bluuebunny/crossref_metadata_2025_split huggingface dataset:
Converging and evolving immuno-genomic routes toward immune escape in breast cancer
Authors: Blanco-Heredia Juan , Souza Carla Anjos , Trincado Juan L. , Gonzalez-Cao Maria , Gonçalves-Ribeiro Samuel , Gil Sara Ruiz , Pravdyvets Dmytro , Cedeño Samandhy , Callari Maurizio , Marra Antonio , Gazzo Andrea M. , Weigelt Britta , Pareja Fresia , Vougiouklakis Theodore , Jungbluth Achim A. , Rosell Rafael , Brander Christian , Tresserra Francesc , Reis-Filho Jorge S. , Tiezzi Daniel Guimarães , de la Iglesia Nuria , Heyn Holger , De Mattos-Arruda Leticia 
Published: February 2024

AbstractThe interactions between tumor and immune cells along the course of breast cancer progression remain largely unknown. Here, we extensively characterize multiple sequential and parallel multiregion tumor and blood specimens of an index patient and a cohort of metastatic triple-negative breast cancers. We demonstrate that a continuous increase in tumor genomic heterogeneity and distinct molecular clocks correlated with resistance to treatment, eventually allowing tumors to escape from immune control. TCR repertoire loses diversity over time, leading to convergent evolution as breast cancer progresses. Although mixed populations of effector memory and cytotoxic single T cells coexist in the peripheral blood, defects in the antigen presentation machinery coupled with subdued T cell recruitment into metastases are observed, indicating a potent immune avoidance microenvironment not compatible with an effective antitumor response in lethal metastatic disease. Our results demonstrate that the immune responses against cancer are not static, but rather follow dynamic processes that match cancer genomic progression, illustrating the complex nature of tumor and immune cell interactions.
Tunable afterglow for mechanical self-monitoring 3D printing structures
Authors: Huang Rongjuan , He Yunfei , Wang Juan , Zou Jindou , Wang Hailan , Sun Haodong , Xiao Yuxin , Zheng Dexin , Ma Jiani , Yu Tao , Huang Wei 
Published: February 2024

AbstractSelf-monitoring materials have promising applications in structural health monitoring. However, developing organic afterglow materials for self-monitoring is a highly intriguing yet challenging task. Herein, we design two organic molecules with a twisted donor-acceptor-acceptor’ configuration and achieve dual-emissive afterglow with tunable lifetimes (86.1–287.7 ms) by doping into various matrices. Based on a photosensitive resin, a series of complex structures are prepared using 3D printing technology. They exhibit tunable afterglow lifetime and Young’s Modulus by manipulating the photocuring time and humidity level. With sufficient photocuring or in dry conditions, a long-lived bright green afterglow without apparent deformation under external loading is realized. We demonstrate that the mechanical properties of complex 3D printing structures can be well monitored by controlling the photocuring time and humidity, and quantitively manifested by afterglow lifetimes. This work casts opportunities for constructing flexible 3D printing devices that can achieve sensing and real-time mechanical detection.
Intestinal IL-22RA1 signaling regulates intrinsic and systemic lipid and glucose metabolism to alleviate obesity-associated disorders
Authors: Gaudino Stephen J. , Singh Ankita , Huang Huakang , Padiadpu Jyothi , Jean-Pierre Makheni , Kempen Cody , Bahadur Tej , Shiomitsu Kiyoshi , Blumberg Richard , Shroyer Kenneth R. , Beyaz Semir , Shulzhenko Natalia , Morgun Andrey , Kumar Pawan 
Published: February 2024

