bluuebunny/crossref_metadata_2025_split huggingface dataset:
Refined Myocardium Segmentation from CT Using a Hybrid-Fusion Transformer
Authors: Qin Shihua , Xing Fangxu , Cho Jihoon , Park Jinah , Liu Xiaofeng , Rouhollahi Amir , Farhat Elias J. Bou , Javadikasgari Hoda , Sabe Ashraf , Nezami Farhad R. , Woo Jonghye , Aganj Iman 
Published: October 2024

AbstractAccurate segmentation of the left ventricle (LV) in cardiac CT images is crucial for assessing ventricular function and diagnosing cardiovascular diseases. Common semi-automatic segmentation often includes unwanted structures, such as papil-lary muscles, due to low contrast between the LV wall and surrounding tissues. In this study, we address this issue by proposing a two-input-channel method within a Hybrid-Fusion Transformer deep-learning framework. Our method refines coarse LV masks by incorporating both the CT images and the semi-automatic rough masks as input channels, effectively removing papillary muscles. Using a small number of manually refined labels, we evaluated the method through leave-one-out cross-validation. The results demonstrate an average Dice similarity coefficient of 95.2%, outperforming models that use only CT images or rough masks. This approach reduces the need for extensive manual labeling while maintaining high segmentation accuracy and stability, making it suitable for clinical applications.
Microfluidic Formation of Ultrathin, Handleable Collagen Sheets Exhibiting Toe-heel Tensile Behavior
Authors: Zhang Yuming , Malladi Shashi , Wang Bangan , Chaikof Elliot L. , Günther Axel 
Published: October 2024

AbstractThe extracellular matrix (ECM) of cardiovascular tissues displays a non-linear, strain-dependent elastic modulus, attributed to the hierarchical organization of collagen. At low loads, these tissues exhibit compliance, permitting contraction or dilation, while at high loads, they stiffen considerably, increasing their mechanical strength by at least tenfold. Although collagen gels are widely used in 3D cell culture, tissue engineering, and biofabrication, current engineering techniques fail to replicate this hierarchical organization at the microscale. As a result, they lack both the non-linear tensile behavior and the physiologically relevant strength of native tissues. To address this limitation, we present templated collagen sheets that are 1.8 microns thin and 10 mm wide that demonstrate non-linear tensile behavior. Collagen sheets are obtained from an acidic collagen solution via a microfluidic flow focusing process, incorporating and subsequently removing emulsified oil droplets (mean diameters 2.1 microns and 5.0 microns, volume concentration 2.25%). Templated collagen sheets exhibit a two-fold increase in fibril alignment dispersion compared with non-templated ones. When assessed along their length, the Young’s modulus of templated sheets increases 62-fold at 90% failure strain, closely matching the properties of native load-bearing tissues. We anticipate that these ultrathin templated collagen sheets will have broad applications as a substrate material for the bottom-up fabrication of load-bearing biomaterials and tissue structures for in vitro applications and implantation.
Cortex-wide spatiotemporal motifs of theta oscillations are coupled to freely moving behavior
Authors: Sattler Nicholas J , Wehr Michael 
Published: October 2024

AbstractMultisensory information is combined across the cortex and assimilated into the continuous production of ongoing behavior. In the hippocampus, theta oscillations (4-12 Hz) radiate as large-scale traveling waves, and serve as a scaffold for neuronal ensembles of multisensory information involved in memory and movement-related processing. An extension of such an encoding framework across the neocortex could similarly serve to bind disparate multisensory signals into ongoing, coherent, phase-coded processes. Whether the neocortex exhibits unique large-scale traveling waves distinct from that of the hippocampus however, remains unknown. Here, using cortex-wide electrocorticography in freely moving mice, we find that theta oscillations are organized into bilaterally-symmetric spatiotemporal “modes” that span virtually the entire neocortex. The dominant mode (Mode 1) is a divergent traveling wave that originates from retrosplenial cortex and whose amplitude correlates with mouse speed. Secondary modes are asynchronous spiral waves centered over primary somatosensory cortex (Modes 2 & 3), which become prominent during rapid drops in amplitude and synchrony (null spikes) and which underlie a phase reset of Mode 1. These structured cortex-wide traveling waves may provide a scaffold for large-scale phase-coding that allows the binding of multisensory information across all the regions of the cortex.Bulleted list of key resultsCortical theta oscillations are organized into bilaterally-symmetric spatiotemporal modes that span the neocortex.The dominant mode appears as a divergent traveling wave that originates in retrosplenial cortex and is correlated with mouse speed.Secondary modes are asynchronous spiral waves centered over somatosensory cortex.Secondary modes become prominent during transient drops in synchrony that underlie a phase reset of the dominant mode.We hypothesize that spiral waves may provide a mechanism to exert large-scale phase separability, and assimilate information into ongoing multisensory processing across the neocortex.
Simultaneous observation of Pol II and potato spindle tuber viroid RNA in the nucleus by combining immunofluorescence and RNA in situ hybridization
Authors: Ma Junfei , Wang Yunhan , Folimonova Svetlana Y. , Liu Bin , Wang Ying 
Published: October 2024

