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| Open AccessOpen-source, high performance miniature 2-photon microscopy systems for freely behaving animals
Madruga and colleagues present an open-source, miniature 2-photon microscope that can fit on a mouse’s head. Using this system, the authors perform high-resolution brain activity measurements in fine neuronal structures, which they can achieve even in conditions where the mouse is freely-moving within its cage.
- Blake A. Madruga
- , Conor C. Dorian
- & Peyman Golshani
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Article
| Open AccessScn2a-linked myelination deficits and synaptic plasticity alterations drive auditory processing disorders in an ASD mouse model
Myelin abnormalities in ASD remain poorly understood. Here authors investigate Scn2a deletion in oligodendrocytes, and report disruptions in myelin, ion channel distribution, and axonal conduction lead to abnormal synaptic plasticity and auditory hypersensitivity.
- Han-Gyu Bae
- , Wan-Chen Wu
- & Jun Hee Kim
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Article
| Open AccessSporadic ALS induced pluripotent stem cell derived neurons reveal hallmarks of TDP-43 loss of function
In this study, the authors analyzed iPSC-derived neurons from 180 ALS patients and controls, finding that TDP-43 dysfunction is variable and mirrors changes seen in postmortem brain and repairing nuclear pore damage is sufficient to reverse TDP-43 proteinopathy.
- Jeffrey D. Rothstein
- , Olivia Keeley
- & Alyssa N. Coyne
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Article
| Open AccessSynaptotagmin-1 serves as a primary Zn2+ sensor to mediate spontaneous neurotransmitter release under pathological conditions
In the pre-synapse, vesicle fusion is a key process for neurotransmitter release in the nervous system. Here authors demonstrate under pathological condition, synaptotagmin1 with Zn2+ adopts an alternative mode to regulate spontaneous neurotransmitter release.
- Yijuan Xiang
- , Lele Cui
- & Ying Lai
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Article
| Open AccessNeural function of Netrin-1 in precancerous lesions of the pancreas
The nervous system can influence cancer progression. Here, authors show in mouse models that Netrin-1 promotes sympathetic nerve remodeling in early pancreatic cancer lesions and has a protective effect against their progression.
- Hiba Haidar
- , Anaïs Bellon
- & Fanny Mann
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Article
| Open AccessWhole-exome sequencing analysis identifies risk genes for schizophrenia
Here the authors analyse rare coding variants to identify schizophrenia risk genes. Associations are reported at exome-wide significance for STAG1 and ZNF136, and at a false discovery rate of 5% for SLC6A1, PCLO, ZMYND11, BSCL2, KLC1 and CGREF1.
- Sophie L. Chick
- , Peter Holmans
- & Elliott Rees
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Article
| Open AccessAmyloid fibril structures link CHCHD10 and CHCHD2 to neurodegeneration
Lv et al. discover that homologous disordered regions of proteins linked to ALS/FTD and Parkinson’s, CHCHD10 and CHCHD2, form amyloid fibrils in vitro and that the structures of these fibrils are consistent with potential roles for them in disease.
- Guohua Lv
- , Nicole M. Sayles
- & David Eliezer
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Article
| Open AccessNeuropeptide Y neurons mediate opioid-induced itch by disinhibiting GRP-GRPR microcircuits in the spinal cord
The specific circuits mediating opioid-induced itch remain not fully understood. Here, authors reveal that morphine suppresses spinal NPY+ inhibitory neurons via μ-opioid receptors, which disinhibit GRP-GRPR circuits to trigger itching in mice.
- Qian Zeng
- , Yitong Li
- & Zilong Wang
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Article
| Open AccessCryo-EM structures of ρ1 GABAA receptors with antagonist and agonist drugs
The ρ-type GABAA receptors are potential therapeutic targets in several neurological conditions. Here, authors elucidate interactions of it with three therapeutic drugs, offering mechanistic insights and a prospective basis for further pharmaceutical development.
- Chen Fan
- , John Cowgill
- & Erik Lindahl
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Article
| Open AccessThe CCL2-CCR2 axis drives neuromuscular denervation in amyotrophic lateral sclerosis
Neuromuscular junctions (NMJs) are denervated in amyotrophic lateral sclerosis (ALS) through unknown mechanisms. Here, the authors show immune cells infiltrating muscle of ALS patients and mouse models, driven by CCL2-CCR2, which can be blocked to protect NMJs.
