bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radiation Reveal: Moving from research engagement to involvement
Authors: Whittaker Lisa , Dean Jamie A. , Veiga Catarina , Langdon Sophie , Drake Rebecca , Taylor Daniel , Williams Myfanwy-Cerys , Masters Holly , Britton Alex , Cumbo Mia , Burdis Nicole , Mason Kate , Fay Gemma , Smith Emma , Benson Sam , Halil Alfie , Lambert Sophie , Gaze Mark N. , Gains Jenny , Spencer Bella , Taylor-Gee Alice , Terry Samantha Y. A. 
Published: April 2024

AbstractHere, we report on the process of a highly impactful and successful creative, collaborative, and multi-partner public engagement project, Radiation Reveal. It brought together ten young adults aged 17–25-year-olds with experience of radiotherapy with researchers at Cancer Research UK RadNet City of London across three 2-hour online workshops. Our aims were to 1) initiate discussions between young adults and radiation researchers, and 2) identify what people wish they had known about radiotherapy before or during treatment. These aims were surpassed; other benefits included peer support, participants’ continued involvement in subsequent engagement projects, lasting friendships, creation of support groups for others, and creation and national dissemination of top ten tips for medical professionals and social media resources. A key learning was that this project required a dedicated and (com)passionate person with connections to national cancer charities. When designing the project, constant feedback is also needed from charities and young adults with and without radiotherapy experience. Finally, visually capturing discussions and keeping the door open beyond workshops further enhanced impact. Here, we hope to inform and inspire people to help project the patient voice in all we do.
Mcl-1 mediates intrinsic resistance to RAF inhibitors in mutant BRAF papillary thyroid carcinoma
Authors: Cavallo Maria R. , Yo Jacob C. , Gallant Kayla C. , Cunanan Camille J. , Amirfallah Amirali , Daniali Marzieh , Sanders Alyssa B. , Aplin Andrew E. , Pribitkin Edmund A. , Hartsough Edward J. 
Published: April 2024

AbstractPapillary thyroid carcinoma (PTC) is the most frequent form of thyroid cancer. PTC commonly presents with mutations of the serine/threonine kinase BRAF (BRAFV600E), which drive ERK1/2 pathway activation to support growth and suppress apoptosis. PTC patients often undergo surgical resection; however, since the average age of PTC patients is under 50, adverse effects associated with prolonged maintenance therapy following total thyroidectomy are a concern. The development of mutant-selective BRAF inhibitors (BRAFi), like vemurafenib, has been efficacious in patients with metastatic melanoma, but the response rate is low for mutant BRAF PTC patients. Here, we assay the therapeutic response of BRAFi in a panel of human PTC cell lines and freshly biopsied patient samples. We observed heterogeneous responses to BRAFi, and multi-omic comparisons between susceptible and resistant mutant BRAF PTC revealed overrepresented stress response pathways and the absence of compensatory RTK activation – features that may underpin innate resistance. Importantly, resistant cell lines and patient samples had increased hallmarks of failed apoptosis; a cellular state defined by sublethal caspase activation and DNA damage. Further analysis suggests that the failed apoptotic phenotypes may have features of “minority mitochondrial outer membrane permeabilization (MOMP)” – a stress-related response characterized by fragmented and porous mitochondria known to contribute to cancer aggressiveness. We found that cells presenting with minority MOMP-like phenotypes are dependent on the apoptotic regulator, Mcl-1, as treatment with the Mcl-1 inhibitor, AZD5991, potently induced cell death in resistant cells. Furthermore, PI3K/AKT inhibitors sensitized resistant cells to BRAFi; an effect that was at least in part associated with reduced Mcl-1 levels. Together, these data implicate minority MOMP as a mechanism associated with intrinsic drug resistance and underscore the benefits of targeting Mcl-1 in mutant BRAF PTC.
Microenvironmental reorganization in brain tumors following radiotherapy and recurrence revealed by hyperplexed immunofluorescence imaging
Authors: Watson Spencer S. , Duc Benoit , Kang Ziqi , de Tonnac Axel , Eling Nils , Font Laure , Whitmarsh Tristan , Massara Matteo ,   iMAXT Consortium, Joyce Johanna A. , Watson Spencer S. , Whitmarsh Tristan , Bodenmiller Bernd , Bodenmiller Bernd , Hausser Jean , Joyce Johanna A. 
Published: April 2024

