bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges in Paediatric Xenotransplantation: Ethical Components Requiring Distinct Attention in Children and Obligations to Patients and Society
Authors: Merlocco Anthony , Hurst Daniel J. 
Published: October 2024

AbstractThe transplantation of non-human organs into humans, or xenotransplantation (XTx), has recently garnered new attention and is being developed to help address the problem of organ scarcity in transplantation. Ethical issues surrounding XTx have been studied since initial interest arose decades ago and have experienced renewed discussion in the literature. However, the distinct and relevant differences when applied to children has largely been overlooked with few groups attending to the concerns that XTx in children raises. In this paper, we explore ethical challenges to be expected in paediatric XTx, in particular exploring organ sizing concerns, infectious risks, psychological burdens, and issues of moral hazard. We review these domains with the aim of highlighting the implications of pursuing paediatric XTx and the cross-disciplinary approach needed to solve these issues. Children require a unique analysis from a bioethical perspective to best prepare for the issues XTx presents.
Maximizing efficiency in C45 steel machining: an integrated AI-based approach to coated insert optimization
Authors: Shunmugesh K. , Kurian Sony , Adam Khan M. , Satish Kumar D. , Mishra Priyanka 
Published: October 2024

Abstract
Machining involves the subtraction of the material from the sample workpiece to achieve the desired shape or surface. This versatile method is capable of producing a wide range of parts, varying from simple to intricate profiles. Coating materials are increasingly being utilized in tool inserts in the production industry owing to their superior thermal properties and wear resistance. The shielding of hard coatings, with thicknesses of only a few microns, enhances performance and durability. In this study, machining of C45 steel using distinct coated inserts was explored. The experimental trials employed PVD and CVD methods for coated tungsten carbide (WC) tools/inserts and PVD-coated cermet tools/inserts with different machining parameters. Performance metrics, such as the surface finish and reliability of the tool, were considered for the evaluation. The average tool life variation between the PVD-coated cermet and PVD-coated WC was 178.86%, and 30.11% between the PVD-coated cermet and CVD-coated WC at 1 mm DOC. ANOVA was performed using Response Surface Methodology to explore the influence of input parameters on output. The results indicate that the depth of machining and spindle speed significantly influence Ra, whereas spindle speed and type of tool insert have a considerable impact on the life span of the tool. The developed mathematical model for the prediction of tool life and Ra indicates its potential for performance forecasting during C45 steel machining. Grey relation analysis was employed to optimize the process parameters. Optimal results were achieved with a spindle speed of 400 m/min, 0.5 mm depth of cut, and cermet tool inserts. PVD-coated WC inserts performed better. ANFIS was applied for the prediction and optimization of the machining parameters.
Chronic Physiological Dysregulation and Changes in Depressive Symptoms: Testing Sex and Race as Vulnerability Factors
Authors: Doan Stacey N. , Aringer Alexandra S. , Vicman Jessica M. , Fuller-Rowell Thomas 
Published: October 2024

AbstractDepression is a growing public health concern that affects approximately 5% of adults in their lifetime (WHO in Depression, 2021). Understanding the biological correlates of depression is imperative for advancing treatment. Of particular interest is allostatic load, a multisystem indicator of chronic physiological dysregulation (McEwen and Seeman in, Ann N Y Acad Sci, 1999). The current longitudinal study examined the association between allostatic load, depressive symptoms, and the moderating roles of sex and race. Participants consisted of 150 young adults (Mage = 18.81) who reported their demographics and depressive symptoms at T1 and T2, a year and a half later. Allostatic load was computed using indicators of metabolic, cardiovascular, and neuroendocrine functioning. Allostatic load was found to predict changes in depressive symptoms. Moreover, interaction effects models revealed that the associations between allostatic load and depressive symptoms at follow-up were further influenced by sex, such that the relationship was significant for males, with pronounced effects for Black males in particular. Black males may be particularly vulnerable to the mental health consequences of biological dysregulation.
Discourse comprehension and referential processing: effects of contextual distance and semantic plausibility on presupposition processing
Authors: Dietrich Susanne , Seibold Verena C. , Rolke Bettina 
Published: October 2024

