bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges in Implementing a Mobile AI Chatbot Intervention for Depression Among Youth on Psychiatric Waiting Lists: A Randomized Control Study Termination Report
Authors: Fujita Junichi , Yano Yuichiro , Shinoda Satoru , Sho Noriko , Otsuki Masaki , Suda Akira , Takayama Mizuho , Moroga Tomoko , Yamaguchi Hiroyuki , Ishii Mio , Miyazaki Tomoyuki 
Published: November 2024

AbstractBackgroundThe mental health of children and adolescents is a growing public health concern, with increasing rates of depression and anxiety impacting their emotional, social, and academic well-being. In Japan, access to timely psychiatric care is limited, leading to extended waiting periods that can range from three months to a year. AI-driven chatbots, such as emol, which integrate Acceptance and Commitment Therapy (ACT), show potential as digital solutions to support young patients during these waiting times. The AI chatbot emol was selected based on a comprehensive review of Japanese mental health technology applications, including in-person evaluations with company representatives.ObjectiveThis exploratory, parallel-group randomized controlled trial examined the feasibility of using AI chatbot emol with pediatric and adolescent individuals on psychiatric waiting lists.MethodsParticipants aged 12-18 years were recruited from four hospitals in Kanagawa Prefecture and randomly assigned to either an intervention group, receiving eight weekly chatbot sessions, or a control group, receiving standard mental health information. The primary outcome was change in Patient Health Questionnaire-9 (PHQ-9) scores from pre- to post-intervention. Secondary assessments, such as voice and writing pressure analysis, provided additional engagement metrics, with data collected at baseline, during the intervention, and at week 9.ResultsOf the 96 eligible individuals on psychiatric waiting lists, eight expressed interest, and three provided initial consent. However, all participants subsequently withdrew or were excluded, resulting in no evaluable data for analysis. Low engagement may have been influenced by the perceived irrelevance of digital tools, complex protocols, and privacy concerns.ConclusionsSignificant barriers to engagement suggest that digital interventions may need simpler protocols and trusted environments to improve feasibility. Future studies could test these interventions in supportive settings, like schools or community centers, to enhance accessibility and participation among youth.Trial RegistrationJapan Registry of Clinical Trials (jRCT) jRCT1032230427
Extreme weather events in the UK and resulting public health outcomes
Authors: Dickinson Natalie , Spencer Llinos Haf , Yang Shuhua , Miller Caroline , Hursthouse Andrew , Lynch Mary 
Published: November 2024

AbstractObjectivesExtreme Weather Events (EWEs) are increasingly frequent in the UK and can lead to adverse physical and mental health outcomes which may result in additional pressure on the NHS. The objective of this study is therefore to investigate the health impacts of EWEs on the population in the UK.MethodA systematic review of the evidence was conducted. Seven databases were searched for studies related to the public health outcomes of EWEs.Results48 papers met the criteria for inclusion (22 flood, 25 extreme temperature, 1 wind). Flooding is most associated with mental health concerns and associated social effects, whilst temperature extremes impact more on physical health.ConclusionsWhilst there is a great deal of research on the physical and mental health impacts of EWEs in the UK, there is limited evidence on social health impacts, and little consideration of the economic costs of holistic health outcomes. Building resilience against the health impacts of EWEs is essential. Future studies should consider incorporating cost-benefit analyses (CBA) to investigate the economic costs of EWEs on populations and health systems in the UK.
Expression of recombinant human glutamylating TTLLs in human cells leads to differential tubulin glutamylation patterns, with only TTLL6 disrupting microtubule dynamics
Authors: Al Kabbani Mohamed Aghyad , Jatoo Pragya , Klebl Kathrin , Klebl Bert M. , Zempel Hans 
Published: November 2024

