bluuebunny/crossref_metadata_2025_split huggingface dataset:
A simple, cost-effective microfluidic device using a 3D cross-flow T-junction for producing decellularized extracellular matrix-derived microcarriers
Authors: Kamar Farah , Gillis Connor J. , Bischoff Grace , Ali Anorin , de Bruyn John R. , Flynn Lauren E. , Poepping Tamie L. 
Published: November 2024

ABSTRACTCell therapies using human mesenchymal stromal cells (MSCs) are promising for a wide variety of clinical applications. However, broad-scale clinical translation is limited by conventional culture methods for MSC expansion within 2D tissue-culture flasks. MSC expansion on ECM-derived microcarriers within stirred bioreactor systems offers a promising approach to support MSC growth. Previously, our team established methods for fabricating ECM-derived microcarriers from a variety of decellularized tissue sources using electrospraying techniques. However, these microcarriers are relatively large and have a broad size distribution, which may limit their utility. Smaller and more uniform microcarriers may be favorable for MSC growth within bioreactors and have greater potential to serve as a minimally invasive injectable cell delivery platform. To address these limitations, the current project focused on the development of a new microfluidic-based approach enabling both uniform and small microcarrier production. Using a novel, modified 3D T-junction design, we successfully generated microcarriers using human decellularized adipose tissue (DAT) as the ECM source. Our new cost-effective device produced microbeads that were small and monodisperse, at a range of flow rate combinations and with high production rates. Photo-crosslinking using rose bengal allowed for the generation of microcarriers that were stable following rehydration, with a mean diameter of 196 ± 47 µm. Following methods optimization and microcarrier characterization,in vitrostudies confirmed that the new microcarriers supported human adipose-derived stromal cell (hASC) attachment and growth, as well as ECM production, across 14 days within spinner flask bioreactors. Overall, this study demonstrates the feasibility of using our novel, cost-effective, and reusable microfluidics device to generate cell-supportive microcarriers comprised exclusively of ECM in a size range that could be injected via a small gauge needle and were stable in long-term culture.
CIWARS: a web server for waterborne antibiotic resistance surveillance using longitudinal metagenomic data
Authors: Emon Muhit Islam , Cheung Yat Fei , Stoll James , Rumi Monjura Afrin , Brown Connor , Choi Joung Min , Moumi Nazifa Ahmed , Ahmed Shafayat , Song Haoqiu , Sein Justin , Yao Shunyu , Khan Ahmad , Gupta Suraj , Kulkarni Rutwik , Butt Ali , Vikesland Peter , Pruden Amy , Zhang Liqing 
Published: November 2024

AbstractThe rise of antibiotic resistance (AR) is a major global health crisis, exacerbated by the overuse and misuse of antibiotics, leading to the rapid spread of antibiotic resistance genes (ARGs) in bacterial pathogens. This phenomenon poses significant threats to human and animal health, food security, and economic stability. Water bodies, particularly wastewater treatment plants (WWTPs), serve as critical reservoirs for ARGs, creating environments that favor the proliferation of resistant bacteria. Wastewater-based surveillance (WBS) has emerged as a cost-effective strategy for monitoring AR at the population level, providing real-time data to guide public health and policy decisions. Despite advancements in WBS, there are no comprehensive online analytical platforms for continuous environmental AR surveillance. This paper introduces CIWARS, a web server designed for AR analyses of longitudinal metagenomic data. CIWARS offers comprehensive ARG profiling, taxonomic annotation, and anomalous AR risk points detection. We demonstrate its capabilities through an interactive temporal data visualization, showcasing its potential for enhancing AR risk monitoring and guiding effective mitigation strategies. CIWARS is broadly applicable to longitudinal metagenomic data generated from any environment and aims to support global efforts in addressing the AR crisis by providing cyberinfrastructure for continuous AR surveillance. The web server is freely available athttps://ciwars.cs.vt.edu/.
Neuroprotection by chronic administration of Fluoroethylnormemantine (FENM) in mouse models of Alzheimer’s disease
Authors: Carles Allison , Freyssin Aline , Guehairia Sarra , Reguero Thomas , Vignes Michel , Hirbec Hélène , Rubinstenn Gilles , Maurice Tangui 
Published: November 2024

