bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biopolymers can be used for consolidation of lunar and Martian regoliths
Authors: Gupta Nitin , Kumar Aloke , Viswanathan Koushik 
Published: January 2025

AbstractCreating long-term extraterrestrial habitats to support continuous human occupation requires structures that can bear load, while remaining resilient to large temperature fluctuations. Exploiting locally available regolith is part of a paradigm termedin situresource utilization (ISRU) that advocates minimal dependence on terrestrial supplies via local resource exploitation for construction. In this work, we report on a consolidation method for making load-bearing structures out of lunar and Martian regolith simulants using biopolymer binders. We quantify the compressive and tensile strength of the final brick-like structures, termed biopolymer regolith composites, and investigate their dependence on biopolymer concentration and chemistry. A pressure-assisted die casting process is developed that can produce bricks with compressive strengths of ∼ 15 MPa and tensile strengths of around 2 MPa, from regolith simulants. We finally report on the performance of these bricks under large temperature and pressure variations and find that their strengths remain unchanged. We believe that this makes biopolymer regolith composite bricks suitable candidates for use in harsh extraterrestrial environments, while adhering to the guidelines of the ISRU paradigm.Keyword:Lunar regolith; Martian regolith; Space habitation; Extraterrestrial construction; Biopolymers; Regolith simulant
Deciphering Functional Heterogeneity of Cancer-Associated Fibroblasts Across Molecular Subtypes of Breast Cancer
Authors: Kashyap Dharambir 
Published: January 2025

AbstractBreast cancer heterogeneity has been well understood based solely on tumor components. However, the tumor microenvironment, which plays a crucial role in cancer by regulating tumor cells’ differentiation, maturation, and malignant potential, remains under-explored. This study conducted high-throughput RNA-Seq analysis on fresh breast cancer tissues from each molecular subtype and a pure population of cancer-associated fibroblasts (CAFs) isolated from cancer tissue and adjacent normal parts. Based on their functions, we identified three populations of CAFs: a) immune response-related, b) ECM remodeling, and c) calcium/protein binding. Validation of differentially expressed genes among these CAF populations revealed subtype-specific correlations. For instance, CAFs expressing immune response-related genes were significantly enriched in Luminal A/B and TNBC (log +1-fold; p =0.00047), compared to Her-2 positive (log -2.3-fold; p =0.0026). ECM remodeling genes exhibited greater expression in Her-2 positive and TNBC (log +4 to +11-fold; p =7.87E-08) when compared to Luminal subtypes (log +1.5-fold to +6-fold; p =8.66E-05). Calcium binding genes displayed overall similar expression across breast cancer subtypes. Thus, this study identified and underscored the functional heterogeneity of CAFs within the tumor microenvironment across the molecular subtypes of breast cancer.
Prospective screening for monkeypox infection among men who have sex with men at an infectious diseases’ outpatient clinic in Copenhagen, Denmark
Authors: Miranda Freire De Andrade Nuno Felipe , Pinholt Mette , Korsholm Mindedahl Nyamadi Julie Maria , Kronborg Gitte , Engsig Frederik Neess 
Published: January 2025

AbstractSince 2022, over 102,000 cases of mpox clade IIb have been reported worldwide, primarily affecting men who have sex with men. Key risk factors include the use of HIV pre-exposure prophylaxis (PrEP) and HIV infection. In Denmark, the smallpox vaccine (Imvanex®) has been available to at-risk individuals since 2022. However, cases of reinfection with mpox have raised concerns about immunity, asymptomatic transmission.Between August and October 2023, we screened 123 PrEP users for mpox at an outpatient clinic at Copenhagen University Hospital Hvidovre, Denmark. Mpox PCR testing was conducted using rectal swabs. Among the participants, 97% had received at least one dose of the mpox vaccine. No mpox cases were detected.These findings suggest that, in a highly vaccinated high-risk population during a period of very low mpox prevalence in Denmark, asymptomatic mpox circulation is unlikely. The results support the current strategy of focusing mpox testing on symptomatic individuals and contact tracing during low-prevalence periods with high vaccination coverage.
Potential of ChatGPT in Youth Mental Health Emergency Triage: Comparative Analysis with Clinicians
Authors: Thotapalli Samanvith , Yilanli Musa , McKay Ian , Leever William , Youngstrom Eric , Harvey-Nuckles Karah , Lowder Kimberly , Schweitzer Steffanie , Sunderland Erin , Jackson Daniel I. , Sezgin Emre 
Published: January 2025