AbstractIL-22 is critical for ameliorating obesity-induced metabolic disorders. However, it is unknown where IL-22 acts to mediate these outcomes. Here we examine the importance of tissue-specific IL-22RA1 signaling in mediating long-term high fat diet (HFD) driven metabolic disorders. To do so, we generated intestinal epithelium-, liver-, and white adipose tissue (WAT)-specific Il22ra1 knockout and littermate control mice. Intestinal epithelium- and liver-specific IL-22RA1 signaling upregulated systemic glucose metabolism. Intestinal IL-22RA1 signaling also mediated liver and WAT metabolism in a microbiota-dependent manner. We identified an association between Oscillibacter and elevated WAT inflammation, likely induced by Mmp12 expressing macrophages. Mechanistically, transcription of intestinal lipid metabolism genes is regulated by IL-22 and potentially IL-22-induced IL-18. Lastly, we show that Paneth cell-specific IL-22RA1 signaling, in part, mediates systemic glucose metabolism after HFD. Overall, these results elucidate a key role of intestinal epithelium-specific IL-22RA1 signaling in regulating intestinal metabolism and alleviating systemic obesity-associated disorders.
Meiotic protein SYCP2 confers resistance to DNA-damaging agents through R-loop-mediated DNA repair
Authors: Wang Yumin , Gao Boya , Zhang Luyuan , Wang Xudong , Zhu Xiaolan , Yang Haibo , Zhang Fengqi , Zhu Xueping , Zhou Badi , Yao Sean , Nagayama Aiko , Lee Sanghoon , Ouyang Jian , Koh Siang-Boon , Eisenhauer Eric L. , Zarrella Dominique , Lu Kate , Rueda Bo R. , Zou Lee , Su Xiaofeng A. , Yeku Oladapo , Ellisen Leif W. , Wang Xiao-Song , Lan Li 
Published: February 2024

AbstractDrugs targeting the DNA damage response (DDR) are widely used in cancer therapy, but resistance to these drugs remains a major clinical challenge. Here, we show that SYCP2, a meiotic protein in the synaptonemal complex, is aberrantly and commonly expressed in breast and ovarian cancers and associated with broad resistance to DDR drugs. Mechanistically, SYCP2 enhances the repair of DNA double-strand breaks (DSBs) through transcription-coupled homologous recombination (TC-HR). SYCP2 promotes R-loop formation at DSBs and facilitates RAD51 recruitment independently of BRCA1. SYCP2 loss impairs RAD51 localization, reduces TC-HR, and renders tumors sensitive to PARP and topoisomerase I (TOP1) inhibitors. Furthermore, our studies of two clinical cohorts find that SYCP2 overexpression correlates with breast cancer resistance to antibody-conjugated TOP1 inhibitor and ovarian cancer resistance to platinum treatment. Collectively, our data suggest that SYCP2 confers cancer cell resistance to DNA-damaging agents by stimulating R-loop-mediated DSB repair, offering opportunities to improve DDR therapy.
Exosomes define a local and systemic communication network in healthy pancreas and pancreatic ductal adenocarcinoma
Authors: Adem Bárbara , Bastos Nuno , Ruivo Carolina F. , Sousa-Alves Sara , Dias Carolina , Vieira Patrícia F. , Batista Inês A. , Cavadas Bruno , Saur Dieter , Machado José C. , Cai Dawen , Melo Sonia A. 
Published: February 2024

AbstractPancreatic ductal adenocarcinoma (PDAC), a lethal disease, requires a grasp of its biology for effective therapies. Exosomes, implicated in cancer, are poorly understood in living systems. Here we use the genetically engineered mouse model (ExoBow) to map the spatiotemporal distribution of exosomes from healthy and PDAC pancreas in vivo to determine their biological significance. We show that, within the PDAC microenvironment, cancer cells establish preferential communication routes through exosomes with cancer associated fibroblasts and endothelial cells. The latter being a conserved event in the healthy pancreas. Inhibiting exosomes secretion in both scenarios enhances angiogenesis, underscoring their contribution to vascularization and to cancer. Inter-organ communication is significantly increased in PDAC with specific organs as most frequent targets of exosomes communication occurring in health with the thymus, bone-marrow, brain, and intestines, and in PDAC with the kidneys, lungs and thymus. In sum, we find that exosomes mediate an organized intra- and inter- pancreas communication network with modulatory effects in vivo.
A hybrid transistor with transcriptionally controlled computation and plasticity
Authors: Gao Yang , Zhou Yuchen , Ji Xudong , Graham Austin J. , Dundas Christopher M. , Miniel Mahfoud Ismar E. , Tibbett Bailey M. , Tan Benjamin , Partipilo Gina , Dodabalapur Ananth , Rivnay Jonathan , Keitz Benjamin K. 
Published: February 2024