AbstractBackgroundFluoroethylnormemantine (FENM), a new Memantine (MEM) derivative, prevented amyloid-β[25–35] peptide (Aβ25–35)-induced neurotoxicity in mice, a pharmacological model of Alzheimer’s disease (AD) with high predictive value for drug discovery. Here, as drug infusion is likely to better reflect drug bioavailability due to the interspecies pharmacokinetics variation, we analyzed the efficacy of FENM after chronic subcutaneous (SC) infusion, in comparison with IP injections in two AD mouse models, Aβ25–35–injected mice and the transgenic APP /PSEN1∂E9(APP/PS1) line.MethodsIn Aβ25–35-treated mice, FENM was infused at 0.03-0.3 mg/kg/day during one week after Aβ25–35injection. For comparison, FENM and MEM were administered IP daily at 0.03-0.3 mg/kg. In 10-month-old APP/PS1 mice, FENM was administered during four weeks by daily IP injections at 0.3 mg/kg or chronic SC infusion at 0.1 mg/kg/day. Memory deficits, spatial working memory and recognition memory, were analysed. Markers of neuroinflammation, apoptosis, oxidative stress, and amyloid burden in APP/PS1 mice, were quantified. Markers of synaptic plasticity such as PSD-95 and GluN2A/B/D subunits expression in hippocampus homogenates or synaptosomes were quantified in Aβ25–35-treated mice and synaptic long-term potentiation (LTP) in hippocampal slices was analysed in APP/PS1 mice.ResultsDeficits in spontaneous alternation and object recognition in Aβ25–35mice were prevented by infused FENM at all doses tested. Similar effects were observed with the daily FENM or MEM treatments. Animals infused with 0.1 mg/kg/day FENM showed prevention of Aβ25–35-induced neuroinflammation, oxidative stress and apoptosis. FENM infusion restored Aβ25–35-induced alterations in synaptosomal PSD-95, GluN2A and P-GluN2B levels. GluN2D levels were unchanged whatever the treatment. In APP/PS1 mice, FENM infused or administered IP alleviated spontaneous alternation deficits, neuroinflammation, increases in Aβ1-40/Aβ1-42and hippocampal LTP alteration.ConclusionThese data confirmed the neuroprotective potential of FENM in the pharmacological Aβ25–35and transgenic APP/PS1 mouse models of AD, with a superiority to MEM, and showed that the drug can be efficiently infused chronically.
Rapamycin Enhances CAR-T Control of HIV Replication and Reservoir Eliminationin vivo
Authors: Mu Wenli , Tomer Shallu , Harding Jeffrey , Kedia Nandita , Rezek Valerie , Cook Ethan , Patankar Vaibahavi , Carrillo Mayra , Martin Heather , Ng Hwee , Wang Li , Marsden Matthew D. , Kitchen Scott G. , Zhen Anjie 
Published: November 2024

ABSTRACTChimeric Antigen Receptor (CAR) T cell therapy has emerged as a powerful immune therapy for various diseases. Our studies in humanized mice and non-human primates (NHPs) demonstrate that hematopoietic stem cell (HSCs) modified with anti-HIV CAR leads to lifelong engraftment and supply of functional anti-viral CAR-T cells, leading to significantly reduced viral rebound after ART withdrawal. However, T cell exhaustion, driven by chronic immune activation, remains a major challenge for the continuous efficacy of CAR-T therapy, necessitating additional measures to achieve functional cure. We recently showed thatin vivotreatment with low dose rapamycin reduced chronic inflammation and improved anti-HIV T cell function in HIV-infected humanized mice. Here, we report that rapamycin significantly improved CAR-T cell function bothin vitroandin vivo.In vitrotreatment with rapamycin improved CAR-T cell mitochondria respiration and cytotoxicity.In vivotreatment with low-dose rapamycin in HIV-infected, CAR-HSC treated mice reduced chronic inflammation, prevented exhaustion of CAR-T cells and improved CAR-T control of viral replication compared to CAR-HSCs treatment alone. RNAseq analysis of sorted CAR-T cells from humanized mice showed that rapamycin significantly modified the CAR-T cell transcriptome, including the downregulation of multiple check point inhibitors and the upregulation of key genes related to cell survival. We also observed significantly delayed viral rebound after ART withdrawal and diminished HIV reservoir in mice that were treated with rapamycin and CAR-HSCs as compared to CAR-HSCs treatment alone. Taken together, our data indicate that HSCs-based anti-HIV CAR-T combined with rapamycin treatment is a promising approach for treating persistent inflammation and improving immune control of HIV replication.
Deep learning-based detection and segmentation of osseous metastatic prostate cancer lesions on computed tomography
Authors: Pawan S J , Rich Joseph , Malewar Shreyas , Patel Daksh , Muellner Matt , Hwang Darryl H , Lei Xiaomeng , Cen Steven Y , Triche Timothy , Goldkorn Amir , Mohammed Passant , Oberai Assad , Duddalwar Vinay 
Published: November 2024