AbstractThe tumor microenvironment plays a crucial role in determining response to treatment. This involves a series of interconnected changes in the cellular landscape, spatial organization, and extracellular matrix composition. However, assessing these alterations simultaneously is challenging from a spatial perspective, due to the limitations of current high-dimensional imaging techniques and the extent of intratumoral heterogeneity over large lesion areas. In this study, we introduce a spatial proteomic workflow termed Hyperplexed Immunofluorescence Imaging (HIFI) that overcomes these limitations. HIFI allows for the simultaneous analysis of > 45 markers in fragile tissue sections at high magnification, using a cost-effective high-throughput workflow. We integrate HIFI with machine learning feature detection, graph-based network analysis, and cluster-based neighborhood analysis to analyze the microenvironment response to radiation therapy in a preclinical model of glioblastoma, and compare this response to a mouse model of breast-to-brain metastasis. Here we show that glioblastomas undergo extensive spatial reorganization of immune cell populations and structural architecture in response to treatment, while brain metastases show no comparable reorganization. Our integrated spatial analyses reveal highly divergent responses to radiation therapy between brain tumor models, despite equivalent radiotherapy benefit.
Optogenetic control of mRNA condensation reveals an intimate link between condensate material properties and functions
Authors: Lee Min , Moon Hyungseok C. , Jeong Hyeonjeong , Kim Dong Wook , Park Hye Yoon , Shin Yongdae 
Published: April 2024

AbstractBiomolecular condensates, often assembled through phase transition mechanisms, play key roles in organizing diverse cellular activities. The material properties of condensates, ranging from liquid droplets to solid-like glasses or gels, are key features impacting the way resident components associate with one another. However, it remains unclear whether and how different material properties would influence specific cellular functions of condensates. Here, we combine optogenetic control of phase separation with single-molecule mRNA imaging to study relations between phase behaviors and functional performance of condensates. Using light-activated condensation, we show that sequestering target mRNAs into condensates causes translation inhibition. Orthogonal mRNA imaging reveals highly transient nature of interactions between individual mRNAs and condensates. Tuning condensate composition and material property towards more solid-like states leads to stronger translational repression, concomitant with a decrease in molecular mobility. We further demonstrate that β-actin mRNA sequestration in neurons suppresses spine enlargement during chemically induced long-term potentiation. Our work highlights how the material properties of condensates can modulate functions, a mechanism that may play a role in fine-tuning the output of condensate-driven cellular activities.
Functional protein dynamics in a crystal
Authors: Klyshko Eugene , Kim Justin Sung-Ho , McGough Lauren , Valeeva Victoria , Lee Ethan , Ranganathan Rama , Rauscher Sarah 
Published: April 2024

AbstractProteins are molecular machines and to understand how they work, we need to understand how they move. New pump-probe time-resolved X-ray diffraction methods open up ways to initiate and observe protein motions with atomistic detail in crystals on biologically relevant timescales. However, practical limitations of these experiments demands parallel development of effective molecular dynamics approaches to accelerate progress and extract meaning. Here, we establish robust and accurate methods for simulating dynamics in protein crystals, a nontrivial process requiring careful attention to equilibration, environmental composition, and choice of force fields. With more than seven milliseconds of sampling of a single chain, we identify critical factors controlling agreement between simulation and experiments and show that simulated motions recapitulate ligand-induced conformational changes. This work enables a virtuous cycle between simulation and experiments for visualizing and understanding the basic functional motions of proteins.
Donor regulatory T cells rapidly adapt to recipient tissues to control murine acute graft-versus-host disease
Authors: Dittmar David J. , Pielmeier Franziska , Strieder Nicholas , Fischer Alexander , Herbst Michael , Stanewsky Hanna , Wenzl Niklas , Röseler Eveline , Eder Rüdiger , Gebhard Claudia , Schwarzfischer-Pfeilschifter Lucia , Albrecht Christin , Herr Wolfgang , Edinger Matthias , Hoffmann Petra , Rehli Michael 
Published: April 2024