AbstractPolyglutamylation, a post-translational modification (PTM) catalyzed by a subset of Tubulin Tyrosine Ligase-Like (TTLL) family enzymes, regulates microtubule dynamics through its influence on interactions with microtubule-associated, motor, and severing proteins, and has recently also been implicated in genetic and neurodegenerative diseases. In this study, we characterized the glutamylation activity of various glutamylating TTLLs in human embryonic kidney 293T (HEK293T) cells, revealing distinct patterns of mono- and polyglutamylation among TTLL family members, with TTLL4 and TTLL11 exhibiting the strongest chain initiation and elongation activities, respectively. We found that TTLL6 expression uniquely decreased microtubule stability, with live-cell imaging of end-binding protein (EB3) showing a TTLL6-induced decrease in microtubule stability. To explore therapeutic modulation of TTLL activity, we tested LDC10, a novel TTLL inhibitor, which successfully blocked glutamylation across all TTLLs investigated in this study, while also reversing the microtubule-destabilizing effects of TTLL6. These findings identify a potential pathogenic role of TTLL6 in microtubule dynamics and highlight LDC10 as a promising pharmacological tool to counteract TTLL-induced microtubule destabilization.
Eosinophils promote monocyte to macrophage differentiation and anti-bacterial immunity
Authors: Wilson Gillian J , Foley Lily Koumbas , Pocalun Zuzanna , Pitmon Elise , Fukuoka Ayumi , Lee Kit M , Fernandez Lauren , Mathie Heather , Bartolini Robin , Cole John J. , Graham Gerard J 
Published: November 2024

AbstractChemokine receptors control cell migration within the body. Here we reveal a novel interaction between eosinophils and monocytes in the bone marrow, indirectly controlled by the atypical chemokine receptor ACKR2. We demonstrate that ACKR2 maintains eosinophil levels within the bone marrow by scavenging CCL11. In the absence of ACKR2, elevated CCL11 leads to increased egress of eosinophils from the bone marrow into the bloodstream. As a result, eosinophil and monocyte interactions are reduced within the bone marrow niche, leading to changes in monocyte gene expression. Monocytes from ACKR2-/- mice are recruited to the tissues but are fundamentally altered in their ability to differentiate into macrophages, in the lung, peritoneal cavity and cavity wall. Bacterial elimination is impaired in ACKR2-/- mice during peritoneal infection. ACKR2 is therefore a key regulator of eosinophil-driven monocyte education in the bone marrow, required for full monocyte differentiation and macrophage function within the tissues.
Reduced regulatory complexity associated with the evolutionary transition to sociality from cockroaches to termites despite evolutionary parallels with Hymenoptera
Authors: Jones Alun R.C. , Dohmen Elias , Berger Juliette , Legendre Frédéric , Harrison Mark , Bornberg-Bauer Erich 
Published: November 2024

AbstractIn social species, the phenotypic diversity within a single species has often been associated with more complex genetic regulation. Transcription factors (TFs) being key to genetic regulation, have been studied in the origins of eusociality in Hymenoptera (Bees, Ants and Wasps) but less so in Blattodea (Cockroaches and Termites). Here we show that the social transition in Blattodea, from cockroaches to termites, displays similar patterns of regulatory change to those found in Hymenoptera. Specifically, by analysing 3 cockroach and 5 termite genomes, we find more TF families with relaxed selection compared to intensified selection and lineage-specific gene family expansions in termites. We also find that genes under selection support neotenic caste determination. There are key differences in TF regulation in comparison with Hymenoptera with contractions in TF gene families and reduced diversity in enriched DNA binding motifs of TFs.Furthermore, we show that with increased social complexity TF activating domain diversity, one of the evolutionary and structural building blocks of TFs, decreases with gene family size while DNA binding domain diversity and number increases. This study highlights similarities in social transitions between Hymenoptera and Blattodea, with evidence of large changes in transcriptional regulation followed by lineage specific adaptations. We also show that phenotypic diversity in termites does not necessitate greater transcriptional complexity.
Stepwise Assembly Of Crown Reptile Anatomy Clarified By Late Paleozoic Outgroups Of Neodiapsida
Authors: Jenkins Xavier A. , Benson Roger B. J. , Ford David P. , Browning Claire , Fernandez Vincent , Dollman Kathleen , Gomes Timothy , Griffiths Elizabeth , Choiniere Jonah N. , Peecook Brandon R. 
Published: November 2024

