bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deciphering the performance of macrophages in tumour microenvironment: a call for precision immunotherapy
Authors: Toledo Belén , Zhu Chen Linrui , Paniagua-Sancho María , Marchal Juan Antonio , Perán Macarena , Giovannetti Elisa 
Published: June 2024

AbstractMacrophages infiltrating tumour tissues or residing in the microenvironment of solid tumours are known as tumour-associated macrophages (TAMs). These specialized immune cells play crucial roles in tumour growth, angiogenesis, immune regulation, metastasis, and chemoresistance. TAMs encompass various subpopulations, primarily classified into M1 and M2 subtypes based on their differentiation and activities. M1 macrophages, characterized by a pro-inflammatory phenotype, exert anti-tumoural effects, while M2 macrophages, with an anti-inflammatory phenotype, function as protumoural regulators. These highly versatile cells respond to stimuli from tumour cells and other constituents within the tumour microenvironment (TME), such as growth factors, cytokines, chemokines, and enzymes. These stimuli induce their polarization towards one phenotype or another, leading to complex interactions with TME components and influencing both pro-tumour and anti-tumour processes.This review comprehensively and deeply covers the literature on macrophages, their origin and function as well as the intricate interplay between macrophages and the TME, influencing the dual nature of TAMs in promoting both pro- and anti-tumour processes. Moreover, the review delves into the primary pathways implicated in macrophage polarization, examining the diverse stimuli that regulate this process. These stimuli play a crucial role in shaping the phenotype and functions of macrophages. In addition, the advantages and limitations of current macrophage based clinical interventions are reviewed, including enhancing TAM phagocytosis, inducing TAM exhaustion, inhibiting TAM recruitment, and polarizing TAMs towards an M1-like phenotype. In conclusion, while the treatment strategies targeting macrophages in precision medicine show promise, overcoming several obstacles is still necessary to achieve an accessible and efficient immunotherapy.
BUB1 regulates non-homologous end joining pathway to mediate radioresistance in triple-negative breast cancer
Authors: Sriramulu Sushmitha , Thoidingjam Shivani , Chen Wei-Min , Hassan Oudai , Siddiqui Farzan , Brown Stephen L. , Movsas Benjamin , Green Michael D. , Davis Anthony J. , Speers Corey , Walker Eleanor , Nyati Shyam 
Published: June 2024

Abstract
Background
Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer subtype often treated with radiotherapy (RT). Due to its intrinsic heterogeneity and lack of effective targets, it is crucial to identify novel molecular targets that would increase RT efficacy. Here we demonstrate the role of BUB1 (cell cycle Ser/Thr kinase) in TNBC radioresistance and offer a novel strategy to improve TNBC treatment.

Methods
Gene expression analysis was performed to look at genes upregulated in TNBC patient samples compared to other subtypes. Cell proliferation and clonogenic survivals assays determined the IC50 of BUB1 inhibitor (BAY1816032) and radiation enhancement ratio (rER) with pharmacologic and genomic BUB1 inhibition. Mammary fat pad xenografts experiments were performed in CB17/SCID. The mechanism through which BUB1 inhibitor sensitizes TNBC cells to radiotherapy was delineated by γ-H2AX foci assays, BLRR, Immunoblotting, qPCR, CHX chase, and cell fractionation assays.

Results
BUB1 is overexpressed in BC and its expression is considerably elevated in TNBC with poor survival outcomes. Pharmacological or genomic ablation of BUB1 sensitized multiple TNBC cell lines to cell killing by radiation, although breast epithelial cells showed no radiosensitization with BUB1 inhibition. Kinase function of BUB1 is mainly accountable for this radiosensitization phenotype. BUB1 ablation also led to radiosensitization in TNBC tumor xenografts with significantly increased tumor growth delay and overall survival. Mechanistically, BUB1 ablation inhibited the repair of radiation-induced DNA double strand breaks (DSBs). BUB1 ablation stabilized phospho-DNAPKcs (S2056) following RT such that half-lives could not be estimated. In contrast, RT alone caused BUB1 stabilization, but pre-treatment with BUB1 inhibitor prevented stabilization (t1/2, ~8 h). Nuclear and chromatin-enriched fractionations illustrated an increase in recruitment of phospho- and total-DNAPK, and KAP1 to chromatin indicating that BUB1 is indispensable in the activation and recruitment of non-homologous end joining (NHEJ) proteins to DSBs. Additionally, BUB1 staining of TNBC tissue microarrays demonstrated significant correlation of BUB1 protein expression with tumor grade.

