bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retrospective Study of Bacteremia Caused byAlistipesSpecies in Japan, 2016–2023
Authors: Watanabe Naoki , Watari Tomohisa , Hosokawa Naoto , Otsuka Yoshihito 
Published: August 2024

AbstractThe clinical characteristics ofAlistipesbacteremia remain insufficiently described. Therefore, here, we retrospectively analyzed 13 cases ofAlistipesbacteremia at a tertiary care center to evaluate their clinical and microbiological characteristics. Ten patients were aged ≥ 65 years, and seven were female. Nine patients had comorbidities, including seven with solid tumors or hematological malignancies. Eleven patients presented with gastrointestinal symptoms. The isolates included fourAlistipes finegoldii, fourAlistipes onderdonkii, threeAlistipes putredinis, twoAlistipes indistinctus, and oneAlistipes ihumiiisolates. Ten available strains exhibited low minimum inhibitory concentrations against β-lactam/β-lactamase inhibitors and metronidazole, whereas they exhibited high minimum inhibitory concentrations for penicillin, ceftriaxone, and minocycline. Several strains harbored antimicrobial resistance genes, includingadeF,tet(Q),cfxA3,cfxA4, anderm(G). Twelve patients received β-lactam/β-lactamase inhibitors, and two elderly patients with solid tumors developed septic shock and died.Alistipesspecies can translocate from the gastrointestinal tract into the bloodstream, leading to severe infections.
Cost-utility of a new psychosocial goal-setting and manualised support intervention for Independence in Dementia (NIDUS-Family) versus goal-setting and routine care: economic evaluation embedded within a randomised controlled trial
Authors: Isaaq Abdinasir , Cooper Claudia , Vickerstaff Victoria , Barber Julie A. , Walters Kate , Lang Iain A. , Rapaport Penny , Orgeta Vasiliki , Rockwood Kenneth , Butler Laurie T , Lord Kathryn , Livingston Gill , Banerjee Sube , Manthorpe Jill , Kales Helen C. , Budgett Jessica , Hunter Rachael , Hoe J 
Published: August 2024

SummaryBackgroundNIDUS-Family is a 6-8 session, psychosocial and behavioural intervention, delivered by non-clinical facilitators, tailored to goals set by dementia-unpaid/family carer dyads. It is effective in terms of attainment of personalised client goals. We aimed to determine if it is cost-effective.MethodsThis cost utility and cost-effectiveness analysis is within a two-armed, single masked, multi-site, superiority Randomised Controlled Trial (RCT). We recruited 302 dyads from community settings. Randomisation was blocked and site-stratified, using a 2:1 ratio (intervention: control (goal-setting and routine care)), with allocation by remote web-based system. We calculated the probability that NIDUS-Family is cost-effective for a client with dementia based on Quality Adjusted Life Year (QALY) from health and personal social services and societal perspectives, at £20,000-£30,000 decision thresholds for QALY gained, compared to usual care over 12 months. Analyses were intention-to-treat.Trial registration:ISRCTN11425138.FindingsFrom 30.4.2020-9.5.2022, 204 participants (109 (53.4%) female) were randomised to intervention and 98 (60 (61.2%) female) to control. 218 (72.2%) participants at 6 months and 178 (58.9%) at 12 months provided cost data. There was 89% and 87% probability that NIDUS-Family was cost-effective compared to usual care from personal social services and societal perspectives respectively. Intervention participants accrued on average £8934 (37%) less costs than control participants (95% CI -£59,460 to £41,592).InterpretationNIDUS-Family is the first personalised care and support intervention to demonstrate cost-effectiveness from the perspective of the quality of life of people with dementia, as well as clinical effectiveness and should be part of routine dementia care.FundingThis work was supported by the Alzheimer’s Society (Centre of Excellence grant 330).
Movement-independent representation of reward-predicting cues in the medial part of the primate premotor cortex
Authors: Sehara Keisuke , Kondo Masashi , Hirayama Yuka , Ebina Teppei , Takaji Masafumi , Watakabe Akiya , Inoue Ken-ichi , Takada Masahiko , Yamamori Tetsuo , Matsuzaki Masanori 
Published: August 2024

