bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine vision based frailty assessment for genetically diverse mice
Authors: Sabnis Gautam S. , Churchill Gary A. , Kumar Vivek 
Published: October 2024

1AbstractFrailty indexes (FIs) capture health status in humans and model organisms. To accelerate our understanding of biological aging and carry out scalable interventional studies, high-throughput approaches are necessary. We previously introduced a machine vision-based visual frailty index (vFI) that uses mouse behavior in the open field to assess frailty using C57BL/6J (B6J) data. Aging trajectories are highly genetic and are frequently modeled in genetically diverse animals. In order to extend the vFI to genetically diverse mouse populations, we collect frailty and behavior data on a large cohort of aged Diversity Outbred (DO) mice. Combined with previous data, this represents one of the largest video-based aging behavior datasets to date. Using these data, we build accurate predictive models of frailty, chronological age, and even the proportion of life lived. The extension of automated and objective frailty assessment tools to genetically diverse mice will enable better modeling of aging mechanisms and enable high-throughput interventional aging studies.
In vitro models to mimic tumor endothelial cell-mediated immune cell reprogramming in lung adenocarcinoma
Authors: Krejbich Morgane , Fresquet Judith , Navarro Emilie , Forest Virginie , Cotinat Marine , Isen Valentin , Perdrieau Hortense , Chatelain Camille , Dochez Vincent , Roulois David , Boisgerault Nicolas , Redon Richard , Corre Isabelle , Blanquart Christophe , Treps Lucas 
Published: October 2024

AbstractTumor endothelial (TECs) cells play a critical role in regulating immune responses within the tumor microenvironment (TME). However, the mechanisms by which TECs modulate immune cell population remain unclear, particularly in non-small cell lung cancer (NSCLC). Here, we investigated how NSCLC cells tweak normal endothelial cells (NECs) into TECs and the subsequent effects on immune regulation. NECs were cocultured with various NSCLC cell lines, using 2D and 3D coculture models to evaluate TEC-mediated effects on immune cells. We show that direct coculture led to significant transcriptomic, proteomic and kinomic alterations in TECs, especially in pro-inflammatory pathways. We identified a downregulation of the co-stimulatory molecule OX40L in TECs compared to NECs, suggesting impaired T-cell proliferation support. While TECs showed a limited effect on CD8+ T-cell activation, TECs supported CD4 T-cells polarization into Treg and Th22 subsets. Moreover, TECs also promoted M2-like macrophages polarization, thereby potentially contributing to the TME immunosuppression. State-of-the-art single-cell RNA sequencing of 3D multicellular tumor spheroids (MCTS) revealed distinct TEC subpopulations, including an inflammatory subset with UPR signature. The latter was absent in 2D-cultured NECs but present in freshly isolated and 2D-cultured TECs from NSCLC patients. Importantly, we also identified within MCTS a perivascular M2-like macrophage subset, predicted to interact with TECs with MIF and Midkine signaling. In conclusion, TECs in NSCLC tumors play a pivotal role in remodeling the TME immune landscape by promoting immune suppression. This study highlights the complex immunoregulatory functions of TECs within our differentin vitromodels that mimic aspects of the TME. Our data may provide new insights into potential therapeutic strategies targeting TECs or regulatory signaling to improve the efficacy of immunotherapy in NSCLC.
Mutant p53 regulates cancer cell invasion in complex three-dimensional environments through mevalonate pathway-dependent Rho/ROCK signaling
Authors: Guzman Asja , Kawase Tatsuya , Devanny Alexander J. , Efe Gizem , Navaridas Raúl , Yu Karen , Regunath Kausik , Mercer Iris G. , Avard Rachel C. , Muniz de Queiroz Rafaela , Rustgi Anil K. , Kaufman Laura J. , Prives Carol 
Published: October 2024

