Featured
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| Open AccessA theory of evolutionary dynamics on any complex population structure reveals stem cell niche architecture as a spatial suppressor of selection
Evolutionary models can help understand how the spatial arrangement of a population shapes its evolutionary dynamics. This study presents such a method and shows that the spatial architectures of stem cell populations in bone marrow are suppressors of selection, hinting at a potential evolutionary design.
- Yang Ping Kuo
- , César Nombela-Arrieta
- & Oana Carja
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Article
| Open AccessGene expression signatures in blood from a West African sepsis cohort define host response phenotypes
Sepsis is a global challenge and a significant burden in Sub-Saharan Africa. Here, Chenoweth et al profile host gene expression signatures from a cohort in Ghana to define molecular phenotypes and identify potential targets to improve patient outcomes.
- Josh G. Chenoweth
- , Carlo Colantuoni
- & Danielle V. Clark
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Article
| Open AccessLoop-extruders alter bacterial chromosome topology to direct entropic forces for segregation
Bacterial chromosomes segregate while undergoing replication. Here the authors show that such concurrent replication and segregation cannot be achieved by passive entropic forces alone, and that loop-extruders could be sufficient to explain segregation.
- Janni Harju
- , Muriel C. F. van Teeseling
- & Chase P. Broedersz
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Article
| Open AccessRemote sensing of emperor penguin abundance and breeding success
Emperor penguins colony occupancy is variable and chiefly estimated with remote sensing images at end of the breeding season. Here, the authors provide a phenological model that can extrapolate occupancy from sparse data and can predict phenological events, breeding pairs and fledging chicks.
- Alexander Winterl
- , Sebastian Richter
- & Daniel P. Zitterbart
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Article
| Open AccessA protein sequence-based deep transfer learning framework for identifying human proteome-wide deubiquitinase-substrate interactions
The specificity of protein deubiquitination relies on deubiquitinase-substrate interactions (DSIs). Here, authors leverage evolutionary information from the proteome to predict DSIs, even with an inadequate training dataset.
- Yuan Liu
- , Dianke Li
- & Dong Li
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Article
| Open AccessStructure prediction of protein-ligand complexes from sequence information with Umol
Here the authors report the AI system Umol that predicts flexible all-atom structures of protein-ligand complexes from sequence information, advancing AI-driven drug discovery: accurate structures and affinity can be selected from predicted confidence metrics (plDDT).
- Patrick Bryant
- , Atharva Kelkar
- & Frank Noé
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Article
| Open AccessHuman movement and environmental barriers shape the emergence of dengue
Here, using a dynamic modelling approach, the authors find that the spread of dengue through Mexico and Brazil is shaped by specific interactions between human mobility, climate, and the environment. Their models can also be applied to predict future spread in these geographic areas.
- Vinyas Harish
- , Felipe J. Colón-González
- & Oliver J. Brady
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Article
| Open AccessSmall body size is associated with increased evolutionary lability of wing skeleton proportions in birds
Birds vary in body mass by many orders of magnitude, but how this effects the evolution of their skeletal proportions is unclear. This study shows that small body size is associated with decreased evolutionary integration between wing bone sizes, facilitating increased evolutionary lability.
- Andrew Orkney
- & Brandon P. Hedrick
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Article
| Open AccessCrykey: Rapid identification of SARS-CoV-2 cryptic mutations in wastewater
Wastewater surveillance has the potential to be used for early detection of new SARS-CoV-2 lineages. Here, the authors present Crykey, a computational method for detecting cryptic SARS-CoV-2 mutations in wastewater that co-occur on the same sequencing read, potentially representing new lineages.
- Yunxi Liu
- , Nicolae Sapoval
- & Lauren B. Stadler
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Article
| Open AccessA variational expectation-maximization framework for balanced multi-scale learning of protein and drug interactions
Multi-scale learning still struggles with imbalanced information and greedy characteristics. Here the authors present MUSE, an Expectation-Maximization-based multi-scale framework, improving predictions across molecular interactions and atomic interfaces.
