bluuebunny/crossref_metadata_2025_split huggingface dataset:
INCREASED PLATELET MITOCHONDRIAL FUNCTION CORRELATES WITH CLOT STRENGTH IN A RODENT FRACTURE MODEL
Authors: Littlejohn James Blake , Grenn Emily Evans , Carter Kristen T. , Palei Ana C. , Spradley Frank T. , Hosler Jonathan P. , Hoang Ngoc H. , Edwards Kristin S. , Kutcher Matthew E. 
Published: November 2023

Abstract

Background
Thromboelastographic measures of clot strength increase early after injury, portending higher risks for thromboembolic complications during recovery. Understanding the specific role of platelets is challenging due to a lack of clinically relevant measures of platelet function. Platelet mitochondrial respirometry may provide insight to global platelet function, but has not yet been correlated with functional coagulation studies.

Methods
Wistar rats underwent anesthesia and either immediate sacrifice for baseline values [n = 6] or (1) bilateral hindlimb orthopedic injury [n = 12], versus (2) sham anesthesia [n = 12] with terminal phlebotomy/hepatectomy after 24 hours. High resolution respirometry was used to measure basal respiration, mitochondrial leak, maximal oxidative phosphorylation, and Complex IV activity in intact platelets; Complex-I and Complex-II driven respiration was measured in isolated liver mitochondria. Results were normalized to platelet number and protein mass, respectively. Citrated native thromboelastography (TEG) was performed in triplicate.

Results
Citrated native TEG maximal amplitude (MA) was significantly higher (81.0 ± 3.0 vs. 73.3 ± 3.5 mm, p < 0.001) in trauma compared to sham rats 24 hours after injury. Intact platelets from injured rats had higher basal oxygen consumption (17.7 ± 2.5 vs. 15.1 ± 3.2 pmol/s*108 cells, p = 0.045), with similar trends in mitochondrial leak rate (p = 0.19) when compared to sham animals. Overall, platelet basal respiration significantly correlated with TEG-MA (r = 0.44, p = 0.034). As a control for sex-dependent systemic mitochondrial differences, females displayed higher liver mitochondria Complex-I driven respiration (895.6 ± 123.7 vs. 622.1 ± 48.7 mmol e-/min/mg protein, p = 0.02); as a control for systemic mitochondrial effects of injury, no liver mitochondrial respiration differences were seen.

Conclusions
Platelet mitochondrial basal respiration is increased after injury and correlates with clot strength in this rodent hindlimb fracture model. Several mitochondrial-targeted therapeutics exist in common use that are underexplored but hold promise as potential antithrombotic adjuncts that can be sensitively evaluated in this preclinical model.
SIRT1 downregulation in pneumonia is associated with an immature neutrophil response and increased disease severity
Authors: Labiner Hanna E. , Sas Kelli M. , Hoying Joseph , Sepeda Jesse A. , Wolf Nick , Perez Emma C. , Sas Andrew R. , Sims Carrie A. 
Published: November 2023

BACKGROUND
Pneumonia remains a common complication in trauma patients. Sirtuin 1 (SIRT1) is an anti-inflammatory NAD+-dependent deacetylase that has been shown to reduce the severity of ARDS in polymicrobial sepsis. The impact of SIRT1 in acute pneumonia, however, remains unknown. We hypothesized that SIRT1 deletion in pneumonia would worsen the inflammatory response and clinical severity, and that increased SIRT1 expression would be protective.

METHODS
Ten- to 14-week-old male and female SIRT1 knockout (S1KO) mice, SIRT1 overexpressor (S1OE) mice, and their wildtype (WT) littermates underwent intra-tracheal inoculation with Pseudomonas aeruginosa. Rectal temperature was recorded, SIRT1 lung protein was quantified by western blotting, Sirt1 mRNA was measured by qPCR, and lung leukocyte subpopulations were analyzed by flow cytometry. Data were analyzed by one-way ANOVA using Prism software.