AbstractCertain mutations can confer neomorphic gain of function (GOF) activities to the p53 protein that affect cancer progression. Yet the concept of mutant p53 GOF has been challenged. Here, using various strategies to alter the status of mutant versions of p53 in different cell lines, we demonstrate that mutant p53 stimulates cancer cell invasion in three-dimensional environments. Mechanistically, mutant p53 enhances RhoA/ROCK-dependent cell contractility and cell-mediated extracellular matrix (ECM) re-organization via increasing mevalonate pathway-dependent RhoA localization to the membrane. In line with this, RhoA-dependent pro-invasive activity is also mediated by IDI-1, a mevalonate pathway product. Further, the invasion-enhancing effect of mutant p53 is dictated by the biomechanical properties of the surrounding ECM, thereby adding a cell-independent layer of regulation to mutant p53 GOF activity that is mediated by dynamic reciprocal cell-ECM interactions. Together our findings link mutant p53 metabolic GOF activity with an invasive cellular phenotype in physiologically relevant and context-dependent settings.SignificanceThis study addresses the contribution of mutant p53 to the process of cancer cell dissemination in physiologically relevant three-dimensional environments – a key characteristic of metastatic disease. Several mutant p53 proteins display pro-oncogenic activity with respect to cancer cell invasion in 3D environments via mevalonate pathway-dependent Rho/ROCK signaling axis.
Mitochondrial DNA Mutations Linking Leigh Syndrome and Carotid Atherosclerosis: A Study of Shared Genetic Pathways
Authors: Sharma Abdd , Shukla Dhruvam , Ravi Anand Kalambur , Simon Neha 
Published: October 2024

AbstractMitochondrial DNA encodes the genetic information necessary for mitochondrial function. In humans, mitochondrial DNA spans 16,569 base pairs while representing a small fraction of the genetic material in humans. Due to their higher mutation rates compared to nuclear DNA, Mitochondrial DNA mutations are emerging as promising biomarkers for assessing disease predisposition and progression. This in-silico analyzes the correlation between Mitochondrial DNA mutations and two conditions: Leigh syndrome, a severe neurodegenerative disorder, and carotid atherosclerosis, a major cardiovascular disease. We focus on five single nucleotide variants (SNVs) – m.14459G>A, m.13513G>A, m.12315G>A, m.1555A>G, and m.15059G>A – to explore their roles in both diseases. Our findings suggest that mutations m.14459G>A, m.1555A>G, and m.15059G>A contribute to the pathogenesis of both conditions. In contrast, m.12315G>A is linked to MELAS syndrome and carotid atherosclerosis. Interestingly, the m.13513G>A mutation is associated with Leigh syndrome but negatively correlated with atherosclerosis, suggesting a potential protective effect. These SNVs could serve as targets for diagnostic and therapeutic approaches, enhancing our understanding of the genetic basis of these diseases.
Developing a Core Outcome Set for capturing and measuring nurse wellbeing: A Delphi study
Authors: Klepacz Naomi , Baldwin David S. , Simons Gemma 
Published: October 2024

ABSTRACTBackgroundPoor nurse wellbeing is a significant concern, adversely affecting patient care quality and satisfaction, contributing to poor job satisfaction, increased sickness absence and workforce retention issues. There are calls for evidence-based policies and interventions to address poor nurse wellbeing, but no consensus exists on how it should be captured and measured. We used a salutogenic and consensus approach to develop a core outcome set (COS) for capturing and measuring nurse wellbeing.MethodsA Delphi methodology was employed. Participants were recruited from two stakeholder groups: 1) nurse wellbeing professionals, identified through relevant publications, conference/meeting attendance lists, and peer recommendations, and 2) Registered Nurses, recruited via social media, professional nursing bodies, and practitioner networks. The stakeholder panel completed two rounds of an online Delphi survey, rating 43 previously identified wellbeing outcomes on a nine-point Likert Scale, from ‘not important’ to ‘critical’. Consensus was defined as>75% of stakeholders agreeing a wellbeing outcome was critical for inclusion in the COS.ResultsFifty-four stakeholders completed the first Delphi Round, and 45 participated in both rounds. Thirteen wellbeing outcomes met thea-priorithreshold for inclusion in the COS: General Wellbeing, Health, Sleep, Positive Relationships, Personal Safety, Psychological Needs Satisfaction, Psychological Safety, Job Satisfaction, Morale, Life Work Balance, Compassion Satisfaction, Satisfaction with Patient Care, and Good Nursing Practice. The final COS was agreed by the stakeholder panel, without amendments.ConclusionThis study establishes a COS for capturing and measuring nurse wellbeing. Implementing this COS has the potential to enable consistent data collection and evidence synthesis needed to support the development of nurse wellbeing strategies, policies and interventions. Future research will focus on identifying valid and reliable measurement tools.Trial RegistrationThis study was prospectively registered with the COMET initiativewww.comet-initiative.org(Registration: 2433)
Transitions from smoking to exclusive e-cigarette use, dual use, or stopping nicotine use in ALSPAC and their association with modifiable and sociodemographic factors
Authors: Andrayas Alexandria , Heron Jon , Khouja Jasmine , Jones Hannah , Sallis Hannah , Munafò Marcus R , Hines Lindsey , Curnow Elinor 
Published: October 2024

