bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thoracic Aortic Three-Dimensional Geometry
Authors: Beeche Cameron , Dib Marie-Joe , Zhao Bingxin , Azzo Joe David , Tavolinejad Hamed , Maynard Hannah , Duda Jeffrey , Gee James , Salman Oday , BioBank Penn Medicine , Witschey Walter R. , Chirinos Julio A. 
Published: May 2024

AbstractBackgroundAortic structure impacts cardiovascular health through multiple mechanisms. Aortic structural degeneration occurs with aging, increasing left ventricular afterload and promoting increased arterial pulsatility and target organ damage. Despite the impact of aortic structure on cardiovascular health, three-dimensional (3D) aortic geometry has not been comprehensively characterized in large populations.MethodsWe segmented the complete thoracic aorta using a deep learning architecture and used morphological image operations to extract multiple aortic geometric phenotypes (AGPs, including diameter, length, curvature, and tortuosity) across various subsegments of the thoracic aorta. We deployed our segmentation approach on imaging scans from 54,241 participants in the UK Biobank and 8,456 participants in the Penn Medicine Biobank.ConclusionOur method provides a fully automated approach towards quantifying the three-dimensional structural parameters of the aorta. This approach expands the available phenotypes in two large representative biobanks and will allow large-scale studies to elucidate the biology and clinical consequences of aortic degeneration related to aging and disease states.
Open-Channel Droplet Microfluidic Platform for Passive Generation of Human Sperm Microdroplets
Authors: Nicholson Tristan M. , Tokihiro Jodie C. , Tu Wan-chen , Khor Jian Wei , Lee Ulri N. , Berthier Erwin , Amory John K. , Walsh Thomas J. , Muller Charles H. , Theberge Ashleigh B. 
Published: May 2024

ABSTRACTSperm cryopreservation is important for many individuals across the globe. Recent studies show that vitrification is a valuable approach for maintaining sperm quality after freeze-thawing processes and requires sub-microliter to microliter volumes. A major challenge for the adoption of vitrification in fertility laboratories is the ability to pipette small volumes of sample. Here, we present an open droplet generator that leverages open-channel microfluidics to passively generate sub-microliter to microliter volumes of purified human sperm samples and preserves sperm kinematics. We conclude that our platform is compatible with human sperm, an important foundation for future implementation of vitrification in fertility laboratories.Table of contents artwork
Exploiting gene expression profiles of circulating extracellular vesicles for breast cancer detection
Authors: Gupta Aritra , Ahmed Rosina , Agarwal Sanjit , Mukherjee Geetashree , Desai Kartiki V. 
Published: May 2024

AbstractBackgroundLiquid biopsy-based biomarkers offer several advantages since they are minimally invasive, can be useful in longitudinal monitoring of the disease and have higher patient compliance. We hypothesize that RNA content of circulating EVs differs in breast cancer patients and healthy women. EV RNAs may provide an opportunity to diagnose, detect subtypes and metastatic states.Experimental DesignRNA-seq analysis and qRT-PCR from matched tumor biopsy, circulating EVs from breast cancer patients (EV-C) and healthy donors (EV-H) was performed to find genes that discriminate between these groups.ResultsEV-C to EV-H comparison yielded 320 DEGs (adjustedpvalue ≤0.05) enriched for cancer related pathways like Myc, Reactive oxygen species, and Angiogenesis. Allograft rejection and Interferon pathway genes were over-represented in the cancer group. Top 6 genes were validated by qRT-PCR in a validation cohort. 5 genes consistently and correctly classified cancer and healthy groups. An independent set of 374 and 640 DEGs could segregate ER positive/ER negative and non-metastatic versus metastatic samples, respectively. EVs from metastatic samples had higher variability in gene expression patterns whereas those from non-metastatic samples showed better correlation. Ability of 4 genes to classify metastases state was explored.ConclusionWe report five EV RNAs that can be used to diagnose breast cancer in a subtype independent manner. Initial analysis indicates that EV RNA content differs based on subtype specificity and metastasis status.
Empowering bioinformatics communities with Nextflow and nf-core
Authors: Langer Björn E. , Amaral Andreia , Baudement Marie-Odile , Bonath Franziska , Charles Mathieu , Chitneedi Praveen Krishna , Clark Emily L. , Di Tommaso Paolo , Djebali Sarah , Ewels Philip A. , Eynard Sonia , Yates James A. Fellows , Fischer Daniel , Floden Evan W. , Foissac Sylvain , Gabernet Gisela , Garcia Maxime U. , Gillard Gareth , Gundappa Manu Kumar , Guyomar Cervin , Hakkaart Christopher , Hanssen Friederike , Harrison Peter W. , Hörtenhuber Matthias , Kurylo Cyril , Kühn Christa , Lagarrigue Sandrine , Lallias Delphine , Macqueen Daniel J. , Miller Edmund , Mir-Pedrol Júlia , Moreira Gabriel Costa Monteiro , Nahnsen Sven , Patel Harshil , Peltzer Alexander , Pitel Frederique , Ramayo-Caldas Yuliaxis , da Câmara Ribeiro-Dantas Marcel , Rocha Dominique , Salavati Mazdak , Sokolov Alexey , Espinosa-Carrasco Jose , Notredame Cedric ,   the nf-core community.
Published: May 2024