RESULTS
Pneumonia created a functional SIRT1 knockdown in the lungs of WT mice by 4 hours, resulting in comparable SIRT1 levels and temperatures to the S1KO mice by 12 hours. Pneumonia also partially reduced SIRT1expression in S1OE mice, but S1OE mice still had improved thermoregulation 12 hours after pneumonia. In all groups, Sirt1 mRNA expression was not affected by infection. Sirtuin 1 deletion was associated with decreased neutrophil infiltration in the lung, as well as a shift toward a more immature neutrophil phenotype. SIRT1 deletion was also associated with decreased myeloperoxidase-positive neutrophils in the lungs following pneumonia, indicating decreased neutrophil activity. S1OE mice had no change in lung leukocyte subpopulations when compared to WT.

CONCLUSION
Pneumonia creates a functional SIRT1 knockdown in mice. SIRT1 deletion altered the early inflammatory cell response to pneumonia, resulting in a neutrophil response that would be less favorable for bacterial clearance. Despite overexpression of SIRT1, S1OE mice also developed low SIRT1 levels and exhibited only minimal improvement. This suggests increasing SIRT1 transcription is not sufficient to overcome pneumonia-induced downregulation and has implications for future treatment options. Targeting SIRT1 through increasing protein stability may promote a more efficient inflammatory cell response to pneumonia, thereby preventing subsequent lung injury.
Intraoperative Monitoring of the External Urethral Sphincter Reflex: A Novel Adjunct to Bulbocavernosus Reflex Neuromonitoring for Protecting the Sacral Neural Pathways Responsible for Urination, Defecation and Sexual Function
Authors: Silverstein Justin W. , Block Jon , Olmsted Zachary T. , Green Ross , Pieters Thomas , Babarevech Kristiana , Ballas-Williamson Alicia , Skinner Stanley A. , Sciubba Daniel M. , Larry Lo Sheng-Fu 
Published: November 2023

Purpose:
Intraoperative bulbocavernosus reflex neuromonitoring has been utilized to protect bowel, bladder, and sexual function, providing a continuous functional assessment of the somatic sacral nervous system during surgeries where it is at risk. Bulbocavernosus reflex data may also provide additional functional insight, including an evaluation for spinal shock, distinguishing upper versus lower motor neuron injury (conus vs. cauda syndromes) and prognosis for postoperative bowel and bladder function. Continuous intraoperative bulbocavernosus reflex monitoring has been utilized to provide the surgeon with an ongoing functional assessment of the anatomical elements involved in the S2–S4 mediated reflex arc including the conus, cauda equina and pudendal nerves. Intraoperative bulbocavernosus reflex monitoring typically includes the electrical activation of the dorsal nerves of the genitals to initiate the afferent component of the reflex, followed by recording the resulting muscle response using needle electromyography recordings from the external anal sphincter.

Methods:
Herein we describe a complementary and novel technique that includes recording electromyography responses from the external urethral sphincter to monitor the external urethral sphincter reflex. Specialized foley catheters embedded with recording electrodes have recently become commercially available that provide the ability to perform intraoperative external urethral sphincter muscle recordings.

Results:
We describe technical details and the potential utility of incorporating external urethral sphincter reflex recordings into existing sacral neuromonitoring paradigms to provide redundant yet complementary data streams.

Conclusions:
We present two illustrative neurosurgical oncology cases to demonstrate the utility of the external urethral sphincter reflex technique in the setting of the necessary surgical sacrifice of sacral nerve roots.
The Cardiac Calcium Handling Machinery is Remodeled in Friedreich’s Ataxia
Authors: Czornobil Roman , Abou-Assali Obada , Remily-Wood Elizabeth , Lynch David R , Noujaim Sami F. , Chidipi Bojjibabu 
Published: November 2023

