bluuebunny/crossref_metadata_2025_split huggingface dataset:
CIRC_0001818 TARGETS MIR-136-5P TO INCREASE LIPOPOLYSACCHARIDE-INDUCED HK2 CELL INJURIES BY ACTIVATING TXNIP/NLRP3 INFLAMMASOME PATHWAY
Authors: Kuang Feng , Wang Baiqi , You Ting , Liu Yu , Li Pei , Wang Jian , Peng Liangshan 
Published: May 2023

ABSTRACT

Background: The implication of circular RNAs (circRNAs) in sepsis-related complications arouses much attention, which provides additional treatment options for sepsis-related complications. The purpose of this study is to unveil the function and functional mechanism of circ_0001818 in cell models of septic acute kidney injury (AKI). Methods: Septic AKI cell models were constructed using HK2 cells treated with lipopolysaccharide (LPS). The expression levels of circ_0001818, miR-136-5p, and thioredoxin interacting protein (TXNIP) mRNA were examined by quantitative real-time polymerase chain reaction. Cell viability and death were explored by CCK-8 and flow cytometry assays. The activity of oxidative stress-related markers was examined using commercial kits. The secretion of inflammatory factors was examined using ELISA kits. The binding between miR-136-5p and circ_0001818 or TXNIP was validated by dual-luciferase reporter test and pull-down assay. The receiver operating characteristic curve was depicted to assess the diagnostic value of circ_0001818, miR-136-5p, and TXNIP in serumal exosomes from patients with septic AKI. Results: Circ_0001818 expression was elevated in LPS-treated HK2 cells. Loss-of-function assays displayed that circ_0001818 downregulation alleviated LPS-induced HK2 cell death, oxidative stress, inflammatory release, and inflammasome activation. MiR-136-5p was targeted by circ_0001818, and inhibition of miR-136-5p attenuated the effects of circ_0001818 downregulation, thus recovering LPS-induced HK2 cell injuries. MiR-136-5p targeted the downstream TXNIP, and circ_0001818 dysregulation could affect TXNIP expression via targeting miR-136-5p. Overexpression of TXNIP overturned the effects of circ_0001818 downregulation. Moreover, circ_0001818, miR-136-5p, and TXNIP in serumal exosomes had diagnostic values. Conclusions: Circ_0001818 targets miR-136-5p to activate TXNIP expression, leading to the contribution of LPS-induced HK2 cell injury.
DANGER Signals Activate G-Protein Receptor Kinases Suppressing Neutrophil Function and Predisposing to Infection After Tissue Trauma
Authors: Kim Hyo In , Park Jinbong , Gallo David , Shankar Sidharth , Konecna Barbora , Han Yohan , Banner-Goodspeed Valerie , Capers Krystal R. , Ko Seong-Gyu , Otterbein Leo E. , Itagaki Kiyoshi , Hauser Carl J. 
Published: May 2023

Objective:
Surgery injures tissue and predisposes to local and systemic infections. We studied injury-induced immune dysfunction seeking novel means to reverse such predisposition.

Background:
Injury mobilizes primitive ‘DANGER signals’ (DAMPs) activating innate immunocyte (neutrophils, PMN) signaling and function. Mitochondrial (mt) formyl peptides (FP) activate G-protein coupled receptors (GPCR) like FPR1. mtDNA and heme activate toll-like receptors (TLR9, TLR2/4). GPCR kinases (GRKs) can regulate GPCR activation.

Methods:
We studied human and mouse PMN signaling elicited by mtDAMPs (GPCR surface expression; protein phosphorylation or acetylation; Ca2+ flux) and antimicrobial functions (cytoskeletal reorganization, chemotaxis (CTX), phagocytosis, bacterial killing) in cellular systems and clinical injury samples. Predicted rescue therapies were assessed in cell systems and mouse injury-dependent pneumonia models.

Results:
mtFPs activate GRK2, internalizing GPCRs and suppressing CTX. mtDNA suppresses CTX, phagocytosis and killing via TLR9 through a novel, non-canonical mechanism that lacks GPCR endocytosis. Heme also activates GRK2. GRK2 inhibitors like paroxetine restore functions. GRK2 activation via TLR9 prevented actin reorganization, implicating histone deacetylases (HDACs). Actin polymerization, CTX, bacterial phagocytosis and killing were also rescued therefore by the HDAC inhibitor valproate. Trauma repository PMN showed GRK2 activation and cortactin deacetylation which varied with severity and was most marked in patients developing infections. Either GRK2 or HDAC inhibition prevented loss of mouse lung bacterial clearance, but only the combination rescued clearance when given post-injury.