AbstractBackgroundE-cigarettes can aid smoking cessation and reduce carcinogen exposure. Understanding differences in characteristics between young adults in the UK who quit smoking, with or without e-cigarettes, or who dual use can help identify and tailor interventions.MethodsThere were 858 participants in the Avon Longitudinal Study of Parents and Children who reported smoking at 21 years. Transitions to the first reported non-exclusive smoking event were measured at 22-30 years and include stopping nicotine use (not currently smoking nor using e-cigarettes), exclusive e-cigarette use, and dual use (smoking and using e-cigarettes). Associations between these transitions and substance use, sociodemographic, and health characteristics were examined through discrete-time survival analysis. Analyses were adjusted for early life confounders, and weighted to mitigate bias. Multiple imputation was used to analyse partially-observed data.ResultsMore participants reported stopping nicotine use (52%) than using e-cigarettes (dual use = 27%; exclusive e-cigarette use = 9%). Smoking frequently at age 21 (Subdistribution Hazard Ratio [SHR] = 0.28, CI = 0.22-0.35) and having many friends who smoke at age 21 (SHR = 0.64, CI = 0.50-0.81) decreased the likelihood of stopping nicotine use, and increased the likelihood of dual use (frequent smoking SHR = 3.00, CI = 1.96-4.59; peer smoking SHR = 1.55, CI = 1.07-2.24) and exclusive e-cigarette use (frequent smoking SHR = 2.84, CI = 1.26-6.42). Participants with lower education at age 20 were less likely to stop using nicotine (SHR = 0.68, CI = 0.52-0.90), and more likely to dual use (SHR = 1.72, CI = 1.03-2.90). Cannabis use at age 20 (SHR = 0.67, CI = 0.49-0.92), drug use at age 20 (SHR = 0.77, CI = 0.59-0.99), less exercise at age 18 (SHR = 0.71, CI = 0.53-0.95), and parenthood at age 21 (SHR = 0.46, CI = 0.27-0.79) reduced the likelihood of stopping nicotine use. Higher BMI at age 18 (SHR = 1.58, CI = 1.08-2.31) increased the likelihood of dual use.ConclusionsYoung adults who smoke more frequently, have many peers who smoke, have lower education, exercise less, use cannabis or other drugs likely need greater efforts from stop smoking intervention. Those with greater smoking frequency, more friends who smoke or lower education may need additional support to completely switch to e-cigarettes. Others not engaging with e-cigarettes may benefit from targeted interventions to encourage harm reduction.
Light-guided actin polymerization drives directed motility in protocells
Authors: Matsubayashi Hideaki T. , Razavi Shiva , Rock T. Willow , Nakajima Daichi , Nakamura Hideki , Kramer Daniel A. , Matsuura Tomoaki , Chen Baoyu , Murata Satoshi , Nomura Shinichiro M. , Inoue Takanari 
Published: October 2024

AbstractMotility is a hallmark of life’s dynamic processes, enabling cells to actively chase prey, repair wounds, and shape organs. Recreating these intricate behaviors using well-defined molecules remains a major challenge at the intersection of biology, physics, and molecular engineering. Although the polymerization force of the actin cytoskeleton is characterized as a primary driver of cell motility, recapitulating this process in protocellular systems has proven elusive. The difficulty lies in the daunting task of distilling key components from motile cells and integrating them into model membranes in a physiologically relevant manner. To address this, we developed a method to optically control actin polymerization with high spatiotemporal precision within cell-mimetic lipid vesicles known as giant unilamellar vesicles (GUVs). Within these active protocells, the reorganization of actin networks triggered outward membrane extensions as well as the unidirectional movement of GUVs at speeds of up to 0.43 µm/min, comparable to typical adherent mammalian cells. Notably, our findings reveal a synergistic interplay between branched and linear actin forms in promoting membrane protrusions, highlighting the cooperative nature of these cytoskeletal elements. This approach offers a powerful platform for unraveling the intricacies of cell migration, designing synthetic cells with active morphodynamics, and advancing bioengineering applications, such as self-propelled delivery systems and autonomous tissue-like materials.
Virulence-linked adhesin drives mutualist colonization of the bee gut via biofilm formation
Authors: Lariviere Patrick J. , Ashraf A. H. M. Zuberi , Gifford Isaac , Tanguma Sylvia L. , Barrick Jeffrey E. , Moran Nancy A. 
Published: October 2024