AbstractNeural activity across the dorsal neocortex of rodents is dominated by orofacial and limb movements, irrespective of whether the movements are task-relevant or task-irrelevant. To examine the extent to which movements and a primitive cognitive signal, i.e., reward expectancy, modulate the activity of multiple cortical areas in primates, we conducted unprecedented wide-field one-photon calcium imaging of frontoparietal and auditory cortices in common marmosets while they performed a classical conditioning task with two auditory cues associated with different reward probabilities. Licking, eye movement, and hand movement strongly modulated the neuronal activity after cue presentation in the motor and somatosensory cortices in accordance with the somatotopy. By contrast, the posterior parietal cortex and primary auditory cortex did not show much influence from licking. Licking increased the activity in the caudal part of the dorsal premotor cortex, but decreased the activity in the central and lateral parts of the rostral part of the dorsal premotor cortex (PMdr). Reward expectancy that was separable from both spontaneous and goal-directed movements was mainly represented in the medial part of PMdr. Our results suggest that the influence of movement on primate cortical activity varies across areas and movement types, and that the premotor cortex processes motor and cognitive information in different ways within further subdivided areas.
Fornix and Uncinate Fasciculus Support Metacognition-Driven Cognitive Offloading
Authors: Zheng Yunxuan , Bo Bin , Wang Danni , Liu Yiyang , Gilbert Sam J. , Li Yao , Kwok Sze Chai 
Published: August 2024

AbstractPeople often use external tools to offload cognitive demands in remembering future intentions. While previous research has identified the causal role of metacognition in cognitive offloading, the neural mechanisms underlying this metacognitive control process remain unclear. To address this gap, we conducted a study with 34 participants using diffusion tensor imaging (DTI) to investigate how connections between brain regions support metacognition-driven cognitive offloading. Behaviorally, we confirmed that under-confidence in using internal memory to execute delayed intentions predicts a bias towards using external reminders. At the brain level we found that the fractional anisotropy (FA) of the fornix, a memory-related white matter tract connected to the hippocampus, positively correlated with the bias in setting up reminders. Additionally, the FA of the left uncinate fasciculus, which links the hippocampus to the prefrontal cortex and is involved in memory error monitoring, negatively correlated with deviations from optimal reminder use. Furthermore, the FA of the superior longitudinal fasciculus, a tract involved in metacognitive monitoring, moderated how confidence influenced the use of reminders. Taken together, our findings reveal a temporal-frontal neural circuit underlying metacognition-driven cognitive offloading, and provide new insights into the interaction between metacognitive monitoring and control.
Switch-like Gene Expression Modulates Disease Susceptibility
Authors: Aqil Alber , Li Yanyan , Wang Zhiliang , Islam Saiful , Russell Madison , Kunovac Kallak Theodora , Saitou Marie , Gokcumen Omer , Masuda Naoki 
Published: August 2024

AbstractA fundamental challenge in biomedicine is understanding the mechanisms predisposing individuals to disease. While previous research has suggested that switch-like gene expression is crucial in driving biological variation and disease susceptibility, a systematic analysis across multiple tissues is still lacking. By analyzing transcriptomes from 943 individuals across 27 tissues, we identified 1,013 switch-like genes. We found that only 31 (3.1%) of these genes exhibit switch-like behavior across all tissues. These universally switch-like genes appear to be genetically driven, with large exonic genomic structural variants explaining five (∼18%) of them. The remaining switch-like genes exhibit tissue-specific expression patterns. Notably, tissue-specific switch-like genes tend to be switched on or off in unison within individuals, likely under the influence of tissue-specific master regulators, including hormonal signals. Among our most significant findings, we identified hundreds of concordantly switched-off genes in the stomach and vagina that are linked to gastric cancer (41-fold,p<10-4) and vaginal atrophy (44-fold,p<10-4), respectively. Experimental analysis of vaginal tissues revealed that low systemic levels of estrogen lead to a significant reduction in both the epithelial thickness and the expression of the switch-like geneALOX12. We propose a model wherein the switching off of driver genes in basal and parabasal epithelium suppresses cell proliferation therein, leading to epithelial thinning and, therefore, vaginal atrophy. Our findings underscore the significant biomedical implications of switch-like gene expression and lay the groundwork for potential diagnostic and therapeutic applications.
The genetic relationships between post-traumatic stress disorder and its corresponding neural circuit structures
Authors: Gong Qian , Lyu Honggang , Kang Lijun , Ma Simeng , Zhang Nan , Xie Xin-hui , Zhou Enqi , Deng Zipeng , Liu Jiewei , Liu Zhongchun 
Published: August 2024