AbstractRNA comprises a versatile group of biomolecules that play diverse roles in a wide range of biological processes. From synthesis to degradation, RNAs interact with cognate proteins that assist in processes such as transcription, splicing, modification, trafficking, and the execution of their functions. While numerous valuable techniques exist to study RNA-protein interactions, observing RNAs and their associated proteins simultaneously within cells remains a challenge, despite its potential to provide deeper insights into RNA-protein interactions. In this study, we adapted a modified immunofluorescence (IF) assay combined with RNA fluorescence in situ hybridization (FISH) to successfully visualize the colocalization of potato spindle tuber viroid with RNA polymerase II in the nucleus. This new method that combines IF and FISH will facilitate future studies on RNA and protein colocalization in various plant systems.
Effects of systemic oxytocin and beta-3 receptor agonist (CL 316243) treatment on body weight and adiposity in male diet-induced obese rats
Authors: Slattery Jared D. , Rambousek June R. , Tsui Edison , Honeycutt Mackenzie K. , Goldberg Matvey , Graham James L. , Wietecha Tomasz A. , Wolden-Hanson Tami , Williams Amber L. , O’Brien Kevin D. , Havel Peter J. , Blevins James E. 
Published: October 2024

AbstractPrevious studies have implicated hindbrain oxytocin (OT) receptors in the control of food intake and brown adipose tissue (BAT) thermogenesis. We recently demonstrated that hindbrain [fourth ventricle (4V)] administration of oxytocin (OT) could be used as an adjunct to drugs that directly target beta-3 adrenergic receptors (β3-AR) to elicit weight loss in diet-induced obese (DIO) rodents. What remains unclear is whether systemic OT can be used as an adjunct with the β3-AR agonist, CL 316243, to increase BAT thermogenesis and elicit weight loss in DIO rats. We hypothesized that systemic OT and β3-AR agonist (CL 316243) treatment would produce an additive effect to reduce body weight and adiposity in DIO rats by decreasing food intake and stimulating BAT thermogenesis. To test this hypothesis, we determined the effects of systemic (subcutaneous) infusions of OT (50 nmol/day) or vehicle (VEH) when combined with daily systemic (intraperitoneal) injections of CL 316243 (0.5 mg/kg) or VEH on body weight, adiposity, food intake and brown adipose tissue temperature (TIBAT). OT and CL 316243 monotherapy decreased body weight by 8.0±0.9% (P<0.05) and 8.6±0.6% (P<0.05), respectively, but OT in combination with CL 316243 produced more substantial weight loss (14.9±1.0%;P<0.05) compared to either treatment alone. These effects were associated with decreased adiposity, energy intake and elevated TIBATduring the treatment period. The findings from the current study suggest that the effects of systemic OT and CL 316243 to elicit weight loss are additive and appear to be driven primarily by OT-elicited changes in food intake and CL 316243-elicited increases in BAT thermogenesis.
LPS-induced delirium-like behavior and microglial activation in mice correlate with bispectral electroencephalography (BSEEG)
Authors: Nishiguchi Tsuyoshi , Yamanishi Kyosuke , Gorantla Nipun , Shimura Akiyoshi , Seki Tomoteru , Ishii Takaya , Aoyama Bun , Malicoat Johnny R. , Phuong Nathan James , Dye Nicole Jade , Yamanashi Takehiko , Iwata Masaaki , Shinozaki Gen 
Published: October 2024