AbstractStandardised analysis pipelines are an important part of FAIR bioinformatics research. Over the last decade, there has been a notable shift from point-and-click pipeline solutions such as Galaxy towards command-line solutions such as Nextflow and Snakemake. We report on recent developments in the nf-core and Nextflow frameworks that have led to widespread adoption across many scientific communities. We describe how adopting nf-core standards enables faster development, improved interoperability, and collaboration with the >8,000 members of the nf-core community. The recent development of Nextflow Domain-Specific Language 2 (DSL2) allows pipeline components to be shared and combined across projects. The nf-core community has harnessed this with a library of modules and subworkflows that can be integrated into any Nextflow pipeline, enabling research communities to progressively transition to nf-core best practices. We present a case study of nf-core adoption by six European research consortia, grouped under the EuroFAANG umbrella and dedicated to farmed animal genomics. We believe that the process outlined in this report can inspire many large consortia to seek harmonisation of their data analysis procedures.
Silicification of Cyanobacteria
Authors: Sun Jun , Han Yabo , Thanagaraj Satheeswaran 
Published: May 2024

AbstractThe ability to use dissolved silicon has been found in various oceanic phytoplankton, including eukaryotic diatoms and prokaryotic cyanobacteria. While the silicification process in diatoms has been extensively studied, it is poorly known in cyanobacteria. In this study, the Cyanobacteria (Synechococcus) silicification and its evolutionary relationships of silicon-related proteins with different phytoplankton and algae were compared. Results showed that, compared to others, cyanobacteria have similar silicification proteins as diatoms. In detail, cyanobacteria and diatoms displayed three silicification-related proteins (SIT, Silaffins, and Pleuralins), while several genera showed one or two of them, suggesting that cyanobacteria might have developed a Si related mechanism earlier than the diatoms and other species. Our findings show that, despite cyanobacteria’s earlier silicon mechanism compared to others, they might not use efficient Si accumulation, perhaps adapting unique intracellular elemental variation for their cellular processes for growth potential.
ACKR3 agonism induces heterodimerization with chemokine receptor CXCR4 and attenuates platelet function
Authors: Dicenta-Baunach Valerie , Laspa Zoi , Schaale David , Sigle Manuel , Bayrak Alp , Castor Tatsiana , Pillaiyar Thanigaimalai , Laufer Stefan , Gawaz Meinrad Paul , Rohlfing Anne-Katrin 
Published: May 2024

AbstractBackgroundPlatelet receptors ACKR3 and CXCR4 play a crucial role in a variety of cardio-vascular diseases. Like most chemokine receptors, CXCR4 is a G protein coupled receptor that induces platelet activation. In contrast, the atypical chemokine receptor 3 (ACKR3) lacks the ability to activate heterotrimeric G proteins and its activation leads to platelet inhibition and attenuates thrombus formation. In nucleated cells, heterodimerization of ACKR3 with CXCR4 regulates CXCL12-dependent signaling. The aim of our study was to investigate the formation of ACKR3/CXCR4 heterodimers in platelets and the subsequent consequences for platelet function.Methods and resultsUsing a microscopy proximity ligation assay (PLA, Duolink®) to screen for CXCR4/ACKR3 heterodimerization inducing compounds, we found that ACKR3 agonism but not conventional platelet agonists or endogen ligands lead to heterodimer formation. To further characterize the formation of ACKR3/CXCR4 heterodimers, we studied the CXCL12-dependent platelet activation via CXCR4. Both, CXCL12-dependent platelet aggregation and collagen-dependentex vivothrombus formation were significantly downregulated by ACKR3 agonism. Moreover, platelet intracellular calcium and Akt signaling were increased by CXCL12 and again suppressed by ACKR3-specific agonists. Previously, CXCL12 was shown to decrease platelet cAMP levels via CXCR4. Treatment with a specific ACKR3 agonist counteracted this CXCL12/CXCR4-dependent cAMP decrease.ConclusionOur results reveal that the formation of platelet ACKR3/CXCR4 heterodimers is dependent on ACKR3 rather than CXCR4. Furthermore, ACKR3 agonism induced heterodimerization is associated with mitigating CXCL12/CXCR4-dependent platelet activation possibly by modulating CXCR4-dependent G protein signaling. Our results indicate possible ACKR3 agonist functions and reinforce the potential therapeutic applications of ACKR3 agonists.Abstract FigureGraphical abstract:CXCR4/ACKR3 heterodimerization in platelets.
The effects of pressure on anticipatory postural adjustments during a jump shot in basketball
Authors: Konno Kiyohiro , Itaya Atsushi , Kizuka Tomohiro , Ono Seiji 
Published: May 2024