Conclusions:
Tissue injury-derived DAMPs suppress antimicrobial immunity via canonical GRK2 activation and a novel TLR-activated GRK2 pathway impairing cytoskeletal organization. Simultaneous GRK2/HDAC inhibition rescues susceptibility to infection after tissue injury.
HIF-stabilizing Biomaterials: from Hypoxia-mimicking to Hypoxia-inducing
Authors: Colombani Thibault , Bhatt Khushbu , Epel Boris , Kotecha Mrignayani , Bencherif Sidi A. 
Published: May 2023

AbstractRecent advances in our understanding of hypoxia and hypoxia-mediated mechanisms shed light on the critical implications of the hypoxic stress on cellular behavior. However, tools emulating hypoxic conditions (i.e., low oxygen tensions) for research are limited and often suffer from major shortcomings, such as lack of reliability and off-target effects, and they usually fail to recapitulate the complexity of the tissue microenvironment. Fortunately, the field of biomaterials is constantly evolving and has a central role to play in the development of new technologies for conducting hypoxia-related research in several aspects of biomedical research, including tissue engineering, cancer modeling, and modern drug screening. In this perspective, we provide an overview of several strategies that have been investigated in the design and implementation of biomaterials for simulating or inducing hypoxic conditions—a prerequisite in the stabilization of hypoxia-inducible factor (HIF), a master regulator of the cellular responses to low oxygen. To this end, we discuss various advanced biomaterials, from those that integrate hypoxia-mimetic agents to artificially induce hypoxia-like responses, to those that deplete oxygen and consequently create either transient (< 1 day) or sustained (> 1 day) hypoxic conditions. We also aim to highlight the advantages and limitations of these emerging biomaterials for biomedical applications, with an emphasis on cancer research.
Aird-ComboComp: A combinable compressor framework with a dynamic-decider for lossy mass spectrometry data compression
Authors: Lu Miaoshan , Tong Junjie , Wang Ruimin , An Shaowei , Wang Jinyin , Yu Changbin 
Published: May 2023

AbstractMass spectrum (MS) data volumes increase with an improved ion acquisition ratio and a highly accurate mass spectrometer. However, the most widely used data format, mzML, does not take advantage of compression methods and improved read performances. Several compression algorithms have been proposed in recent years, and they consider a number of factors, including, numerical precision, metadata read strategies and the compression performance. Due to limited compression ratio, the high-throughput MS data format is still quite large. High bandwidth and memory requirements severely limit the applicability of MS data analysis in cloud and mobile computing. ComboComp is a comprehensive improvement to the Aird data format. Instead of using the general-purpose compressor directly, ComboComp uses two integer-purpose compressors and four general-purpose compressors, and obtains the best compression combination with a dynamic decider, achieving the most balanced compression ratio among all the numerous varieties of compressors. ComboComp supports a seamless extension of the new integer and generic compressors, making it an evolving compression framework. The improvement of compression rate and decoding speed greatly reduces the cost of data exchange and real-time decompression, and effectively reduces the hardware requirements of MS data analysis. Analyzing mass spectrum data on IoT devices can be useful in real-time quality control, decentralized analysis, collaborative auditing, and other scenarios. We tested ComboComp on 11 datasets generated by commonly used MS instruments. Compared with Aird-ZDPD, the compression size can be reduced by an average of 12.9%. The decompression speed is increased by an average of 27.1%. The average compression time is almost the same as that of ZDPD. The high compression rate and decoding speed make the Aird format effective for data analysis on small memory devices. This will enable MS data to be processed normally even on IoT devices in the future. We provide SDKs in three languages, Java, C# and Python, which offer optimized interfaces for the various acquisition modes. All the SDKs can be found on Github:https://github.com/CSi-Studio/Aird-SDK.
A Machine Learning One-Class Logistic Regression Model to Predict Stemness in Single Cell Transcriptomics and Spatial Omics Datasets
Authors: Dezem Felipe Segato , Marção Maycon , Ben-Cheikh Bassem , Nikulina Nadya , Omotoso Ayodele , Burnett Destiny , Coelho Priscila , Badal Simone , Hurley Judith , Gomez Carmen , Phan-Everson Tien , Ong Giang , Martelotto Luciano , Lewis Zachary R. , George Sophia , Braubach Oliver , Malta Tathiane , Plummer Jasmine 
Published: May 2023