AbstractPurposeProstate adenocarcinoma frequently metastasizes to bone and is detected via computed tomography (CT) scans. Accurate detection and segmentation of these lesions are critical for diagnosis, prognosis, and monitoring. This study aims to automate lesion detection and segmentation using deep learning models.Methods and MaterialsWe evaluated several deep learning models for lesion detection (EfficientNet, ResNet34, DenseNet) and segmentation (nnUNetv2, UNet, ResUNet, ResAttUNet). Performance metrics included F1 score, precision, recall, Area Under the Curve (AUC), and Dice Similarity Coefficient (DSC). Pairwise t-tests compared segmentation accuracy. Additionally, we conducted radiomic analyses to compare lesions segmented by deep learning to manual segmentationsResultsEfficientNet achieved the highest detection performance, with an F1 score of 0.82, precision of 0.88, recall of 0.79, and AUC of 0.71. Among segmentation models, nnUNetv2 performed best, achieving a DSC of 0.74, with precision and recall values of 0.73 and 0.83, respectively. Pairwise t-tests showed that nnUNetv2 outperformed ResAttUNet, ResUNet, and UNet in segmentation accuracy (p < 0.01). Clinically, nnUNetv2 also demonstrated superior specificity for lesion detection (0.9) compared to the other models. All models performed similarly in distinguishing diffuse and focal lesions, predicting weight-bearing lesions, and identifying lesion locations, although nnUNetv2 had higher specificity for these tasks. Sensitivity was highest for rib lesions and lowest for spine lesions across all models.ConclusionsEfficientNet and nnUNetv2 were the top-performing models for detection and segmentation, respectively. The radiomic features derived from deep learning-based segmentations were comparable to those from manual segmentations, supporting the clinical applicability of these methods. Further analysis of lesion detection and spatial distribution, as well as lesion quality differentiation, underscores the models’ potential for improving diagnostic workflows and patient outcomes in clinical settings.
Low-pressure Isochoric Freezing as a scalable technique for fresh food preservation
Authors: Maida Alan L. , Consiglio Anthony N. , Bilbao-Sainz Cristina , Karman Andrew , Takeoka Gary , Powell-Palm Matthew J. , Rubinsky Boris 
Published: November 2024

AbstractEfficient means of reducing food waste are critically needed to meet the demands of a growing global population, while mounting consumer interest in minimally-processed food products has simultaneously driven renewed interest in non-chemical preservation modalities. Here, we investigate the potential of low-pressure isochoric freezing (LPIF) at –1.5°C / 15 MPa to simultaneously inhibit microbial growth and preserve fresh-like physiochemical and bioactive properties during storage. Using raw cow’s milk as a model product, we demonstrate synergistic effects of mild low temperature and mild enhanced pressure that significantly improve preservation for storage periods up to 5 weeks. Given the passive nature of the technique and the compatibility of the employed pressures with standard industrial compressed gas containers, these results suggest a route towards a scalable new cold storage modality.
Modulating adipose-derived stromal cells’ secretomes by culture conditions: effects on angiogenesis, collagen deposition, and immunomodulation
Authors: Pinheiro-Machado Erika , Koster Claudia C. , Smink Alexandra M. 
Published: November 2024

AbstractThe secretome of adipose-derived stromal cells (ASC) presents a promising avenue for cell-free therapies due to their rich mixture of bioactive molecules. Different culture conditions can modulate the composition of this mixture, but how this affects the functional properties of the secretome remains to be investigated. This study investigated thein vitroeffects of normoxia, cytokines, high glucose, hypoxia, and hypoxia + high glucose-derived ASC secretomes on angiogenesis (tube formation assay), collagen deposition (Picrosirius-Red staining), and immunomodulation (One-way Mixed Lymphocyte Reaction in combination with an antibody-mediated cell-dependent cytotoxicity assay). The data showed that normoxia and hypoxia-derived secretomes consistently exhibited potent proangiogenic effects in both human and rat models. These secretomes also demonstrated positive influences on collagen deposition and immunomodulation. Interestingly, the human ASC hypoxia + high glucose-derived secretome emerged as a stimulator of collagen deposition and modulator of the immune system. Conversely, cytokines and high glucose-derived secretomes have shown less strong effects in almost all functional parameters. In conclusion, our findings indicate that modulating culturing conditions results in secretomes with different functional properties and emphasizes the multifaceted role of ASC secretomes in regenerative processes.
AURKA controls oocyte spindle assembly checkpoint and chromosome alignment by HEC1 phosphorylation
Authors: Blengini Cecilia S. , Mendola Robert J. , Garrisi G. John , Swain Jason E. , Schindler Karen 
Published: November 2024