AbstractBackgroundAnticipatory postural adjustments (APAs) play an important role in feedforward control of dynamic movement, such as jump shot performance in basketball. It is known that jump shot performance declines under pressure from a defender (shot blocker).Research questionDoes pressure from a shot blocker affect APAs of a jump shot in basketball? Is jump shot performance in basketball associated with APAs?MethodsFourteen healthy male university basketball players performed jump shots under pressure and non-pressure (free) conditions by a shot blocker. Using a force plate, the APAs were defined as occurring until the point of thrust (TH) phase, and ground reaction force (GRF) and center of pressure (COP) at that moment were assessed. To assess jump shot performance, the maximum GRF during the TH phase (THmax), jumping height, and success score of the shot (accuracy score: AS) were measured by using the vertical component of the force plate. Two-way ANOVA examined the effects of the phase and condition on APA duration. Pairwise t-tests analyzed pressure effects on subjective pressure intensity, AS, and kinetics measures. Relationships between condition changes in AS and COP or GRF variables were assessed via Pearson correlations. Differences between the pressure and free conditions were denoted by Δ.ResultsThe APA duration was shorter under the pressure condition compared to the free condition. The THmaxand jump height values were greater under the pressure condition relative to the free condition. Across conditions, changes in COP variables were significantly and negatively correlated with AS.SignificanceThe results of this study suggest that pressure from a shot blocker shortens APA duration and decreases jump shot performance. Additionally, by measuring players’ APAs and evaluating relationships with jump shooting proficiency, APA variables could potentially serve as indicators of skill expertise.
Probing the effects of polysaccharide hydrogel composition on the viability and pro-angiogenic function of human adipose-derived stromal cells
Authors: Serack Fiona E. , Fennell Kaylee A. , Iliopoulos Christina , Walker John T. , Ronald John A. , Amsden Brian G. , Hess David A. , Flynn Lauren E. 
Published: May 2024

