bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measuring Frailty: A Comparison of the Cumulative Deficit Model of Frailty in Survey and Routine Data
Authors: Johnson Lara , Guthrie Bruce , Anand Atul , Marshall Alan , Seth Sohan 
Published: January 2025

ABSTRACTPurposeFrailty, a state of increased vulnerability to adverse health outcomes, impacts individuals and healthcare systems. The cumulative deficit model provides a flexible frailty measure but its application across diverse data remains underexplored. This study compares frailty indices derived from survey and routine data.MethodsFrailty indices in the Clinical Practice Research Datalink (CPRD) Aurum (N = 1,625,677) and the English Longitudinal Study of Ageing (ELSA) (N = 5190) were compared for adults aged 65+ in England. Deficits were categorised as "one-to-one", "one-to-many", and "one-to-none". Age-sex-standardised deficit prevalence, frailty distribution and associations with demographics were analysed using summary statistics and regression.ResultsMean frailty index scores were similar (CPRD: 0.13 ± 0.10; ELSA: 0.13 ± 0.12) but differences were observed in the capture of specific deficits. The majority of deficits had a “one-to-none” or “one-to-many” mapping. Among 14 comparable deficits, visual impairment, fractures and heart failure were more common in CPRD, while falls, sleep disturbance and arthritis were more frequent in ELSA. Severe frailty and greater fitness were more prevalent in ELSA than CPRD. Sex and age influenced frailty similarly in both datasets, with frailty index scores increasing more rapidly with age in CPRD.ConclusionDifferences in the number and types of deficits measured offset each other overall, supporting the cumulative deficit model’s premise that including a sufficient range of deficits does not significantly alter population-level frailty measures. This interchangeability may alleviate concerns about deficit selection, supporting more flexible approaches to population frailty assessment across both survey and routine data.KEY SUMMARY POINTSAimWe assess whether similar frailty prevalence is observed in survey and routine data despite differences in the number, types and prevalence of the individual deficits measured in frailty indices.FindingsFrailty index calculations using established principles showed strong comparability between survey and routine data. Including a sufficient range of deficits does not significantly alter population-level frailty measures.MessageThe cumulative deficit model’s robustness to deficit selection supports flexible approaches to population frailty assessment across diverse data sources, such as survey and routine data.
In vitroantioxidant and anti-inflammatory activities, total phenolic and flavonoid contents ofAnadenanthera colubrinafrom Northern Peru
Authors: Samame-Caramutti Edert Abel , Salcedo-Valdez Luis , Suárez-Cunza Silvia 
Published: January 2025

AbstractThe antioxidant and anti-inflammatory activities of the hydroethanolic extract from bark ofAnadenanthera colubrina(ACE), as well as its total phenolic (TPC) and flavonoid (TFC) contents, were studiedin vitro. The ACE showed a high antioxidant activity both in the DPPH●radical scavenging (747.6mg Trolox equivalents/g dry extract) and in the FRAP (435.9mg FeSO4equivalents/g dry extract) chemical assays. The extract (50 to 1000μg/mL) inhibited the lipid peroxidation (formation of TBARS), hemolysis induced by H2O2, and egg albumin denaturation. No activity was observed in the hypotonicity-induced hemolysis assay. The TPC and TFC were 642.7mg GAE/g and 416.2mg CE/g dry extract, respectively. To the best of our knowledge, these activities were reported for the first time forA. colubrinafrom northern Peru, and suggest that the ACE has notable antioxidant and anti-inflammatory properties, and that the high TPC and TFC could be responsible, at least partially, for these activities.
Dual regulatory role of IS91-encoded Orf121 in IS91transposition
Authors: Fauconnier Aurélien , Da Re Sandra , Gaschet Margaux , Jové Thomas , Ploy Marie-Cécile , Pasternak Cécile 
Published: January 2025

