA in the proliferation of PH remains largely unexplored. In this study, we aimed to identify the function and mechanism of chromatin-associated circRNA in PASMC proliferation in PH.

METHODS:
The role of ca-circFOXP1 was investigated in hypoxic mouse PASMCs and SuHX (Sugen5416+hypoxia) model mice through the use of antisense oligonucleotide knockdown and adeno-associated virus–mediated knockdown. Through bioinformatic sequence alignment, chromatin isolation by RNA purification, Cell Counting Kit 8, 5-ethynyl-2-deoxyuridine, Western blot, and other experiments, the function and mechanism of ca-circFOXP1 were verified.

RESULTS:

The expression of ca-circFOXP1 was found to be significantly increased in SuHX model mice and hypoxic mouse PASMCs. Moreover, ca-circFOXP1 was found to regulate the level of the host protein FOXP1 (forkhead box protein 1) through the R loop, thereby influencing the phosphorylation activity of SMAD2 (SMAD family member 2) and, consequently, the proliferation of mouse PASMCs. It is noteworthy that the m6A modification was found to promote the formation of the R loop between ca-circFOXP1 and the host gene
FOXP1
, thereby regulating the expression of the host protein. Furthermore, we have identified that the splicing factor SRSF4 (serine/arginine rich splicing factor 4) can upregulate the expression of ca-circFOXP1 by splicing exons 6 and 9 of FOXP1 pre-mRNA.

CONCLUSIONS:
The results demonstrated that the splicing factor SRSF4 upregulated the expression of ca-circFOXP1, and m6A methylation promoted R-loop formation between ca-circFOXP1 and host genes, regulated the level of host protein FOXP1, and then affected the phosphorylation activity of SMAD2, mediating PASMC proliferation, leading to pulmonary vascular remodeling. These results provide a theoretical basis for further study of the pathological mechanisms of hypoxic PH and may provide certain insights.
Independent External Evaluation of Pediatric Hypertrophic Cardiomyopathy Risk Scores in Predicting Severe Ventricular Arrhythmias
Authors: Wilkin Marie , Khraiche Diala , Panaioli Elena , Pontailler Margaux , Raisky Olivier , Marijon Eloi , Bonnet Damien , Waldmann Victor 
Published: February 2025

BACKGROUND:
Sudden cardiac death is the most common cause of death in childhood hypertrophic cardiomyopathy (HCM). Recently, 2 risk scores have been developed to estimate the 5-year risk of sudden cardiac death. We aimed to assess their respective performances in an independent cohort.

METHODS:
All patients with HCM aged <18 years from a single center were retrospectively included between 2003 and 2023. HCM Risk-Kids and PRIMaCY risk scores were calculated at diagnosis and during follow-up. The primary composite outcome included sustained ventricular arrhythmia, appropriate implantable cardioverter defibrillator (ICD) therapy, aborted cardiac arrest, or sudden cardiac death.

RESULTS:
A total of 100 primary prevention children were included (7.1±5.6 years, 59.0% males), with a mean follow-up of 8.6±5.5 years. Overall, 13 (13.0%) patients experienced the primary composite outcome. When only considering events during the 5 first years, Harrel C index was 0.52 (95% CI, 0.27–0.77) for HCM Risk-Kids (≥6%) and 0.70 (95% CI, 0.59–0.80) for PRIMaCY (>8.3%), with 1 patient potentially treated by ICD for every 25 ICDs implanted for HCM Risk-Kids and 1 for every 14 ICDs implanted for PRIMaCY. When risk scores were repeated and all primary outcomes during follow-up were considered, 12 of 13 (92.3%) events were correctly identified using both risk scores, with 1 patient potentially treated by ICD for every 5.6 ICDs implanted for HCM Risk-Kids and 1 for every 5.3 ICDs implanted for PRIMaCY. Among 44 (44.0%) patients implanted with an ICD, all primary prevention patients who had ≥1 appropriate ICD therapy during follow-up had an HCM Risk-Kids ≥6% and PRIMaCY >8.3% at implantation.

CONCLUSIONS:
In this independent evaluation, our findings suggest imperfect discrimination between low and high-risk patients using the HCM Risk-Kids and PRIMaCY risk scores, with predicted risks tending to be overestimated compared with the actual observed events. The performance or risk scores was substantially improved by periodic reassessment during follow-up.
P-NP instance decomposition based on the Fourier transform for solving the Linear Ordering Problem
Authors: Benavides Xabier , Hernando Leticia , Ceberio Josu , Lozano Jose A. 
Published: February 2025