- Jiahua Rao
- , Jiancong Xie
- & Yuedong Yang
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Article
| Open AccessBiochemical-free enrichment or depletion of RNA classes in real-time during direct RNA sequencing with RISER
It is difficult to detect low abundance RNAs in sequencing experiments, and biochemical methods to enrich or deplete specific RNAs are time-consuming, costly and can damage RNA. Here, authors develop a biochemical-free technology to enrich or deplete RNA classes in real-time during direct RNA sequencing.
- Alexandra Sneddon
- , Agin Ravindran
- & Eduardo Eyras
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Article
| Open AccessA comprehensive benchmarking with interpretation and operational guidance for the hierarchy of topologically associating domains
TAD hierarchy demonstrates cell-to-cell variability, leading to the development of numerous callers. Here, authors present a comprehensive benchmark of TAD hierarchy callers and introduce the ‘air conditioner’ model to illustrate TAD hierarchy’s role in transcription.
- Jingxuan Xu
- , Xiang Xu
- & Hebing Chen
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Article
| Open AccessArtificial intelligence enables precision diagnosis of cervical cytology grades and cervical cancer
Cervical screening is a key method for detecting cervical cancer, but is limited by pathologist detection. Here, the authors use artificial intelligence to predict cytology grades from whole slide images.
- Jue Wang
- , Yunfang Yu
- & Herui Yao
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Article
| Open AccessRevealing the mechanism and function underlying pairwise temporal coupling in collective motion
It is known that spatially localized interactions can give rise to self-organized collective motion. Here, by studying pairwise interactions in juvenile zebrafish, authors reveal the role of reciprocal temporal coupling and find that temporal coordination considerably improves spatial responsiveness, such as reacting to changes in the direction of motion of a partner.
- Guy Amichay
- , Liang Li
- & Iain D. Couzin
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Article
| Open AccessPrediction of Klebsiella phage-host specificity at the strain level
Bacterial viruses (phages) are promising alternatives to treat antibiotic-resistant bacterial infections, but finding matching phages against bacteria of interest is challenging. Here, Boeckaerts et al. present a machine learning approach that predicts phage-bacteria pairs at the strain level for Klebsiella pathogens.
- Dimitri Boeckaerts
- , Michiel Stock
- & Yves Briers
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Article
| Open AccessHippocampal sharp-wave ripples correlate with periods of naturally occurring self-generated thoughts in humans
Whether and how sharp-wave ripples (SWRs) accompany mental states that are less closely linked to events in the immediate environment are not fully understood. Here authors recorded SWRs from hippocampus of 10 epilepsy patients for up to 15 days with experience sampling. SWR rates showed circadian fluctuation and were associated with self-generated thoughts such as mind wandering.
- Takamitsu Iwata
- , Takufumi Yanagisawa
- & Haruhiko Kishima
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Article
| Open AccessDeep learning of left atrial structure and function provides link to atrial fibrillation risk
In this study, a deep learning-based model of left atrial size in UK Biobank enabled genome-wide association studies in 35,049 healthy participants. Several lines of evidence, including the PITX2 locus, linked left atrial dysfunction to atrial fibrillation risk.
- James P. Pirruccello
- , Paolo Di Achille
- & Patrick T. Ellinor
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Article
| Open AccessSelf-organization of modular activity in immature cortical networks
How the cortex forms spatially structured modules during development is poorly understood. Here, the authors show that activity in early developing cortex is self-organized though local-excitation and lateral inhibition.
- Haleigh N. Mulholland
- , Matthias Kaschube
- & Gordon B. Smith
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Article
| Open AccessDesigning meaningful continuous representations of T cell receptor sequences with deep generative models
Relating T cell receptor (TCR) sequencing to antigen specificity is a challenge especially when TCR specificity is unclear. Here the authors use a low dimensional generative approach to model TCR sequence similarity and to associate TCR sequences with the same specificity.
- Allen Y. Leary
- , Darius Scott
- & Peter G. Hawkins
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Article
| Open AccessAI-enhanced integration of genetic and medical imaging data for risk assessment of Type 2 diabetes
Type 2 diabetes is a global health threat demanding precise healthcare methods. Here, the authors show that their AI-driven risk assessment models, integrating genetic, imaging, and demographic data, achieve high accuracy in identifying high-risk groups, promising advancements in prevention strategies.
