bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of mitochondrial bioenergetics and hypoxia to radiosensitize diffuse intrinsic pontine glioma
Authors: Shen Han , Mudassar Faiqa , Ma Shiyong , Wang Xingyu , Nguyen Sandy , Bal Neha , Huynh Quy-Susan , Wang Dongwei , Chang Cecilia , Ing Prunella , Varikatt Winny , Lai Joey , Gloss Brian , Holst Jeff , O’Neill Geraldine M , Gee Harriet , Cook Kristina M , Hau Eric 
Published: November 2024

Abstract

Background
Diffuse intrinsic pontine gliomas (DIPGs) and other H3K27M-mutated diffuse midline gliomas (DMGs) are brain tumors that primarily affect children. Radiotherapy is the standard of care but only provides only temporary symptomatic relief due to radioresistance. Although hypoxia is a major driver of radioresistance in other tumors, there is no definitive evidence that DIPGs are hypoxic. Diffuse intrinsic pontine gliomas often contain histone mutations, which alter tumor metabolism and are also associated with radioresistance. Our objective was to identify the metabolic profiles of DIPG cells, detect hypoxia signatures, and uncover metabolism-linked mechanisms of radioresistance to improve tumor radiosensitivity.

Methods
Using DIPG models combined with clinical datasets, we examined mitochondrial metabolism and signatures of hypoxia. We explored DIPG reliance on mitochondrial metabolism using extracellular flux assays and targeted metabolomics. In vitro and in vivo models were used to explore the mechanisms of targeting mitochondrial bioenergetics and hypoxia for radiosensitization. Treatment-induced transcriptomics and metabolomics were also investigated.

Results
Comprehensive analyses of DIPG cells show signatures of enhanced oxidative phosphorylation (OXPHOS). We also identified increased expression of specific OXPHOS-related genes and signatures of hypoxia gene expression in datasets obtained from DIPG patients. We found the presence of hypoxia in orthotopic mouse models bearing DIPG tumors. These findings enabled us to develop a proof-of-concept treatment strategy to enhance radiosensitivity of DIPGs in vitro and in animal models.

Conclusions
Diffuse intrinsic pontine glioma cells rely on mitochondrial metabolism for growth, and targeting mitochondria disrupts bioenergetics, alleviates hypoxia, and enhances radiosensitivity. These findings warrant further exploration of OXPHOS inhibition as a radiosensitizing strategy for DIPG treatment.
Phase 1b/2 study of orally administered pexidartinib in combination with radiation therapy and temozolomide in patients with newly diagnosed glioblastoma
Authors: Mendez Joe S , Cohen Adam L , Eckenstein Midori , Jensen Randy L , Burt Lindsay M , Salzman Karen L , Chamberlain Marc , Hsu Henry H , Hutchinson Marguerite , Iwamoto Fabio , Ligon Keith L , Mrugala Maciej M , Pelayo Michael , Plotkin Scott R , Puduvalli Vinay K , Raizer Jeffrey , Reardon David A , Sterba Michael , Walbert Tobias , West Brian L , Wong Eric T , Zhang Chao , Colman Howard 
Published: November 2024

Abstract

Background
Glioblastoma (GBM) has a median survival of &lt;2 years. Pexidartinib (PLX3397) is a small-molecule inhibitor of CSF1R, KIT, and oncogenic FTL3, which are implicated in GBM treatment resistance. Results from glioma models indicate that combining radiation therapy (RT) and pexidartinib reduces radiation resistance. We added pexidartinib to standard-of-care RT/temozolomide (TMZ) in patients with newly diagnosed GBM to assess the therapeutic benefit of altering the tumor microenvironment with pexidartinib.

Methods
In this open-label, dose-escalation, multicenter, Phase 1b/2 trial, pexidartinib was administered in combination with RT/TMZ followed by adjuvant pexidartinib + TMZ. During Phase 1b, pexidartinib was given 5 or 7 days/week at multiple dosing levels. The primary Phase 1b endpoint was the recommended Phase 2 dose (RP2D). Phase 2 patients received the RP2D with the primary endpoint of median progression-free survival (mPFS). Secondary objectives were median overall survival (mOS), pharmacokinetics, and safety.