AbstractProkaryotic insertion sequences (IS) are pivotal in the propagation of bacterial multidrug resistance, with IS91notably linked to virulence and antibiotic resistance genes. However, the precise mechanism by which IS91contributes to gene dissemination remains elusive. Unique among its family, IS91features a small open reading frame (orf) upstream of thetnpAtransposase gene, potentially encoding a 121-amino acid protein,orf121, which may be translationally coupled withtnpA.Using a genetic system based on the mating-out assay inEscherichia coli, we explored the role oforf121in thein vivotransposition of IS91. Our findings indicate that the overlap betweenorf121andtnpAis crucial fortnpAtranscription, with both being primarily transcribed as bicistronic mRNAs from the Porf121promoter. Additionally, the expression oforf121(whetherin cisortrans) significantly reduces the frequency of IS91transposition and the rate of one-ended transposition. Furthermore, only the single-stranded DNA circles of IS91intermediates can integrate into new target sequences, and Orf121 negatively influences this insertion step.In summary,orf121acts as a negative regulator of transposition while ensuring the expression oftnpA, thus providing insights into the complex mechanisms underlying IS91-mediated gene dissemination and its potential role in antibiotic resistance propagation.
CalciumNetExploreR: An R Package for Network Analysis of Calcium Imaging Data
Authors: Lenci Simone , Sieger Dirk 
Published: January 2025

1AbstractAnalyzing calcium imaging data to understand complex functional networks can be challenging, often requiring multiple tools, custom scripts, and some coding expertise. To address these challenges, we present CalciumNetExploreR (CNER), an R package designed to streamline and standardize the analysis of time-series data from neuronal populations. While originally developed with calcium imaging in mind, CNER’s modular design also makes it adaptable to other sources of neural time-series data, such as fMRI or electrophysiological recordings.CNER integrates essential steps—normalization, binarization, population activity visualization, network construction, degree distribution analysis, principal component analysis (PCA), power spectral density (PSD) evaluation, and event frequency calculations—into a single, cohesive pipeline. This comprehensive approach enables users to efficiently extract and compare network metrics, including clustering coefficients, global efficiency, community structures, and principal component variances. By offering a flexible and customizable framework, CNER simplifies the examination of functional connectivity and network topology, effectively providing the means to characterize a cellular functional network or analogous structures in other modalities.Designed as a user-friendly package, CNER allows both experimental and computational neuroscientists to incorporate robust statistical and graphical analyses into their workflows without extensive coding knowledge. By unifying key analytical components into one pipeline, CNER reduces barriers associated with large-scale data analyses, ultimately facilitating deeper insights into the functional organization and dynamic properties of neuronal networks across diverse recording techniques.
Crossmodal pitch-luminance association in tortoises
Authors: Loconsole Maria , Malaman Beatrice , Stancher Gionata , Versace Elisabetta 
Published: January 2025

AbstractIf you think that high-pitched sounds match bright colours more than dark ones, you are not alone. Spontaneous associations between different sensory modalities —crossmodal associations— are widely observed in humans. More recently, crossmodal associations have been reported in chimpanzees, monkeys, dogs, chickens, and tortoises, indicating a general cognitive strategy that reflects natural correlations in the environment or similarities in the architecture of the nervous system. Alternatively, or complementarily, crossmodal associations may arise from learning of species-specific occurrences. Recent research on primates has tentatively linked human pitch-luminance associations to the evolution of language. While humans and chimpanzees spontaneously match a high-pitched sound with a white shape and a low-pitched sound with a black shape, baboons and chickens do not exhibit any preferential association. Identifying spontaneous pitch-luminance associations in species that do not rely on vocal communication, such as the solitary Hermann’s tortoises, would support the idea of a language-independent phenomenon. To test this idea, we studied tortoises for pitch-luminance associations in a spontaneous food-searching task. After hearing a high-pitched (700 Hz) vs low-pitched (450 Hz) sound, animals could choose to search for food behind either a light- or dark-coloured wall. When hearing the high-pitched sound, tortoises chose the white stimulus, whereas when hearing the low-pitched sound, they chose the black stimulus, similarly to what humans and chimpanzees do. These results demonstrate crossmodal pitch-luminance associations in tortoises. While showing this commonality in the perceptual organization of phylogenetically distant species, we shift the question on whether pitch-luminance associations reflect homology or convergent evolution.
ST-FFPE-mIF: Integrating Spatial Transcriptomics and Multiplex Immunofluorescence in Formalin-Fixed Paraffin-Embedded Tissues Using Stereo-seq
Authors: Zhang Xue , Zhang Meng , Xu Yuan , Song Yangyang , Yang Xinfeng , Wu Yanan , Zhao Xuelin , Ran Dongsheng , Liu Xin , Huang Huaqiang , Lei Wenxiao , Li Hongyan , Zhang Yongfen , Xi Feng , Li Guibo , Liu Xing , Xu Luohao , Chen Ao , Liao Sha , Zhang Jiajun 
Published: January 2025