ABSTRACTBackgroundLarge language models (LLMs), such as GPT-4, are increasingly integrated into healthcare to support clinicians in making informed decisions. Given ChatGPT’s potential, it is necessary to explore such applications as a support tool, particularly within mental health telephone triage services. This study evaluates whether GPT-4 models can accurately triage psychiatric emergency vignettes and compares its performance to clinicians.MethodsA cross-sectional study with qualitative analysis was conducted. Two clinical psychologists developed 22 psychiatric emergency vignettes. Responses were generated by three versions of GPT-4 (GPT-4o, GPT-4o Mini, GPT-4 Legacy) using ChatGPT, and two independent nurse practitioners (clinicians). The responses focused on three triage criteria: risk (Low 1-3 High), admission (Yes-1; No-2), and urgency (Low 1-3 High).ResultsSubstantial interrater reliability was observed between clinicians and GPT-4 responses across the three triage criteria (Cohen’s Kappa: Admission = 0.77; Risk = 0.78; Urgency = 0.76). Among the GPT-4 models, Kappa values indicated moderate to substantial agreement (Fleiss’ Kappa: Admission = 0.69, Risk = 0.63, Urgency = 0.72). The mean scores for triage criteria responses between GPT-4 models and clinicians exhibited consistent patterns with minimal variability. Admission responses had a mean score of 1.73 (SD = 0.45), risk scores had a mean of 2.12 (SD= 0.83), and urgency scores averaged 2.27 (SD = 0.44).ConclusionThis study suggests that GPT-4 models could be leveraged as a support tool in mental health telephone triage, particularly for psychiatric emergencies. While findings are promising, further research is required to confirm clinical relevance.
One-carbon metabolism-related compounds are associated with epigenetic aging biomarkers: Results from National Health and Nutrition Examination Survey (NHANES) 1999-2002
Authors: Bozack Anne , Khodasevich Dennis , Nwanaji-Enwerem Jamaji C. , Gladish Nicole , Shen Hanyang , Daredia Saher , Gamble Mary , Needham Belinda L. , Rehkopf David H. , Cardenas Andres 
Published: January 2025

AbstractBackgroundOne-carbon metabolism (OCM), a biochemical pathway dependent on micronutrients including folate and vitamin B12, plays an essential role in aging-related physiological processes. DNA methylation-based aging biomarkers may be influenced by OCM.ObjectiveThis study investigated associations of OCM-related biomarkers with epigenetic aging biomarkers in the National Health and Nutrition Examination Survey (NHANES).MethodsBlood DNA methylation was measured in adults aged ≥50 years in the 1999-2000 and 2001-2002 cycles of NHANES. The following epigenetic aging biomarkers were included: Horvath1, Horvath2, Hannum, PhenoAge, GrimAge2, DunedinPoAm, and DNA methylation telomere length (DNAmTL). We tested for associations of serum folate, red blood cell (RBC) folate, vitamin B12, homocysteine, and methylmalonic acid concentrations with epigenetic age deviation (EAD) among 2,346 participants with epigenetic and nutritional status biomarkers using survey weighted general linear regression models adjusting for sociodemographics, BMI, and behavioral factors.ResultsA doubling of serum folate concentration was associated with −0.82 years (95% confidence interval (CI) = −1.40, −0.23) lower GrimAge EAD, −0.13 SDs (−0.22, −0.03) lower DunedinPoAm, and 0.02 kb (0.00, 0.04) greater DNAmTL EAD. Associations were attenuated after adjusting for smoking status and alcohol intake, folate antagonists. Conversely, a doubling in homocysteine concentration was associated with 1.05 years (0.06, 2.04) greater PhenoAge EAD, 1.93 years (1.16, 2.71) greater GrimAge2 EAD, and 0.26 SDs (0.10, 0.41) greater DunedinPoAm. Associations with GrimAge2 EAD and DunedinPoAm were robust to alcohol and smoking adjustment.ConclusionsIn a nationally representative sample of U.S. adults, greater folate, a carbon donor, was associated with lower EAD, and greater homocysteine, an indicator of OCM deficiencies, was associated with greater EAD; however, some associations were influenced by smoking status. Future research should focus on high-risk populations. Randomized controlled trials with long-term follow-up are also needed to established causality and investigate the clinical relevance of changes in EAD.
Endocannabinoids facilitate transitory reward engagement through retrograde gain-control
Authors: Marcus David J. , English Anthony E. , Chun Gunn , Seth Emmaline F. , Oomen Rachel , Hwang Sabrina , Wells Bailey , Piantadosi Sean C. , Suko Azra , Li Yulong , Zweifel Larry S. , Land Benjamin B. , Stella Nephi , Bruchas Michael R. 
Published: January 2025