AbstractLiving reptiles include more than 20,000 species with disparate ecologies. Direct anatomical evidence from Neodiapsida, which includes the reptile crown-group Sauria and its closest extinct relatives, shows that this diversity originates from a single common reptilian ancestor that lived some 255 million years ago in the Paleozoic. However, the evolutionary assembly of crown reptile traits is poorly understood due to the lack of anatomically close outgroups to Neodiapsida1–7. We present a substantially revised phylogenetic hypothesis, informed by new anatomical data derived from high-resolution synchrotron tomography of Paleozoic reptiles8–12. We find strong evidence placing the clade Millerettidae as a close sister to Neodiapsida, which uniquely share a suite of derived features among Paleozoic stem reptiles. This grouping, for which we name the new clade Parapleurota, replaces previous phylogenetic paradigms by rendering the group Parareptilia as a polyphyletic assemblage of stem reptiles, of which millerettids are the most crownward. Our analysis presents hypotheses that resolve long-standing issues in Paleozoic reptile evolution, including the placement of captorhinids on the amniote stem lineage and firm support for varanopids as synapsids, which taken together provide a greatly improved fit to the observed stratigraphic record. Optimizations of character evolution on our phylogenetic hypothesis reveals gradual assembly of crown reptile anatomy, including a Permian origin of tympanic hearing, the presence of a lower temporal fenestra in the amniote common ancestor, with subsequent modifications on the reptile stem lineage, leading to the loss of the lower temporal bar. This evolutionary framework provides a platform for investigating the subsequent radiations of the reptile crown group in the Early Triassic, including the lines leading to dinosaurs (including birds), crocodilians, lepidosaurs, and extinct marine reptiles.
Shaping the developing homunculus: the roles of deprivation and compensatory behaviour in sensory remapping
Authors: Tucciarelli Raffaele , Bird Laura , Straka Zdenek , Szymanska Maggie , Kollamkulam Mathew , Sonar Harshal , Paik Jamie , Clode Danielle , Hoffmann Matej , Cowie Dorothy , Makin Tamar R. 
Published: November 2024

ABSTRACTSome of the most dramatic examples of neuroplasticity in the human brain follow congenital sensory deprivation, though we have limited understanding of the plasticity mechanisms driving such large-scale remapping. Hand loss due to congenital limb differences (CLD) offers a unique temporal dissociation of developmental neuroplasticity mechanisms: While sensory deprivation is congenital, compensatory motor behaviours develop progressively across childhood. Using paediatric neuroimaging and semi-ecological behavioural analysis in children (5-7 years old) and adults (>25 years old) with unilateral upper-limb CLD, we studied deprivation- and use-dependent plasticity in the deprived primary somatosensory cortex and beyond. We reveal that global remapping, encompassing the entire sensory homunculus, is established early and maintained in adulthood. We demonstrate that deprivation-driven homeostatic plasticity can drive this global remapping, with Hebbian-based compensatory learning further contributing to inter-individual differences both in childhood and adulthood. Our findings emphasise the early establishment and stability of cortical maps, despite extensive daily-life behavioural adaptation.
Impaired spatial coding and neuronal hyperactivity in the medial entorhinal cortex of agedAppNL-G-Fmice
Authors: Rodriguez Gustavo A. , Rothenberg Eva F. , Shetler C. Oliver , Aoun Andrew , Posani Lorenzo , Vajram Srujan V. , Tedesco Thomas , Fusi Stefano , Hussaini S. Abid 
Published: November 2024