Conclusions
BUB1 ablation sensitizes TNBC cell lines and xenografts to RT and BUB1 mediated radiosensitization may occur through NHEJ. Together, these results highlight BUB1 as a novel molecular target for radiosensitization in women with TNBC.
FoldPAthreader: predicting protein folding pathway using a novel folding force field model derived from known protein universe
Authors: Zhao Kailong , Zhao Pengxin , Wang Suhui , Xia Yuhao , Zhang Guijun 
Published: June 2024

AbstractProtein folding has become a tractable problem with the significant advances in deep learning-driven protein structure prediction. Here we propose FoldPAthreader, a protein folding pathway prediction method that uses a novel folding force field model by exploring the intrinsic relationship between protein evolution and folding from the known protein universe. Further, the folding force field is used to guide Monte Carlo conformational sampling, driving the protein chain fold into its native state by exploring potential intermediates. On 30 example targets, FoldPAthreader successfully predicts 70% of the proteins whose folding pathway is consistent with biological experimental data.
The effect of an improved ICU physical environment on outcomes and post-ICU recovery—a protocol
Authors: Tronstad Oystein , Zangerl Barbara , Patterson Sue , Flaws Dylan , Yerkovich Stephanie , Szollosi Irene , White Nicole , Garcia-Hansen Veronica , Leonard Francisca Rodriguez , Weger Benjamin D. , Gachon Frédéric , Brain David , Lavana Jayshree , Hodgson Carol , Fraser John F. 
Published: June 2024

AbstractBackgroundIntensive care medicine continues to improve, with advances in technology and care provision leading to improved patient survival. However, this has not been matched by similar advances in ICU bedspace design. Environmental factors including excessive noise, suboptimal lighting, and lack of natural lights and views can adversely impact staff wellbeing and short- and long-term patient outcomes. The personal, social, and economic costs associated with this are potentially large. The ICU of the Future project was conceived to address these issues. This is a mixed-method project, aiming to improve the ICU bedspace environment and assess impact on patient outcomes. Two innovative and adaptive ICU bedspaces capable of being individualised to patients’ personal and changing needs were co-designed and implemented. The aim of this study is to evaluate the effect of an improved ICU bedspace environment on patient outcomes and operational impact.MethodsThis is a prospective multi-component, mixed methods study including a randomised controlled trial. Over a 2-year study period, the two upgraded bedspaces will serve as intervention beds, while the remaining 25 bedspaces in the study ICU function as control beds. Study components encompass (1) an objective environmental assessment; (2) a qualitative investigation of the ICU environment and its impact from the perspective of patients, families, and staff; (3) sleep investigations; (4) circadian rhythm investigations; (5) delirium measurements; (6) assessment of medium-term patient outcomes; and (7) a health economic evaluation.DiscussionDespite growing evidence of the negative impact the ICU environment can have on patient recovery, this is an area of critical care medicine that is understudied and commonly not considered when ICUs are being designed. This study will provide new information on how an improved ICU environment impact holistic patient recovery and outcomes, potentially influencing ICU design worldwide.Trial registrationACTRN12623000541606. Registered on May 22, 2023.https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385845&isReview=true.
Distinct effects of blood pressure parameters on Alzheimer’s and vascular markers in 1,952 Asian individuals without dementia
Authors: Lee Sungjoo , Kim Si Eun , Jang Hyemin , Kim Jun Pyo , Sohn Gyeongmo , Park Yu Hyun , Ham Hongki , Gu Yuna , Park Chae Jung , Kim Hee Jin , Na Duk L. , Kim Kyunga , Seo Sang Won 
Published: June 2024

Abstract
Background
Risk factors for cardiovascular disease, including elevated blood pressure, are known to increase risk of Alzheimer’s disease. There has been increasing awareness of the relationship between long-term blood pressure (BP) patterns and their effects on the brain. We aimed to investigate the association of repeated BP measurements with Alzheimer’s and vascular disease markers.