- Yi-Jia Huang
- , Chun-houh Chen
- & Hsin-Chou Yang
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Article
| Open AccessSpatial disparities in the mortality burden of the covid-19 pandemic across 569 European regions (2020-2021)
Excess mortality can be used as an indicator of the impacts of the COVID-19 pandemic. Here, the authors estimate excess mortality in 569 European regions in 25 countries for 2020 and 2021 and describe how impacts changed over time.
- Florian Bonnet
- , Pavel Grigoriev
- & Carlo-Giovanni Camarda
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Article
| Open AccessEnhancing in vivo cell and tissue targeting by modulation of polymer nanoparticles and macrophage decoys
Targeted drug delivery in vivo is a complex challenge, and understanding the characteristics that define the behavior of delivery vehicles in vivo is vital for advancing delivery vehicle design. Here the authors use a library of polymeric delivery vehicles and high-throughput tools to study the structure-function relationships guiding the physiological fate of nanomedicines.
- Alexandra S. Piotrowski-Daspit
- , Laura G. Bracaglia
- & W. Mark Saltzman
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Article
| Open AccessDeepDive: estimating global biodiversity patterns through time using deep learning
Estimates of palaeodiversity are biased by the incompleteness of the fossil record. Here, the authors develop DeepDive, a deep learning approach that infers richness while accounting for record heterogeneity, and test it with two empirical datasets.
- Rebecca B. Cooper
- , Joseph T. Flannery-Sutherland
- & Daniele Silvestro
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Article
| Open AccessAn improved epigenetic counter to track mitotic age in normal and precancerous tissues
DNA methylation (DNAm) clocks can track mitotic age, but their potential use for cancer risk prediction remains less explored. Here, the authors develop a DNAm counter of total mitotic age (stemTOC) that shows an increase of mitotic age in normal tissues and precancerous lesions.
- Tianyu Zhu
- , Huige Tong
- & Andrew E. Teschendorff
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Article
| Open AccessBenchmarking of methods for DNA methylome deconvolution
Determining the different cell types that contribute to a mixture of DNA is key for research and diagnostic applications. Here, authors comprehensively benchmark DNA methylation-based deconvolution methods, evaluating their performance and robustness to technical bias.
- Kobe De Ridder
- , Huiwen Che
- & Bernard Thienpont
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Article
| Open Access1q amplification and PHF19 expressing high-risk cells are associated with relapsed/refractory multiple myeloma
Translocations and copy number variations that affect multiple myeloma (MM) have not been investigated at the single cell level. Here, single cell multi-omics reveal the relationship between epigenetic regulation and cytogenetic events that lead to the increase of cell proliferation in MM.
- Travis S. Johnson
- , Parvathi Sudha
- & Brian A. Walker
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Article
| Open AccessImportance of social inequalities to contact patterns, vaccine uptake, and epidemic dynamics
Contact patterns influence the spread of infectious diseases, but mathematical models of epidemics typically only account for age differences in contacts. Here, the authors investigate the importance of other sociodemographic characteristics in shaping contact patterns and vaccine uptake using survey data from Hungary.
- Adriana Manna
- , Júlia Koltai
- & Márton Karsai
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Article
| Open AccessConserved regulatory switches for the transition from natal down to juvenile feather in birds
Natal downs adapted for heat conservation transition to juvenile feathers that support simple flight during bird development. Here the authors characterize gene expression networks and epigenetic changes and use functional perturbations to characterize evolutionarily conserved regulatory switches that control this transition in birds.
- Chih-Kuan Chen
- , Yao-Ming Chang
- & Wen‐Hsiung Li
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Article
| Open AccessMAPP unravels frequent co-regulation of splicing and polyadenylation by RNA-binding proteins and their dysregulation in cancer
Here the authors apply the Motif Activity on Pre-mRNA Processing (MAPP) tool to standard RNA sequencing data, thereby unravelling the co-regulation of splicing and polyadenylation by RNA-binding proteins and their dysregulation in cancer.
- Maciej Bak
- , Erik van Nimwegen
- & Andreas J. Gruber
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Article
| Open AccessInterplay between Mg2+ and Ca2+ at multiple sites of the ryanodine receptor
Skeletal ryanodine receptor controls calcium mobilization indispensable for muscle contraction. Here, authors combine cryo-EM and molecular dynamics to uncover the structural basis of the intricate regulation of this channel by calcium and magnesium.