AbstractBackgroundFriedreich’s ataxia (FA) is an inherited neurodegenerative disorder that causes progressive nervous system damage resulting in impaired muscle coordination. FA is the most common autosomal recessive form of ataxia and is caused by an expansion of the DNA triplet guanine–adenine–adenine (GAA) in the first intron of the Frataxin gene (FXN), located on chromosome 9q13. In the unaffected population, the number of GAA repeats ranges from 6 to 27 repetitions. In FA patients, GAA repeat expansions range from 44 to 1,700 repeats which decreases frataxin protein expression. Frataxin is a mitochondrial protein essential for various cellular functions, including iron metabolism. Reduced frataxin expression is thought to negatively affect mitochondrial iron metabolism, leading to increased oxidative damage. Although FA is considered a neurodegenerative disorder, FA patients display heart disease that includes hypertrophy, heart failure, arrhythmias, conduction abnormalities, and cardiac fibrosis.ObjectiveIn this work, we investigated whether abnormal Ca2+handling machinery is the molecular mechanism that perpetuates cardiac dysfunction in FA.MethodsWe used the frataxin knock-out (FXN-KO) mouse model of FA as well as human heart samples from donors with FA and from unaffected donors. ECG and echocardiography were used to assess cardiac function in the mice. Expression of calcium handling machinery proteins was assessed with proteomics and western blot. In left ventricular myocytes from FXN-KO and FXN-WT mice, the IonOptix system was used for calcium imaging, the seahorse assay was utilized to measure oxygen consumption rate (OCR), and confocal imaging was used to quantify the mitochondrial membrane potential (Δψm) and reactive oxygen species (ROS).ResultsWe found that major contractile proteins, including SERCA2a and Ryr2, were downregulated in human left ventricular samples from deceased donors with FA compared to unaffected donors, similar to the downregulation of these proteins in the left ventricular tissue from FXN-KO compared to FXN-WT. On the ECG, the RR, PR, QRS, and QTc were significantly longer in the FXN-KO mice compared to FXN-WT. The ejection fraction and fractional shortening were significantly decreased and left ventricular wall thickness and diameter were significantly increased in the FXN-KO mice versus FXN-WT. The mitochondrial membrane potential Δψm was depolarized, ROS levels were elevated, and OCR was decreased in ventricular myocytes from FXN-KO versus FXN-WT.ConclusionThe development of left ventricular contractile dysfunction in FA is associated with reduced expression of calcium handling proteins and mitochondrial dysfunction.
Intrinsic epigenetic state of primary osteosarcoma drives metastasis
Authors: Singh Irtisha , Rainusso Nino , Kurenbekova Lyazat , Nirala Bikesh K. , Dou Juan , Muruganandham Abhinaya , Yustein Jason T. 
Published: November 2023

AbstractOsteosarcoma (OS) is the most common primary malignant bone tumor affecting the pediatric population with high potential to metastasize to distal sites, most commonly the lung. Insights into defining molecular features contributing to metastatic potential are lacking. We have mapped the active chromatin landscapes of OS tumors by integrating histone H3 lysine acetylated chromatin (H3K27ac) profiles (n=13), chromatin accessibility profiles (n=11) and gene expression (n=13) to understand the differences in their active chromatin profiles and its impact on molecular mechanisms driving the malignant phenotypes. Primary OS tumors from patients with metastasis (primary met) have a distinct active chromatin landscape compared to primary tumors from patients without metastatic disease (localized). The difference in chromatin activity shapes the transcriptional profile of OS. We identified novel candidate genes involved in OS pathogenesis and metastasis, includingPPP1R1B,PREX1andIGF2BP1, which exhibit increased chromatin activity in primary met along with higher transcript levels. Overall, differential chromatin activity in primary met occurs in proximity of genes regulating actin cytoskeleton organization, cellular adhesion, and extracellular matrix suggestive of their role in facilitating OS metastasis. Furthermore, chromatin profiling of tumors from metastatic lung lesions noted increases in chromatin activity in genes involved in cell migration and key intracellular signaling cascades, including the Wnt pathway. Thus, this data demonstrates that metastatic potential is intrinsically present in primary metastatic tumors and the cellular chromatin profiles further adapt to allow for successful dissemination, migration, and colonization at the distal metastatic site.
Connecting Syncmers to FracMinHash: similarities and advantages
Authors: Liu Shaopeng , Koslicki David 
Published: November 2023

AbstractMotivationSketching methods provide scalable solutions for analyzing rapidly growing genomic data. A recent innovation in sketching methods, syncmers, has proven effective and has been employed for read alignment. Syncmers share fundamental features with the FracMinHash technique, a recent modification of the popular MinHash algorithm for set similarity estimation between sets of different sizes. Although previous researchers have demonstrated the effectiveness of syncmers in read alignment, their potential for broader usages in metagenomic analysis (the primary purpose for which FracMinHash was designed) and sequence comparisons remains underexplored.ResultsWe demonstrated that a open syncmer sketch is equivalent to a FracMinHash sketch when appled tok-mer-based similarities, yet it exhibits superior distance distribution and genomic conservation. Moreover, we expanded the concept ofk-mer truncation to open syncmers, creating multi-resolution open syncmers for metagenomic applications as well as flexible-sized seeding for sequence comparisons.ReproducibilityAll analysis scripts can be found onGitHub.
Exploring the Mosaic-like Tissue Architecture of Kidney Diseases Using Relation Equivariant Graph Neural Networks on Spatially Resolved Transcriptomics
Authors: Raina Mauminah , Cheng Hao , Suryadevara Hari Naga Sai Kiran , Stransfield Treyden , Xu Dong , Ma Qin , Eadon Michael T. , Wang Juexin 
Published: November 2023