AbstractThe present study aimed to investigate whether contextual factors influence how a reference is processed in discourse. We used intact and violated presuppositions (PSP), triggered by a definite or indefinite noun phrase, to monitor the reference process. In one sentence set, a contextual referent was explicitly mentioned close or far from the PSP-triggering noun phrase (memory context). In another sentence set, a referent was not explicitly mentioned in the context, but an inference to a referent was either plausible or implausible due to contextual semantic relations (inference context). Participants were asked to rate the coherence of the discourse after listening to it. Our results revealed a strong influence of the temporal distance of the contextual presentation of a referent. When the referent was far in the context (memory context), PSP violations were judged to be less severe than for close referents, suggesting that they are less clearly represented in memory. Furthermore, PSP violations seemed to play a subordinate role when the semantic context provided a basis for the plausible presence of a referent (inference context). Our results suggest that discourse comprehension involves referential processes whose importance may fade with distance in memory or may be obscured by semantic contextual content.
Decision-making for children and adolescents: a scoping review of interventions increasing participation in decision-making
Authors: Bosch Inga , Siebel Hermann , Heiser Maike , Inhestern Laura 
Published: October 2024

Abstract
Purpose
To review and synthesize the literature on interventions to facilitate shared decision-making or to increase participation in decision-making in pediatrics focusing on interventions for children and adolescents.

Methods
We systematically searched three electronic databases (September 2021, update in September 2022). We included studies that aimed to increase involvement of children and adolescents in medical or treatment decisions, regardless of study design and reported outcomes. Study quality was assessed using the MMAT. The synthesis strategy followed a narrative methodology.

Results
21 studies met the inclusion criteria. Interventions aimed to increase participation by provision of information, encouraging active participation and collaboration. Didactic strategies included digital interactive applications (n = 12), treatment protocols and guiding questions (n = 12), questionnaires or quizzes about patients’ condition or their knowledge (n = 8), visual aids (n = 4), and educational courses (n = 1). Findings indicate positive effects on some of the investigated outcomes. However, the heterogeneity of studies made it difficult to draw consistent conclusions about the effectiveness of interventions.

Conclusions
Interventions used a variety of approaches to facilitate SDM and increase participation. The findings suggest that interventions have inconsistent effects across different outcome variables. The evidence was limited due to the methodological shortcomings of the included studies.

Impact

To increase the participation of children and adolescents in decision-making, interventions targeting them are needed. Most intervention focus on the provision of information and encouragement for active participation.

The results suggest high feasibility and, mostly, positive effects in participation, health-related knowledge, patient-HCP relationship, and adherence

The study highlights that further high-quality studies using similar outcome parameters are needed to investigate the effects of interventions to facilitate participation in decision-making.
In vitro models of the crosstalk between multiple myeloma and stromal cells recapitulate the mild NF-κB activation observed in vivo
Authors: Colombo Federica , Guzzeloni Virginia , Kizilirmak Cise , Brambilla Francesca , Garcia-Manteiga Jose Manuel , Tascini Anna Sofia , Moalli Federica , Mercalli Francesca , Ponzoni Maurilio , Mezzapelle Rosanna , Ferrarini Marina , Ferrero Elisabetta , Visone Roberta , Rasponi Marco , Bianchi Marco E. , Zambrano Samuel , Agresti Alessandra 
Published: October 2024