Results
The RP2D of pexidartinib was 800 mg/day for 5 days/week during RT/TMZ, followed by 800 mg/day for 7 days/week with adjuvant TMZ. mPFS was 6.7 months (90% CI: 4.5, 11.5) for the modified intention-to-treat population. The actual mOS was 13.1 months (90% CI: 11.5, 24.5), and the mOS corrected for comparison with matched historical controls was 18.8 months (95% CI: 12.6, 28.0).

Conclusions
This trial established the RP2D of pexidartinib in combination with RT/TMZ and adjuvant TMZ. Pexidartinib was generally safe and well tolerated. Although the study regimen with pexidartinib was not efficacious, pharmacodynamic studies showed modulation of systemic markers that could lead to alteration of the tumor microenvironment.
GmERFVII transcription factors upregulate PATHOGENESIS-RELATED10 and contribute to soybean cyst nematode resistance
Authors: Deng Miaomiao , Zhang Lei , Yang Chao , Zeng Qian , Zhong Linlin , Guo Xiaoli 
Published: November 2024

Abstract
Low oxygen availability within plant cells arises during plant development but is exacerbated under environmental stress conditions. The group VII ETHYLENE RESPONSE FACTOR (ERFVII) transcription factors have been identified as pivotal regulators in the hypoxia response to abiotic stress. However, their roles in transcriptional regulation during biotic stresses remain less defined. In this study, we investigated the biological function and regulatory mechanism of soybean (Glycine max) ERFVII transcription factors during soybean cyst nematode (Heterodera glycines Ichinohe) infection. We provide evidence that soybean cyst nematode infection induces responses at the infection sites similar to those induced by hypoxia, characterized by the stabilization of ERFVII proteins and increased expression of hypoxia-responsive genes. Hypoxia pretreatment of soybeans enhances their resistance to nematode infection. We demonstrate that ERFVII members GmRAP2.12 and GmRAP2.3 act as transcriptional activators to drive the expression of GmPR10-09g, a member of the PR10 gene family highly induced by soybean cyst nematode and positively impacting nematode resistance. Transgenic hairy root analysis of nematode infection for either GmRAP2.12 or N-end rule pathway components (GmATE or GmPRT6) indicates a positive role of ERFVIIs in soybean defense responses against cyst nematode. The results of our study emphasize the important functions of GmERFVIIs in strengthening soybean’s immune responses against cyst nematode by transcriptional activation of GmPR10.
Protoplast transient transformation facilitates subcellular localization and functional analysis of walnut proteins
Authors: Gao Yanli , Tang Tianyu , Cao Wenhan , Ali Muhammad , Zhou Qirong , Zhu Dongmei , Ma Xiaohui , Cai Yi , Zhang Qixiang , Wang Zhengjia , Pei Dong , Huang Jianqin , Shen Jinbo 
Published: November 2024

Abstract
Walnut (Juglans regia L.), an important contributor to oil production among woody plants, encounters research constraints due to difficulties in the subcellular localization and functional analysis of its proteins. These limitations arise from the protracted fruiting cycle and the absence of a reliable transient gene transformation system and organelle markers. In this study, we established a transient expression system using walnut protoplasts and generated fluorescent-tagged organelle markers, whose localization was validated against Arabidopsis (Arabidopsis thaliana) organelle markers. The versatility of this system was demonstrated through pharmaceutical treatments, confirming its ability to determine the subcellular localization of endogenous proteins. We determined the subcellular localization of walnut oleosin proteins and explored protein–protein interactions through bimolecular fluorescence complementation analysis. We also explored the effects of abscisic acid signaling on oil body morphology and the regulation of walnut WRINKLED1 (JrWRI1) in lipid biosynthesis. Overall, this stable and versatile protoplast-based transient expression system, integrated with walnut organelle markers, enhances the subcellular localization and functional studies of uncharacterized walnut proteins. This advancement accelerates research into walnut gene function and streamlines molecular breeding processes with high-throughput efficiency.
Continuous Quasi-Attractors dissolve with too much – or too little – variability
Authors: Schönsberg Francesca , Monasson Rémi , Treves Alessandro 
Published: November 2024