AbstractThe adoptive transfer of regulatory T cells is a promising strategy to prevent graft-versus-host disease after allogeneic bone marrow transplantation. Here, we use a major histocompatibility complex-mismatched mouse model to follow the fate of in vitro expanded donor regulatory T cells upon migration to target organs. Employing comprehensive gene expression and repertoire profiling, we show that they retain their suppressive function and plasticity after transfer. Upon entering non-lymphoid tissues, donor regulatory T cells acquire organ-specific gene expression profiles resembling tissue-resident cells and activate hallmark suppressive and cytotoxic pathways, most evidently in the colon, when co-transplanted with graft-versus-host disease-inducing conventional T cells. Dominant T cell receptor clonotypes overlap between organs and across recipients and their relative abundance correlates with protection efficacy. Thus, this study reveals donor regulatory T cell selection and adaptation mechanisms in target organs and highlights protective features of Treg to guide the development of improved graft-versus-host disease prevention strategies.
3D printable strong and tough composite organo-hydrogels inspired by natural hierarchical composite design principles
Authors: Liu Quyang , Dong Xinyu , Qi Haobo , Zhang Haoqi , Li Tian , Zhao Yijing , Li Guanjin , Zhai Wei 
Published: April 2024

AbstractFabrication of composite hydrogels can effectively enhance the mechanical and functional properties of conventional hydrogels. While ceramic reinforcement is common in many hard biological tissues, ceramic-reinforced hydrogels lack a similar natural prototype for bioinspiration. This raises a key question: How can we still attain bioinspired mechanical mechanisms in composite hydrogels without mimicking a specific composition and structure? Abstracting the hierarchical composite design principles of natural materials, this study proposes a hierarchical fabrication strategy for ceramic-reinforced organo-hydrogels, featuring (1) aligned ceramic platelets through direct-ink-write printing, (2) poly(vinyl alcohol) organo-hydrogel matrix reinforced by solution substitution, and (3) silane-treated platelet-matrix interfaces. Unit filaments are further printed into a selection of bioinspired macro-architectures, leading to high stiffness, strength, and toughness (fracture energy up to 31.1 kJ/m2), achieved through synergistic multi-scale energy dissipation. The materials also exhibit wide operation tolerance and electrical conductivity for flexible electronics in mechanically demanding conditions. Hence, this study demonstrates a model strategy that extends the fundamental design principles of natural materials to fabricate composite hydrogels with synergistic mechanical and functional enhancement.
An update on recent advances in targeted memory reactivation during sleep
Authors: Carbone Julia , Diekelmann Susanne 
Published: April 2024

AbstractTargeted Memory Reactivation (TMR) is a noninvasive tool to manipulate memory consolidation during sleep. TMR builds on the brain’s natural processes of memory reactivation during sleep and aims to facilitate or bias these processes in a certain direction. The basis of this technique is the association of learning content with sensory cues, such as odors or sounds, that are presented during subsequent sleep to promote memory reactivation. Research on TMR has drastically increased over the last decade with rapid developments. The aim of the present review is to highlight the most recent advances of this research. We focus on effects of TMR on the strengthening of memories in the declarative, procedural and emotional memory domain as well as on ways in which TMR can be used to promote forgetting. We then discuss advanced technical approaches to determine the optimal timing of TMR within the ongoing oscillatory activity of the sleeping brain as well as the specificity of TMR for certain memory contents. We further highlight the specific effects of TMR during REM sleep and in influencing dream content. Finally, we discuss recent evidence for potential applications of TMR for mental health, educational purposes and in the home setting. In conclusion, the last years of research have provided substantial advances in TMR that can guide future endeavors in research and application.
Chromospheric and coronal heating in an active region plage by dissipation of currents from braiding
Authors: Bose Souvik , De Pontieu Bart , Hansteen Viggo , Sainz Dalda Alberto , Savage Sabrina , Winebarger Amy 
Published: April 2024