AbstractCell therapies harnessing the pro-vascular regenerative capacities of mesenchymal stromal cell (MSC) populations, including human adipose-derived stromal cells (hASCs), have generated considerable interest as an emerging treatment strategy for peripheral arterial disease (PAD) and its progression to critical limb ischemia (CLI). There is evidence to support that polysaccharide hydrogels can enhance therapeutic efficacy when applied as minimally-invasive delivery systems to support MSC survival and retention within ischemic tissues. However, there has been limited research to date on the effects of hydrogel composition on the phenotype and function of encapsulated cell populations. Recognizing this knowledge gap, this study compared the pro-angiogenic function of hASCs encapsulated in distinct but similarly-modified natural polysaccharide hydrogels composed of methacrylated glycol chitosan (MGC) and methacrylated hyaluronic acid (MHA). Initialin vitrostudies confirmed high viability (>85%) of the hASCs following encapsulation and culture in the MGC and MHA hydrogels over 14 days, with a decrease in the cell density observed over time. Moreover, higher levels of a variety of secreted pro-angiogenic and immunomodulatory factors were detected in conditioned media samples collected from the hASCs encapsulated in the MGC-based hydrogels compared to the MHA hydrogels. Subsequent testing focused on comparing hASC delivery within the MGC and MHA hydrogels to saline controls in a femoral artery ligation-induced CLI (FAL-CLI) model in athymicnu/numice over 28 days. For thein vivostudies, the hASCs were engineered to express tdTomato and firefly luciferase to quantitatively compare the efficacy of the two platforms in supporting the localized retention of viable ASCs through longitudinal cell tracking with bioluminescence imaging (BLI). Interestingly, hASC retention was significantly enhanced when the cells were delivered in the MHA hydrogels as compared to the MGC hydrogels or saline. However, laser Doppler perfusion imaging (LDPI) indicated that the restoration of hindlimb perfusion was similar between the treatment groups and controls. These findings were corroborated by endpoint immunofluorescence (IF) staining showing similar levels of CD31+cells in the ligated limbs at 28 days in all groups. Overall, this study demonstrates that enhanced MSC retention may be insufficient to augment vascular regeneration, emphasizing the complexity of designing biomaterials platforms for MSC delivery for therapeutic angiogenesis. In addition, the data points to a potential challenge in approaches that seek to harness the paracrine functionality of MSCs, as strategies that increase the secretion of immunomodulatory factors that can aid in regeneration may also lead to more rapid MSC clearancein vivo.
LGR4 is essential for maintaining β-cell homeostasis through suppression of RANK
Authors: Filipowska Joanna , Cisneros Zelda , Leon-Rivera Nancy , Wang Peng , Kang Randy , Lu Geming , Yuan Yate-Ching , Bhattacharya Supriyo , Dhawan Sangeeta , Garcia-Ocaña Adolfo , Kondegowda Nagesha Guthalu , Vasavada Rupangi C. 
Published: May 2024

AbstractPancreatic β-cell stress contributes to diabetes progression. This study demonstrates that Leucine-rich repeat-containing G-protein-coupled-receptor-4 (LGR4) is critical for maintaining β-cell health and is modulated by stressors.In vitro,Lgr4knockdown decreases proliferation and survival in rodent β-cells, while overexpression protects against cytokine-induced cell death in rodent and human β-cells. Mechanistically, LGR4 suppresses Receptor Activator of Nuclear Factor Kappa B (NFκB) (RANK) and its subsequent activation of NFκB to protect β-cells. β-cell-specificLgr4-conditional knockout (cko) mice exhibit normal glucose homeostasis but increased β-cell death in both sexes and decreased proliferation only in females. MaleLgr4cko mice under stress display reduced β-cell proliferation and a further increase in β-cell death. Upon aging, both male and femaleLgr4cko mice display impaired β-cell homeostasis, however, only female mice are glucose intolerant with decreased plasma insulin. We show that LGR4 is required for maintaining β-cell health under basal and stress-induced conditions, through suppression of RANK.TeaserLGR4 receptor is critical for maintaining β-cell health under basal and stressed conditions, through suppression of RANK.
Patient-derived tumor explant models of tumor immune microenvironment reveal distinct and reproducible immunotherapy responses
Authors: Turpin Rita , Peltonen Karita , Rannikko Jenna H. , Liu Ruixian , Kumari Anita N. , Nicorici Daniel , Lee Moon Hee , Mutka Minna , Kovanen Panu E. , Niinikoski Laura , Meretoja Tuomo , Mattson Johanna , Järvinen Petrus , Lahdensuo Kanerva , Järvinen Riikka , Tornberg Sara , Mirtti Tuomas , Boström Pia , Koskivuo Ilkka , Thotakura Anil , Pouwels Jeroen , Hollmén Maija , Mustjoki Satu , Klefström Juha 
Published: May 2024

ABSTRACTTumor-resident immune cells play a crucial role in eliciting anti-tumor immunity and immunomodulatory drug responses, yet these functions have been difficult to study without tractable models of tumor immune microenvironment (TIME). Patient-derivedex vivomodels contain authentic resident immune cells and therefore, could provide new mechanistic insights into how TIME responds to tumor or immune cell-directed therapies. Here, we assessed the reproducibility and robustness of immunomodulatory drug responses across two differentex vivomodels of breast cancer TIME and one of renal cell carcinoma. These independently developed TIME models were treated with a panel of clinically relevant immunomodulators, revealing remarkably similar changes in gene expression and cytokine profiles among the three models in response to T cell activation and STING-agonism while still preserving individual patient-specific response patterns. Moreover, we found two common core signatures of adaptive or innate immune responses present across all three models and both types of cancer, potentially serving as a benchmark for drug-induced immune activation inex vivomodels of TIME. The robust reproducibility of immunomodulatory drug responses observed across diverseex vivomodels of TIME underscores the significance of human patient-derived models in elucidating the complexities of antitumor immunity and therapeutic interventions.
Caspase-11 drives macrophage hyperinflammation in models of Polg-related mitochondrial disease
Authors: VanPortfliet Jordyn J. , Lei Yuanjiu , Ramanathan Muthumeena , Martinez Camila Guerra , Wong Jessica , Stodola Tim J. , Hoffmann Brian R. , Pflug Kathryn , Sitcheran Raquel , Kneeland Stephen C. , Murray Stephen A. , McGuire Peter. J. , Cannon Carolyn L. , West A. Phillip 
Published: May 2024