Methods
We recruited 1,952 participants without dementia between August 2015 and February 2022. During serial clinic visits, we assessed both systolic BP (SBP) and diastolic BP (DBP), and visit-to-visit BP variability (BPV) was quantified from repeated measurements. In order to investigate the relationship of mean SBP (or DBP) with Alzheimer’s and vascular markers and cognition, we performed multiple linear and logistic regression analyses after controlling for potential confounders (Model 1). Next, we investigated the relationship of with variation of SBP (or DBP) with the aforementioned variables by adding it into Model 1 (Model 2). In addition, mediation analyses were conducted to determine mediation effects of Alzheimer’s and vascular makers on the relationship between BP parameters and cognitive impairment.

Results
High Aβ uptake was associated with greater mean SBP (β = 1.049, 95% confidence interval 1.016–1.083). High vascular burden was positively associated with mean SBP (odds ratio = 1.293, 95% CI 1.015–1.647) and mean DBP (1.390, 1.098–1.757). High tau uptake was related to greater systolic BPV (0.094, 0.001–0.187) and diastolic BPV (0.096, 0.007–0.184). High Aβ uptake partially mediated the relationship between mean SBP and the Mini-Mental State Examination (MMSE) scores. Hippocampal atrophy mediated the relationship between diastolic BPV and MMSE scores.

Conclusions
Each BP parameter affects Alzheimer’s and vascular disease markers differently, which in turn leads to cognitive impairment. Therefore, it is necessary to appropriately control specific BP parameters to prevent the development of dementia. Furthermore, a better understanding of pathways from specific BP parameters to cognitive impairments might enable us to select the managements targeting the specific BP parameters to prevent dementia effectively.
The circular bioeconomy: a driver for system integration
Authors: Schipfer Fabian , Burli Pralhad , Fritsche Uwe , Hennig Christiane , Stricker Fabian , Wirth Maria , Proskurina Svetlana , Serna-Loaiza Sebastian 
Published: June 2024

Abstract
Background
Human and earth system modeling, traditionally centered on the interplay between the energy system and the atmosphere, are facing a paradigm shift. The Intergovernmental Panel on Climate Change’s mandate for comprehensive, cross-sectoral climate action emphasizes avoiding the vulnerabilities of narrow sectoral approaches. Our study explores the circular bioeconomy, highlighting the intricate interconnections among agriculture, forestry, aquaculture, technological advancements, and ecological recycling. Collectively, these sectors play a pivotal role in supplying essential resources to meet the food, material, and energy needs of a growing global population. We pose the pertinent question of what it takes to integrate these multifaceted sectors into a new era of holistic systems thinking and planning.

Results
The foundation for discussion is provided by a novel graphical representation encompassing statistical data on food, materials, energy flows, and circularity. This representation aids in constructing an inventory of technological advancements and climate actions that have the potential to significantly reshape the structure and scale of the economic metabolism in the coming decades. In this context, the three dominant mega-trends—population dynamics, economic developments, and the climate crisis—compel us to address the potential consequences of the identified actions, all of which fall under the four categories of substitution, efficiency, sufficiency, and reliability measures. Substitution and efficiency measures currently dominate systems modeling. Including novel bio-based processes and circularity aspects might require only expanded system boundaries. Conversely, paradigm shifts in systems engineering are expected to center on sufficiency and reliability actions. Effectively assessing the impact of sufficiency measures will necessitate substantial progress in inter- and transdisciplinary collaboration, primarily due to their non-technological nature. In addition, placing emphasis on modeling the reliability and resilience of transformation pathways represents a distinct and emerging frontier that highlights the significance of an integrated network of networks.