AbstractOrganic electrochemical transistors (OECTs) are ideal devices for translating biological signals into electrical readouts and have applications in bioelectronics, biosensing, and neuromorphic computing. Despite their potential, developing programmable and modular methods for living systems to interface with OECTs has proven challenging. Here we describe hybrid OECTs containing the model electroactive bacterium Shewanella oneidensis that enable the transduction of biological computations to electrical responses. Specifically, we fabricated planar p-type OECTs and demonstrated that channel de-doping is driven by extracellular electron transfer (EET) from S. oneidensis. Leveraging this mechanistic understanding and our ability to control EET flux via transcriptional regulation, we used plasmid-based Boolean logic gates to translate biological computation into current changes within the OECT. Finally, we demonstrated EET-driven changes to OECT synaptic plasticity. This work enables fundamental EET studies and OECT-based biosensing and biocomputing systems with genetically controllable and modular design elements.
Integrating single-cell and spatially resolved transcriptomic strategies to survey the astrocyte response to stroke in male mice
Authors: Scott Erica Y. , Safarian Nickie , Casasbuenas Daniela Lozano , Dryden Michael , Tockovska Teodora , Ali Shawar , Peng Jiaxi , Daniele Emerson , Nie Xin Lim Isabel , Bang K. W. Annie , Tripathy Shreejoy , Yuzwa Scott A. , Wheeler Aaron R. , Faiz Maryam 
Published: February 2024

AbstractAstrocytes, a type of glial cell in the central nervous system (CNS), adopt diverse states in response to injury that are influenced by their location relative to the insult. Here, we describe a platform for spatially resolved, single-cell transcriptomics and proteomics, called tDISCO (tissue-digital microfluidic isolation of single cells for -Omics). We use tDISCO alongside two high-throughput platforms for spatial (Visium) and single-cell transcriptomics (10X Chromium) to examine the heterogeneity of the astrocyte response to a cortical ischemic stroke in male mice. We show that integration of Visium and 10X Chromium datasets infers two astrocyte populations, proximal or distal to the injury site, while tDISCO determines the spatial boundaries and molecular profiles that define these populations. We find that proximal astrocytes show differences in lipid shuttling, with enriched expression of Apoe and Fabp5. Our datasets provide a resource for understanding the roles of astrocytes in stroke and showcase the utility of tDISCO for hypothesis-driven, spatially resolved single-cell experiments.
Chiral and flat-band magnetic quasiparticles in ferromagnetic and metallic kagome layers
Authors: Riberolles S. X. M. , Slade Tyler J. , Han Tianxiong , Li Bing , Abernathy D. L. , Canfield P. C. , Ueland B. G. , Orth P. P. , Ke Liqin , McQueeney R. J. 
Published: February 2024

AbstractMagnetic kagome metals are a promising platform to develop unique quantum transport and optical phenomena caused by the interplay between topological electronic bands, strong correlations, and magnetic order. This interplay may result in exotic quasiparticles that describe the coupled electronic and spin excitations on the frustrated kagome lattice. Here, we observe novel elementary magnetic excitations within the ferromagnetic Mn kagome layers in TbMn6Sn6 using inelastic neutron scattering. We observe sharp, collective acoustic magnons and identify flat-band magnons that are localized to a hexagonal plaquette due to the special geometry of the kagome layer. Surprisingly, we observe another type of elementary magnetic excitation; a chiral magnetic quasiparticle that is also localized on a hexagonal plaquette. The short lifetime of localized flat-band and chiral quasiparticles suggest that they are hybrid excitations that decay into electronic states.
Accurate global and local 3D alignment of cryo-EM density maps using local spatial structural features
Authors: He Bintao , Zhang Fa , Feng Chenjie , Yang Jianyi , Gao Xin , Han Renmin 
Published: February 2024