- Ashok R. Nayak
- , Warin Rangubpit
- & Montserrat Samsó
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Article
| Open AccessGRouNdGAN: GRN-guided simulation of single-cell RNA-seq data using causal generative adversarial networks
Benchmarking GRN inference methods remains a challenge. Here, authors present GRouNdGAN, a causal generative model that imposes a user-defined GRN in its architecture to simulate realistic single-cell data, bridging the gap between synthetic and biological data benchmarks of GRN inference methods.
- Yazdan Zinati
- , Abdulrahman Takiddeen
- & Amin Emad
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Article
| Open AccessQuantifying 3′UTR length from scRNA-seq data reveals changes independent of gene expression
While gene expression analysis is commonly performed, 3′UTR length analysis is limited due to technical challenges. Here the authors provide an open-access analysis pipeline for scRNA-seq data to simultaneously quantify gene expression and 3′UTR length.
- Mervin M. Fansler
- , Sibylle Mitschka
- & Christine Mayr
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Article
| Open AccessTransfer learning enables identification of multiple types of RNA modifications using nanopore direct RNA sequencing
Simultaneous profiling of multiple RNA modifications is a promising yet understudied field of research. Here, authors develop a transferable deep learning framework capable of detecting multiple types of RNA modifications in single nanopore sequencing sample.
- You Wu
- , Wenna Shao
- & Xiang Yu
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Article
| Open AccessDouble-negative B cells and DNASE1L3 colocalise with microbiota in gut-associated lymphoid tissue
Intestinal homeostasis is maintained by interactions between the gut-associated lymphoid tissue and the resident flora. Here Montorsi et al use multiplexed single cell omics to describe double negative type 2 B cells and DNASE1L3-expressing dendritic cells that interact and associate with microbiota on the human gut antigenic front line.
- Lucia Montorsi
- , Michael J. Pitcher
- & Jo Spencer
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Article
| Open AccessLong-read powered viral metagenomics in the oligotrophic Sargasso Sea
The Sargasso Sea is a natural laboratory for understanding future conditions of warmer oceans and associated nutrient limitation. Here, the authors combined short- and long-read sequencing to survey Sargasso Sea viral communities.
- Joanna Warwick-Dugdale
- , Funing Tian
- & Ben Temperton
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Article
| Open AccessLoCoHD: a metric for comparing local environments of proteins
The techniques available for comparing protein structures do not focus directly on the chemical nature of residue environments. Here, authors describe a computational method that can capture both the spatial and chemical dissimilarities of residue surroundings.
- Zsolt Fazekas
- , Dóra K. Menyhárd
- & András Perczel
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Article
| Open AccessDeep mutational scanning reveals a correlation between degradation and toxicity of thousands of aspartoacylase variants
The details of how the protein folding and degradation systems collaborate to combat potentially toxic non-native proteins are unknown. Here the authors perform systematic studies of missense and nonsense variants of the cytosolic aspartoacylase, ASPA, where loss-of-function variants are linked to Canavan disease.
- Martin Grønbæk-Thygesen
- , Vasileios Voutsinos
- & Rasmus Hartmann-Petersen
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Article
| Open AccessMultiscale modelling of chromatin 4D organization in SARS-CoV-2 infected cells
In this work, the authors apply polymer models to reconstruct the 3D structure of the genome during SARS-CoV-2 infection and examine how the virus impacts key mechanisms of chromatin organization.
- Andrea M. Chiariello
- , Alex Abraham
- & Mario Nicodemi
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Article
| Open AccessStructural insights into drug transport by an aquaglyceroporin
Pentamidine and melarsoprol are drugs used to treat sleeping sickness caused by Trypanosoma brucei. Here, authors present cryo-EM structures of TbAQP2 with molecular dynamic simulations, revealing mechanisms shaping substrate specificity and drug permeation.
- Wanbiao Chen
- , Rongfeng Zou
- & Chongyuan Wang
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Article
| Open AccessDiscovering allatostatin type-C receptor specific agonists
Pesticides safeguard crops against pest infestations and mitigate associated risks. In this work, the authors develop a pesticide targeting AlstR-C of T.pityocampa pests, showing promising results without harming other insects, and advancing the development of GPCR-targeted pesticides for insect control.