AbstractDelirium is a multifactorial medical condition characterized by impairment across various mental functions and is one of the greatest risk factors for prolonged hospitalization, morbidity, and mortality. Research focused on delirium has proven to be challenging due to a lack of objective measures for diagnosing patients, and few laboratory models have been validated. Our recent studies report the efficacy of bispectral electroencephalography (BSEEG) in diagnosing delirium in patients and predicting patient outcomes. We applied BSEEG to validate a lipopolysaccharide (LPS)-induced mouse model of delirium. Moreover, we investigated the relationship between BSEEG score, delirium-like behaviors, and microglia activation in hippocampal dentate gyrus and cortex regions in young and aged mice. There was a significant correlation between BSEEG score and impairment of attention in young mice. Additionally, there was a significant correlation between BSEEG score and microglial activation in hippocampal dentate gyrus and cortex regions in young and aged mice. We have successfully validated the BSEEG method by showing its associations with a level of behavioral change and microglial activation in an LPS-induced mouse model of delirium. In addition, the BSEEG method was able to sensitively capture an LPS-induced delirium-like condition that behavioral tests could not capture because of a hypoactive state.
Diagnostic Efficacy of Various Imaging Modalities Across Different Stages of Prostate Cancer: A Network Meta-Analysis of Diagnostic Studies
Authors: Shi Chengdong , Yu Kai , Hu Yu , Wang Yuantao , Bu Fan , Lu Ji , Wang Weigang 
Published: October 2024

AbstractPurposeTo assess the diagnostic performance of various imaging modalities in detecting and monitoring prostate cancer across different disease stages using diagnostic test accuracy (DTA) and network meta-analysis (NMA).MethodsA systematic literature review was conducted to identify studies evaluating mpMRI, PSMA PET/CT, MRE, MRSI, BS, CT, PET, and other tracers for prostate cancer detection. Data on sensitivity, specificity, PPV, NPV, and detection rate were extracted and analyzed using NMA.ResultAcross 123 studies involving 9,371 patients, 68Ga-P16-093 PET/CT and 68Ga-PSMA-617 PET/CT showed high diagnostic accuracy in early-phase prostate cancer. For lymph node metastasis, 68Ga-PSMA-11 PET/MRI was the most sensitive. 18F-DCFPyL PET/CT had the highest specificity and PPV, while 18F-PSMA-1007 PET/CT had the highest NPV. In bone metastasis, 18F-PSMA-1007 PET/MRI excelled in sensitivity and NPV, while 18F-Fluciclovine PET/CT had the highest specificity and PPV. For biochemical recurrence, 18F-PSMA-1007 PET/CT had the highest lesion detection rate, and for different radiotracers, 18F-PSMA-1007 had the highest detection rate.ConclusionThis network meta-analysis comprehensively evaluated the diagnostic efficacy of various imaging modalities for prostate cancer across different stages. Our findings underscore the strengths and limitations of each imaging technique in detecting and staging prostate cancer.
Distinct gene regulatory networks govern hematopoietic and leukemia stem cells
Authors: Zhang Boyang , Murison Alex , Varesi Angelica , Takayama Naoya , Jin Liqing , Mbong Nathan , Schoof Erwin M. , Xie Stephanie , Mitchell Amanda , Etchin Julia , Look A. Thomas , Lupien Mathieu , Minden Mark D. , Wang Jean C.Y. , Zandstra Peter W. , Wagenblast Elvin , Dick John E. , Ng Stanley W.K. 
Published: October 2024

