bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myocardial Elasticity Imaging Correlates with Histopathology in a Model of Anthracycline-Induced Cardiotoxicity
Authors: Miller Caroline E. , Jordan Jennifer H. , Thomas Alexandra , Friday Sarah R. , Meléndez Giselle C. , Weis Jared A. 
Published: October 2023

AbstractBackgroundThere is considerable focus on developing strategies for identifying subclinical cardiac decline prior to cardiac failure. Myocardial tissue elasticity changes may precede irreversible cardiac damage, providing promise for an early biomarker for cardiac decline. Biomarker strategies are of particular interest in cardio-oncology due to cardiotoxic effects of anti-neoplastic therapies, particularly anthracycline-based chemotherapeutics. Current clinical methods for diagnosing cardiotoxicity are too coarse to identify cardiac decline early enough for meaningful therapeutic intervention, or too cumbersome for clinical implementation.MethodsUtilizing changes in myocardial elasticity as a biomarker for subclinical cardiac decline, we developed a biomechanical model-based elasticity imaging methodology (BEIM) to estimate spatial maps of left ventricle (LV) myocardial elasticity. In this study, we employ this methodology to assess changes in LV elasticity in a non-human primate model of doxorubicin-induced cardiotoxicity. Cardiac magnetic resonance imaging of five African Green monkeys was acquired at baseline prior to doxorubicin administration, 6-weeks, and 15-weeks after final doxorubicin dose and histopathological samples of the LV were taken at 15-weeks after final doxorubicin dose. Spatial elasticity maps of the mid-short axis plane of the LV were estimated at each image acquisition. Global and regional LV elasticity were calculated and changes between imaging time points was assessed. LV elasticity at baseline and final time point were compared to cardiomyocyte size and collagen volume fraction measurements calculated from histopathological staining of archived tissue bank samples and study endpoint tissue samples utilizing Pearson’s correlation coefficients.ResultsWe identify significant changes in LV elasticity between each imaging time point both globally and regionally. We also demonstrate strong correlation between LV elasticity and cardiomyocyte size and collagen volume fraction measurements. Results indicate that LV elasticity estimates calculated using BEIM correlate with histopathological changes that occur due to doxorubicin administration, validating LV elasticity solutions and providing significant promise for use of BEIM to non-invasively elucidate cardiac injury.ConclusionsThis methodology can show progressive changes in LV elasticity and has potential to be a more sensitive indicator of elasticity changes than current clinical measures of cardiotoxicity. LV elasticity may provide a valuable biomarker for cardiotoxic effects of anthracycline-based chemotherapeutics and cardiac disease detection.
Genetic ablation of neuronal mitochondrial calcium uptake halts Alzheimer’s disease progression
Authors: Jadiya Pooja , Kolmetzky Devin W. , Tomar Dhanendra , Thomas Manfred , Cohen Henry M. , Khaledi Salman , Garbincius Joanne F. , Hildebrand Alycia N. , Elrod John W. 
Published: October 2023

AbstractAlzheimer’s disease (AD) is characterized by the extracellular deposition of amyloid beta, intracellular neurofibrillary tangles, synaptic dysfunction, and neuronal cell death. These phenotypes correlate with and are linked to elevated neuronal intracellular calcium (iCa2+) levels. Recently, our group reported that mitochondrial calcium (mCa2+) overload, due to loss ofmCa2+efflux capacity, contributes to AD development and progression. We also noted proteomic remodeling of the mitochondrial calcium uniporter channel (mtCU) in sporadic AD brain samples, suggestive of alteredmCa2+uptake in AD. Since the mtCU is the primary mechanism for Ca2+uptake into the mitochondrial matrix, inhibition of the mtCU has the potential to reduce or preventmCa2+overload in AD. Here, we report that neuronal-specific loss of mtCU-dependentmCa2+uptake in the 3xTg-AD mouse model of AD reduced Aβ and tau-pathology, synaptic dysfunction, and cognitive decline. Knockdown ofMcuin a cellular model of AD significantly decreased matrix Ca2+content, oxidative stress, and cell death. These results suggest that inhibition of neuronalmCa2+uptake is a novel therapeutic target to impede AD progression.
Divergent changes in PBN excitability in a mouse model of neuropathic pain
Authors: Torruella-Suárez María L , Neugebauer Benjamin , Flores-Felix Krystal , Keller Asaf , Carrasquillo Yarimar , Cramer Nathan 
Published: October 2023