AbstractCell annotation is a crucial methodological component to interpreting single cell and spatial omics data. These approaches are often biased and manually curated. Here we harness an existing stemness model for assessing oncogenic states to transform its application to single cell and spatial omic datasets. This one-class logistic regression machine learning algorithm is used to extract transcriptomic or proteomic features from non-transformed stem cells to identify dedifferentiated cell states. We found this method identifies single cell states in metastatic tumor cell populations without the requirement of cell annotation. Finally these stemness indices are applicable across a variety of spatial transcriptomic and proteomic technologies for the identification of oncogenic cell types in the tumor microenvironment.Graphical Abstract
The image-based ultrasonic cell shaking test
Authors: Ballard Miranda , Marek Aleksander , Pierron Fabrice 
Published: May 2023

AbstractMechanical signals play a vital role in cell biology and is a vast area of research. Thus, there is motivation to understand cell deformation and mechanobiological responses. However, the ability to controllably deform cells in the ultrasonic regime and test their response is a noted challenge throughout the literature. Quantifying and eliciting an appropriate stimulus has proven to be difficult, resulting in methods that are either too aggressive or oversimplified. Furthermore, the ability to gain a real-time insight into cell deformation and link this with the biological response is yet to be achieved. One application of this understanding is in ultrasonic surgical cutting, which is a promising alternative to traditional methods, but with little understanding of its effect on cells. Here we present the image based ultrasonic cell shaking test, a novel method that enables controllable loading of cells and quantification of their response to ultrasonic vibrations. Practically, this involves seeding cells on a substrate that resonates at ultrasonic frequencies and transfers the deformation to the cells. This is then incorporated into microscopic imaging techniques to obtain high-speed images of ultrasonic cell deformation that can be analysed using digital image correlation techniques. Cells can then be extracted after excitation to undergo analysis to understand the biological response to the deformation. This method could aid in understanding the effects of ultrasonic stimulation on cells and how activated mechanobiological pathways result in physical and biochemical responses.
Mortality surrogates in combined pulmonary fibrosis and emphysema
Authors: Zhao An , Gudmundsson Eyjolfur , Mogulkoc Nesrin , van Moorsel Coline , Corte Tamera J. , Romei Chiara , Chapman Robert , Wallis Tim J.M. , Denneny Emma , Goos Tinne , Savas Recep , Ahmed Asia , Brereton Christopher J. , van Es Hendrik W. , Jo Helen , De Liperi Annalisa , Duncan Mark , Pontoppidan Katarina , De Sadeleer Laurens J. , van Beek Frouke , Barnett Joseph , Cross Gary , Procter Alex , Veltkamp Marcel , Hopkins Peter , Moodley Yuben , Taliani Alessandro , Taylor Magali , Verleden Stijn , Tavanti Laura , Vermant Marie , Nair Arjun , Stewart Iain , Janes Sam M. , Young Alexandra L. , Barber David , Alexander Daniel C. , Porter Joanna C. , Wells Athol U. , Jones Mark G. , Wuyts Wim A. , Jacob Joseph 
Published: May 2023

AbstractBackgroundIdiopathic pulmonary fibrosis (IPF) with co-existent emphysema, termed combined pulmonary fibrosis and emphysema (CPFE) may be associated with reduced FVC decline compared to non-CPFE IPF patients. We examined associations between mortality and functional measures of disease progression in two IPF cohorts.MethodsVisual emphysema extent (CPFE:non-CPFE: derivation cohort=317:183; replication cohort=358:152), scored on computed tomography imaging subgrouped CPFE patients using either a) 10%, or b) 15% visual emphysema threshold, or c) an unsupervised machine learning model considering emphysema and ILD extents. Baseline characteristics, 1-year forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLco) decline (linear mixed effects models), and their associations with mortality (multivariable Cox regression models) were compared across CPFE and non-CPFE subgroups.ResultsIn both IPF cohorts, CPFE patients with >10% emphysema had a greater smoking history and lower baseline DLco compared to CPFE patients with <10% emphysema. Using multivariable Cox regression analyses in patients with >10% emphysema, 1-year DLco decline was a better indicator of mortality than 1-year FVC decline. Results were maintained in patients suitable for therapeutic IPF trials.Results were replicated in the >15% emphysema population and using unsupervised machine learning. Importantly, the unsupervised machine learning approach identified CPFE patients in whom FVC decline did not associate strongly with mortality. In non-CPFE IPF patients, 1-year FVC declines >5% and >10% showed comparable mortality associations.ConclusionWhen assessing disease progression in IPF, DLco decline should be considered in patients with >10% emphysema and a >5% 1-year FVC decline threshold considered in non-CPFE IPF patients.
Efficacy of Intrawound Vancomycin in Prevention of Periprosthetic Joint Infection After Primary Total Knee Arthroplasty
Authors: Mulpur Praharsha , Jayakumar Tarun , Yakkanti Ramakanth R , Apte Aditya , Hippalgaonkar Kushal , Annapareddy Adarsh , Masilamani A B Suhas , Gurava Reddy A V 
Published: May 2023