AbstractMultiple myeloma (MM) is linked to chronic NF-κB activity in myeloma cells, but this activity is generally considered a cell-autonomous property of the cancer cells. The precise extent of NF-κB activation and the contributions of the physical microenvironment and of cell-to-cell communications remain largely unknown. By quantitative immunofluorescence, we found that NF-κB is mildly and heterogeneously activated in a fraction of MM cells in human BMs, while only a minority of MM cells shows a strong activation. To gain quantitative insights on NF-κB activation in living MM cells, we combined advanced live imaging of endogenous p65 Venus-knocked-in in MM.1S and HS-5 cell lines to model MM and mesenchymal stromal cells (MSCs), cell co-cultures, microfluidics and custom microbioreactors to mimic the 3D-interactions within the bone marrow (BM) microenvironment. We found that i) reciprocal MM-MSC paracrine crosstalk and cell-to-scaffold interactions shape the inflammatory response in the BM; ii) the pro-inflammatory cytokine IL-1β, abundant in MM patients’ plasma, activates MSCs, whose paracrine signals are responsible for strong NF-κB activation in a minority of MM cells; iii) IL-1β, but not TNF-α, activates NF-κB in vivo in BM-engrafted MM cells, while its receptor inhibitor Anakinra reduces the global NF-κB activation. We propose that NF-κB activation in the BM of MM patients is mild, restricted to a minority of cells and modulated by the interplay of restraining physical microenvironmental cues and activating IL-1β-dependent stroma-to-MM crosstalk.
BCKDH kinase promotes hepatic gluconeogenesis independent of BCKDHA
Authors: Zhou Feiye , Sheng Chunxiang , Ma Xiaoqin , Li Tianjiao , Ming Xing , Wang Shushu , Tan Jialin , Yang Yulin , Sun Haipeng , Lu Jieli , Liu Jianmin , Deng Ruyuan , Wang Xiao , Zhou Libin 
Published: October 2024

AbstractElevated circulating branched-chain amino acids (BCAAs) are tightly linked to an increased risk in the development of type 2 diabetes mellitus. The rate limiting enzyme of BCAA catabolism branched-chain α-ketoacid dehydrogenase (BCKDH) is phosphorylated at E1α subunit (BCKDHA) by its kinase (BCKDK) and inactivated. Here, the liver-specific BCKDK or BCKDHA knockout mice displayed normal glucose tolerance and insulin sensitivity. However, knockout of BCKDK in the liver inhibited hepatic glucose production as well as the expression of key gluconeogenic enzymes. No abnormal gluconeogenesis was found in mice lacking hepatic BCKDHA. Consistent with the vivo results, BT2-mediated inhibition or genetic knockdown of BCKDK decreased hepatic glucose production and gluconeogenic gene expressions in primary mouse hepatocytes while BCKDK overexpression exhibited an opposite effect. Whereas, gluconeogenic gene expressions were not altered in BCKDHA-silenced hepatocytes. Mechanistically, BT2 treatment attenuated the interaction of cAMP response element binding protein (CREB) with CREB-binding protein and promoted FOXO1 protein degradation by increasing its ubiquitination. Our findings suggest that BCKDK regulates hepatic gluconeogenesis through CREB and FOXO1 signalings, independent of BCKDHA-mediated BCAA catabolism.
Targeting oncogenic MAGEA6 sensitizes triple negative breast cancer to doxorubicin through its autophagy and ferroptosis by stabling AMPKα1
Authors: Zhu Hui , Jiang Cheng-wei , Zhang Wen-long , Yang Zhao-ying , Sun Guang 
Published: October 2024