Abstract
Recent research involving bats flying in long tunnels has confirmed that hippocampal place cells can be active at multiple locations, with considerable variability in place field size and peak rate. With self-organizing recurrent networks, variability implies inhomogeneity in the synaptic weights, impeding the establishment of a continuous manifold of fixed points. Are continuous attractor neural networks still valid models for understanding spatial memory in the hippocampus, given such variability? Here, we ask what are the noise limits, in terms of an experimentally inspired parametrization of the irregularity of a single map, beyond which the notion of continuous attractor is no longer relevant. Through numerical simulations we show that (i) a continuous attractor can be approximated even when neural dynamics ultimately converge onto very few fixed points, since a quasi-attractive continuous manifold supports dynamically localized activity; (ii) excess irregularity in field size however disrupts the continuity of the manifold, while too little irregularity, with multiple fields, surprisingly prevents localized activity; and (iii) the boundaries in parameter space among these three regimes, extracted from simulations, are well matched by analytical estimates. These results lead to predict that there will be a maximum size of a 1D environment which can be retained in memory, and that the replay of spatial activity during sleep or quiet wakefulness will be for short segments of the environment.
Sanctioning political speech on social media is driven by partisan norms and identity signaling
Authors: Ahn Chloe , Lelkes Yphtach , Levendusky Matthew 
Published: November 2024

Abstract
Social media is marked by online firestorms where people pile-on and shame those who say things perceived to be offensive, especially about politically relevant topics. What explains why individuals engage in this sort of sanctioning behavior? We show that two key factors help to explain this pattern. First, on these topics, both offensive speech and subsequent sanctioning are seen as informative about partisanship: people assume that those who say offensive things are out-partisans, and those who criticize them are co-partisans. Second, individuals perceive that such sanctioning is an injunctive norm and believe that their fellow co-partisans approve of it—sanctioning someone allows them to signal their partisanship by adhering to that norm. Using three original experiments, we show strong support for this argument. Sanctioning this type of offensive speech is as informative about perceived partisanship as explicit partisan electioneering. Further, people perceive that a wide variety of sanctioning behaviors are (partisan) group norms. We also show that while people are reluctant to be the first to criticize someone online, they are quite willing to pile-on to others’ criticisms, which helps to explain why this behavior spreads so rapidly in online firestorms. Our results have implications for online social dynamics, as well as partisanship and partisan animosity more broadly.
A Cognitive View of Policing
Authors: Dube Oeindrila , MacArthur Sandy Jo , Shah Anuj K 
Published: November 2024

Abstract
What causes adverse policing outcomes, such as excessive uses of force and unnecessary arrests? Prevailing explanations focus on problematic officers or deficient regulations and oversight. We introduce an overlooked perspective. We suggest that the cognitive demands inherent in policing can undermine officer decision making. Unless officers are prepared for these demands, they may jump to conclusions too quickly without fully considering alternative ways of seeing a situation. This can lead to adverse policing outcomes. To test this perspective, we created a new training that teaches officers to consider different ways of interpreting the situations they encounter. We evaluated this training using a randomized controlled trial with 2,070 officers from the Chicago Police Department. In a series of lab assessments, we find that treated officers were significantly more likely to consider a wider range of evidence and develop more explanations for subjects’ actions. Critically, we also find that training affected officer performance in the field, leading to reductions in uses of force, discretionary arrests, and arrests of Black civilians. Meanwhile, officer activity levels remained unchanged, and trained officers were less likely to be injured on duty. Our results highlight the value of considering the cognitive aspects of policing and demonstrate the power of using behaviorally informed approaches to improve officer decision making and policing outcomes.
Engineered bio-functional material-based nerve guide conduits for optic nerve regeneration: a view from the cellular perspective, challenges and the future outlook
Authors: Obeng Enoch , Shen Baoguo , Wang Wei , Xie Zhenyuan , Zhang Wenyi , Li Zhixing , Yao Qinqin , Wu Wencan 
Published: November 2024