AbstractEmerging spatially resolved transcriptomics (SRT) technologies provide unprecedented opportunities to discover the spatial patterns of gene expression at the cellular or tissue levels. Currently, most existing computational tools on SRT are designed and tested on the ribbon-like brain cortex. Their present expressive power often makes it challenging to identify highly heterogeneous mosaic-like tissue architectures, such as tissues from kidney diseases. This demands heightened precision in discerning the cellular and morphological changes within renal tubules and their interstitial niches. We present an empowered graph deep learning framework, REGNN (Relation Equivariant Graph Neural Networks), for SRT data analyses on heterogeneous tissue structures. To increase expressive power in the SRT lattice using graph modeling, the proposed REGNN integrates equivariance to handle the rotational and translational symmetries of the spatial space, and Positional Encoding (PE) to identify and strengthen the relative spatial relations of the nodes uniformly distributed in the lattice. Our study finds that REGNN outperforms existing computational tools in identifying inherent mosaic-like heterogenous tissue architectures in kidney samples sourced from different kidney diseases using the 10X Visium platform. In case studies on acute kidney injury and chronic kidney diseases, the results identified by REGNN are also validated by experienced nephrology physicians. This proposed framework explores the expression patterns of highly heterogeneous tissues with an enhanced graph deep learning model, and paves the way to pinpoint underlying pathological mechanisms that contribute to the progression of complex diseases. REGNN is publicly available athttps://github.com/Mraina99/REGNN.
SpatialCells: Automated Profiling of Tumor Microenvironments with Spatially Resolved Multiplexed Single-Cell Data
Authors: Wan Guihong , Maliga Zoltan , Yan Boshen , Vallius Tuulia , Shi Yingxiao , Khattab Sara , Chang Crystal , Nirmal Ajit J. , Yu Kun-Hsing , Liu David , Lian Christine G. , DeSimone Mia S. , Sorger Peter K. , Semenov Yevgeniy R. 
Published: November 2023

AbstractBackgroundCancer is a complex cellular ecosystem where malignant cells coexist and interact with immune, stromal, and other cells within the tumor microenvironment. Recent technological advancements in spatially resolved multiplexed imaging at single-cell resolution have led to the generation of large-scale and high-dimensional datasets from biological specimens. This underscores the necessity for automated methodologies that can effectively characterize the molecular, cellular, and spatial properties of tumor microenvironments for various malignancies.ResultsThis study introduces SpatialCells, an open-source software package designed for region-based exploratory analysis and comprehensive characterization of tumor microenvironments using multiplexed single-cell data.ConclusionsSpatialCells efficiently streamlines the automated extraction of features from multiplexed single-cell data and can process samples containing millions of cells. Thus, SpatialCells facilitates subsequent association analyses and machine learning predictions, making it an essential tool in advancing our understanding of tumor growth, invasion, and metastasis.Availability of code and materialshttps://github.com/SemenovLab/SpatialCells.
Sequential Image Classification of Human-Robot Walking Environments using Temporal Neural Networks
Authors: Ivanyuk-Skulskiy Bogdan , Kurbis Andrew Garrett , Mihailidis Alex , Laschowski Brokoslaw 
Published: November 2023