AbstractStereo-seq is the state-of-the-art technique, which allows capturing of spatial transcriptomic data at sub-cellular resolution and in large scale of view. Stereo-seq FFPE technique is recently launched with the capability to obtain spatially resolved gene expression in FFPE tissue sections. However, the omic information is limited to transcriptome. To delineate spatial molecular hierarchy from transcriptome to phenome, we present the protocol that implements nine-plex immunofluorescence staining with detection of spatial transcriptomics in one FFPE tissue section (short for ST-FFPE-mIF). This protocol details the modified biochemistry procedure and also provides analytical framework to achieve single-cell resolution through nuclear or membrane staining-based cell segmentation. We demonstrated the application of ST-FFPE-mIF in colorectal cancer sample to illustrate how ST-FFPE-mIF facilitates a robust analysis of spatially resolved multi-omic data at the single-cell level.
Single-molecule mitochondrial DNA imaging reveals heteroplasmy dynamics shaped by developmental bottlenecks and selection in different organsin vivo
Authors: Chandrasegaram Rajini , Hynes-Allen Antony M. , Gao Beitong , Dhawanjewar Abhilesh , Frison Michele , Petridi Stavroula , Chinnery Patrick F. , Ma Hansong , van den Ameele Jelle 
Published: January 2025

AbstractMitochondrial DNA (mtDNA) occurs in many copies per cell, with cell-to-cell variability in mutation load, known as heteroplasmy. Developmental and age-related expansion of pathogenic mtDNA mutations contributes to mitochondrial and neurodegenerative disease pathogenesis. Here, we describe an approach forin situsequence-specific detection of single mtDNA molecules (mtDNA-smFISH). We apply this method to visualize and measurein situmtDNA and heteroplasmy levels at single-cell resolution in whole-mountDrosophilatissue and cultured human cells. InDrosophila, we identify a somatic mtDNA bottleneck during neurogenesis. This amplifies heteroplasmy variability between neurons, as predicted from a mathematical bottleneck model, predisposing individual neurons to a high mutation load and degeneration. However, both during neurogenesis and oogenesis, mtDNA segregation is accompanied by purifying selection, promoting wild-type over mutant mtDNA. mtDNA-smFISH thus elucidates novel mechanisms whereby developmental cell-fate transitions, accompanied by changes in cell morphology, behaviour and metabolism, will shape disease-relevant and tissue-specific transmission and selection of mtDNA mutations.
Tet3 Mediates O-GlcNAcylation-Induced Remyelination
Authors: Li Yawen , Li Pingping , Song Yixuan , Zhang Mingliang 
Published: January 2025

ABSTRACTThe failure of oligodendrocyte precursor cells (OPCs) to generate mature oligodendrocytes represents a major hurdle impeding myelin repair. However, the cellular determinants for OPC differentiation and the pharmacological targets driving remyelination remain rudimentary. Here, we demonstrate that O-GlcNAcylation intrinsically drives remyelination, in which Tet3 is one downstream effector. Enhanced O-GlcNAcylation significantly promotes OPC differentiation, whereas conditional depletion of Ogt in OPCs seriously impairs myelin formation in the developing central nervous system (CNS). Intriguingly, O-GlcNAcylation in OPCs positively correlates with the myelin status, and enhanced O-GlcNAcylation dramatically accelerates remyelination. Proteomic analyses reveal a cohort of proteins uniquely O-GlcNAcylated in OPCs. Among these, Tet3 is exclusively O-GlcNAcylated in OPCs within CNS, which in turn modulates its demethylation activity, thereby regulating myelin gene expression and remyelination. Our findings highlight the crucial role of the Ogt-Tet3 axis in OPC differentiation and suggest O-GlcNAcylation as a druggable target for treating demyelinating diseases.
Misclassification in memory modification inAppNL-G-Fknock-in mouse model of Alzheimer’s disease
Authors: Huang Mei-Lun , Suzuki Yusuke , Sasaguri Hiroki , Saito Takashi , Saido Takaomi C , Imayoshi Itaru 
Published: January 2025