AbstractNeuromodulatory signaling is poised to serve as a neural mechanism for gain control, acting as a crucial tuning factor to influence neuronal activity by dynamically shaping excitatory and inhibitory fast neurotransmission. The endocannabinoid (eCB) signaling system, the most widely expressed neuromodulatory system in the mammalian brain, is known to filter excitatory and inhibitory inputs through retrograde, pre-synaptic action. However, whether eCBs exert retrograde gain control to ultimately facilitate reward-seeking behaviors in freely moving mammals is not established. Using a suite of in vivo physiological, imaging, genetic and machine learning-based approaches, we report a fundamental role for eCBs in controlling behavioral engagement in reward-seeking behavior through a defined thalamo-striatal circuit.
DNA topological regulation by topoisomerase IIβ-DNA-PK interaction is important for controlled hypoxia-inducible gene expression
Authors: Bunch Heeyoun , Park Jihye , Seu Min-Seok , Farmakes Jasmin K. , Lee Jeongho , Yoo Ji-Seung , Lu Huiming , Yoon Young-Ran , Jeon Jae-Han , Schellenberg Matthew J. , Kang Keunsoo , Calderwood Stuart K. , Davis Anthony J. 
Published: January 2025

ABSTRACTHypoxic stress responses are crucial for cellular and organismal survival and provoke gene regulation in diverse biological pathways including cell cycle progression and energy metabolism. Here, we show that topoisomerase IIβ (TOP2B) regulates DNA topology and transcription in hypoxia-inducible genes (HIGs) in a DNA-PK-dependent manner. Cellular, mutational, and genomic analyses showed an antagonistic relationship between TOP2B and DNA-PK activities. TOP2B associates with HIGs and represses transcription by suppressing negative supercoiling formation under normoxic conditions. Under hypoxia, TOP2B is released, while DNA-PK and HIF1α are recruited to and activate HIGs. Intriguingly, DNA-PK is responsible for TOP2B to function repressively because DNA-PK knockout overturns both TOP2B release and activity and increases the expression of a number of HIGs. Mutational and genomic analyses confirmed that DNA-PK phosphorylates TOP2B at T1403 to stimulate TOP2B catalysis to suppress the open DNA conformation, which is important for controlled HIG transcription. Collectively, our findings suggest a novel role for TOP2B and DNA-PK-mediated TOP2B regulation as important transcriptional elements in HIG expression. We propose that TOP2B catalysis modulated by protein phosphorylation is coordinated with transcriptional states and determines DNA topology to regulate Pol II transcription.
An improved rapid and sensitive long amplicon method for nanopore-based RSV whole genome sequencing
Authors: Dong Xiaomin , Edwards Steven , Deng Yi-Mo , Dapat Clyde , Hirankitti Arada , Wordsworth Rachel , Whitney Paul , Baird Rob , Freeman Kevin , Daley Andrew J , Barr Ian G. 
Published: January 2025

AbstractBackgroundWhole-genome sequencing (WGS) provides critical insights into the Respiratory syncytial virus (RSV) transmission and any emerging mutations that could impair the efficacy of monoclonal antibodies or vaccines that have been recently licenced for clinical use worldwide. However, the ability to sequence RSV genomes at large scale is limited by expensive and time-consuming sequencing methods. Oxford Nanopore Technology (ONT) offers significant improvements in next generation sequencing (NGS) both in turnaround time and cost, compared to other platforms for viral WGS.MethodsWe have developed and modified an RSV long amplicon-based WGS protocol for the ONT platform using a one-step multiplex RT-PCR assay and the rapid library barcoding kit. 135 RSV positive Australian clinical specimens (91 RSV-A and 44 RSV-B) sampled in 2023 with Cycle threshold (Ct) values between 14 to 35 were tested in this study. This ONT workflow was compared with other recent RSV WGS amplification assays based on short amplicons.ResultsA PCR amplicon clean-up step prior to library preparation significantly improved WGS result for samples with poor amplicon generation, but it is not necessary or beneficial for ones that generated high concentrations of amplicons. Overall, a success rate of 85.9% was achieved for WGS. This method performed as well as the more complex short amplicon methods in terms of genome coverage and sequencing depth.ConclusionsThe workflow described here was highly successful in generating RSV WGS on ONT platform and had improved turnaround times and excellent results with RSV clinical samples with Ct values up to 30.
Delineating JunB’s Crucial Function in Mature Th17 Cells through Inducible Targeted Protein Degradation
Authors: Whitaker Charles , Sasaki Daiki , Miyagi Mio , Hirota Masato , Tamai Miho , Wang Ke , Chien Hsiao-Chiao , Sarkar Shukla , Toma Takeshi , Taira Naoyuki , Ishikawa Hiroki 
Published: January 2025