AbstractThe transition from acute to chronic pain involves maladaptive plasticity in central nociceptive pathways. Growing evidence suggests that changes within the parabrachial nucleus (PBN), an important component of the spino–parabrachio–amygdaloid pain pathway, are key contributors to the development and maintenance of chronic pain. In animal models of chronic pain, PBN neurons become sensitive to normally innocuous stimuli and responses to noxious stimuli become amplified and more often produce after-discharges that outlast the stimulus. Usingex vivoslice electrophysiology and two mouse models of neuropathic pain, sciatic cuff and chronic constriction of the infraorbital nerve (CCI-ION), we find that changes in the firing properties of PBN neurons and a shift in inhibitory synaptic transmission may underlie this phenomenon. Compared to PBN neurons from shams, a larger proportion of PBN neurons from mice with a sciatic cuff were spontaneously active at rest, and these same neurons showed increased excitability relative to shams. In contrast, quiescent PBN neurons from cuff mice were less excitable than those from shams. Despite an increase in excitability in a subset of PBN neurons, the presence of after-discharges frequently observedin vivowere largely absentex vivoin both injury models. However, GABAB-mediated presynaptic inhibition of GABAergic terminals is enhanced in PBN neurons after CCI-ION. These data suggest that the amplified activity of PBN neurons observed in rodent models of chronic pain arise through a combination of changes in firing properties and network excitability.Significance StatementHyperactivity of neurons in the parabrachial nucleus (PBN) is causally linked to exaggerated pain behaviors in rodent models of chronic pain but the underlying mechanisms remain unknown. Using two mouse models of neuropathic pain, we show the intrinsic properties of PBN neurons are largely unaltered following injury. However, subsets of PBN neurons become more excitable and GABABreceptor mediated suppression of inhibitory terminals is enhanced after injury. Thus, shifts in network excitability may be a leading factor in injury induced potentiation of PBN activity.
Numerical simulation and analysis of droplet formation within an amphiphilic particle
Authors: Song Xinpei , Destgeer Ghulam 
Published: October 2023

ABSTRACTAn instrument-free particle-templated droplet formation can be achieved upon simple mixing of amphiphilic particles with aqueous and oil phases in a well plate by using a common lab pipette. Here, a two-dimensional, two-phase flow model was established using a finite element method to mimic the droplet formation within a concentric amphiphilic particle, which consisted of an outer hydrophobic layer and an inner hydrophilic layer. Immiscible water and oil phases selectively interacted with the hydrophilic and hydrophobic layers of the particle, respectively, to form an isolated aqueous compartment within a cavity. Three extreme models were also simulated, including completely hydrophilic, completely hydrophobic, and oppositely amphiphilic particle, which indicated that a right order of the particle layers was necessary to capture the droplet inside the cavity. Moreover, we performed a systematic study of particle-templated droplet formation by varying the individual layer thicknesses of particle, particle height, interfacial tension between water and oil, contact angle of interface with different surfaces, velocity of incoming oil media, and distance between neighboring particles. The volume fraction of water droplet trapped within the target cavity region was calculated to characterize the droplet formation. Our work will help to optimize the particle fabrication process, predict the experiment droplet formation, and explain the physical mechanism underlying compartmentalization phenomena.
Scalable distance-based phylogeny inference using divide-and-conquer
Authors: Arvestad Lars 
Published: October 2023