AbstractRobotic prosthetic legs and exoskeletons require real-time and accurate estimation of the walking environment for smooth transitions between different locomotion mode controllers. However, previous studies have mainly been limited to static image classification, therein ignoring the temporal dynamics of human-robot locomotion. Motivated by these limitations, here we developed several state-of-the-art temporal convolutional neural networks (CNNs) to compare the performances between static vs. sequential image classification of real-world walking environments (i.e., level-ground terrain, incline stairs, and transitions to and from stairs). Using our large-scale image dataset, we trained a number of encoder networks such as VGG, MobileNetV2, ViT, and MobileViT, each coupled with a temporal long short-term memory (LSTM) backbone. We also trained MoViNet, a new video classification model designed for mobile and embedded devices, to further compare the performances between 2D and 3D temporal deep learning models. Our 3D network outperformed all the hybrid 2D encoders with LSTM backbones and the 2D CNN baseline model in terms of classification accuracy, suggesting that network architecture can play an important role in performance. However, although our 3D neural network achieved the highest classification accuracy, it had disproportionally higher computational and memory storage requirements, which can be disadvantageous for real-time control of robotic leg prostheses and exoskeletons with limited onboard resources.
Integration of metataxonomic datasets into microbial association networks highlights shared bacterial community dynamics in fermented vegetables
Authors: Junker Romane , Valence Florence , Mistou Michel-Yves , Chaillou Stéphane , Chiapello Hélène 
Published: November 2023

ABSTRACTThe management of food fermentation is still largely based on empirical knowledge, as the dynamics of microbial communities and the underlying metabolic networks that produce safe and nutritious products remain beyond our understanding. Although these closed ecosystems contain relatively few taxa, they have not yet been thoroughly characterized with respect to how their microbial communities interact and dynamically evolve. However, with the increased availability of metataxonomic datasets on different fermented vegetables, it is now possible to gain a comprehensive understanding of the microbial relationships that structure plant fermentation.In this study, we present a bioinformatics approach that integrates public metataxonomic 16S datasets targeting fermented vegetables. Specifically, we developed a method for exploring, comparing, and combining public 16S datasets in order to perform meta-analyses of microbiota. The workflow includes steps for searching and selecting public time-series datasets and constructing association networks of amplicon sequence variants (ASVs) based on co-abundance metrics. Networks for individual datasets are then integrated into a core network of significant associations. Microbial communities are identified based on the comparison and clustering of ASV networks using the “stochastic block model” method. When we applied this method to 10 public datasets (including a total of 931 samples), we found that it was able to shed light on the dynamics of vegetable fermentation by characterizing the processes of community succession among different bacterial assemblages.IMPORTANCEWithin the growing body of research on the bacterial communities involved in the fermentation of vegetables, there is particular interest in discovering the species or consortia that drive different fermentation steps. This integrative analysis demonstrates that the reuse and integration of public microbiome datasets can provide new insights into a little-known biotope. Our most important finding is the recurrent but transient appearance, at the beginning of vegetable fermentation, of ASVs belonging toEnterobacteralesand their associations with ASVs belonging toLactobacillales. These findings could be applied in the design of new fermented products.
Multiomic analysis reveals cellular, transcriptomic and epigenetic changes in intestinal pouches of ulcerative colitis patients
Authors: Zhao Yu , Zhou Ran , Xie Bingqing , Liu Cambrian Y , Kalski Martin , Cham Candace M , Jiang Zhiwei , Koval Jason , Weber Christopher R , Rubin David T , Sogin Mitch , Crosson Sean , Chen Mengjie , Huang Jun , Fiebig Aretha , Dalal Sushila , Chang Eugene B , Basu Anindita , Pott Sebastian 
Published: November 2023

AbstractTotal proctocolectomy with ileal pouch anal anastomosis is the standard of care for patients with severe ulcerative colitis. We generated a cell-type-resolved transcriptional and epigenetic atlas of ileal pouches using scRNA-seq and scATAC-seq data from paired biopsy samples of the ileal pouch and the ileal segment above the pouch (pre-pouch) from patients (male=4, female=2), and paired biopsies of the terminal ileum and ascending colon from healthy individuals (male=3, female=3) serving as reference. Our study finds previously uncharacterized populations of absorptive and secretory epithelial cells within the pouch but not the pre-pouch. These pouch- specific enterocytes express a subset of colon-specific genes, includingCEACAM5andCD24. However, compared to normal colonocytes, expression of these genes is lower, and these enterocytes also express inflammatory and secretory genes while maintaining expression of some ileal-specific genes. This cell-type-resolved transcriptomic and epigenetic atlas of the ileal pouch establishes a reference for investigating pouch physiology and pathology.