AbstractThe AP-1 transcription factor JunB is essential for the differentiation of pathogenic T helper 17 (Th17) cells, which are key mediators of autoimmune diseases such as multiple sclerosis and colitis. While the importance of JunB during Th17 polarization is known, its role in mature Th17 cells—critical therapeutic targets in these diseases—remains unclear. In this study, we employed the dTAG system, a targeted protein degradation approach, to deplete JunB in Th17 cells generated bothin vitroandin vivo. During pathogenic Th17 cell differentiation, JunB degradation replicated known effects of JunB deficiency, including reduced expression of interleukin (IL)-17A and the genes encoding RORγt (Rorc) and the IL-23 receptor (Il23r). In contrast, in mature pathogenic Th17 cells, JunB degradation downregulatedIl23rwithout affecting IL-17A orRorcexpression. Furthermore, JunB degradation compromised the viability of mature pathogenic Th17 cells. Transcriptomic analyses revealed that JunB regulates distinct gene sets during Th17 polarization compared to mature Th17 cells. The geneInhba, which encodes activin A, was identified as a JunB target in both stages. Supplementation with activin A restored IL-17A andRorcexpression during pathogenic Th17 cell differentiation. These findings demonstrate that JunB maintains mature pathogenic Th17 cell phenotypes, including IL-23 receptor expression, and supports pathogenic Th17 cell survival. As IL-23 signaling is crucial for sustaining pathogenic Th17 cells, targeting JunB may offer a therapeutic strategy to limit Th17-driven autoimmune inflammation.
Recent breeding experience improves egg ejection behaviour
Authors: Mari Lisandrina , Hughes Anna E. , Troscianko Jolyon , Tomášek Oldřich , Albrecht Tomáš , Jelínek Václav , Šulc Michal 
Published: January 2025

AbstractRecognizing one’s own eggs is crucial for birds, especially for hosts of brood parasites that must identify and reject different-looking parasitic eggs. While birds seem to possess a ‘template image’ of their eggs, whether it is innate or learnt remains unclear. We addressed this question by experimentally inserting either artificial mimetic eggs (ME) or non-mimetic eggs (NME) into the nests of barn swallows (Hirundo rustica) during pre-laying stage. Our individually marked population allowed a unique comparison between naïve first-time breeders and experienced females, as well as females with ‘old’ (from a previous season) and ‘recent’ (from the previous breeding attempt within the same season) experience allowing to investigate the role of memory. We found that both naïve and experienced females ejected ME and NME at similar rates, indicating that the template image is neither innate nor learnt and does not play a primary role in egg recognition. Instead, our findings suggest that awareness of own egg-laying is the crucial mechanism at play, and may facilitate nest sanitation behaviour. Finally, we provide the first evidence that this mechanism improves with recent breeding experience. Future studies should investigate the role of non-visual factors that may modulate nest sanitation, such as endocrine regulation.
Modeling mucociliary mixing and transport at tissue scale
Authors: Xu Ling , Senaei Pejman , Jiang Yi 
Published: January 2025