Conclusions
Existing and emerging circular bioeconomy practices can serve as prime examples of system integration. These practices facilitate the interconnection of complex biomass supply chain networks with other networks encompassing feedstock-independent renewable power, hydrogen, CO2, water, and other biotic, abiotic, and intangible resources. Elevating the prominence of these connectors will empower policymakers to steer the amplification of synergies and mitigation of tradeoffs among systems, sectors, and goals.
Farm animal welfare regulatory preferences and food choice: survey evidence from the US
Authors: Boaitey Albert 
Published: June 2024

AbstractPublic support is critical for the incorporation of farm animal welfare (FAW) standards into national food policies. Multiple pathways, e.g., market-based policies, political mandates, and donations to animal charities, exist for the public to influence these standards. The challenge often remains that citizens may express significantly different regulatory preferences from consumers thereby disproportionally overburdening the latter. For food, this consumer–citizen role is directly linked to dietary choice. Although a large body of research has examined the determinants of dietary choice on the one hand, and FAW policy preferences, on the other, no attempt has been made to address these issues side by side. This study explores the preferences for FAW regulatory mechanisms and strategic behavior among dietary groups. Preferences for private labeling, political mandates, and donations to charities in support of and against conventional agriculture are examined. Data are from an online survey of 1020 residents conducted in the US. The results show a proclivity among segments of the public who do not consume livestock products for political mandates and the tendency to behave strategically. Regulatory preferences are embedded within distinct human value orientations. Urban—non-urban, generational and gender divides in regulatory preferences are also identified. These insights are relevant for the ongoing development of FAW standards given the portfolio of mechanisms at the disposal of stakeholders.
The walnut-derived peptide TW-7 improves mouse parthenogenetic embryo development of vitrified MII oocytes potentially by promoting histone lactylation
Authors: Wei Yaozong , Pan Bo , Qin Jianpeng , Cao Beijia , Lv Tianyi , Ye Jiangfeng , Ning Ao , Du Kunlin , Chen Xiangyi , Zou Shuqi , Zang Shengqin , Yu Guozhi , Song Tianzeng , Liang Qiuxia , Zhou Guangbin 
Published: June 2024

Abstract
Background
Previous studies have shown that the vitrification of metaphase II (MII) oocytes significantly represses their developmental potential. Abnormally increased oxidative stress is the probable factor; however, the underlying mechanism remains unclear. The walnut-derived peptide TW-7 was initially isolated and purified from walnut protein hydrolysate. Accumulating evidences implied that TW-7 was a powerful antioxidant, while its prospective application in oocyte cryopreservation has not been reported.

Result
Here, we found that parthenogenetic activation (PA) zygotes derived from vitrified MII oocytes showed elevated ROS level and delayed progression of pronucleus formation. Addition of 25 μmol/L TW-7 in warming, recovery, PA, and embryo culture medium could alleviate oxidative stress in PA zygotes from vitrified mouse MII oocytes, furtherly increase proteins related to histone lactylation such as LDHA, LDHB, and EP300 and finally improve histone lactylation in PA zygotes. The elevated histone lactylation facilitated the expression of minor zygotic genome activation (ZGA) genes and preimplantation embryo development.

Conclusions
Our findings revealed the mechanism of oxidative stress inducing repressed development of PA embryos from vitrified mouse MII oocytes and found a potent and easy-obtained short peptide that could significantly rescue the decreased developmental potential of vitrified oocytes, which would potentially contribute to reproductive medicine, animal protection, and breeding.
The probable direction of impact at Dhala impact structure, India deciphered from microfracture intensity and X-ray diffractometry: a new potential impact direction indicator
Authors: Behera Swastik Suman , Tiwari Sonal , Pandey Ambrish Kumar , Agarwal Amar , Ojha Arun Kumar 
Published: June 2024