- Bernát Nógrádi
- , Kinga Molnár
- & Thomas H. Gillingwater
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Article
| Open AccessAberrant pace of cortical neuron development in brain organoids from patients with 22q11.2 deletion syndrome-associated schizophrenia
This study shows that brain organoids from individuals with 22q11.2 deletion syndrome and schizophrenia have delayed neuron development, linked to altered gene regulation and microRNAs, offering insight into how this deletion raises psychiatric disease risk.
- Sneha B. Rao
- , Zhixiong Sun
- & Joseph A. Gogos
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Article
| Open AccessA role for the thalamus in danger evoked awakening during sleep
The extent to which the sleeping brain can discern safety from danger is poorly understood. In mice, the authors show that centro-medial thalamic neurons detect threat-related sounds and selectively trigger awakenings during NREM, but not REM, sleep.
- Ida Luisa Boccalaro
- , Mattia Aime
- & Antoine Adamantidis
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Article
| Open AccessDifferential impacts of social isolation and enriched environment on multi-sensory brain-wide functionality and network segregation
Using evoked and resting-state fMRI, the effects of isolation and enrichment housing on sensory development in male mice were tested. Enrichment improved sensorimotor responses, while isolation impaired network segregation and olfactory function.
- Taeyi You
- , Taekwan Lee
- & Jung Hee Lee
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Article
| Open AccessEvidence accumulation in the pre-supplementary motor area and insula drives confidence and changes of mind
Decisions are typically associated with a sense of confidence and can be followed by an impulse to change our minds. Here, the authors use intracranial recordings in humans to show that confidence and changes of mind derive from a cortical process called evidence accumulation.
- Dorian Goueytes
- , François Stockart
- & Nathan Faivre
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Article
| Open AccessDual lineage origins contribute to neocortical astrocyte diversity
Astrocytes display diverse molecular and functional features in the brain, but the developmental origins of this heterogeneity are not well understood. Here, the authors show that two separate progenitor types give rise to distinct cortical astrocyte subtypes with specialized roles.
- Jiafeng Zhou
- , Ilaria Vitali
- & Riccardo Bocchi
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Article
| Open AccessSpiking dynamics of individual neurons reflect changes in the structure and function of neuronal networks
Neuronal firing shows complex dynamical patterns not captured by conventional statistics. Here, authors perform the multifractal analysis of spike trains to reveal hidden temporal structures linked to circuit connectivity, offering a tool to decode brain architecture and dynamics.
- Ruochen Yang
- , Heng Ping
- & Paul Bogdan
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Article
| Open AccessSleep drive, not total sleep amount, increases seizure risk
Sleep loss has been known to increase seizure risk since antiquity, but the underlying mechanisms remain unclear. Using fruit-fly epilepsy models, the authors show that rising “sleep drive”, not sleep duration, is what triggers seizures.
- Vishnu Anand Cuddapah
- , Cynthia T. Hsu
- & Amita Sehgal
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Article
| Open AccessA central and unified role of corticocortical feedback in parsing visual scenes
It is unclear how higher brain areas use feedback to help early visual cortex analyze complex scenes. Here, the authors show that feedback is crucial for various figure-ground percepts and involves distinct facilitatory and inhibitory signals.
- Ye Xin
- , Yin Yan
- & Wu Li
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Article
| Open AccessA dedicated skin-to-brain circuit for cool sensation in mice
The neural circuits that transmit cool signals remain not fully understood. Here, authors identify a spinal circuit in mice that transmits cool sensations from the skin to the brain, revealing a dedicated neural pathway for detecting innocuous cool temperatures.
- Hankyu Lee
- , Chia Chun Hor
- & Bo Duan
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Article
| Open AccessDistinct role of claustrum and anterior cingulate cortex bidirectional circuits in methamphetamine taking and seeking
Here, authors show both CLA and ACC as key mediators of methamphetamine (METH) use and relapse. Specifically, the CLA → ACC circuit modulates intake, while reciprocal ACC → CLA circuit drive cue-induced relapse, revealing a maladaptive positive feedback loop that perpetuates METH addiction.