AbstractBacterial biofilms are stable multicellular structures that can enable long term host association. Yet, the role of biofilms in supporting gut mutualism is still not fully understood. Here, we investigateSnodgrassella alvi, a beneficial bacterial symbiont of honey bees, and find that biofilm formation is required for its colonization of the bee gut. We constructed fifteenS. alvimutants containing knockouts of genes known to promote colonization with putative roles in biofilm formation. Genes required for colonization includedstaAandstaB, encoding trimeric autotransporter adhesins (TAAs) andmltA, encoding a lytic transglycosylase. Intriguingly, TAAs are considered virulence factors in pathogens but support mutualism by the symbiontS. alvi. In vitro, biofilm formation was reduced in ΔstaBcells and abolished in the other two mutants. Loss ofstaAalso reduced auto-aggregation and cell-cell connections. Based on structural predictions, StaA/B are massive (>300 nm) TAAs with many repeats in their stalk regions. Further, we find that StaA/B are conserved acrossSnodgrassellaspecies, suggesting that StaA/B-dependent colonization is characteristic of this symbiont lineage. Finally,staAdeletion increases sensitivity to bactericidal antimicrobials, suggesting that the biofilm indirectly buffers against antibiotic stress. In all, the inability of two biofilm-deficient strains (ΔstaAand ΔmltA) to effectively mono-colonize bees indicates thatS. alvibiofilm formation is required for colonization of the bee gut. We envision the bee gut system as a genetically tractable model for studying the physical basis of biofilm-mutualist-gut interactions.
Covalent conjugation of glucose oxidase on single-walled carbon nanotubes for glucose sensing
Authors: Wang Hanxuan , Dehury Subhasis , Reggente Melania , Zubkovs Vitalijs , Boghossian Ardemis 
Published: October 2024

AbstractGlucose sensing and monitoring are crucial for biological and medical applications. Compared to existing methods, real-time detection and long-term monitoring are still required. Single-walled carbon nanotubes (SWCNTs) have excellent optical properties for sensing applications, which provide the possibility for designing a new generation of glucose sensors. In this study, we describe a method for covalently conjugate glucose oxidase (GOx) on SWCNTs as an optical glucose sensor. The functional groups are introduced by a photocatalytic reaction which acts as the handle for protein loading on SWCNTs. In this sp3 defect reaction, the optical properties of SWCNTs can be maintained. With a convenient bioconjugation reaction, the GOx could be covalently linked with SWCNTs. Compared to the non-covalent immobilization conjugates, the covalent conjugate sensor exhibits a much stronger optical response toward glucose, and the stability of the biosensor also increases in harsh conditions. At the same time, we also report the changing ratio of the original E11and defected E11* peak during the bioconjugation reaction, which is also inspiring for reaction monitoring on SWCNTs.Abstract Figure
Constitutive expression of Cas9 and rapamycin-inducible Cre recombinase facilitates conditional genome editing inPlasmodium berghei
Authors: Das Samhita , Unhale Tanaya , Marinach Carine , Valeriano Alegria Belsy del Carmen , Roux Camille , Madry Hélène , Mohand Oumoussa Badreddine , Amino Rogerio , Iwanaga Shiroh , Briquet Sylvie , Silvie Olivier 
Published: October 2024

AbstractMalaria is caused by protozoan parasites of the genusPlasmodiumand remains a global health concern. The parasite has a highly adaptable life cycle comprising successive rounds of asexual replication in a vertebrate host and sexual maturation in the mosquito vectorAnopheles. Genetic manipulation of the parasite has been instrumental for deciphering the function ofPlasmodiumgenes. Conventional reverse genetic tools cannot be used to study essential genes of the asexual blood stages, thereby necessitating the development of conditional strategies. Among various such strategies, the rapamycin-inducible dimerisable Cre (DiCre) recombinase system emerged as a powerful approach for conditional editing of essential genes in human-infectingP. falciparumand in the rodent malaria model parasiteP. berghei. We previously generated a DiCre-expressingP. bergheiline and validated it by conditionally deleting several essential asexual stage genes, revealing their important role also in sporozoites. The advent of CRISPR enabled targeted genome editing with higher accuracy and specificity and greatly advanced genome engineering inPlasmodiumspp. Here, we developed newP. bergheiparasite lines by integrating the DiCre cassette and a fluorescent marker in parasites constitutively expressing Cas9. Owing to the dual integration of CRISPR-Cas9 and DiCre, these new lines allow unparalleled levels of gene modification and conditional regulation simultaneously. To illustrate the versatility of this new tool, we conditionally knocked-out the essential gene encoding the claudin-like apicomplexan micronemal protein (CLAMP) inP. bergheiand confirm the role of CLAMP during invasion of erythrocytes.
Optical imaging of treatment-naïve human NSCLC reveals changes associated with metastatic recurrence
Authors: Diaz Paola Monterroso , Ivers Jesse D. , Byrum Stephanie , Quick Charles M. , Arnaoutakis Konstantinos , Quinn Kyle P. , Rajaram Narasimhan 
Published: October 2024