Abstract
Nerve injuries can be tantamount to severe impairment, standard treatment such as the use of autograft or surgery comes with complications and confers a shortened relief. The mechanism relevant to the regeneration of the optic nerve seems yet to be fully uncovered. The prevailing rate of vision loss as a result of direct or indirect insult on the optic nerve is alarming. Currently, the use of nerve guide conduits (NGC) to some extent has proven reliable especially in rodents and among the peripheral nervous system, a promising ground for regeneration and functional recovery, however in the optic nerve, this NGC function seems quite unfamous. The insufficient NGC application and the unabridged regeneration of the optic nerve could be a result of the limited information on cellular and molecular activities. This review seeks to tackle two major factors (i) the cellular and molecular activity involved in traumatic optic neuropathy and (ii) the NGC application for the optic nerve regeneration. The understanding of cellular and molecular concepts encompassed, ocular inflammation, extrinsic signaling and intrinsic signaling for axon growth, mobile zinc role, Ca2+ factor associated with the optic nerve, alternative therapies from nanotechnology based on the molecular information and finally the nanotechnological outlook encompassing applicable biomaterials and the use of NGC for regeneration. The challenges and future outlook regarding optic nerve regenerations are also discussed. Upon the many approaches used, the comprehensive role of the cellular and molecular mechanism may set grounds for the efficient application of the NGC for optic nerve regeneration.
A mobile app to support self-management and remotely monitor disease impact in rheumatoid arthritis: the randomized controlled AEGORA trial
Authors: Doumen Michaël , De Meyst Elias , Bertrand Delphine , Pazmino Sofia , Piessens Marine , Joly Johan , Devinck Mieke , Westhovens René , Verschueren Patrick 
Published: November 2024

Abstract

Objectives
The aim of this work was to determine whether smartphone applications could support the self-management of RA and to investigate engagement and potential negative psychological effects with app-use.

Methods
App-based Education and GOal-setting in RA (AEGORA) was a multicentre randomized controlled trial with 2:1:1 allocation to usual care or two versions of an app-based self-management intervention for RA. The 16-week programme involved patient education, goal-setting and remote monitoring of the Rheumatoid Arthritis Impact of Disease (RAID) instrument, either weekly or monthly depending on randomization. The primary end point was improvement in the Arthritis Self-Efficacy Scale (ASES) after 16 weeks. Secondary endpoints included non-inferiority regarding the Pain Catastrophizing Scale (PCS) and superiority regarding patient-reported physical activity, sleep quality and RAID. App engagement and RAID scores were analysed descriptively.

Results
Overall, 122 patients were included: mean (s.d.) disease duration 12 (9) years, age 58 (11), 68% female, DAS28-CRP 2.4 (0.9). The intervention did not improve the ASES score over usual care (β 0.44, P = 0.87). Non-inferiority was established for the PCS (β −0.95 [95% CI −3.30, +1.40] favouring the intervention). Other predefined outcomes did not differ. App retention steadily declined to 43% by 16 weeks. Although the RAID remained stable over time overall, 35% of app users reported ≥1 episode of clinically relevant worsening over 16 weeks.

Conclusion
This app-based self-management intervention was not superior to usual care regarding self-efficacy improvement. However, remote symptom monitoring provided valuable insight and did not increase pain catastrophizing, alleviating concerns regarding the psychological impact of remote monitoring with apps.