AbstractThe progressive accumulation of amyloid beta (Aβ) pathology in the brain has been associated with aberrant neuronal network activity and poor cognitive performance in preclinical mouse models of Alzheimer’s disease (AD). Presently, our understanding of the mechanisms driving pathology-associated neuronal dysfunction and impaired information processing in the brain remains incomplete. Here, we assessed the impact of advanced Aβ pathology on spatial information processing in the medial entorhinal cortex (MEC) of 18-monthAppNL-G-F/NL-G-Fknock-in (APP KI) mice as they explored contextually novel and familiar open field arenas in a two-day, four-session recording paradigm. We tracked single unit firing activity across all sessions and found that spatial information scores were decreased in MEC neurons from APP KI mice versus those in age-matched C57BL/6J controls. MEC single unit spatial representations were also impacted in APP KI mice. Border cell firing preferences were unstable across sessions and spatial periodicity in putative grid cells was disrupted. In contrast, MEC border cells and grid cells in Control mice were intact and stable across sessions. We then quantified the stability of MEC spatial maps across sessions by utilizing a metric based on the Earth Mover’s Distance (EMD). We found evidence for increased instability in spatially-tuned APP KI MEC neurons versus Controls when mice were re-exposed to familiar environments and exposed to a novel environment. Additionally, spatial decoding analysis of MEC single units revealed deficits in position and speed coding in APP KI mice in all session comparisons. Finally, MEC single unit analysis revealed a mild hyperactive phenotype in APP KI mice that appeared to be driven by narrow-spiking units (putative interneurons). These findings tie Aβ-associated dysregulation in neuronal firing to disruptions in spatial information processing that may underlie certain cognitive deficits associated with AD.
Neural Mechanisms of Intersensory Switching: Evidence for Delayed Sensory Processing and Increased Cognitive Effort
Authors: Vanneau Theo , Quiquempoix Michael , Foxe John J. , Molholm Sophie 
Published: November 2024

AbstractIntersensory switching (IS), the ability to shift attention between different sensory systems, is essential for cognitive flexibility, yet leads to slower responses compared to repeating the same sensory modality. The underlying neural mechanisms of IS remain largely unknown. In this study, high-density EEG was used to investigate these mechanisms in healthy adults (n=53) performing a speeded reaction time (RT) task involving visual and auditory stimuli. Trials were categorized as Repeat (same preceding modality) or Switch (different preceding modality). Switch trials showed slower RTs and delayed sensory responses (N1 and P2 components). Furthermore, across both Repeat and Switch trials, RT correlated with the latency of these neural responses. Additionally, lower alpha-band inter-trial phase coherence (ITPC) in primary sensory regions was noted for Switch compared to Repeat trials, suggesting reduced efficiency of sensory processing. Greater induced theta activity over fronto-central scalp regions in Switch trials suggested increased cognitive control demands, potentially involving the anterior cingulate cortex (ACC). These findings reveal that IS is characterized by delayed sensory processing and heightened cognitive load, supporting a model where prior stimulus primes the sensory cortex for faster processing in Repeat trials, while Switch trials demand more cognitive resources for adjustment. The similarity of effects across both auditory and visual sensory modalities suggests that IS effects represent core features of sensory processing, potentially reflecting a fundamental, modality-independent mechanism of attentional switching across sensory domains.
Enterococcal cell wall remodelling underpins pathogenesis via the release of the Enteroccocal Polysaccharide Antigen (EPA)
Authors: Smith Robert E , Christena Rene L , Michno Bartosz J , Davis Jessica L , Lidbury Ian DEA , Alaman-Zarate Marcel , Stefanidi Danai , Maes Emmanuel , Fisher Hannah , Prajsnar Tomasz K , Mesnage Stéphane 
Published: November 2024

ABSTRACTEnterococci are opportunistic pathogens displaying a characteristic ovoid shape, typically forming pairs of cells (diplococci) and short chains. Control of cell chain length in Enterococci is critical during pathogenesis for dissemination in the host and to limit recognition by innate immune effectors such as complement molecules and phagocytes. Here, we identify AtlE, an N-acetylmuramidase responsible for peptidoglycan hydrolysis-mediated septum cleavage during stationary phase. AtlE is encoded by the locus required to produce the decoration subunits of the Enterococcal Polysaccharide Antigen (EPA), which mediate evasion of phagocytosis. We show that peptidoglycan hydrolysis by AtlE is essential for pathogenesis and demonstrate that soluble cell wall fragments containing EPA decorations increase the virulence ofEnterococcus faecalis, suggesting that EPA plays a role as a decoy molecule to evade host defences. This research sheds light on the complex interplay between bacterial cell division, cell wall remodelling, and the host immune system, providing valuable insights into a novel mechanism underlying the virulence ofE. faecalis.
Behavioral and Neural Correlates of Temperament Traits: Insights from Temperament and Character Inventory and fMRI-Based Choice Tasks
Authors: Sisara Majid Abbasi , Hosseini Seyed Hamid Khodadad , Mahjoub Hossein , Kordnaeij Asadollah , Esmaeilinasab Maryam 
Published: November 2024