AbstractAlzheimer’s disease (AD), the leading cause of dementia, could potentially be mitigated through early detection and interventions. However, it remains challenging to assess subtle cognitive changes in the early AD continuum. Computational modeling is a promising approach to explain a generative process underlying subtle behavioral changes with a number of putative variables. Nonetheless, internal models of the patient’s reasoning process remain underexplored in AD. Determining the states of an internal model between measurable pathological states and behavioral phenotypes would advance explanations about the generative process in earlier disease stages beyond assessing behavior alone. In this study, we assumed the latent cause model as an internal model and estimated internal states defined by the model parameters being in conjunction with measurable behavioral phenotypes. The 6- and 12-month-oldAppNL-G-Fknock-in AD model mice and the age-matched control mice underwent memory modification learning, which consisted of classical fear conditioning, extinction, and reinstatement. The results showed thatAppNL-G-Fmice exhibited a lower extent of reinstatement of fear memory. Computational modeling revealed that the deficit in theAppNL-G-Fmice would be due to their internal states being biased toward overgeneralization or overdifferentiation of their observations, and consequently the competing memories were not retained. This deficit was replicated in another type of memory modification learning in the reversal Barnes maze task. Following reversal learning,AppNL-G-Fmice, given spatial cues, failed to infer coexisting memories for two goal locations during the trial. We concluded that the altered internal states ofAppNL-G-Fmice illustrated their misclassification in the memory modification process. This novel approach highlights the potential of investigating internal states to precisely assess cognitive changes in early AD and multidimensionally evaluate how early interventions may work.
Neuroactive steroids activate membrane progesterone receptors to induce sex specific effects on protein kinase activity
Authors: Lemons Abigail H. S. , Murphy Briana , Dengler Jake S. , Salar Seda , Davies Paul A. , Smalley Joshua L. , Moss Stephen J. 
Published: January 2025

SummaryNeuroactive steroids (NAS), which are synthesized in the brain from progesterone, exert potent effects on behavior and are used to treat postpartum depression, yet how these compounds induce sustained modifications in neuronal activity are ill-defined. Here, we examined the efficacy of NAS for membrane progesterone receptors (mPRs) δ and ε, members of a family of GPCRs for progestins that are expressed in the CNS. NAS increase PKC activity via Gqactivation of mPRδ with EC50s between 3-11nM. In contrast, they activate Gsvia mPRε to potentiate PKA activity with similar potencies. NAS also induced rapid internalization of only mPRδ. In the forebrain of female mice, mPRδ expression levels were 8-fold higher than males. Consistent with this, activation of PKC by NAS was evident in acute brain slices from female mice. Collectively, our results suggests that NAS may exert sex-specific effects on intracellular signaling in the brain via activation of mPRs.
Different artificial lighting spectra change the mating behavior of generalist predatorOrius insidiosus(Say), and photoperiod extension promotes its development
Authors: Canovas Morgane L. , Abram Paul K. , Labbé Roselyne , Cormier Jean-François , Galstian Tigran , Dorais Martine 
Published: January 2025