AbstractThe underlying gene regulatory networks (GRN) that govern leukemia stem cells (LSC) in acute myeloid leukemia (AML) and hematopoietic stem cells (HSC) are not well understood. Here, we identified GRNs by integrating gene expression (GE) and chromatin accessibility data derived from functionally defined cell populations enriched for HSC and LSC. We analyzed n=32 LSC+ and n=32 LSC-cell fractions from n=22 AML patients, along with n=7 stem and n=10 progenitor enriched cell populations sorted from human umbilical cord blood (hUCB), producing a database of n≈17,000 transcription factor (TF) regulatory interactions for hUCB-HSPC and AML. We developed an iterative algorithm that associates the degree of chromatin openness with TF binding preferences, and the GE of candidate TF and target genes within 100kb upstream of transcription start sites. A putative regulatory structure was found to be enriched in HSC-enriched cell populations, comprising TF-target gene interactions between ETS1, EGR1, RUNX2, and ZNF683 oriented in a self-reinforcing configuration. A regulatory loop comprising FOXK1 and MEIS1, rather than the 4-factor HSC subnetwork, was detected in the LSC-specific GRN. The core HSC and LSC TF networks were extended using protein-protein interaction (PPI) data to determine connectivity with interacting genes whose expression strongly associated with LSC/HSC frequency estimates, producing a database of n=103,516 PPI target pathways. The effect of perturbing genes along the identified pathways on functional HSC and LSC frequency was predicted based on statistical regression analyses. To validate GRN predictions, we used pharmacologic and CRISPR targeting, in addition to re-examining published functional data associated with several network nodes that were predicted to impact stemness. Notably, we found that inhibition of CDK6 in AML samples markedly reduced LSC numbers as assessed in de novo serial xenotransplantation studies (fold change ≈ 10), as predicted by the LSC GRN model. Additionally, in-house CRISPR-based knockdown of ETS1 resulted in a significant decrease in HSC quiescence-associated microRNA-126 expression, and increased HSC frequency. Taken together, our models provide a comprehensive view of the underlying regulatory structures governing functional human HSC and LSC. This approach has translational potential as it can be used as a high-throughput in-silico screening tool for the systematic identification of gene targets for LSC elimination and HSC expansion.
Activation of the endoplasmic reticulum stress regulator IRE1α compromises pulmonary host defenses
Authors: Sharma Amit , Heffernan Linda M. , Hoang Ky , Jeyaseelan Samithamby , Beavers William N. , Abuaita Basel H. 
Published: October 2024

SummaryThe endoplasmic reticulum (ER) stress sensor inositol-requiring enzyme 1-α (IRE1α) is associated with lung infections where innate immune cells are drivers for progression and resolution of inflammation. Yet, the role of IRE1α in pulmonary innate immune host defense during acute respiratory infection remains unexplored. Here, we found that activation of IRE1α in infected lungs compromises immunity against methicillin-resistantStaphylococcus aureus(MRSA)-induced primary and secondary pneumonia. Moreover, activation of IRE1α in MRSA-infected lungs and alveolar macrophages (AMs) leads to exacerbated production of inflammatory mediators followed by cell death. Ablation of myeloid IRE1α or global IRE1α inhibition confers protection against MRSA-induced pneumonia with improves survival, bacterial clearance, cytokine reduction, and lung injury. In addition, loss of myeloid IRE1α protects mice against MRSA-induced secondary to influenza pneumonia by promoting AM survival. Thus, activation of IRE1α is detrimental to pneumonia and therefore, it shows potential as a target to control excessive unresolved lung inflammation.
Model-Based Reinforcement Learning for Ultrasound-Driven Autonomous Microrobots
Authors: Medany Mahmoud , Piglia Lorenzo , Achenbach Liam , Mukkavilli S. Karthik , Ahmed Daniel 
Published: October 2024

AbstractAI has catalyzed transformative advancements across multiple sectors, from medical diagnostics to autonomous vehicles, enhancing precision and efficiency. As it ventures into microrobotics, AI offer innovative solutions to the formidable challenge of controlling and manipulating microrobots, which typically operate within imprecise, remotely actuated systems—a task often too complex for human operators. We implement state-of-the-art model-based reinforcement learning for autonomous control of an ultrasound-driven microrobot learning from recurrent imagined environments. Our non-invasive, AI-controlled microrobot offers precise propulsion, which efficiently learns from images in data-scarce environments. Transitioning from a pre-trained simulation environment, we achieve sample-efficient collision avoidance and channel navigation, reaching a 90% success rate in target navigation across various channels within an hour of fine-tuning. Moreover, our model initially successfully generalized in 50% of tasks in new environments, improving to over 90% with 30 minutes of further training. Furthermore, we have showcased real-time manipulation of microrobots within complex vasculatures and across stationary and physiological flows, underscoring AI’s potential to revolutionize microrobotics in biomedical applications, potentially transforming medical procedures.
Allo-Allo: Data-efficient prediction of allosteric sites
Authors: Dong Tianze , Kan Christopher , Devkota Kapil , Singh Rohit 
Published: October 2024