AbstractThe question of what heats the outer solar atmosphere remains one of the longstanding mysteries in astrophysics. Statistical studies of Sun-like stars reveal a correlation between global chromospheric and coronal emissions, constraining theoretical models of potential heating mechanisms. However, spatially resolved observations of the Sun have surprisingly failed to show a similar correlation on small spatial scales. Here we use unique coordinated observations of the chromosphere (from the IRIS satellite) and the low corona (from the Hi-C 2.1 sounding rocket), and machine-learning-based inversion techniques, to show a strong correlation on spatial scales of a few hundred kilometres between heating in the chromosphere and emission in the upper transition region in strong magnetic field regions (‘plage’). Our observations are compatible with an advanced three-dimensional magnetohydrodynamic simulation in which the dissipation of current sheets caused by magnetic field braiding is responsible for heating the plasma simultaneously to chromospheric and coronal temperatures. Our results provide deep insight into the nature of the heating mechanism in solar active regions.
Extensive targeted metabolomics analysis reveals the identification of major metabolites, antioxidants, and disease-resistant active pharmaceutical components in Camellia tuberculata (Camellia L.) seeds
Authors: Ran Zhaohui , Li Zhi , Xiao Xu , Yan Chao , An Mingtai , Chen Juyan , Tang Ming 
Published: April 2024

AbstractSect. tuberculata plant belongs to the Camellia genus and is named for the “tuberculiform protuberance on the surface of the ovary and fruit”. It is a species of great ornamental value and potential medicinal value. However, little has been reported on the metabolites of C. tuberculata seeds. Therefore, this study was conducted to investigate the metabolites of C. tuberculata seeds based on UPLC/ESI-Q TRAP-MS/MS with extensively targeted metabolomics. A total of 1611 metabolites were identified, including 107 alkaloids, 276 amino acids and derivatives, 283 flavonoids, 86 lignans and coumarins, 181 lipids, 68 nucleotides and derivatives, 101 organic acids, 190 phenolic acids, 10 quinones, 4 steroids, 17 tannins, 111 terpenoids, and 177 other metabolites. We compared the different metabolites in seeds between HKH, ZM, ZY, and LY. The 1311 identified different metabolites were classified into three categories. Sixty-three overlapping significant different metabolites were found, of which lignans and coumarins accounted for the largest proportion. The differentially accumulated metabolites were enriched in different metabolic pathways between HKH vs. LY, HKH vs. ZM, HKH vs. ZY, LY vs. ZY, ZM vs. LY and ZM vs. ZY, with the most abundant metabolic pathways being 4, 2, 4, 7, 7 and 5, respectively (p < 0.05). Moreover, among the top 20 metabolites in each subgroup comparison in terms of difference multiplicity 7, 8 and 13. ZM and ZY had the highest phenolic acid content. Ninety-six disease-resistant metabolites and 48 major traditional Chinese medicine agents were identified based on seven diseases. The results of this study will not only lead to a more comprehensive and in-depth understanding of the metabolic properties of C. tuberculata seeds, but also provide a scientific basis for the excavation and further development of its medicinal value.
Radon concentration in seawater as a geochemical indicator of submarine fault activity in the Yatsushiro Sea, Japan
Authors: Kawabata Kuniyo , Tsunomori Fumiaki , Kitamura Yujin , Lin Yen-Yu , Chan Chung-Han , Ma Kuo-Fong 
Published: April 2024