- Manqing Wu
- , Miaojun Lai
- & Wenhua Zhou
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Article
| Open AccessLarge-scale RNA-Seq mining reveals ciclopirox olamine induces TDP-43 cryptic exons
TDP-43 nuclear clearance and loss-of-function, a hallmark of ALS-FTD and other neurodegenerative diseases, causes widespread inclusion of harmful cryptic exons. Here, the authors developed SnapMine to analyze cryptic exon inclusion across public RNA-seq datasets and identified that the antifungal ciclopirox olamine (CPX) induces such inclusion via heavy metal toxicity and oxidative stress.
- Irika R. Sinha
- , Parker S. Sandal
- & Jonathan P. Ling
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Article
| Open AccessNeurophysiological evidence of human hippocampal longitudinal differentiation in associative memory
This study provides direct neurophysiological evidence from over 30 human subjects showing that the anterior and posterior hippocampus are functionally distinct, with differences in theta activity linked to recollection and novelty processing.
- Tung V. To
- , David X. Wang
- & Bradley C. Lega
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Article
| Open AccessHuman hippocampal reactivation of amygdala encoding-related gamma patterns during aversive memory retrieval
Human intracranial recordings reveal that during aversive memory retrieval, memory-specific gamma activity patterns, shaped by the amygdala during encoding, are reactivated in hippocampus.
- Manuela Costa
- , Daniel Pacheco-Estefan
- & Bryan A. Strange
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Article
| Open AccessDNMT1-mediated regulation of somatostatin-positive interneuron migration impacts cortical architecture and function
The function of DNMT1 (DNA methyltransferase 1) in these subsets of immature, migrating cortical inhibitory interneurons is not fully understood. This study shows that DNMT1 regulates cortical development by orchestrating the migration of postmitotic SST+ interneurons and their signaling to cortical progenitors, with implications for proper cortical architecture and function.
- Julia Reichard
- , Philip Wolff
- & Geraldine Zimmer-Bensch
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Article
| Open AccessHomeostatic scaling of dynorphin signaling by a non-canonical opioid receptor
Li et al. identify dynorphin as an endogenous ligand for orphan receptor GPR139 introducing it as a non-canonical member of the opioid receptor family that triggers excitatory signaling to balance the inhibitory effects of opioids.
- Xiaona Li
- , Nathan D. Winters
- & Kirill A. Martemyanov
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Article
| Open AccessImpaired vasopressin neuromodulation of the lateral septum leads to social behavior deficits in Shank3B+/- male mice
This study reveals how vasopressin release in the lateral septum regulates social interaction and social aggression through distinct receptors, shedding light on the mechanisms behind autism-related social deficits.
- Maria Helena Bortolozzo-Gleich
- , Guillaume Bouisset
- & Félix Leroy
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Article
| Open AccessSmall intestinal γδ T17 cells promote SAE through STING/C1q-induced microglial synaptic pruning in male mice
Sepsis-associated encephalopathy (SAE) is a severe and often fatal consequence of sepsis. Here authors show in a mouse model of sepsis that γδ T17 cells, migrating from the small intestine to the meninges, play a pathological role via activation of STING in microglia, leading to an increase in C1q-tagged synapses, which are subsequently pruned.
- Yuming Wu
- , Yujing Zhang
- & Jiancheng Zhang
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Article
| Open AccessTaming the chaos gently: a predictive alignment learning rule in recurrent neural networks
The study presents Predictive Alignment, a local learning rule for recurrent neural networks that aligns internal network predictions with feedback. This biologically inspired method tames chaos and enables robust learning of complex patterns.
- Toshitake Asabuki
- & Claudia Clopath
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Article
| Open AccessChoroid plexus-mediated CSF secretion remains stable in aging rats via high and age-resistant metabolic activity
Choroid plexus produces the cerebrospinal fluid (CSF) that serves as the brain dispersion route for nutrients and waste products. Here, the authors show that CSF secretion remains high in aging rats with intact choroid plexus morphology, gene expression, and high metabolic rate.