AbstractAllostery, a fundamental structural mechanism where ligand binding at a protein site affects protein function at another site, plays a crucial role in key drug-target proteins like GPCRs. Unfortunately, existing methods for predicting allosteric sites have limited performance– they are particularly constrained by scarce ground-truth experimental data. We introduce Allo-Allo, a data-efficient, sequence-based method that predicts allosteric sites by leveraging protein language models (PLMs). Honing in on ESM-2 attention heads that capture allosteric residue associations, Allo-Allo achieves a 67% higher AUPRC than state-of-the-art methods. Our innovative, data-efficient pipeline not only outperforms alternate, commonly-used PLM-based prediction architectures but also generalizes well. Notably, mutations in Allo-Allo-predicted sites show significant association with elevated disease risk scores from AlphaMissense, highlighting its translational potential. Beyond Allo-Allo’s biological and translational applicability, its architecture presents a powerful framework for other data-scarce problems in protein analysis.
Integrating cold hardiness and deacclimation resistance demonstrates a conserved response to chilling accumulation in grapevines
Authors: Londo Jason P , Kovaleski Al P 
Published: October 2024

AbstractTo survive the harsh conditions of winter, woody perennial species such as grapevine have adapted to use environmental cues to trigger physiological changes to induce dormancy, acquire cold hardiness, and measure the length of winter to properly time spring budbreak. Human induced climate change disrupts these cues by prolonging warm temperatures in fall, reducing the depth and consistency of midwinter, and triggering early budbreak through false spring events. We evaluated variation in dormant bud cold hardiness and chilling hour requirements of 31 different grapevine varieties over 3 years. Differential thermal analysis was used to track changes in cold hardiness and deacclimation resistance was assessed throughout the season to track dormancy progression. Results demonstrate wide variation in maximum deacclimation rate (1.03 – 2.87 °C/day) among varieties under forcing conditions. Absolute maximum rates of deacclimation show signatures of species-level responses to forcing temperatures. When integrated with variation in cold hardiness, these rates revealed a relationship between winter cold hardiness, changes in deacclimation rate and budbreak phenology. Standardizing rates among varieties as deacclimation potential demonstrated a conserved response to chilling exposure among varieties that alters our interpretation of the concept of high and low chill varieties and chilling requirement in grapevine.
Biomechanical and Compositional Changes in the Murine Uterus with Age
Authors: Domingo Mari J.E. , Vanoven Triniti N. , De Vita Raffaella , Florian Rodriguez Maria E. , Miller Kristin S. , Pence Isaac J. 
Published: October 2024

AbstractThe uterus is a hollow, fibromuscular organ involved in physiologic processes such as menstruation and pregnancy. The content and organization of extracellular matrix constituents such as fibrillar collagen dictates passive (non-contractile) biomechanical tissue function; however, how extracellular matrix composition and biomechanical function change with age in the uterus remains unknown. This study utilizes Raman spectroscopy coupled with biaxial inflation testing to investigate changes in the murine uterus with age (2-3 months, 4-6 months, 10-12 months, and 20-24 months). Linear and toe moduli significantly decreased with reproductive aging (2 to 12 months); however, moduli increased in the oldest age group (20-24 months). The optical signature of combined elastin and collagen content was significantly higher in the oldest group (20-24 month), while the glycogen contribution was the highest in the 2-3 month murine uterus. The presented workflow couples biaxial inflation testing and Raman spectroscopy, representing a critical first step to correlating biomechanics and optical signatures in the aging uterus with the potential for clinical translation. Further, this study may provide critical compositional and structure-function information regarding age-related uterine disorders.