AbstractPost-traumatic stress disorder (PTSD) may be linked to abnormalities in neural circuits that facilitate fear learning and memory processes. The precise degree to which this connection is influenced by genetic factors is still uncertain. This study aimed to investigate the genetic association between PTSD and its corresponding brain circuitry components. We first conducted a meta-analysis using the summary of PTSD genome-wide association studies (GWAS) from multiple cohorts to enhance statistical power (sample size = 306,400). Then, based on the result of the GWAS meta-analysis, and utilizing the lifetime trauma events (LTE) trait as a control for PTSD, we proceeded with subsequent investigations. We investigated the genetic association of PTSD and LTE with nine brain structure traits related to the brain circuitry by various methodologies, including heritability tissue enrichment analysis, global and local genetic correlations, polygenic overlap analysis, and causal inference. As a result, we discovered an enrichment of heritability for PTSD within circuitry-relevant brain regions such as the cingulate cortex and frontal cortex, alongside the identification of weak genetic correlations between PTSD and these brain regions. We have observed a polygenic overlap between the two trauma-related traits and nine traits of brain circuitry components such as global cortical area and cingulum. A total of 31 novel jointly significant genetic loci (conjunction FDR<0.05) associated with PTSD and nine brain structures were identified, suggesting a potential connection between them, and these loci are involved in the process of DNA damage and repair as well as the pathway of neurodegenerative diseases. We also identified a potential causal relationship between PTSD and the surface area of the frontal pole. Our findings offer a valuable understanding of the genetic mechanisms underlying PTSD and its associated brain circuitry.
Cholinergic basal forebrain neurons regulate vascular dynamics and cerebrospinal fluid flux
Authors: Chuang Kai-Hsiang , Zhou Xiaoqing Alice , Xia Ying , Li Zengmin , Qian Lei , Eeles Eamonn , Ngiam Grace , Fripp Jurgen , Coulson Elizabeth J. 
Published: August 2024

AbstractWaste from the brain is cleared via a cerebrospinal fluid (CSF) exchange pathway, the dysfunction of which is suggested to underlie the pathogenesis of many brain conditions. Coherent cerebrovascular oscillation that couples with pulsatile CSF inflow is suggested to drive the fluid flux. However, how this coupling is regulated, whether it mediates waste clearance, and why fluid flux is impaired in disease status remain unclear. Here we show that vascular-CSF coupling correlates with cortical cholinergic activity in non-demented aged humans. The causal role of basal forebrain cholinergic neurons that project to the cortex is then verified by specific lesioning in mice, revealing correlated changes in vascular-CSF coupling, arterial pulsation and glymphatic flux, which can be altered by an acetylcholinesterase inhibitor. These results suggest a neurovascular mechanism by which CSF/glymphatic flux is modulated by cholinergic neuronal activity, thereby providing a conceptual basis for the development of diagnostics and treatments for glymphatic dysfunction.
Integrated structural model of the palladin-actin complex using XL-MS, docking, NMR, and SAXS
Authors: Sargent Rachel , Liu David H. , Yadav Rahul , Glennenmeier Drew , Bradford Colby , Urbina Noely , Beck Moriah R. 
Published: August 2024