AbstractDistance-based methods for inferring evolutionary trees are important subroutines in computational biology, sometimes as a first step in a statistically more robust phylogenetic method. The most popular method is Neighbor Joining, mainly to to its relatively good accuracy, but Neighbor Joining has a cubic time complexity, which limits its applicability on larger datasets. Similar but faster algorithms have been suggested, but the overall time complexity remains essentially cubic as long as the input is a distance matrix. This paper investigates a randomized divide-and-conquer heuristic,dnctree, which selectively estimates pairwise sequence distances and infers a tree by connecting increasingly large subtrees. The divide-and-conquer approach avoids computing all pairwise distances and thereby saves both time and memory. The time complexity is at worst quadratic, and seems to scale likeO(nlgn) on average. A simple Python implementation,dnctree, available on GitHub and PyPI.org, has been tested and we show that it is a scalable solution. In fact, it is applicable to very large datasets even as plain Python program.
Reassessing the Role of Foot Power in Human Gait
Authors: Yetman Quinn , Welte Lauren , Shimizu Aidan , Rainbow Michael J 
Published: October 2023

AbstractThe foot acts as the primary interface to the ground during bipedal locomotion. It absorbs and returns energy over stance as the longitudinal arch deforms and recoils. The term ‘arch recoil’ evokes the concept that the foot’s returned energy directly propels the centre of mass forward by lifting the talus. However, recent work has shown that arch recoil does not directly drive the body forward; instead, it lowers and posteriorly tilts the talus, putting it into a more favourable position for upright gait. Here, we aim to supply a kinetic explanation for this mechanism. We applied the unified deformable power approach to highly accurate talus kinematics from biplanar videoradiography and force plate measurements to measure the power absorbed/produced by the foot. We coupled these measurements with a simple mathematical model that allowed us to restrict rotation and linear actuation of the talus caused by the recoil of the arch to demonstrate that positive foot power primarily contributes to posteriorly tilting the talus. This suggests the role of positive foot power during propulsion is to keep the talocrural surface in a more favourable position for upright gait rather than directly propelling the centre of mass forwards. These findings highlight that arch mobility during push-off is critical for allowing the ankle to directly propel the body forward and upward during the propulsive phase of gait.
Designing efficient randstrobes for sequence similarity analyses
Authors: Karami Moein , Mohammadi Aryan Soltani , Martin Marcel , Ekim Barış , Shen Wei , Guo Lidong , Xu Mengyang , Pibiri Giulio Ermanno , Patro Rob , Sahlin Kristoffer 
Published: October 2023

AbstractSubstrings of lengthk, commonly referred to ask-mers, play a vital role in sequence analysis, reducing the search space by providing anchors between queries and references. However,k-mers are limited to exact matches between sequences. This has led to alternative constructs, such as spacedk-mers, that can match across substitutions. We recently introduced a class of new constructs,strobemers, that can match across substitutions and smaller insertions and deletions.Randstrobes, the most sensitive strobemer proposed in [18], has been incorporated into several bioinformatics applications such as read classification, short read mapping, and read overlap detection. Randstrobes are constructed by linking togetherk-mers in a pseudo-random fashion and depend on a hash function, alink function, and a comparator for their construction. Recently, we showed that the more random this linking appears (measured in entropy), the more efficient the seeds for sequence similarity analysis. The level of pseudo-randomness will depend on the hashing, linking, and comparison operators. However, no study has investigated the efficacy of the underlying operators to produce randstrobes.In this study, we propose several new construction methods. One of our proposed methods is based on a Binary Search Tree (BST), which lowers the time complexity and practical runtime to other methods for some parametrizations. To our knowledge, we are also the first to describe and study the types of biases that occur during construction. We designed three metrics to measure the bias. Using these new evaluation metrics, we uncovered biases and limitations in previous methods and showed that our proposed methods have favorable speed and sampling uniformity to previously proposed methods. Lastly, guided by our results, we change the seed construction in strobealign, a short-read mapper, and find that the results change substantially. Also, we suggest combining the two versions to improve accuracy for the shortest reads in our evaluated datasets. Our evaluation highlights sampling biases that can occur and provides guidance on which operators to use when implementing randstrobes.
Endocannabinoids and their receptors modulate endometriosis pathogenesis and immune response
Authors: Lingegowda Harshavardhan , Zutautas Katherine B , Wei Yuhong , Yolmo Priyanka , Sisnett Danielle J , McCallion Alison , Koti Madhuri , Tayade Chandrakant 
Published: October 2023