A cognitive conflict that is negatively arousing and results in a divergence in preference attitudes toward the chosen and rejected alternatives occurs when individuals are compelled to choose between alternatives that are similarly preferable. This phenomenon, which is frequently referred to as “cognitive dissonance,” is of interest in the fields of decision neuroscience and psychology. This study examines the behavioral and neural underpinnings of Cloninger’s temperament traits—Novelty Seeking (NS), Harm Avoidance (HA), Reward Dependence (RD), and Persistence (PS)—in a decision-making context.Functional magnetic resonance imaging (fMRI) and a modified free-choice paradigm were used to formalize the effect of Cloninger temperaments on cognitive conflict induced by choice. Behavioral analysis revealed significant individual differences across the four TCI dimensions, highlighting distinct variability in participants’ responses. Imaging data showed that participants with the highest and lowest scores in each temperament trait exhibited unique brain activation patterns during difficult and easy decision tasks. Notably, novelty-seeking was linked to heightened activation in brain regions associated with exploration and cognitive flexibility, while harm avoidance was associated with emotional processing and conflict detection. These findings provide deeper insights into how personality traits influence both behavior and neural responses during cognitive dissonance and decision-making tasks, offering implications for understanding individual differences in decision-related behaviors. The results of this study confirm the effect of temperaments on the degree of perceived dissonance of people, which can be used in many areas such as consumer behavior in marketing. The reason for this is the hesitancy of customers after purchasing the products.Significance StatementThis study provides novel insights into how Cloninger’s temperament traits—Novelty Seeking, Harm Avoidance, Reward Dependence, and Persistence—modulate both neural and behavioral responses during decision-making processes. By combining fMRI with a modified free-choice paradigm, we reveal that temperament traits significantly impact cognitive dissonance, with distinct brain activation patterns corresponding to individual differences in decision conflict. These findings enhance our understanding of the neural basis of cognitive dissonance and have practical implications for areas such as consumer behavior, where temperament-driven decision conflict can influence post-purchase attitudes. This research highlights the importance of accounting for personality traits when examining decision-related behaviors and suggests that tailoring strategies based on temperament could improve decision outcomes in various applied fields.
Polarized ATP synthase in synaptic mitochondria induced by learning and plasticity signals
Authors: Hu Yi , Wang Xi , Liu Kaiyuan , Xiong Songhai , Guan Ji-Song , Xie Hong , Gu Min 
Published: November 2024

AbstractMINFLUX represents a state-of-the-art single-molecule localization microscopy technology that surpasses the conventional diffraction limit, enabling the visualization and analysis of nanostructures with exceptional precision. Despite its potential, the utilization of MINFLUX has been primarily confined to in vitro cultured cell environments. In this research, we have refined the sample preparation protocols to facilitate 3D MINFLUX imaging in fixed brain tissue sections, focusing on the mitochondrial distribution within dendritic spines and engram cells of the dentate gyrus. Probing single moleculesin vivoreveals an interesting finding: the reorganization of mitochondrial inner membrane proteins during synaptic plasticity within dendritic spines of engram cells. Utilizing 3D MINFLUX nanoscopy, we identified a significant redistribution of α-F1-ATP synthase, which correlates with learning related activities. This redistribution implies a pivotal function for polarized ATP synthesis in the vicinity of the postsynaptic zone, which may modulate both short-term and long-term synaptic modifications, thereby influencing synaptic plasticity and memory consolidation. Furthermore, dual-color 3D MINFLUX imaging has uncovered distinct patterns of mitochondrial reorganization involving both the inner and outer membranes within dendritic spines. These patterns, induced by plasticity signals, persist for up to 12 hours in neuronal cultures. This distinction highlights the presence of distinct regulatory mechanisms governing mitochondrial proteins during synaptic plasticity. These results offer new insights into the molecular mechanisms underlying synaptic plasticity and underscore the transformative potential of 3D MINFLUX imaging for studying neuronal processes in the brain.