bluuebunny/crossref_metadata_2025 huggingface dataset:
Ticagrelor Compared to Clopidogrel in aCute Coronary syndromes (TC4) – A Bayesian pragmatic cluster randomized controlled trial
Authors: Kutcher Stephen A. , Dendukuri Nandini , Dandona Sonny , Nadeau Lyne , Brophy James M.
Published: November 2024

Background

Dual-antiplatelet therapy (DAPT) is the standard of care for acute coronary syndromes, but uncertainty exists regarding the optimal regime for North American patients.

Methods

This pragmatic, open-label, time clustered, randomized trial (ClinicalTrials.Gov(NCT04057300) compared the effectiveness and safety of DAPT with ticagrelor or clopidogrel in acute coronary syndrome patients from a single tertiary academic center in Montreal, Canada. The primary effectiveness endpoint was a composite of all-cause mortality, non-fatal myocardial infarction, or ischemic stroke. The primary safety endpoint were bleeding hospitalizations. Twelve-month outcomes were ascertained from the Québec universal electronic health databases. The study was designed and analyzed within a Bayesian paradigm to supplement existing knowledge. The primary analysis was a Bayesian logistic regression models with an informed focused prior from previously randomized North American patients. Robustness was evaluated with vague and other pre-specified informative priors, spanning reasonable pre-existing beliefs. Clinically significant benefits and harms were defined as risk reductions exceeding a 10% difference.

Results

1,005 ACS patients were randomized to ticagrelor (n = 450) or clopidogrel (n = 555). MACE occurred in 50 (11.1%) ticagrelor and 64 (11.5%) clopidogrel patients (relative risk (RR), 0.95; 95% credible interval [95% CrI]: 0.67, 1.35 with a vague prior). The primary analysis with an informed focused prior resulted in probabilities of a clinically meaningful ticagrelor benefit (RR<0.9), equivalence (0.9 ≦ RR ≧, 1.1) or harm (RR ≧, 1.1) of 2%, 41% and 57%, respectively. For the safety endpoint, there was no consistent signal of benefit or harm with ticagrelor. Sensitivity analyses with a range of prior beliefs gave generally consistent results.

Conclusions

Whether this trial was analysed with a vague, or a range of reasonable informed priors, no strong evidence for the superiority of ticagrelor over clopidogrel was found.
Sex differences in the impact of nerve injury on Locus Coeruleus function and behaviour in mice
Authors: Mariscal Patricia , Martínez-Cortés Adrián , Llorca-Torralba Meritxell , Razquin Jone , Miguelez Cristina , Ulecia-Morón Cristina , García-Bueno Borja , Leza Juan Carlos , Bravo Lidia , Berrocoso Esther
Published: November 2024

Chronic pain often coexists with stress-related disorders such as anxiety and depression, with a higher prevalence in women. Rodent studies reveal significant sex differences in pain and stress-related behaviours, emphasising the need to explore underlying neurobiological mechanisms. The locus coeruleus (LC), the main noradrenergic nucleus in the brainstem, plays a crucial role in modulating pain and stress responses and exhibits sex-specific characteristics.

In this study, we investigated the effects of neuropathic pain on the LC in male and female mice, focusing on sensory thresholds, emotional states, and cognitive function. Nerve injury caused immediate sensory hypersensitivity in both sexes, while depressive-like behaviours and cognitive impairments emerged only after prolonged injury. Interestingly, anxiety-like behaviours and heightened fear conditioning were exclusive to males, which correlated with specific structural and functional changes in the male LC, such as increased noradrenergic cell counts, larger somato-dendritic volume, and greater neuron excitability. In females, however, neuronal excitability was reduced. Chemogenetic inhibition of LC neurons alleviated depressive- and anxiety-like behaviours, as well as fear conditioning, but only in males.

Overall, neuropathic pain induces distinct behavioural and neurobiological responses in males and females, challenging traditional views on female vulnerability to pain-induced anxiety and highlighting the need for sex-specific LC-targeted therapies.
Lrp1 facilitates infection of neurons by Jamestown Canyon virus
Authors: Frey Zachary D. , Price David A. , Connors Kaleigh A. , Rush Rachael E. , Brown Griffin , Sterling Cade E. , Fatma Farheen , Schwarz Madeline M. , Ganaie Safder , Cui Xiaoxia , Wills Zachary P. , Leung Daisy W. , Amarasinghe Gaya K. , Hartman Amy L.
Published: November 2024

Jamestown Canyon virus (JCV) is a bunyavirus and arbovirus responsible for neuroinvasive disease in the United States. Little is known about JCV pathogenesis, and no host factors required for cellular infection have been identified. Recently, we identified low-density lipoprotein receptor related protein 1 (Lrp1) as a host entry factor for two other bunyaviruses Rift Valley fever virus (RVFV) and Oropouche virus (OROV). Here, we assessed the role of Lrp1 in mediating JCV cellular infection of neurons. Both neuronal and non-neuronal immortalized cell lines deficient for Lrp1 displayed reduction in infection with JCV, and early stages of infection such as binding and internalization were impacted by lack of Lrp1. In primary rat neurons, Lrp1 was highly expressed, and the neurons were highly permissive for JCV infection. Treatment of primary neurons with recombinant receptor-associated protein (RAP), a high affinity ligand for Lrp1, resulted in reduced infectivity with JCV. In addition, pretreatment of cells with RVFV Gn inhibited JCV infection, suggesting that the two viruses may share overlapping binding sites. These results provide compelling evidence that Lrp1 is an important cellular factor for efficient infection by JCV, and thus multiple bunyaviruses with varying clinical manifestations and tissue tropism are facilitated by the host cell Lrp1. Reliance of multiple bunyaviruses on Lrp1 makes it a promising target for pan-bunyaviral antivirals and therapeutics.
Fractional Calculus in Epigenetics
Authors: Nasrolahpour Hosein , Pellegrini Matteo , Skovranek Tomas
Published: November 2024