AbstractEndometriosis (EM), characterized by the presence of endometrial-like tissue outside the uterus, is the leading cause of chronic pelvic pain and infertility in females of reproductive age. Despite its high prevalence, the molecular mechanisms underlying EM pathogenesis remain poorly understood. The endocannabinoid system (ECS) is known to influence several cardinal features of this complex disease including pain, vascularization, and overall lesion survival, but the exact mechanisms are not known. Utilizing CNR1 knockout (k/o), CNR2 k/o and wild type (WT) mouse models of EM, we reveal contributions of ECS and these receptors in disease initiation, progression, and immune modulation. Particularly, we identified EM-specific T cell dysfunction in the CNR2 k/o mouse model of EM. We also demonstrate the impact of decidualization- induced changes on ECS components, and the unique disease-associated transcriptional landscape of ECS components in EM. Imaging Mass Cytometry (IMC) analysis revealed distinct features of the microenvironment between CNR1, CNR2, and WT genotypes in the presence or absence of decidualization. This study, for the first time provides an in-depth analysis of the involvement of the ECS in EM pathogenesis and lays the foundation for the development of novel therapeutic interventions to alleviate the burden of this debilitating condition.
Development of an MR-guided focused ultrasound (MRgFUS) lesioning approach for small and deep structures in the rat brain
Authors: Cornelssen Carena , Payne Allison , Parker Dennis , Alexander Matthew , Merrill Robb , Senthilkumar Sharayu , Christensen Jacob , Wilcox Karen S. , Odéen Henrik , Rolston John D. 
Published: October 2023

AbstractObjectiveHigh-intensity magnetic resonance-guided focused ultrasound (MRgFUS) is a noninvasive therapy to lesion brain tissue, used clinically in patients and preclinically in several animal models. Challenges with focused ablation in rodent brains can include skull and near-field heating and accurately targeting small and deep brain structures. We overcame these challenges by creating a novel method consisting of a craniectomy skull preparation, a high-frequency transducer (3 MHz) with a small ultrasound focal spot, a transducer positioning system with an added manual adjustment of ∼0.1 mm targeting accuracy, and MR acoustic radiation force imaging for confirmation of focal spot placement.MethodsThe study consisted of two main parts. First, two skull preparation approaches were compared. A skull thinning approach (n=7 lesions) was compared to a craniectomy approach (n=22 lesions), which confirmed a craniectomy was necessary to decrease skull and near-field heating. Second, the two transducer positioning systems were compared with the fornix chosen as a subcortical ablation target. We evaluated the accuracy of targeting using a high-frequency transducer with a small ultrasound focal spot and MR acoustic radiation force imaging.ResultsComparing a motorized adjustment system (∼1 mm precision, n=17 lesions) to the motorized system with an added micromanipulator (∼0.1 mm precision, n=14 lesions), we saw an increase in the accuracy of targeting the fornix by 133%. The described work allows for repeatable and accurate targeting of small and deep structures in the rodent brain, such as the fornix, enabling the investigation of neurological disorders in chronic disease models.
KmerSV: a visualization and annotation tool for structural variants using Human Pangenome derived k-mers
Authors: Meng Qingxi , Ji Hanlee P. , Lee HoJoon 
Published: October 2023