Abstract
The Fourier transform over finite groups has proved to be a useful tool for analyzing combinatorial optimization problems. However, few heuristic and meta-heuristic algorithms have been proposed in the literature that utilize the information provided by this technique to guide the search process. In this work, we attempt to address this research gap by considering the case study of the Linear Ordering Problem (LOP).
Based on the Fourier transform, we propose an instance decomposition strategy that divides any LOP instance into the sum of two LOP instances associated with a P and an NP-Hard optimization problem. By linearly aggregating the instances obtained from the decomposition, it is possible to create artificial instances with modified proportions of the P and NP-Hard components. Conducted experiments show that increasing the weight of the P component leads to a less rugged fitness landscape suitable for local search-based optimization. We take advantage of this phenomenon by presenting a new meta-heuristic algorithm called P-Descent Search (PDS). The proposed method, first, optimizes a surrogate instance with a high proportion of the P component, and then, gradually increases the weight of the NP-Hard component until the original instance is reached. The multi-start version of PDS shows a promising and predictable performance that appears to be correlated to specific characteristics of the problem, which could open the door to an automatic tuning of its hyper-parameters.
Impacts of Climate Change and Population Pressure on Food Consumption Patterns and Economic Consequence
Authors: Lakew Hermela , Bahta Yonas , Ogundeji Abiodun , Sebastian Yong 
Published: February 2025

Abstract
There are discernible trends in severe food insecurity prevalence among the adult population in sub-Saharan Africa. This study delves into the complex interactions of climate change impacts, agricultural factor productivity and changes in population growth, which together exacerbate the issue of food insecurity. To comprehend these intertwined effects on rural and urban food insecurity, we employed the Rural Investment and Policy Analysis data and Computable General Equilibrium modelling system developed by the International Food Policy Research Institute. Our findings revealed a decline in urban food consumption associated with increased urban population and decreased agricultural total factor productivity. However, we observed a slight increase in real consumption for rural households. Our analysis indicates a contraction in the economy and a disruption in the volume of international trade. This research contributes valuable insights into the multifaceted challenges sub-Saharan Africa faces in its pursuit of food security, enabling policymakers to construct informed decisions and design effective interventions.
The Kitāb al-Aṣl of Muḥammad b. al-Ḥasan al-Shaybānī (d. 189/805) and its Riwāyas (Recensions)
Authors: Tsafrir Nurit 
Published: February 2025

Abstract
This essay is a preliminary study of some aspects of the transmission of Kitāb al-Aṣl by Muḥammad b. al-Ḥasan al-Shaybānī. The essay examines information, preserved in later, mainly Ḥanafī works, about two major riwāyas of al-Aṣl, and analyses some points of doctrine on which they differ. These differences are shown to be substantial, as emerges from biographical sources. Given the divergence from each other and also, in one instance, from a third riwāya, I propose that the two riwāyas do not represent the content of a single original text. They may reflect either different stages in the development of a text that was still fluid, or else doctrinal changes that were introduced into a fixed text by its transmitters. The disparity between the riwāyas must be taken into consideration in any attempt to reconstruct the teachings and history of Kitāb al-Aṣl.
“Overcoming the Slumps in Performance”: Metacognition, Grit and Self-Efficacy in Sports among Athletes
Authors: Pandey Kashish , K Khusboo 
Published: February 2025

Abstract
Predictably, millions of dollars get invested in sport science by the federation for impeccable performance of an athlete. However, there is a gap which exist to understand the nature of cognitive-motion nexus in sports with regard to performance. Hence, this systematic review synthesized evidence on the influence of metacognition, grit and self-efficacy on performance in sport domain using PRISMA guidelines. A search of Web of Science, PubMed, Google Scholar, PsycINFO and Scopus databases reaped 26 eligible studies. Findings were classified into three domains namely metacognitive inferences, feedback for grit and role of self-efficacy. Grit is positively correlated with metacognition and self-efficacy. We conclude by encouraging the sports system to foster the skills of these constructs.
From an Object to a Tool: On Possible Transformations of Analysis of the Border Problem
Authors: Zaporowski Andrzej 
Published: February 2025

Abstract
The article addresses the border as an object and yet a tool found in the cultural realm, where the object is approached in three stages. Firstly, the border problem is given the form of an assembled representation, and which becomes an object of one’s reflection. Secondly, this object turns into an obstacle as one faces both the abstract and the concrete references of the representation in question. Thirdly, this obstacle requires some steps to cope with it by one; one becomes a user of the assembled representation, where the object becomes a tool. The divisions suggested by the representation are conditioned by means of the cultural actions. Culture as a set of particular attitudes like belief, intention and assessment allows of approaching the border as both an object and a tool, where not only manipulation but also responsibility and creativity is crucial.
Metaphysics of Soul, Universal Spirit, and Consciousness
Authors: Holsapple Ryan J. 
Published: February 2025