- Kübra Kahveci
- , Mustafa Barbaros Düzgün
- & Necla Birgul Iyison
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Article
| Open AccessComprehensive assessment of mRNA isoform detection methods for long-read sequencing data
Recently, various computational tools have emerged for detecting mRNA isoforms using long-read sequencing data. Here, the authors systemically evaluate and compare the performance of these tools.
- Yaqi Su
- , Zhejian Yu
- & Wanlu Liu
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Article
| Open AccessFragment ion intensity prediction improves the identification rate of non-tryptic peptides in timsTOF
Immunopeptidomics is crucial for the discovery of potential immunotherapy and vaccine candidates. Here, the authors generate a ground truth timsTOF dataset to fine-tune the deep learning model Prosit, improving peptide-spectrum match rescoring by up to 3-fold during immunopeptide identification.
- Charlotte Adams
- , Wassim Gabriel
- & Kurt Boonen
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Article
| Open AccessMultiplexed bulk and single-cell RNA-seq hybrid enables cost-efficient disease modeling with chimeric organoids
IPSC-derived organoids model diseases. Multiplexed coculture and demultiplexing natural genetic barcodes aid in studying genetic effects. Here, authors introduce Vireo-bulk to deconvolve bulk RNA-seq data, quantify donor abundance and identify differentially expressed genes.
- Chen Cheng
- , Gang Wang
- & Jin Zhang
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Article
| Open AccessOptimizing differential expression analysis for proteomics data via high-performing rules and ensemble inference
In proteomics, identifying differentially expressed proteins (DEPs) is critical for uncovering biomarkers and drug targets. However, constructing optimal workflows to achieve maximal identification of DEPs is challenging. Here, the authors performed 34,576 combinatorial experiments on 24 gold standard spike-in datasets to discern optimal workflows.
- Hui Peng
- , He Wang
- & Wilson Wen Bin Goh
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Article
| Open AccessPrediction of m6A and m5C at single-molecule resolution reveals a transcriptome-wide co-occurrence of RNA modifications
The epitranscriptome holds many unexplored RNA functions, but detecting multiple modifications from one sample remains challenging. Here, authors devise a strategy combining AI and nanopore sequencing to uncover a transcriptome-wide co-occurrence of two modification types in individual RNA molecules.
- P Acera Mateos
- , A J Sethi
- & E Eyras
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Article
| Open AccessEngineering and evaluation of FXa bypassing agents that restore hemostasis following Apixaban associated bleeding
Direct oral anticoagulants (DOACs) targeting factor Xa that are used to prevent or treat thromboembolic disorders carry the risk of uncontrolled bleeding. Here, the authors present the computational design and evaluation of factor Xa-variants which can be used to reduce DOAC-associated bleeding.
- Wojciech Jankowski
- , Stepan S. Surov
- & Zuben E. Sauna
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Article
| Open AccessNetwork-based elucidation of colon cancer drug resistance mechanisms by phosphoproteomic time-series analysis
Aberrant signalling pathway activity is relevant for tumour growth and resistance to therapy, but remains hard to understand and target. Here, the authors develop VESPA, a phosphoproteomics-based machine learning algorithm that can elucidate response and adaptation to drug perturbations in cancer signalling pathways.
- George Rosenberger
- , Wenxue Li
- & Andrea Califano
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Article
| Open AccessPredicting vaccine effectiveness for mpox
Here, based on a systematic review and meta-analysis, the authors analyze the relationship between vaccine immunogenicity and vaccine protection against mpox and predict the durability of protection after vaccination. This helps inform the optimal vaccine deployment in a health emergency.
- Matthew T. Berry
- , Shanchita R. Khan
- & David S. Khoury
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Article
| Open AccessPlasma proteome profiling reveals dynamic of cholesterol marker after dual blocker therapy
Dual blockade therapy is currently being trialled for multiple tumour types, but efficacy is variable. Here, the authors use longitudinal proteomics profiling of 22 patients to develop a predictive model of therapy response.
- Jiacheng Lyu
- , Lin Bai
- & Chen Ding
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