AbstractIn protected cropping systems such as greenhouses and indoor farming, augmentative biological control depends on release rates, establishment, and reproduction of natural enemies. Light-emitting diodes (LEDs) are widely used to enhance plant growth in these systems and are increasingly implemented in mass-rearing facilities for natural enemies. However, the impacts of LEDs on the life cycle of beneficial predators remain insufficiently explored. This study examined the mating behaviors and developmental performance of generalist predatorOrius insidiosusunder light spectra previously shown to support its predation of the pest thripsFrankliniella occidentalis. In laboratory experiments, predator pairs were exposed to artificial light sequences starting with a 12h base light condition simulating a cloudy winter day, supplemented by 8h photoperiod extensions (blue, blue-red, or blue-green-red spectra), and a control without extension. Mating occurred under all tested conditions, but blue light reduced mating probability, frequency, and duration. Photoperiod extension improved fecundity, fertility, and second-generation numbers ofO. insidiosusadults, with blue light favoring egg laying and hatching but not metamorphosis into adults. The second-generation sex ratio was unaffected by light sequence, maintaining population viability with a balanced proportion of females. Our findings demonstrate thatO. insidiosuscan successfully mate, reproduce, and develop under artificial lighting and highlight the potential of modulating light spectrum to optimize both mass-rearing and establishment in protected crops.HighlightsPhotoperiod extension enhances development of the predatory bugO. insidiosus.Blue light reducesO. insidiosusmating probability, frequency, and duration.Photoperiod extension with blue light favorsO. insidiosusfertility and fecundity.Orius insidiosussex ratio is unaffected by photoperiod.LEDs could enhance natural enemy establishment in protected crops.
Lambda N as a model substrate for studying the mechanism of Escherichia coli ATP-dependent protease Lon as a regulatory enzyme
Authors: Castro Marianita , Lee Sanghyuk , Lee Irene 
Published: January 2025

AbstractAs an ATP-dependent protease, the quality control functions of Lon have been extensively studied and reviewed in the literature. By contrast, very little research has been conducted to investigate Lon’s physiological functions and its mechanism as a regulatory protease. In this manuscript, we provided a survey of literature and data to convey that the lambda N (λN) protein is a suitable Escherichia coli Lon (ELon) substrate for studying the role played by Lon in regulating an RNA transcription process. For proof of principle, we demonstrated that the minimal component of the RNA transcription complex containing RNA polymerase (RNAP) and the σ factor can inhibit λN degradation by ELon through SDS-PAGE, and the carboxyl-terminal of λN is important for Lon competing with RNAP interaction. Using negative stain electron microscopy, we obtained structural evidence to show that λN lacking the carboxyl-terminal flanked by residues 99-107 interacted with ELon differently than full-length λN. Taken together, the activity and EM data provide a starting point for performing a physiological enzymology study on the contribution of ELon toward RNA transcription.
Customized feminine hygiene wash containing postbiotics fromLactobacillusspp. to treat Urinary Tract Infections (UTI)
Authors: Nair Veena G , Chellappan David Raj , Durai Remya Devi , Rajesh Y.B.R.D , Narbhavi Dhiviya , Anupriya A , Prabhusaran N , Nagarajan Saisubramanian 
Published: January 2025

AbstractThe rising prevalence of antimicrobial resistance has intensified the search for innovative therapeutic strategies, particularly in the prevention of urinary tract infections (UTIs). This study presents the development and evaluation of a novel postbiotics vaginal wash formulated to prevent UTIs by utilizing metabolites derived from indigenous vaginal Lactobacillus spp. The primary objective was to create a cost-effective, stable, and non-invasive solution targeting uropathogenic bacteria. Key metabolites, including tryptamine, (-)-terpinen-4-ol, and itaconic anhydride, were identified from cell free supernatant of vaginalLactobacillusand incorporated into a poloxamer 407-based formulation.In vitroassays demonstrated significant bioactivity against uropathogenic bacteria, effectively inhibiting bacterial colonization and biofilm formation. Preclinical validation was conducted using BALB/c mice models to assess both the safety and efficacy of the vaginal wash. Results indicated a substantial reduction in infection rates among treated mice, with no observed adverse effects, confirming the formulation’s safety profile. In conclusion, this novel postbiotics vaginal wash represents a promising non-invasive therapeutic approach for UTI prevention. By harnessing bioactive metabolites from human vaginal Lactobacillus spp., the formulation offers a potential solution to combat antimicrobial resistance while improving women’s health outcomes. Further clinical studies are warranted to validate these findings and explore broader applications in clinical practice, paving the way for new strategies in managing UTIs and enhancing overall female health.