AbstractMucociliary clearance is the primary defense mechanism in our respiratory system against aerosol pathogens and allergens. The rhythmic movement of cilia on airway-lining cells propels mucus flow, driving the movement of trapped particles. We want harmful particles, e.g., pathogens and allergens to be transported rapidly out of the airway and beneficial particles, e.g. vaccines and medicine, to stay and disperse. However, the impact of cilia density and distribution on mucociliary mixing and transport at the tissue scale remains poorly understood. We present three-dimensional (3D) simulations of mucociliary mixing and transport at the tissue scale. We investigate the influence of ciliary cluster spacing, metachronal wave, and ciliary density on mucus mixing and transport. Our findings reveal that: (i) cilia clusters produce swirls of mucus flow, their size scales with ciliary density; (ii) a single cilia cluster generates horizontal and upward transport with horizontal mixing; (iii) for three aligned cilia clusters, an optimal cluster spacing exists for achieving maximum horizontal transport; (iv) asynchronous beating among clusters enhances mixing but hinders transport; and (v) the diffusion of particles exhibits spatial inhomogeneity, leading to particle aggregation into discrete groups over time. These discoveries have implications for understanding particle distributions in the airway and contribute to drug delivery design considerations.Author summaryOur airways are exposed to various foreign particles, including allergens, pathogens, and aerosolized vaccines or medications. The mucus coating the airway surface traps these particles, and the beating cilia extending from the ciliated epithelial cells play a crucial role in propelling the flow of mucus to transport the particles out of the airway. This mucociliary clearance process is closely associated with the initiation and progression of airway tissue response, such as allergic responses, infections, and treatment effects. Changes in ciliated cell density or mucus production can significantly impact this process. Conversely, achieving a homogeneous distribution of aerosol drug particles within the airway is essential for optimizing treatment outcomes. We simulate cilia-mucus coupled flow to examine how the motion of cilia influences the transport and mixing of particles in the mucus. Our key findings suggest that an optimal spacing for ciliated cell clusters that enhances directional transport. Intriguingly, while the metachronal wave promotes mixing, it also tends to hinder the overall transport of particles.
Identification of receptor-binding domains of Bacteroidales antibacterial pore-forming toxins
Authors: Borgini Sofia , Iorga Bogdan , Vertommen Didier , Collet Jean-François , Lauber Frédéric 
Published: January 2025

AbstractBacteroidales are abundant Gram-negative bacteria present in the gut microbiota of most animals, including humans, where they carry out vital functions for host health. To thrive in this competitive environment, Bacteroidales use sophisticated weapons to outmatch competitors. Among these, BSAPs (Bacteroidales Secreted Antimicrobial Proteins) represent a novel class of bactericidal pore-forming toxins that are highly specific to their receptor, typically targeting only a single membrane protein or lipopolysaccharide. The molecular determinants conferring this high selectivity remain unknown. In this study, we therefore investigated the model protein BSAP-1 and determined which of its domains is involved in providing receptor specificity. We clearly demonstrate that receptor recognition is entirely driven by the C-terminal domain (CTD) of BSAP-1 using a combination ofin vivocompetition assays andin vitroprotein binding studies. Specifically, we show that deletion of the CTD abrogates BSAP-1 bactericidal activity by preventing receptor binding, while grafting the CTD to unrelated carrier proteins enables CTD-driven interaction with the BSAP-1 receptor. Building upon this discovery, we show that BSAPs can be categorized according to the structure of their CTD and that BSAPs within the same cluster are likely to target the same type of receptor. Additionally, we show that the CTD of BSAP-1 can be repurposed to generate probes for fluorescent labelling of membrane proteins in live cells. In summary, our research demonstrates that BSAP receptor recognition is driven by their CTD and that these can be engineered to develop novel tools for the investigation of Bacteroidales biology.
Mutation experiments with AcrB and MexB D408A mutants indicate the efflux liability of antibiotics
Authors: Ciusa Maria Laura , Ricci Vito , Piddock Laura JV 
Published: January 2025

SummaryBackgroundWe showed that exposure of an AcrB D408A mutant to efflux inhibitors applied evolutionary pressure to select bacteria with the wild typeacrBsequence. This suggested that reversion to wild type can differentiate between efflux inhibitors. Thus, we hypothesized that this experiment could identify inhibitors of the primary RND pump, AcrB or its homologues in other species.ObjectivesTo construct three mutants,Escherichia coliAcrB D408A,Klebsiella pneumoniaeAcrB D408A andPseudomonas aeruginosaMexB D408A and expose the mutants to substrates and non-substrates of AcrB and/or MexB and determine the rate of reversion to wildtypeacrB/mexBsequence.MethodsMutantEscherichia coliAcrB D408A,Klebsiella pneumoniaeAcrB D408A andPseudomonas aeruginosaMexB D408A were constructed with site-directed mutagenesis of the relevant nucleotide in theacrB/mexBgene. Mutants were exposed on agar to substrates and the mutation frequency and mutation rate determined. The MIC of antibiotics and the presence/absence of the D408A substitution was determined for mutants.ResultsExposure to the AcrB substrates chlorpromazine and minocycline reverted the D408A genotypes to wild type in a species-dependent manner. Exposure to a non-AcrB substrate, spectinomycin, did not select wild typeacrB. Chlorpromazine selected for wild typeacrB K. pneumoniaeas it had forS. Typhimurium, whereas minocycline selected for wild typeE. coli acrB. None of the antibiotics selected wild typemexB, including the tested MexB substrates.ConclusionsEvolutionary paths depend upon the genetic background of the species and availability of alternative routes/genetic pathways that can confer resistance/decreased susceptibility to antibiotics.