AbstractPalladin is an actin binding protein that accelerates actin polymerization and is linked to metastasis of several types of cancer. Previously, three lysine residues in an immunoglobulin-like domain of palladin have been identified as essential for actin binding. However, it is still unknown where palladin binds to F-actin. Evidence that palladin binds to the sides of actin filaments to facilitate branching is supported by our previous study showing that palladin was able to compensate for Arp2/3 in the formation ofListeriaactin comet tails. Here, we used chemical crosslinking to covalently link palladin and F-actin residues based on spatial proximity. Samples were then enzymatically digested, separated by liquid chromatography, and analyzed by tandem mass spectrometry. Peptides containing the crosslinks and specific residues involved were then identified for input to HADDOCK docking server to model the most likely binding conformation. Small angle X-ray scattering was used to provide further insight into palladin flexibility and the binding interface, and NMR spectra identified potential interactions between palladin’s Ig domains. Our final structural model of the F-actin:palladin complex revealed how palladin interacts with and stabilizes F-actin at the interface between two actin monomers. Three actin residues that were identified in this study also appear commonly in the actin binding interface with other proteins such as myotilin, myosin, and tropomodulin. An accurate structural representation of the complex between palladin and actin extends our understanding of palladin’s role in promoting cancer metastasis through regulation of actin dynamics.SignificanceIn this study we have combined various advanced structural biology techniques to provide the first comprehensive model of the palladin-actin complex. Considering palladin’s role in cancer cell metastasis, this structure could be useful in screening and developing chemotherapeutic agents that target this interaction and prevent cancer cell metastasis.
Predicting Alzheimer’s Cognitive Resilience Score: A Comparative Study of Machine Learning Models Using RNA-seq Data
Authors: Kitani Akihiro , Matsui Yusuke 
Published: August 2024

AbstractAlzheimer’s disease (AD) is an important research topic. While amyloid plaques and neurofibrillary tangles are hallmark pathological features of AD, cognitive resilience (CR) is a phenomenon where cognitive function remains preserved despite the presence of these pathological features. This study aimed to construct and compare predictive machine learning models for CR scores using RNA-seq data from the Religious Orders Study and Memory and Aging Project (ROSMAP) and Mount Sinai Brain Bank (MSBB) cohorts. We evaluated support vector regression (SVR), random forest, XGBoost, linear, and transformer-based models. The SVR model exhibited the best performance, with contributing genes identified using Shapley additive explanations (SHAP) scores, providing insights into biological pathways associated with CR. Finally, we developed a tool called the resilience gene analyzer (REGA), which visualizes SHAP scores to interpret the contributions of individual genes to CR. REGA is available athttps://igcore.cloud/GerOmics/REsilienceGeneAnalyzer/.
DNA Methylation Analysis Identifies Clinically Relevant Lung Adenocarcinoma Subgroups
Authors: Afolabi Oluwadamilare I. 
Published: August 2024

AbstractLung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer and is characterized by significant molecular heterogeneity and poor prognosis, primarily due to late-stage diagnoses. Therefore, detailed molecular characterization of LUAD is crucial for developing biomarkers to accurately detect the disease in its early stages. This study investigates the role of DNA methylation in LUAD, emphasizing its potential as a biomarker for cancer detection and as a tool for understanding tumor biology. The study identified 4,925 differentially methylated sites (DMSs) and prioritized the top 200 DMSs for downstream analyses. Functional enrichment analysis revealed that site-specific hypermethylation in exon 1 and distal promoter regions are linked to critical developmental processes, including morphogenesis, pattern specification, stem cell differentiation, and synaptic transmission, suggesting that these epigenetic changes may disrupt normal cellular functions and contribute to tumorigenesis. Support vector machines demonstrated the diagnostic potential of these hypermethylated sites, achieving perfect classification of LUAD and normal adjacent tissues with as few as five features. Additionally, the strong correlation between methylation levels and feature importance scores further explained the predictive accuracy of these methylation markers. The study also identified distinct methylation subgroups within LUAD tumors, independent of traditional staging, each associated with unique transcriptional dysregulation and biological processes, such as DNA repair, immune response, and ribosome biogenesis. These findings not only enhance our understanding of LUAD pathophysiology but also underscore the clinical utility of DNA methylation as a diagnostic tool and guide for patient management.
Medial Entorhinal VIP-expressing interneurons receive direct input from Anterior Dorsal Thalamus and are critical for spatial memory
Authors: Oulé Marie , Badrinarayanan Saishree , Sundar-Maccagno Rosa , Brandon Mark P. 
Published: August 2024