Abstract
Jon Mills’ and Erik Goodwyn’s (2023) work Archetypal Origins establishes a foundation for ongoing dialogue about metaphysical origins for Jungian Psychology. This article explores tensions within their work, particularly concerning consciousness, agency, and the ontological status of matter. Examining Goodwyn’s cosmopsychism, it problematizes its treatment of matter and suggests an alternative framework. Retaining some of Goodwyn’s key themes of holism and formal cause, this variation of ontological idealism gives consciousness more primacy. The proposal suggests Universal Spirit as non-local absolute consciousness and Soul as a localized projection within the appearance of spacetime.
Innovative Capacity in Triple Helix Partnerships: an Assessment of Conditions for Social Learning
Authors: Mudde Huub L. M. , Chekole Alemfrie Derese , Lauer Madeleine 
Published: February 2025

Abstract
The Triple Helix (3H) model has attracted considerable attention in both developed and emerging economies as a tool to enhance innovation for economic development (Etzkowitz and Leydesdorff, 2000). This article examines the assumption underlying the triple helix that the exchange of diverse knowledge between academia, industry, and government stimulates innovativeness. The research underlying this article investigates whether and how learning is facilitated by triple helix based on a case study of three partnerships established by the Bright Future in Agriculture project in Ethiopia. Data was gathered from 57 respondents through in-depth interviews and surveys. The findings show that participant’s learning has taken place due to a more diverse and relevant network, but that 3H partnerships are not by default catalysts for innovation. The authors argue that this would need purposeful orchestration. This study further supports the plea in literature for quadruple or even quintuple helix models, being more apt as inclusive networks for learning and innovation.
New Histories of the Old Left
Authors: Wald Alan M. 
Published: February 2025

Abstract
The United States Communist Party (cp-USA) is a subject rooted in an ample storehouse of research; one chock-full of many confirmable facts amassed by several cohorts of competent academics. At the same time, three new histories demonstrate that polarizing divergencies in perspective and evaluation have never been quelled and continue to emerge. Maurice Isserman’s Reds: The Tragedy of American Communism is a substantially sobering work because the problems in cp-USA history it aspires to tackle are disturbingly real. The other two books, by Robert Cherny and Denise Lynn, are more upbeat, depicting a movement full of charismatic activists who express a resolute political commitment and a willingness to devote themselves to admirable causes. Nevertheless, what stands out after a close, comparative reading of all three volumes is how each historian can curate the archive according to his or her individualized needs; all three smooth contradictions, diminish some aspects and valorize others, and implicitly assign a politically motivated cognitive frame to structure the reader’s perception.
An Act of Infinite Love
Authors: Umbelino Luís António 
Published: February 2025

Abstract
To what extent do we depend on ourselves? The crucial point of this question, constantly asked by Maine de Biran, is that from the point of view of “spiritual life” an “explicit” answer is not really needed: the mystery of what supports us will be solved by a vertical dimension of feeling that welcomes, at the limit of a radical kind of passivity, an act of infinite love – as if one were connected to a divine Presence. In this paper I will try to show in what sense “love” is, according to Biran, the fundamental principle of “spiritual life” and to what extent such a concept can help us understand the fundamental coherence of Maine de Biran’s philosophical path.
On the Body as a Site of Inscription of Colonial Domination: a Visualisation of Colonial Hierarchy in Labour and Porter Scenes in German Cameroon
Authors: Nkouda Sopgui Romuald Valentin 
Published: February 2025

Abstract
The main argument underpinning this reflection is that the German colonies were increasingly present in the media, photographically, during the Empire. Pictures showed what they looked like, what was growing there, what the living conditions were like and what the colonial administration seemed to be achieving. The aim of this article is to examine the visual mediatisation of colonial relations of domination. My interest is to examine colonial practices of domination as they can be seen in colonial images. Using the example of German colonial images in Cameroon that have labour and porter scenes as their motif, the article shows that the body of the colonised was a place where colonial power was expressed or inscribed. In so doing, colonial labour and porter scenes locate colonialism as hegemonic inscription of Foucauldian power/knowledge on the colonised body.
Declining Labour and Strengthening Capital: an Analysis of the ilo Wage Report and ituc Rights Index
Authors: Bellucci Stefano 
Published: February 2025

Abstract
The Global Wage Report and the Global Rights Index are published by the International Labour Organization (ilo) in Geneva and the International Trade Union Confederation (ituc) in Brussels. This article analyses the global data and results presented by these publications and explains how they portray the ineluctable deterioration of workers’ wages and labour rights within the capitalist mode of production. Capitalism implies a tendency towards the dissolution of labour rights and super-exploitation (with wages closer to and below subsistence level). Trade unions’ struggle for labour rights and the improvement of workers’ material conditions and wages only makes sense in relation to a struggle against absolute capitalism.