Trial registration number
clinicaltrials.gov, NCT05888181.
Mechanistic insights into leaf senescence regulation in woody plants: a molecular perspective
Authors: Zhang Ruxue , Zhang Murao , Tan Shuya , Li Zhonghai 
Published: November 2024

Abstract
Leaves, the primary carbon fixers in autotrophic plants, undergo a complex senescence process, which is critical for the redistribution of nutrients and supports ongoing growth and development. This natural aging phenomenon, often triggered at the end of a plant’s life cycle or during the autumn season in perennial species, is finely regulated at multiple levels. Premature senescence can disrupt normal plant development, while the timing and pace of senescence significantly impact crop yield and quality. Notably, accelerated senescence under stress conditions may enhance the survival of future generations, suggesting an evolutionary strategy for plants to cope with harsh environments. Our review focuses on the molecular regulation of leaf senescence in woody plants, emphasizing the intricate determinants and regulatory mechanisms involved, including the role of phytohormones, environmental cues and genetic factors. We highlight recent advances in understanding the regulation of leaf senescence in woody plants, integrating insights from multidisciplinary approaches and cutting-edge technologies.
The influence of the Unidroit Principles on the contract book of the Chinese Civil Code: process and examples
Authors: Ji Wenhua 
Published: November 2024

Abstract
One of the main purposes of the Unidroit Principles of International Commercial Contracts (UPICC) is to serve as a source of inspiration and legal reference for domestic legislators. The evolution of China’s contract law system has been a gradual process, shaped by local characteristics and informed by the experiences of other legal systems. In this process, the UPICC have always been an important source of reference. This article introduces the stages of development of China’s contract law system after the reform and opening-up and shows the impact of the UPICC according to Chinese contact law’s developments over different time periods. It also illustrates examples in the latest Contract Book of the Civil Code that refers to, and incorporates, the rules of the UPICC and cases where the Contract Book to some extent still differs from the relevant provisions of the UPICC, which shows that China’s references to the UPICC are more in the form of consistency with basic concepts and similarities to some specific provisions but that it has not yet shown a systematic and large-scale incorporation or transplantation.
Rapid modulation of interscapular brown adipose tissue mitochondrial activity by ketosis induced by 1,3‐butanediol administration to rats
Authors: Venditti Paola , Pinto Gabriella , Migliaccio Vincenzo , Panico Giuliana , Fasciolo Gianluca , De Matteis Rita , Lionetti Lillà , de Lange Pieter , Serpico Stefania , Napolitano Gaetana , Agnisola Claudio , Amoresano Angela , Lombardi Assunta 
Published: November 2024

AbstractSome studies indicate that brown adipose tissue (BAT) represents a promising target in the fight against dysmetabolic diseases, with indications suggesting it as a potential target for the effects of ketone bodies. We investigate whether the elevation of plasma levels of the ketone body β‐hydroxybutyrate, achieved through the in vivo administration of its precursor 1,3‐butanediol (BD) to rats, could impact interscapular BAT (iBAT) mitochondrial biochemistry and functionality. We examined the effects induced by BD within 3 h and after 2 weeks of treatment. A large‐scale quantitative proteomics approach, coupling liquid chromatography with tandem mass spectrometry (LC–MS/MS) analysis, and Western blot associated with functional studies by respirometry allowed us to evaluate the changes in iBAT mitochondrial protein expression and bioenergetics induced by BD. BD administration increased β‐hydroxybutyrate plasma levels, which correlated with an enhancement in iBAT mitochondrial respiration rate, likely due to the activation of the respiratory chain and uncoupling protein‐1. The proteomic analysis demonstrated that BD influenced the mitochondrial levels of specific subunits belonging to the five respiratory complexes, uncoupling protein‐1, and proteins involved in propanoate metabolism. BD administration also induced lysine β‐hydroxybutyrylation of mitochondrial proteins, including specific subunits of the respiratory chain complexes and uncoupling protein‐1. Most of the BD‐induced effects were observed within 3 h of its administration and persisted/increased after 2 weeks of treatment. In conclusion, by using BD to increase β‐hydroxybutyrate levels, we provide evidence supporting the role of β‐hydroxybutyrate as a signaling molecule capable of rapidly modulating BAT physiology by acting at the mitochondrial level.