AbstractMelanoma-associated antigen A6 (MAGEA6) is well known to have oncogenic activity, but the underlying mechanisms by which it regulates tumor progression and chemo-resistance, especially in triple-negative breast cancer (TNBC), have been unknown. In the study, the differential expression genes (DEGs) in TNBC tumor tissues and TNBC-resistant tumor tissues were analyzed based on TCGA and GEO datasets. MAGEA6, as the most significantly expressed gene, was analyzed by RT-qPCR, western blotting and immunohistochemistry assay in TNBC cell lines and tumor tissues. The potential mechanisms that influence chemo-resistance were also evaluated. Results displayed that MAGEA6 was highly expressed in TNBC and involved in drug resistance. MAGEA6 silencing enhanced the chemo-sensitivity of TNBC to doxorubicin (DOX) in vitro and in vivo, as determined by decreasing IC50 value, proliferation and invasion capacity, and triggering apoptosis. Mechanistically, it was shown that MAGEA6 depletion sensitized TNBC to DOX via regulating autophagy. Ubiquitination assay displayed that knockdown of MAGEA6 decreased the AMPKα1 ubiquitination, thereby elevating the levels of AMPKα1 and p-AMPKα in TNBC cells. Importantly, AMPK inhibitor (Compound C) can reduce the LC3II/I level induced by sh-MAGEA6, indicating that sh-MAGEA6 activated AMPK signaling through suppressing AMPKα1 ubiquitination and then facilitated autophagy in TNBC. Furthermore, we also observed that AMPK is required for SLC7A11 to regulate ferroptosis, and supported the crux roles of MAGEA6/AMPK/SLC7A11-mediated ferroptosis on modulating DOX sensitivity in TNBC cells. These findings indicated that targeting MAGEA6 can enhance the chemo-sensitivity in TNBC via activation of autophagy and ferroptosis; its mechanism involves AMPKα1-dependent autophagy and AMPKα1/SLC7A11-induced ferroptosis.
GLUT1 overexpression in CAR-T cells induces metabolic reprogramming and enhances potency
Authors: Guerrero Justin A. , Klysz Dorota D. , Chen Yiyun , Malipatlolla Meena , Lone Jameel , Fowler Carley , Stuani Lucille , May Audre , Bashti Malek , Xu Peng , Huang Jing , Michael Basil , Contrepois Kévin , Dhingra Shaurya , Fisher Chris , Svensson Katrin J. , Davis Kara L. , Kasowski Maya , Feldman Steven A. , Sotillo Elena , Mackall Crystal L. 
Published: October 2024

AbstractThe intensive nutrient requirements needed to sustain T cell activation and proliferation, combined with competition for nutrients within the tumor microenvironment, raise the prospect that glucose availability may limit CAR-T cell function. Here, we seek to test the hypothesis that stable overexpression (OE) of the glucose transporter GLUT1 in primary human CAR-T cells would improve their function and antitumor potency. We observe that GLUT1OE in CAR-T cells increases glucose consumption, glycolysis, glycolytic reserve, and oxidative phosphorylation, and these effects are associated with decreased T cell exhaustion and increased Th17 differentiation. GLUT1OE also induces broad metabolic reprogramming associated with increased glutathione-mediated resistance to reactive oxygen species, and increased inosine accumulation. When challenged with tumors, GLUT1OE CAR-T cells secrete more proinflammatory cytokines and show enhanced cytotoxicity in vitro, and demonstrate superior tumor control and persistence in mouse models. Our collective findings support a paradigm wherein glucose availability is rate limiting for effector CAR-T cell function and demonstrate that enhancing glucose availability via GLUT1OE could augment antitumor immune function.
Conservation agriculture improves soil health and sustains crop yields after long-term warming
Authors: Teng Jialing , Hou Ruixing , Dungait Jennifer A. J. , Zhou Guiyao , Kuzyakov Yakov , Zhang Jingbo , Tian Jing , Cui Zhenling , Zhang Fusuo , Delgado-Baquerizo Manuel 
Published: October 2024

AbstractClimate warming threatens global food security by exacerbating pressures on degraded soils under intensive crop production. Conservation agriculture is promoted as a sustainable solution that improves soil health and sustains crop yields in a changing climate, but these benefits may be affected by long-term warming. Here, we investigate the effects of conservation agriculture compared to conventional agriculture on 17 soil properties, microbial diversity and crop yields, during eight-years’ experimental warming. An overall positive effect of warming on soil health over time under conservation agriculture is characterized by linear increases in soil organic carbon and microbial biomass carbon. Warming-triggered shifts in microbial biomass carbon and fungal diversity (saprogen richness) are directly linked to a 9.3% increase in wheat yields over eight years, but only under conservation agriculture. Overall, conservation agriculture results in an average 21% increase in soil health and supports similar levels of crop production after long-term warming compared to conventional agriculture. Our work provides insights into the potential benefits of conservation agriculture for long-term sustainable food production because improved soil health improves resilience to the effects of climate warming.
Simultaneous measurement of multiple incompatible observables and tradeoff in multiparameter quantum estimation
Authors: Chen Hongzhen , Wang Lingna , Yuan Haidong 
Published: October 2024