AbstractLung cancer remains the leading cause of cancer deaths, comprising nearly 25% of all cancer deaths [1]. NSCLC accounts for approximately 85% of all cases and encompasses major subtypes such as adenocarcinoma and squamous cell carcinoma. Despite advances in surgical and therapeutic options, NSCLC remains associated with poor prognosis due to a high rate of recurrence, even in early stages. Around 30-55% of patients who undergo complete resection will experience metastatic recurrence, significantly lowering survival outcomes [2]. There is a critical need to develop prognostic markers capable of predicting risk of recurrence at earlier timepoints in order to improve NSCLC management, as it could help clinicians tailor treatment plans, optimize follow-up schedules, and identify high-risk patients who might benefit from adjuvant therapies. Two photon microscopy (TPM) techniques provide non-invasive high-resolution information on cell metabolism within tissue by utilizing an optical redox ratio (ORR) of FAD/[NADH+FAD] autofluorescence. The goal of this study is to use the ORR and NADH fluorescence lifetime decay to identify measurable differences in optical endpoints of human NSCLC that are indicative of their long-term outcome. Twenty-five treatment-naïve NSCLC specimens were classified into metastatic and non-metastatic groups according to subject-detail reports. The ORR and mean NADH lifetime were determined for each sample, revealing a significant increase in the ORR for the metastatic group. Additionally, tumors presenting with high optical redox ratios were found to be correlated with low KEAP1, a prognostic indicator of poor clinical outcome in NSCLC. To evaluate the prognostic potential of optical metabolic endpoints, we trained three classifiers: logistic regression, SVM, and KNN on three different feature sets: optical endpoints, clinicopathological features, and combination of optical and clinical features. We found that SVM trained on optical endpoints alone (AUC = 0.74) outperformed the model built with only clinical features (AUC = 0.62), when classifying tumors based on their metastatic recurrence status. Together, these findings highlight the potential of optical metabolic imaging to provide markers of recurrence in NSCLC.
Avian predator-prey dynamics in a changing climate along the Western Antarctic Peninsula; a scoping review
Authors: Russell Tamara M. , Hermanson Victoria R. 
Published: October 2024

ABSTRACTA unique characteristic of the food web along the Western Antarctic Peninsula (WAP), one of the fastest warming regions in the world, is that the avian tertiary predators seasonally rely on avian secondary predators for their subsistence. We conducted a scoping review to 1.) provide a summary of research on Antarctic avian predator-prey relationships, 2.) investigate potential avian predator-prey relationships and trends with the environment, and 3.) highlight research gaps and provide recommendations for future research. We searched Web of Science and Google Scholar for publications in English during any years. For our first aim, we searched using the terms “predator-prey dynamics” AND “Antarctica.” We excluded results that did not include both avian predators and prey, which resulted in eight publications from around the Southern Ocean, and one along the WAP. For our second aim, we searched using the terms of each species’ common and scientific names (gentoo penguin,Pygoscelis papua, Adelie penguin,P. adeliae, chinstrap penguin,P. antarcticus, southern giant petrel,Macronectes giganteus, south polar skua,Stercorarius maccormicki, brown skua, S. antarcticus) AND “population” AND “Antarctic Peninsula.” We refined our results (N=59) to publications with data on at least one prey and one predator avian species of all papers found in Web of Science, and the first 100 records of Google Scholar. We selected five locations that had data spanning over 10 years and that spread across the northern WAP. We compared predator-prey species trends across time along with sea surface and air temperature. We found that predator-prey dynamics between avian secondary and tertiary predators have had limited investigations in Antarctica. Along the WAP, the relationship between different penguin species and avian tertiary predators are highly variable and many population trends are decoupled from local temperature change. We include recommendations for future data collection and research on these interactions.