AbstractMitochondrial diseases (MtD) represent a significant public health challenge due to their heterogenous clinical presentation, often severe and progressive symptoms, and lack of effective therapies. Environmental exposures, such bacterial and viral infection, can further compromise mitochondrial function and exacerbate the progression of MtD. Infections in MtD patients more frequently progress to sepsis, pneumonia, and other detrimental inflammatory endpoints. However, the underlying immune alterations that enhance immunopathology in MtD remain unclear, constituting a key gap in knowledge that complicates treatment and increases mortality in this vulnerable population. Here we employ in vitro and in vivo approaches to clarify the molecular and cellular basis for innate immune hyperactivity in models of polymerase gamma (Polg)-related MtD. We reveal that type I interferon (IFN-I)-mediated upregulation of caspase-11 and guanylate-binding proteins (GBPs) increase macrophage sensing of the opportunistic microbePseudomonas aeruginosa(PA) inPolgmutant mice. Furthermore, we show that excessive cytokine secretion and activation of pyroptotic cell death pathways contribute to lung inflammation and morbidity after infection with PA. Our work sheds new light on innate immune dysregulation in MtD and reveals potential targets for limiting infection- and inflammation-related complications in Polg-related MtD.
Targeting PI3K-gamma in myeloid driven tumour immune suppression: A Systematic Review and Meta-Analysis of the Preclinical Literature
Authors: Xu H , Russell SN , Steiner K , O’Neill E , Jones KI 
Published: May 2024

AbstractThe intricate interplay between immune and stromal cells within the tumour microenvironment (TME) significantly influences tumour progression. Myeloid cells, including tumour-associated macrophages (TAMs), neutrophils (TANs), and myeloid-derived suppressor cells (MDSCs), contribute to immune suppression in the TME1,2. This poses a significant challenge for novel immunotherapeutics that rely on host immunity to exert their effect. This systematic review explores the preclinical evidence surrounding the inhibition of phosphoinositide 3-kinase gamma (PI3Kγ) as a strategy to reverse myeloid-driven immune suppression in solid tumours.EMBASE, MEDLINE, and PubMed databases were searched on 6thOctober 2022 using keyword and subject heading terms to capture relevant studies. The studies, focusing on PI3Kγ inhibition in animal models, were subjected to predefined inclusion and exclusion criteria. Extracted data included tumour growth kinetics, survival endpoints, and immunological responses which were meta-analysed. PRISMA and MOOSE guidelines were followed.A total of 36 studies covering 73 animal models were included in the review and meta-analysis. Tumour models covered breast, colorectal, lung, skin, pancreas, brain, liver, prostate, head and neck, soft tissue, gastric, and oral cancer. The predominant PI3Kγ inhibitors were IPI-549 and TG100-115, demonstrating favourable specificity for the gamma isoform. Combination therapies, often involving chemotherapy, radiotherapy, immune checkpoint inhibitors, biological agents, or vaccines, were explored in 81% of studies. Analysis of tumour growth kinetics revealed a statistically significant though heterogeneous response to PI3Kγ monotherapy, whereas the tumour growth in combination treated groups were more consistently reduced. Survival analysis showed a pronounced increase in median overall survival with combination therapy.This systematic review provides a comprehensive analysis of preclinical studies investigating PI3Kγ inhibition in myeloid-driven tumour immune suppression. The identified studies underscore the potential of PI3Kγ inhibition in reshaping the TME by modulating myeloid cell functions. The combination of PI3Kγ inhibition with other therapeutic modalities demonstrated enhanced antitumor effects, suggesting a synergistic approach to overcome immune suppression. These findings support the potential of PI3Kγ-targeted therapies, particularly in combination regimens, as a promising avenue for future clinical exploration in diverse solid tumour types.Graphical abstract