AbstractHow well can multiple incompatible observables be implemented by a single measurement? This is a fundamental problem in quantum mechanics with wide implications for the performance optimization of numerous tasks in quantum information science. While existing studies have been mostly focusing on the approximation of two observables with a single measurement, in practice multiple observables are often encountered, for which the errors of the approximations are little understood. Here we provide a framework to study the implementation of an arbitrary finite number of observables with a single measurement. Our methodology yields novel analytical bounds on the errors of these implementations, significantly advancing our understanding of this fundamental problem. Additionally, we introduce a more stringent bound utilizing semi-definite programming that, in the context of two observables, generates an analytical bound tighter than previously known bounds. The derived bounds have direct applications in assessing the trade-off between the precision of estimating multiple parameters in quantum metrology, an area with crucial theoretical and practical implications. To validate the validity of our findings, we conducted experimental verification using a superconducting quantum processor. This experimental validation not only confirms the theoretical results but also effectively bridges the gap between the derived bounds and empirical data obtained from real-world experiments. Our work paves the way for optimizing various tasks in quantum information science that involve multiple noncommutative observables.
Systems profiling reveals recurrently dysregulated cytokine signaling responses in ER+ breast cancer patients’ blood
Authors: Orcutt-Jahns Brian , Lima Junior Joao Rodrigues , Lin Emily , Rockne Russell C. , Matache Adina , Branciamore Sergio , Hung Ethan , Rodin Andrei S. , Lee Peter P. , Meyer Aaron S. 
Published: October 2024

AbstractCytokines operate in concert to maintain immune homeostasis and coordinate immune responses. In cases of ER+ breast cancer, peripheral immune cells exhibit altered responses to several cytokines, and these alterations are correlated strongly with patient outcomes. To develop a systems-level understanding of this dysregulation, we measured a panel of cytokine responses and receptor abundances in the peripheral blood of healthy controls and ER+ breast cancer patients across immune cell types. Using tensor factorization to model this multidimensional data, we found that breast cancer patients exhibited widespread alterations in response, including drastically reduced response to IL-10 and heightened basal levels of pSmad2/3 and pSTAT4. ER+ patients also featured upregulation of PD-L1, IL6Rα, and IL2Rα, among other receptors. Despite this, alterations in response to cytokines were not explained by changes in receptor abundances. Thus, tensor factorization helped to reveal a coordinated reprogramming of the immune system that was consistent across our cohort.
A temporal (phospho-)proteomic dataset of neurotrophic receptor tyrosine kinase signalling in neuroblastoma
Authors: Maher Stephanie , Wynne Kieran , Zhernovkov Vadim , Halasz Melinda 
Published: October 2024

AbstractNeurotrophic receptor tyrosine kinases (TrkA, TrkB, TrkC), despite their homology, contribute to the clinical heterogeneity of the childhood cancer neuroblastoma. TrkA expression is associated with low-stage disease and is often seen with spontaneous tumour regression. Conversely, TrkB is present in unfavourable neuroblastomas that often harbour amplification of the MYCN oncogene. The role of TrkC is less clearly defined, although some studies suggest its association with a favourable outcome. Understanding the differences in activity of Trk receptors that drive divergent clinical phenotypes as well as the influence of MYCN amplification on downstream Trk receptor signalling remains poorly understood. Here, we present a comprehensive label-free mass spectrometry-based total proteomics and phosphoproteomics dataset (432 raw files with FragPipe search outputs; available on PRIDE with accession number PXD054441) where we identified and quantified 4,907 proteins, 16,744 phosphosites and 5,084 phosphoproteins, derived from NGF/BDNF/NT-3 treated TrkA/B/C-overexpressing neuroblastoma cells with differential MYCN status. Analysing our dataset offers valuable insights into TrkA/B/C receptor signalling in neuroblastoma and its modulation by MYCN status; and holds potential for advancing therapeutic strategies in this challenging childhood cancer.