AbstractSummaryKmerSV is a visualization and annotation tool for structural variants (SVs). It can be applied to assembly contigs or long-read sequences. Using k-mers it rapidly generates images and provides genome features of SVs. As an important feature, it utilizes the new Human Pangenome reference which provide haploid specific assemblies, addresses limitations in prior references and improves the discovery of SVs.Availability and implementationKmerSV is implemented in Python and available at github.com/sgtc-stanford/kmerSV
Edge Community Entropy is a Novel Neural Correlate of Aging and Moderator of Fluid Cognition
Authors: Shankar Anita , Tanner Jacob , Mao Tianrui , Betzel Richard , Prakash Ruchika Shaurya 
Published: October 2023

AbstractDecreased neuronal specificity of the brain in response to cognitive demands (i.e., neural dedifferentiation) has been implicated in age-related cognitive decline. Investigations into functional connectivity analogues of these processes have focused primarily on measuring segregation of nonoverlapping networks at rest. Here, we used an edge-centric network approach to derive entropy, a measure of nodal specialization, from spatially overlapping communities during cognitive task fMRI. Using Human Connectome Project Lifespan data (713 participants, 36-100 years old), we characterized a pattern of nodal despecialization differentially affecting the medial temporal lobe and limbic, visual, and subcortical systems. Global entropy uniquely covaried with age when controlling for network segregation. Importantly, relationships between both metrics and fluid cognition were age-dependent, although entropy’s relationship with cognition was specific to older adults. These results suggest entropy is a potentially important metric for examining how neurological processes in aging affect functional specialization at the nodal, network, and whole-brain level.
Inflammatory stress-mediated chromatin changes underlie dysfunction in endothelial cells
Authors: Liu Haibo , Caliz Amada D. , Learnard Heather , Koupenova Milka , Keaney John F. , Kant Shashi , Zhu Lihua Julie , Vertii Anastassiia 
Published: October 2023

ABSTRACTInflammatory stresses underlie endothelial dysfunction and contribute to the development of chronic cardiovascular disorders such as atherosclerosis and vascular fibrosis. The initial transcriptional response of endothelial cells to pro-inflammatory cytokines such as TNF-alpha is well established. However, very few studies uncover the effects of inflammatory stresses on chromatin architecture. We used integrative analysis of ATAC-seq and RNA-seq data to investigate chromatin alterations in human endothelial cells in response to TNF-alpha and febrile-range heat stress exposure. Multi-omics data analysis suggests a correlation between the transcription of stress-related genes and endothelial dysfunction drivers with chromatin regions exhibiting differential accessibility. Moreover, microscopy identified the dynamics in the nuclear organization, specifically, the changes in a subset of heterochromatic nucleoli-associated chromatin domains, the centromeres. Upon inflammatory stress exposure, the centromeres decreased association with nucleoli in a p38-dependent manner and increased the number of transcripts from pericentromeric regions. Overall, we provide two lines of evidence that suggest chromatin alterations in vascular endothelial cells during inflammatory stresses.
Translating electrophysiological signatures of awareness into thalamocortical mechanisms by inverting systems-level computational models across arousal states
Authors: Medel Vicente , Muller Eli J. , Munn Brandon R. , Casey Cameron , Sanders Robert D. , Shine James M. 
Published: October 2023

AbstractWhile consciousness never fades during wakefulness, there is a paradoxical coexistence of consciousness during dreaming states. It’s also possible for sensory awareness to be either present or absent when awakened from seemingly-identical states of sedation and anaesthesia. Traditionally, these states have been characterised in terms of their electroencephalographic neural correlates, however, without clear underlying neurobiological mechanisms. To bridge this gap, we invert a validated neural mass model of the corticothalamic system using scalp EEG collected during nonlinear transitions in conscious experience and sensory awareness across varying depths of dexmedetomidine sedation. We found that a decline in conscious experience and sensory awareness with dexmedetomidine was associated with a decrease in the engagement of excitatory thalamocortical loop resonances, along with an increase in inhibitory intrathalamic loop gains. These findings shed light into the neural mechanisms of conscious experience and sensory awareness, and explain how it fades across arousal states, bridging the gap between the neural correlates of consciousness and its underlying systems-level thalamocortical mechanisms.