AbstractIn human oocytes, meiosis I is error-prone, causing early miscarriages and developmental disorders. The Aurora protein kinases are key regulators of chromosome segregation in mitosis and meiosis and their dysfunction is associated with aneuploidy. Oocytes contain three Aurora kinase (AURK) proteins, but only AURKA is necessary and sufficient to support oocyte meiosis in mice. However, the unique molecular contributions of AURKA remain unclear. Here, using a combination of genetic and pharmacological approaches, we evaluated how AURKA phosphorylation regulates outer kinetochore function during oocyte meiosis. We found that the outer kinetochore protein Ndc80/HEC1 is constitutively phosphorylated at multiple residues by Aurora kinases during meiosis I, but that Serine 69 is specifically phosphorylated by AURKA in mouse and human oocytes. We further show that Serine 69 phosphorylation regulates spindle assembly checkpoint (SAC) activation and chromosome alignment during meiosis I. These results provide a fundamental mechanistic understanding of how AURKA regulates meiosis and kinetochore function to ensure meiosis I fidelity.
Interplay between material properties and cellular effects drives distinct pattern of interaction of graphene oxide with cancer and non-cancer cells
Authors: Chen Yingxian , Rosano Vinicio , Lozano Neus , Shin YuYoung , Mironov Aleksandr , Spiller David , Casiraghi Cinzia , Kostarelos Kostas , Vranic Sandra 
Published: November 2024

AbstractUnderstanding how graphene oxide (GO) interacts with cells is crucial for its safe and efficient biomedical applications. Despite extensive research, a systematic investigation using a panel of cell lines, thoroughly characterized label-free nanomaterials, and complementary analytical techniques is lacking. Here, we examined the uptake of thin GO sheets with distinct lateral dimensions in 13 cell lines: 8 cancer (HeLa, A549, PC3, DU-145, LNCaP, SW-480, SH-SY5Y, U87-MG) and 5 non-cancer (BEAS-2B, NIH/3T3, PNT-2, HaCaT, 293T), using confocal microscopy, transmission electron microscopy, and flow cytometry. Our results reveal a striking difference in GO uptake: non-cancer cells internalized GO efficiently, while in cancer cells, GO predominantly interacted with the plasma membrane, showing minimal to no internalization. Comparison to other nanomaterials (polystyrene beads and graphene flakes) confirmed that cancer cells internalize materials similarly to non-cancer cells, indicating GO-specific interactions. We identified that GO thickness plays a pivotal role in this differential uptake. Additionally, GO disrupted the actin cytoskeleton, impairing migration in cancer but not in non-cancer cells. We propose that thin GO sheets act as a cue upon interaction with the plasma membrane of cancer cell lines, subsequently inducing actin filaments disruption leading to impaired endocytosis, migration activity, and reduced capacity of cancer cells towards GO uptake.
Relationship between calculated total blood count inflammatory readings and the degree of coronary atherosclerosis (Pilot study)
Authors: Agnė Liuizė , Aušra Mongirdienė , Jolanta Laukaitienė 
Published: November 2024