ABSTRACTIntroductionPeri-prosthetic Joint Infection (PJI) after total knee arthroplasty (TKA) is a devastating complication. Intra-wound vancomycin powder has been shown to reduce infection rates in spine surgery. Previous studies on the efficacy of local vancomycin powder in hip or knee arthroplasty are mostly retrospective case series. The aim of this prospective RCT was to evaluate the efficacy and safety of intrawound vancomycin in preventing PJI after primary TKA.MethodsThis study was a National Trial Registry-approved RCT of patients undergoing primary TKA. 1022 patients were randomized to the study group (n=507, received 2g intrawound vancomycin powder before arthrotomy closure) and control groups (n=515, no local vancomycin). The minimum follow-up was 12-months. The primary outcome was PJI rate. Secondary outcomes included surgical site infection (SSI) rates, incidence of revision for PJI/SSI, and incidence of wound complications. High-risk groups (Obesity and Diabetes) in both cohorts were also evaluated.ResultsThe overall infection rate in 1022 patients was 0.66%. There was no significant difference in PJI rate in the study group (0.2%) versus the control group (0.58%), p=0.264. Reoperation rates in the study group (N=4;0.78%) and Control (N=5;0.97%) and SSI rates in the study (N=1;0.2%) and control groups (N=2;0.38%) were comparable. The Vancomycin cohort however demonstrated a significantly higher number of minor wound complications (n=67;13.9%) compared to the control group (n=39;8.4%, p<0.05). There was no difference in PJI/SSI rates or minor surgical complications among high-risk groups and no cases of nephrotoxicity were reported in the study.ConclusionIntra-wound vancomycin powder does not appear to reduce PJI/SSI rate in primary total knee arthroplasties, including high-risk groups. Although safe from a renal perspective, intra-wound vancomycin was associated with an increase in postoperative aseptic wound complications such as persistent wound drainage. Intra-wound vancomycin may not be effective in reducing the rate of PJI in primary TKA.
Dawnn: single-cell differential abundance with neural networks
Authors: Hall George T. , Castellano Sergi 
Published: May 2023

AbstractAnalysis of single-cell transcriptomes can identify cell populations more abundant in one sample or condition than another. However, existing methods to discover them suffer from either low discovery rates or high rates of false positives. We introduce Dawnn, a deep neural network able to find differential abundance with higher accuracy than current tools, both on simulated and biological datasets. Further, we demonstrate that Dawnn recovers published findings and discovers more cells in regions of differential abundance than existing methods, both in abundant and rare cell types, promising novel biological insights at single-cell resolution.
Deconvolution Of Hematopoietic Stem/Progenitor Cell Signaling Predicts Inflammatory Niche Remodeling To Be A Determinant Of Tissue Failure And Outcome In Human AML
Authors: Chen Lanpeng , Pronk Eline , van Dijk Claire , Bian Yujie , Feyen Jacqueline , van Tienhoven Tim , Yildirim Meltem , Pisterzi Paola , de Jong Madelon , Bastidas Alejandro , Hoogenboezem Remco , Wevers Chiel , Bindels Eric , Löwenberg Bob , Cupedo Tom , Sanders Mathijs A. , Raaijmakers Marc H.G.P. 
Published: May 2023