AbstractThe most widely used method of determining impact direction employs asymmetric ejecta distribution around the crater. However, the active terrestrial landscape seldom preserves the pristine ejecta blanket, making it challenging for this analysis to be carried out. The deeply eroded Dhala impact structure, formed during the Proterozoic, is devoid of an ejecta blanket. We, therefore, utilize the variation in the full width at half maxima (FWHM) of the quartz (100) peak in X-ray diffraction (XRD) spectra and the P10microfracture intensity in the monomict breccia to estimate the probable downrange direction of the Dhala impact structure. The monomict breccia rocks of the Dhala impact structure have experienced low shock pressures (< 10 GPa) and are highly fractured, making them the ideal target lithology for our study. Previous studies have used XRD extensively for strain analysis in synthetic materials and rocks. Microfracture intensity acts as an indicator for the degree of fracturing or brittle damage in the rocks, with the maximum shock-induced damage being concentrated in the downrange direction. The results from the XRD are consistent with the microfracture intensity analyses and indicate that the probable direction of impact was from southwest to northeast, with northeast being the downrange direction. Furthermore, we suggest that the degree of fracturing and X-ray diffractometry can be used to identify the downrange direction of an impact crater.Graphical Abstract
Dual-frequency to five-frequency real-time precise point positioning using new BDS-3 PPP-B2b service
Authors: Yang Haochen , Ren Xiaodong , Liu Mingxiu , Zhang Xiaohong 
Published: June 2024

AbstractBeiDou global navigation satellite system (BDS-3), a developed GNSS by China, has the ability to support five different signals, including B1I, B3I, B1C, B2a, and B2b. Meanwhile, BDS-3 has officially provided the satellite-based precise point positioning (PPP) service through the B2b signal (PPP-B2b) since 2021. It’s necessary to conduct a comprehensive analysis on multi-frequency PPP with PPP-B2b corrections. In this study, a multi-frequency undifferenced and uncombined PPP model (UDUC) using PPP-B2b corrections was employed to investigate dual-frequency to five-frequency real-time PPP performance. The results show that compared with the conventional dual-frequency solutions, multi-frequency solutions can improve both the convergence performances and positioning accuracy of PPP-B2b service, especially during the convergence stage. The quad-frequency and five-frequency solutions can achieve the best positioning performance. The static solutions of multi-frequency PPP models reach the centimeter-level accuracy after convergence. In kinematic mode, the convergence time of the five-frequency PPP results is reduced by 23.5% compared with the dual-frequency results. The root mean square (RMS) errors of the five-frequency PPP in the E, N, and U components are 7.1 cm, 4.8 cm, and 12.4 cm, which are improved by 6.8%, 11.5%, and 5.5%, respectively.
Graphical Abstract
Co-designing a participatory evaluation of older adult partner engagement in the mcmaster collaborative for health and aging
Authors: Abousifein Marfy , Falbo A. Tina , Luyckx Joyce , Abelson Julia , Ganann Rebecca , Vrkljan Brenda , Carusone Soo Chan 
Published: June 2024

AbstractEngagement of patients and the public in health research is crucial for ensuring research relevance and alignment with community needs. However, there is a lack of nuanced evaluations and examples that promote collaborative and reflective learning about partnerships with partners. The aim of this paper is to provide a case example of a participatory evaluation of the engagement of older adult partners in an aging-focused research centre. We outline our process of co-planning and implementing an evaluation of the McMaster Collaborative for Health and Aging’s engagement strategy through the use of multiple methods, including a standardized tool and qualitative approaches. The team chose to explore and capture the engagement experiences and perspectives of the older adult partners within the Collaborative using a survey (the Public and Patient Engagement Evaluation Tool (PPEET)), an art-based method (photovoice), and a focus group. We present a brief summary of the findings but primarily focus this paper on the experiences of using each methodology and tool, with an emphasis on promoting dialogue on the benefits, limitations, and challenges. We reflect on the process of co-planning and the integration of both standardized tools and qualitative approaches to adopt a holistic approach to evaluating partnership within the Collaborative. Ultimately, this case example aims to provide practical guidance for other research groups navigating the complexities of partnership engagement and evaluation, thereby promoting meaningful partnerships in research.