- Sara D. Lolansen
- , Eszter O. Révész
- & Nanna MacAulay
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Article
| Open AccessRelating natural image statistics to patterns of response covariability in macaque primary visual cortex
Correlated neural variability is prominent in the visual cortex, yet its role in neural coding is debated. Here, the authors show that covariability is modulated by spatial context and that it encodes uncertainty in a probabilistic representation of natural scenes.
- Amirhossein Farzmahdi
- , Adam Kohn
- & Ruben Coen-Cagli
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Article
| Open AccessHamsters with long COVID present distinct transcriptomic profiles associated with neurodegenerative processes in brainstem
SARS-CoV-2 persists in the brainstem long after the initial infection has passed. Infected animals exhibit symptoms of anxiety, depression, and memory impairment as well as changes in the brain that can be related to neurodegenerative processes.
- Anthony Coleon
- , Florence Larrous
- & Guilherme Dias de Melo
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Article
| Open AccessMachine learning in Alzheimer’s disease genetics
Here the authors apply machine learning approaches to Alzheimer’s genetics, confirm known associations and suggest novel risk loci. These methods demonstrate predictive power comparable to traditional approaches, while also offering potential new insights beyond standard genetic analyses.
- Matthew Bracher-Smith
- , Federico Melograna
- & Valentina Escott-Price
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Article
| Open AccessTranscriptomic decoding of surface-based imaging phenotypes and its application to pharmacotranscriptomics
This study presents an analytic framework to link imaging-derived brain phenotypes to gene expression. In the future, this approach may facilitate in vivo pharmacotranscriptomics and the development of personalized (pharmacological) interventions.
- Christine Ecker
- , Charlotte M. Pretzsch
- & Declan G. Murphy
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Article
| Open AccessEarly intervention with electrical stimulation reduces neural damage after stroke in non-human primates
The therapeutic effects of acute neuromodulation after stroke remain less studied. Here, authors demonstrate that early electrical stimulation after ischemic stroke reduces excessive neural activity and limits tissue damage in primates, supporting the potential of brain stimulation as an acute treatment strategy for stroke.
- Jasmine Zhou
- , Karam Khateeb
- & Azadeh Yazdan-Shahmorad
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Article
| Open AccessMeasurement characteristics and genome-wide correlates of lifetime brain atrophy estimated from a single MRI
A single MRI scan can provide reliable estimates of human lifetime brain atrophy, helping overcome lifespan data collection challenges. This may enhance genetic studies of late-life neurodegeneration and reveal new insights into its underlying mechanisms.
- Anna E. Fürtjes
- , Isabelle F. Foote
- & Simon R. Cox
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Article
| Open AccessA human brain network linked to restoration of consciousness after deep brain stimulation
In people with severe brain injuries, stimulation restored consciousness by engaging a deep brain circuit for wakefulness—revealing a target that may also guide treatment in stroke and epilepsy.
- Aaron E. L. Warren
- , Marina Raguž
- & John D. Rolston
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Article
| Open AccessPrdm16 regulates the postnatal fate of embryonic radial glia via Vcam1-dependent mechanisms
The molecular mechanisms that regulate postnatal termination of neurogenesis remain poorly described. Here authors report Prdm16 deletion leads to the retention of radial glia in adulthood and prolonged postnatal neuroblast production.
- Jiwen Li
- , Marlesa I. Godoy
- & Ye Zhang
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Article
| Open AccessSynaptic enrichment of pSer129 alpha-synuclein correlates with dopaminergic denervation in early-stage Parkinson’s disease
α-Synuclein accumulation in putaminal synapses is hypothesised to drive Parkinson’s disease progression. This study demonstrates synaptic pSer129 α-synuclein enrichment in early-stage Parkinson’s disease, and its link with dopaminergic denervation and cortical Lewy body pathology.
- Irene Frigerio
- , Martino L. Morella
- & Wilma DJ van de Berg
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Article
| Open AccessSomatostatin-expressing interneurons induce early NO-driven and late specific astrocyte-mediated vasodilation
The precise role of somatostatin-expressing interneurons in regulating hemodynamics remains unclear. Here, authors find that the activation of these neurons induces astrocytic calcium signaling, which subsequently drives delayed vasodilation and enhances layer-specific fMRI signals in response to prolonged sensory stimulation.