AbstractAdvances in cryo-electron microscopy (cryo-EM) imaging technologies have led to a rapidly increasing number of cryo-EM density maps. Alignment and comparison of density maps play a crucial role in interpreting structural information, such as conformational heterogeneity analysis using global alignment and atomic model assembly through local alignment. Here, we present a fast and accurate global and local cryo-EM density map alignment method called CryoAlign, that leverages local density feature descriptors to capture spatial structure similarities. CryoAlign is a feature-based cryo-EM map alignment tool, in which the employment of feature-based architecture enables the rapid establishment of point pair correspondences and robust estimation of alignment parameters. Extensive experimental evaluations demonstrate the superiority of CryoAlign over the existing methods in terms of both alignment accuracy and speed.
Iterative design of training data to control intricate enzymatic reaction networks
Authors: van Sluijs Bob , Zhou Tao , Helwig Britta , Baltussen Mathieu G. , Nelissen Frank H. T. , Heus Hans A. , Huck Wilhelm T. S. 
Published: February 2024

AbstractKinetic modeling of in vitro enzymatic reaction networks is vital to understand and control the complex behaviors emerging from the nonlinear interactions inside. However, modeling is severely hampered by the lack of training data. Here, we introduce a methodology that combines an active learning-like approach and flow chemistry to efficiently create optimized datasets for a highly interconnected enzymatic reactions network with multiple sub-pathways. The optimal experimental design (OED) algorithm designs a sequence of out-of-equilibrium perturbations to maximize the information about the reaction kinetics, yielding a descriptive model that allows control of the output of the network towards any cost function. We experimentally validate the model by forcing the network to produce different product ratios while maintaining a minimum level of overall conversion efficiency. Our workflow scales with the complexity of the system and enables the optimization of previously unobtainable network outputs.
Measuring entanglement entropy and its topological signature for phononic systems
Authors: Lin Zhi-Kang , Zhou Yao , Jiang Bin , Wu Bing-Quan , Chen Li-Mei , Liu Xiao-Yu , Wang Li-Wei , Ye Peng , Jiang Jian-Hua 
Published: February 2024

AbstractEntanglement entropy is a fundamental concept with rising importance in various fields ranging from quantum information science, black holes to materials science. In complex materials and systems, entanglement entropy provides insight into the collective degrees of freedom that underlie the systems’ complex behaviours. As well-known predictions, the entanglement entropy exhibits area laws for systems with gapped excitations, whereas it follows the Gioev-Klich-Widom scaling law in gapless fermion systems. However, many of these fundamental predictions have not yet been confirmed in experiments due to the difficulties in measuring entanglement entropy in physical systems. Here, we report the experimental verification of the above predictions by probing the nonlocal correlations in phononic systems. We obtain the entanglement entropy and entanglement spectrum for phononic systems with the fermion filling analog. With these measurements, we verify the Gioev-Klich-Widom scaling law. We further observe the salient signatures of topological phases in entanglement entropy and entanglement spectrum.
Oncogenic c-Myc induces replication stress by increasing cohesins chromatin occupancy in a CTCF-dependent manner
Authors: Peripolli Silvia , Meneguello Leticia , Perrod Chiara , Singh Tanya , Patel Harshil , Rahman Sazia T. , Kiso Koshiro , Thorpe Peter , Calvanese Vincenzo , Bertoli Cosetta , de Bruin Robertus A. M. 
Published: February 2024

AbstractOncogene-induced replication stress is a crucial driver of genomic instability and one of the key events contributing to the onset and evolution of cancer. Despite its critical role in cancer, the mechanisms that generate oncogene-induced replication stress remain not fully understood. Here, we report that an oncogenic c-Myc-dependent increase in cohesins on DNA contributes to the induction of replication stress. Accumulation of cohesins on chromatin is not sufficient to cause replication stress, but also requires cohesins to accumulate at specific sites in a CTCF-dependent manner. We propose that the increased accumulation of cohesins at CTCF site interferes with the progression of replication forks, contributing to oncogene-induced replication stress. This is different from, and independent of, previously suggested mechanisms of oncogene-induced replication stress. This, together with the reported protective role of cohesins in preventing replication stress-induced DNA damage, supports a double-edge involvement of cohesins in causing and tolerating oncogene-induced replication stress.
Learning representations for image-based profiling of perturbations
Authors: Moshkov Nikita , Bornholdt Michael , Benoit Santiago , Smith Matthew , McQuin Claire , Goodman Allen , Senft Rebecca A. , Han Yu , Babadi Mehrtash , Horvath Peter , Cimini Beth A. , Carpenter Anne E. , Singh Shantanu , Caicedo Juan C. 
Published: February 2024