AbstractThis study examined the relationship between radon (222Rn) concentrations in seawater and crustal activity in the Yatsushiro Sea by investigating the submarine fault zone situated at the southern end of the Futagawa–Hinagu fault zone, activated by the 2016 Kumamoto earthquake (M7.3). We conducted an analysis of 222Rn concentration in samples of bottom water just above the seafloor and pore water in sediments, utilizing multiple and piston cores from the Hakuho Maru Expedition KH18-3. The findings revealed significantly elevated 222Rn concentrations in the central sites of the Yatsushiro Sea, coinciding with a high-stress field exhibiting dense active faults. Seismicity analysis revealed heightened moment release and a low b-value post the 2016 Kumamoto earthquake, indicative of increased seismic activity and the potential for substantial earthquakes in the Yatsushiro Sea vicinity. Our results indicate that heightened concentrations of 222Rn in seawater can serve as an effective tracer for identifying and estimating submarine fault activities. Moreover, our research highlights the utility of 222Rn concentrations in detecting active submarine faults and assessing their activity. It contributes to a comprehensive understanding of the potential for significant earthquakes in the Yatsushiro Sea in the future.
Non-invasive biomarkers for detecting progression toward hypovolemic cardiovascular instability in a lower body negative pressure model
Authors: Murphy Ethan K. , Bertsch Spencer R. , Klein Samuel B. , Rashedi Navid , Sun Yifei , Joyner Michael J. , Curry Timothy B. , Johnson Christopher P. , Regimbal Riley J. , Wiggins Chad C. , Senefeld Jonathon W. , Shepherd John R. A. , Elliott Jonathan Thomas , Halter Ryan J. , Vaze Vikrant S. , Paradis Norman A. 
Published: April 2024

AbstractOccult hemorrhages after trauma can be present insidiously, and if not detected early enough can result in patient death. This study evaluated a hemorrhage model on 18 human subjects, comparing the performance of traditional vital signs to multiple off-the-shelf non-invasive biomarkers. A validated lower body negative pressure (LBNP) model was used to induce progression towards hypovolemic cardiovascular instability. Traditional vital signs included mean arterial pressure (MAP), electrocardiography (ECG), plethysmography (Pleth), and the test systems utilized electrical impedance via commercial electrical impedance tomography (EIT) and multifrequency electrical impedance spectroscopy (EIS) devices. Absolute and relative metrics were used to evaluate the performance in addition to machine learning-based modeling. Relative EIT-based metrics measured on the thorax outperformed vital sign metrics (MAP, ECG, and Pleth) achieving an area-under-the-curve (AUC) of 0.99 (CI 0.95–1.00, 100% sensitivity, 87.5% specificity) at the smallest LBNP change (0–15 mmHg). The best vital sign metric (MAP) at this LBNP change yielded an AUC of 0.6 (CI 0.38–0.79, 100% sensitivity, 25% specificity). Out-of-sample predictive performance from machine learning models were strong, especially when combining signals from multiple technologies simultaneously. EIT, alone or in machine learning-based combination, appears promising as a technology for early detection of progression toward hemodynamic instability.
Forward layer-wise learning of convolutional neural networks through separation index maximizing
Authors: Karimi Ali , Kalhor Ahmad , Sadeghi Tabrizi Melika 
Published: April 2024

AbstractThis paper proposes a forward layer-wise learning algorithm for CNNs in classification problems. The algorithm utilizes the Separation Index (SI) as a supervised complexity measure to evaluate and train each layer in a forward manner. The proposed method explains that gradually increasing the SI through layers reduces the input data’s uncertainties and disturbances, achieving a better feature space representation. Hence, by approximating the SI with a variant of local triplet loss at each layer, a gradient-based learning algorithm is suggested to maximize it. Inspired by the NGRAD (Neural Gradient Representation by Activity Differences) hypothesis, the proposed algorithm operates in a forward manner without explicit error information from the last layer. The algorithm’s performance is evaluated on image classification tasks using VGG16, VGG19, AlexNet, and LeNet architectures with CIFAR-10, CIFAR-100, Raabin-WBC, and Fashion-MNIST datasets. Additionally, the experiments are applied to text classification tasks using the DBPedia and AG’s News datasets. The results demonstrate that the proposed layer-wise learning algorithm outperforms state-of-the-art methods in accuracy and time complexity.