- Thanh Tan Vo
- , Won Beom Jung
- & Seong-Gi Kim
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Article
| Open AccessAI-guided patient stratification improves outcomes and efficiency in the AMARANTH Alzheimer’s Disease clinical trial
Alzheimer’s disease (AD) drug discovery has been hampered by patient heterogeneity, and the lack of sensitive tools for precise stratification. Here, the authors show an AI-guided model enhances patient stratification, improving outcomes and increasing efficiency in the AMARANTH trial.
- Delshad Vaghari
- , Gayathri Mohankumar
- & Zoe Kourtzi
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Article
| Open AccessDouble dissociation of dynamic and static face perception provides causal evidence for a third visual pathway
The study shows a double dissociation between static and dynamic face perception in 108 patients with focal lesions, providing direct causal evidence for a third visual pathway via the posterior superior temporal sulcus (pSTS).
- A. T. Prabhakar
- , Anupama Roy
- & Marta I. Garrido
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Article
| Open AccessHuman spinal cord activation during filling and emptying of the bladder
Here, the authors used functional ultrasound imaging to map human spinal cord activity during urodynamically controlled micturition, showing that blood flow closely tracks bladder pressure and offering new insights into spinal cord regulation of micturition.
- Kofi A. Agyeman
- , Darrin J. Lee
- & Vassilios N. Christopoulos
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Article
| Open AccessParadoxical mTORC1-Dependent microRNA-mediated Translation Repression in the Nucleus Accumbens of Male Mice Consuming Alcohol Attenuates Glycolysis
Dysregulation of mTORC1 function is linked to various pathological conditions, including addiction. In this study, the authors show that mTORC1 activation in the nucleus accumbens of mice consuming excessive alcohol triggers translational repression through microRNA machinery, which in turn suppresses glycolysis and increases alcohol intake.
- Yann Ehinger
- , Sophie Laguesse
- & Dorit Ron
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Article
| Open AccessA neurofunctional signature of affective arousal generalizes across valence domains and distinguishes subjective experience from autonomic reactivity
Using fMRI, this study developed a brain signature for affective arousal that demonstrates high sensitivity across valence while remaining distinct from autonomic arousal and wakefulness, offering broad applications.
- Ran Zhang
- , Xianyang Gan
- & Benjamin Becker
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Article
| Open AccessGut microbiota and brain-resident CD4+ T cells shape behavioral outcomes in autism spectrum disorder
Using a germ-free BTBR mouse model of ASD-like behaviors, here the researchers demonstrated that the absence of gut microbiota significantly reduced social deficits, repetitive behaviors, and neuroinflammation.
- John Chulhoon Park
- , Min-A Sim
- & Sin-Hyeog Im
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Article
| Open AccessA tactile discrimination task to study neuronal dynamics in freely-moving mice
Task paradigms allowing studies on the core ethological function of the whiskers are lacking. Authors here present a task for freely moving mice that enables the study of how the brain processes touch and learns. The setup combines behavior, electrophysiology, and imaging, offering insights into naturalistic sensory and decision-making processes.
- Filippo Heimburg
- , Nadin Mari Saluti
- & Alexander Groh
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Article
| Open AccessA neuromorphic processor with on-chip learning for beyond-CMOS device integration
The authors developed a neuromorphic chip with on-chip learning and support for diverse memory devices. It bridges brain-inspired computing and emerging tech, enabling efficient, flexible testing and advancing next-gen neuromorphic architectures.
- Hugh Greatorex
- , Ole Richter
- & Elisabetta Chicca
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Article
| Open AccessDirect entorhinal control of CA1 temporal coding
Temporal coding in the hippocampus is thought to be key for memory and predictions. Here, the authors show that blocking one entorhinal input affects two aspects of hippocampal spike timing - phase precession and sequences - in opposing fashions, suggesting a specific network architecture.
- Matteo Guardamagna
- , Oscar Chadney
- & Francesco P. Battaglia
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Article
| Open AccessNeural dynamics of spontaneous memory recall and future thinking in the continuous flow of thoughts
During spontaneous thought, ideas including memories and imagined futures flow from one to another. This study shows that the brain’s default and control networks respond to these transitions and shape the variability and stability of thoughts.
- Haowen Su
- , Xian Li
- & Hongmi Lee
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