AbstractBackgroundSome calculated total blood count readings are investigated as additional readings to help with evaluation of CAD patients’ clinical management and prognosis.AimWe aimed to investigate the association between readings such as NLR, MLR, PLR, NMR, LMR, MHR, SII, SIRI and the severity of CAD in patients with SAP.MethodsThis retrospective pilot study included 166 patients. All these patients underwent CA or CCTA, or both, to assess severity of CAD. Patients were divided into three ways: 1) according to presence (n=146) or absence (n=20) of CAD; 2) according to Gensini score; 3) according to the CAD-RADS score.ResultsPatients with CAD had lower LMR, higher NLR, SIRI, MLR and SII compared to patients without CAD(p<0.001 and p=0.018,respectively for SII). According to the CAD severity by Gensini score, the NLR, MLR, SII and SIRI values increases and LMR decreases gradually with severity of CAD (p<0.001). It was found moderate correlation between SII (r=0.511, p<0.001), NLR (r=0.567, p<0.001)and SIRI (r=0.474, p<0.001)and severity of CAD according to Gensini score. MLR and LMR low correlated with severity of CAD according to Gensini score (r=0.356, p<0.001; r=-0.355, p<0.001,respectively). The CAD-RADS score weakly correlated with NLR and MHR(r=0.365, p<0.001; r=0.346, p<0.001, respectively), and moderately – with LMR, MLR and SIRI (r=-0.454, p<0.001; r=0.455, p<0.001; r=0.522, p<0.001,respectively).ConclusionsNLR, LMR and SIRI appear to be potential predictors of chronic inflammation, and SIRI is the best predictor of the degree of atherosclerosis of all the other assessed blood parameters.
Gene expression differences in differentially methylated sites associated with HIV status and cocaine use
Authors: Earley Eric J. , Quach Bryan C. , Fang Fang , Bierut Laura J. , Milloy M-J S. , Hayashi Kanna , DeBeck Kora , Hancock Dana B. , Aouizerat Bradley E. , Xu Ke , Johnson Eric Otto 
Published: November 2024

AbstractBackgroundEpigenome studies of human HIV-1 (HIV) in whole blood have uncovered a growing list of differentially methylated genes associated with either HIV acquisition, disease progression, or both. Cocaine use is associated with increased disease severity, and methylation changes in some of the HIV-associated genes mediate this effect. Many of these genes are critical players in innate immune response, including both regulators and targets of interferon-alpha and NF-kB activation. However, no study to date has evaluated the gene expression dynamics for these genes in the context of HIV.MethodsTargeted gene expression analyses were performed on 588 people who used illicit drugs within a harmonized cohort comprised of the Vancouver People Who Inject Drugs Study (VPWIDS) using RNAseq in whole blood, including 227 people living with HIV (PLWH). Eighteen genes were selected from six recent epigenome-wide association studies to test for differential expression by HIV status. Both gene-level and transcript-level expression changes were estimated using negative binomial regression models.ResultsNine of the 18 target genes exhibited significant upregulation in PLWH after multiple hypothesis testing correction:EPSTI1, IFI44L, IFIT3, MX1, NLRC5, PARP9, PLSCR1, RIN2, andRSAD2. Transcript-level analysis detected additional upregulation of isoforms for genesCD44, RASSF3, andTAP1. Stratified analysis by cocaine use revealedMX1andRSAD2to be exclusively upregulated among PLWH who recently used cocaine. Pathway analysis identified significant dysregulation in the interferon alpha/beta signaling pathway.ConclusionsWe confirm the dysregulation of genes previously reported to have differential methylation among PLWH. Results from this study support the model of epigenetic changes altering gene expression for key immune genes such asNLRC5andMX1, and demonstrate systemic dysregulation of genes involved in innate immune function.
Comparative Analysis of MS/MS Search Algorithms in Label-Free Shotgun Proteomics for Monitoring Host-Cell Proteins Using Trapped Ion Mobility and ddaPASEF
Authors: Khalil Somar , Plisnier Michel 
Published: November 2024

ABSTRACTHost cell proteins (HCPs) are critical quality attributes that can impact the safety, efficacy, and quality of biotherapeutics. Label-free shotgun proteomics is a vital approach for HCP monitoring, yet the choice of tandem mass spectrometry (MS/MS) search algorithms directly influences identification depth and quantification reliability. In this study, six prominent MS/MS search tools—Mascot, MaxQuant, SpectroMine, FragPipe, Byos, and PEAKS—were systematically benchmarked for their performance on complex samples spiked with isotopically labeled proteins from Chinese hamster ovary cells, using trapped ion mobility spectrometry and parallel accumulation-serial fragmentation in data-dependent acquisition mode. Key performance metrics, including peptide and protein identifications, data extraction precision, fold-change (FC) accuracy, linearity, and measurement trueness, were evaluated. A Bayesian modeling framework with Hamiltonian Monte Carlo sampling was employed to robustly estimate FC means and variances, alongside local false discovery rates through posterior probability calibration. Bayesian decision theory, implemented via expected utility maximization, was used to balance accuracy against posterior uncertainty, providing a probabilistic assessment of each tool’s performance. Through this cumulative analysis, variability across tools was observed: some excelled in identification sensitivity and protein coverage, others in quantitative accuracy with minimal bias, and a few offered balanced performance across metrics. This study establishes a rigorous, data-driven framework for tool benchmarking, delivering insights for selecting MS/MS tools suited to HCP monitoring in biopharmaceutical development.Graphical abstract