ABSTRACTCancer initiation is orchestrated by interplay between tumor-initiating cells and their stromal/immune environment. Here, by adapted scRNAsequencing, we decipher the predicted signaling between tissue-resident hematopoietic stem/progenitor cells (HSPCs) and their neoplastic counterparts with their native niches in the human bone marrow. LEPR+stromal cells are identified as central regulators of hematopoiesis through predicted interactions with all cells in the marrow. Inflammatory niche remodeling and the resulting deprivation of critical HSPC regulatory factors is predicted to repress distinct high-output HSC subsets inNPM1-mutated AML, with relative resistance of clonal cells. Stromal gene signatures reflective of niche remodeling are associated with reduced relapse rates and favorable outcome after chemotherapy, across all genetic risk categories. Elucidation of the intercellular signaling defining human AML, thus, predicts that inflammatory remodeling of stem cell niches drives tissue repression and clonal selection, but may pose a vulnerability for relapse-initiating cells in the context of chemotherapeutic treatment.statement of significanceTumor-promoting inflammation is considered an enabling characteristic of tumorigenesis, but mechanisms remain incompletely understood. By deciphering the predicted signaling between tissue-resident stem cells and their neoplastic counterparts with their environment, we identify inflammatory remodeling of stromal niches as a determinant of normal tissue repression and clinical outcome in human AML.Key pointsA comprehensive taxonomy of the predicted interactions between LEPR+stromal niches, HSPCs and adaptive/innate immune cells in the human NBM.Inflammation-associated decline of stromal niches in AML represses residual normal hematopoiesis with relative resistance of leukemic cells.Inflammatory decline of stromal niches is associated with reduced relapse risk and favorable outcome.
NON-TOXIC ACID-FREE GLYOXAL FIXATIVE FOR VETERINARY HISTOPATHOLOGY, IMMUNOHISTOCHEMISTRY AND MOLECULAR ANALYSIS
Authors: Zappulli Valentina , Torrigiani Filippo , Moccia Valentina , Detillo Paolo , Gola Cecilia , Minoli Lucia , Morello Emanuela M. , Ferraris Erica I. , Rigillo Antonella , Caicci Federico , Rovere Giulia Dalla , De Biase Davide , Riccio Lorenzo , Rondena Marco , Iussich Selina , Bussolati Benedetta 
Published: May 2023

AbstractFormaldehyde fixation is worldwide the most used system for histopathological examination. However, its toxicity is well known, and preservation of proteins and nucleic acids is not optimal. Alternative fixatives warranting similar morphological quality of tissues and costs, but lacking toxicity and allowing better preservation of proteins and nucleic acids would therefore increase both safety of operators and quality of molecular analysis in pathology.This multi-institutional study aimed to compare the morphological, histochemical, immunohistochemical (IHC), and molecular analyses outcomes of a newly patented, non-toxic, acid-free Glyoxal (GAF) fixative with neutral buffered formaldehyde (NBF). Tissues from a total of 73 subjects were analyzed, including 13 necropsies.Gross features were preserved after GAF fixation, with no tissue hardening or discoloration. Cellular ultrastructure was also better preserved with GAF and histology and histochemistry on GAF-fixed samples showed good results when compared to NBF-fixed samples, with the exception of loss of tinctorial affinity of erythrocytes and mast cell granules. IHC analyses also showed comparable results with only slight and rare protocol adjustment. DNA and RNA yields were higher from GAF-fixed samples (P<0.05) and the tested genes (p53andCOX1) were better amplified. RNA scope showed positive results forc-KITexpression in GAF-fixed mast cell tumors.Based on these data, the non-toxic GAF fixative allows good macroscopical, histological and immunohistochemical analyses of tissue samples, including on-field application, and better molecular analyses when compared to NBF. This represents a promising possibility for teaching, diagnostic, and research in veterinary pathology.
Combinatorial Microgels for 3D ECM Screening and Heterogeneous Microenvironmental Culture of Primary Human Hepatic Stellate Cells
Authors: Ryoo Hyeon , Underhill Gregory H. 
Published: May 2023

ABSTRACTNon-alcoholic fatty liver disease affects 30% of the United States population and its progression can lead to non-alcoholic steatohepatitis (NASH), which can result in cirrhosis and hepatocellular carcinoma. NASH is characterized by a highly heterogeneous liver microenvironment created by the fibrotic activity of hepatic stellate cells (HSCs). While HSCs have been widely studied in 2D, further advancements in physiologically-relevant 3D culture platforms for the in vitro modeling of these heterogeneous environments are needed. In this study, we have demonstrated the use of stiffness-variable, ECM protein-conjugated polyethylene glycol microgels as 3D cell culture scaffolds to modulate HSC activation. We further employed these microgels as a high throughput ECM screening system to identify HSC matrix remodeling and metabolic activities in distinct heterogeneous microenvironmental conditions. In particular, 6 kPa fibronectin microgels were shown to significantly increase HSC matrix remodeling and metabolic activities in single or multiple component microenvironments. Overall, heterogeneous microenvironments consisting of multiple distinct ECM microgels promoted a decrease in HSC matrix remodeling and metabolic activities compared to homogeneous microenvironments. We envision this ECM screening platform being adapted to a broad number of cell types to aid the identification of ECM microenvironments that best recapitulate the desired phenotype, differentiation, or drug efficacy.