AbstractHead-direction (HD) cells are found across several regions in the brain, including the anterodorsal thalamic nucleus (ADN), the subicular complex, and the medial entorhinal cortex (MEC). A fundamental role of head direction cells is to provide input to MEC grid cells, which are thought to translate information about head direction into a metric code for spatial location. However, classic anatomical studies indicate that most thalamic HD projections pass indirectly to the MEC via the post- and para-subiculum, with only a small subset of ADN fibers terminating in the MEC. To further investigate the smaller and direct projection to the MEC, we use rabies-mediated retrograde tracing in mice to determine if this projection explicitly targets a subset of MEC neurons. Our findings reveal that ADN neurons specifically project onto MEC interneurons, with a preference for MEC VIP-expressing cells. Additionally, MEC VIP cells receive input from the hippocampus, the subicular complex, and the retrosplenial cortex - key centers for spatial memory - suggesting a specialized role for MEC VIP cells in spatial memory. Indeed, we find that MEC VIP cells exhibit increased c-Fos expression in a spatial memory task and show that chemogenetic inhibition of these neurons impairs task performance. Together, these data uncover a specific projection of head direction information onto MEC interneurons and confirm that MEC VIP-expressing cells are critical for spatial memory.
Quantum orbits in atomic ionization beyond the dipole approximation
Authors: Jašarević A. S. , Habibović D. , Milošević D. B. 
Published: August 2024

Using the strong-field-approximation theory beyond the dipole approximation we investigate above-threshold ionization induced by the monochromatic and bichromatic laser fields. Particular emphasis is on the approach based on the saddle-point method and the quantum-orbit theory which provides an intuitive picture of the underlying process. In particular, we investigate how the solutions of the saddle-point equations and the corresponding quantum orbits and velocities are affected by the nondipole effects. The photoelectron trajectories are two dimensional for linearly polarized field and three dimensional for two-component tailored fields, and the electron motion in the propagation direction appears due to the nondipole corrections. We show that the influence of these corrections is not the same for all contributions of different saddle-point solutions. For a linearly polarized driving field, we focus our attention only on the rescattered electrons. On the other hand, for the tailored driving field, exemplified by the ω–2ω orthogonally polarized two-color field, which is of the current interest in the strong-field community, we devote our attention to both the direct and the rescattered electrons. In this case, we quantitatively investigate the shift which appears in the photoelectron momentum distribution due to the nondipole effects and explain how these corrections affect the quantum orbits and velocities which correspond to the saddle-point solutions.

Published by the American Physical Society
2024
Minimal U(1) two-Higgs-doublet models for quark and lepton flavor
Authors: Rocha J. R. , Câmara H. B. , Felipe R. G. , Joaquim F. R. 
Published: August 2024

In the context of the 2HDM, and assuming that neutrinos acquire masses via the Weinberg operator, we perform a systematic analysis to determine the minimal quark and lepton flavor patterns, compatible with masses, mixing and CP violation data, realizable by Abelian symmetries. We determine four minimal models for quarks, where the number of independent parameters matches the number of observables. For the lepton sector, three minimal predictive models are identified. Namely, we find scenarios with a preference for the upper/lower octant of the θ23 atmospheric mixing angle, that exhibit lower bounds on the lightest neutrino masses currently probed by cosmology and testable at future neutrinoless double beta decay experiments, even for a normally ordered neutrino masses. We investigate the phenomenology of each model taking into account all relevant theoretical, electroweak precision observables, scalar sector constraints, as well as stringent quark flavor processes such as B¯→Xsγ, Bs→μ−μ+ and meson oscillations, and the charged lepton flavor-violating decays eα−→eβ−eγ+eδ− and eα→eβγ. We show that, in some cases, Abelian flavor symmetries provide a natural framework to suppress flavor-changing neutral couplings and lead to scenarios featuring heavy neutral/charged scalar masses below the TeV scale within the reach of current experiments.

Published by the American Physical Society
2024