AbstractMeasuring the phenotypic effect of treatments on cells through imaging assays is an efficient and powerful way of studying cell biology, and requires computational methods for transforming images into quantitative data. Here, we present an improved strategy for learning representations of treatment effects from high-throughput imaging, following a causal interpretation. We use weakly supervised learning for modeling associations between images and treatments, and show that it encodes both confounding factors and phenotypic features in the learned representation. To facilitate their separation, we constructed a large training dataset with images from five different studies to maximize experimental diversity, following insights from our causal analysis. Training a model with this dataset successfully improves downstream performance, and produces a reusable convolutional network for image-based profiling, which we call Cell Painting CNN. We evaluated our strategy on three publicly available Cell Painting datasets, and observed that the Cell Painting CNN improves performance in downstream analysis up to 30% with respect to classical features, while also being more computationally efficient.
The development of aesthetic experience through virtual and augmented reality
Authors: Zhou Cong , Li JianQi 
Published: February 2024

AbstractEmerging technological innovations offer the potential for experiential engagement through virtual scenarios, yet the viability of this approach for educational purposes remains significantly underexplored. This study aims to assess the feasibility of Augmented Reality (AR) and Virtual Reality (VR) technologies in providing users with aesthetic experiences when visiting digital exhibitions. A total of 190 students participated in this investigation. The control group visited traditional exhibits at the Palace Museum in Beijing. This group underwent a survey to evaluate their acquired aesthetic experience. In contrast, the experimental group, comprising 96 students, engaged with VR/AR scenarios at the Palace Museum in Beijing. Accordingly, students in the experimental group were also surveyed to evaluate both their aesthetic experiences and, additionally, their user experiences. The survey results unveiled significant distinctions in aesthetic experiences between students in the control and experimental groups. Moreover, there were notable correlations between individual variables related to user and aesthetic experiences within the experimental group. Furthermore, the study revealed disparities in both user and aesthetic experiences among male and female students. The findings have implications for aesthetic education teachers and officials in the context of developing sound strategies for providing aesthetic experiences to their students. This information is also of interest to employees of museums, exhibitions, and other cultural facilities, who are interested in holding or hold digital exhibitions.
Heatwaves in Peninsular Malaysia: a spatiotemporal analysis
Authors: Muhammad Mohd Khairul Idlan , Hamed Mohammed Magdy , Harun Sobri , Sa’adi Zulfaqar , Sammen Saad Sh. , Al-Ansari Nadhir , Shahid Shamsuddin , Scholz Miklas 
Published: February 2024

AbstractOne of the direct and unavoidable consequences of global warming-induced rising temperatures is the more recurrent and severe heatwaves. In recent years, even countries like Malaysia seldom had some mild to severe heatwaves. As the Earth's average temperature continues to rise, heatwaves in Malaysia will undoubtedly worsen in the future. It is crucial to characterize and monitor heat events across time to effectively prepare for and implement preventative actions to lessen heatwave's social and economic effects. This study proposes heatwave-related indices that take into account both daily maximum (Tmax) and daily lowest (Tmin) temperatures to evaluate shifts in heatwave features in Peninsular Malaysia (PM). Daily ERA5 temperature dataset with a geographical resolution of 0.25° for the period 1950–2022 was used to analyze the changes in the frequency and severity of heat waves across PM, while the LandScan gridded population data from 2000 to 2020 was used to calculate the affected population to the heatwaves. This study also utilized Sen's slope for trend analysis of heatwave characteristics, which separates multi-decadal oscillatory fluctuations from secular trends. The findings demonstrated that the geographical pattern of heatwaves in PM could be reconstructed if daily Tmax is more than the 95th percentile for 3 or more days. The data indicated that the southwest was more prone to severe heatwaves. The PM experienced more heatwaves after 2000 than before. Overall, the heatwave-affected area in PM has increased by 8.98 km2/decade and its duration by 1.54 days/decade. The highest population affected was located in the central south region of PM. These findings provide valuable insights into the heatwaves pattern and impact.