DNA methylation, a pivotal epigenetic modification, plays a critical role in regulating gene expression. Understanding its dynamics with age is essential for elucidating ageing processes and developing biomarkers. This short note presents a theoretical framework for modelling DNA methylation dynamics using a fractional calculus approach, extending standard exponential models to accommodate the complex, heterogeneous nature of methylation changes over time. The fractional-calculus representation of the methylation process, described by the fractional-order differential equation and its solution based on the Mittag-Leffler function, not only provides better results in the sense of R2, RMSE, and MSE criteria but also offers a more general model, where the standard exponential model is only one special case.
Genomes of Poaceae sisters reveal key metabolic innovations preceding the evolution of grasses
Authors: Takeda-Kimura Yuri , Moore Bethany , Holden Samuel , Deb Sontosh K. , Barrett Matt , Lorence David , de Oliveira Marcos V. V. , Grimwood Jane , Williams Melissa , Boston Lori Beth , Jenkins Jerry , Plott Christopher , Shu Shengqiang , Barry Kerrie , Goodstein David M. , Schmutz Jeremy , Moscou Matthew J. , McKain Michael R. , Leebens-Mack James H. , Maeda Hiroshi A.
Published: November 2024

The grass family (Poaceae, Poales) holds immense economic and ecological significance, exhibiting unique metabolic traits, including dual starch and lignin biosynthetic pathways. To investigate when and how the metabolic innovations known in grasses evolved, we sequenced the genomes of four Poales species, includingJoinvillea ascendensandEcdeiocolea monostachyarepresenting the sister clade to Poaceae. Therhowhole genome duplication (ρWGD) in the ancestral lineage for all grasses contributed to the gene family expansions underlying cytosolic starch biosynthesis, whereas an earlier tandem duplication ofphenylalanine ammonia lyase(PAL) gave rise tophenylalanine/tyrosine ammonia lyase(PTAL) responsible for the dual lignin biosynthesis. Integrated functional genomic and biochemical analyses of grass relatives further revealed the molecular basis of key metabolic innovations predating the evolution of grasses.

Abstract Figure
CXXC5 is a ubiquitinated protein and is degraded by the ubiquitination-proteasome pathway
Authors: Ayten Hazal , Toker Pelin , Turan Gizem , Olgun Çağla Ece , Demiralay Öykü Deniz , Bınarcı Büşra , Güpür Gizem , Yaşar Pelin , Akman Hesna Begüm , Haberkant Per , Muyan Mesut
Published: November 2024

CXXC5 as a member of the zinc-finger CXXC family proteins interacts with unmodified CpG dinucleotides to modulate the expression of genes involved in cellular proliferation, differentiation, and death in physiology and pathophysiology. Various signaling pathways including mitogenic estrogens, particularly 17β-estradiol (E2), contribute to the expression and synthesis of CXXC5. However, how signaling pathways modulate protein levels of CXXC5 in cells is largely unknown. We previously reported that some key regulators, including retinoblastoma 1 and E74 Like ETS Transcription Factor 1, of the G1 to S phase transitions are involved in the expression of CXXC5 in estrogen-responsive MCF7 cells, derived from a breast adenocarcinoma. We, therefore, predict that the synthesis of CXXC5 is regulated in a cell cycle-dependent manner. We report here that although E2 in synchronized MCF7 cells augments both transcription and synthesis of CXXC5 in the G1 phase, CXXC5 protein levels are primarily mediated by ubiquitination independently of cell cycle phases. Utilizing thebioUbiquitination approach, which is based on cellular biotinylation of ubiquitin, in HEK293FT cells derived from immortalized human embryonic kidney cells followed by sequential immunoprecipitation coupled mass spectrometry analyses, we identified multiple ubiquitinated lysine residues of CXXC5. We show in both MCF7 and HEK293FT cells that the ubiquitinated lysine residues contribute to the degradation of CXXC5 through the ubiquitin-proteasome pathway.
Numb provides a fail-safe mechanism for intestinal stem cell self-renewal in adultDrosophilamidgut
Authors: Li Mengjie , Tian Aiguo , Jiang Jin
Published: November 2024

Stem cell self-renewal often relies on asymmetric fate determination governed by niche signals and/or cell-intrinsic factors but how these regulatory mechanisms cooperate to promote asymmetric fate decision remains poorly understood. In adultDrosophilamidgut, asymmetric Notch (N) signaling inhibits intestinal stem cell (ISC) self-renewal by promoting ISC differentiation into enteroblast (EB). We have previously shown that epithelium-derived BMP promotes ISC self-renewal by antagonizing N pathway activity (Tian and Jiang, 2014). Here we show that loss of BMP signaling results in ectopic N pathway activity even when the N ligand Delta (Dl) is depleted, and that the N inhibitor Numb acts in parallel with BMP signaling to ensure a robust ISC self-renewal program. Although Numb is asymmetrically segregated in about 80% of dividing ISCs, its activity is largely dispensable for ISC fate determination under normal homeostasis. However, Numb becomes crucial for ISC self-renewal when BMP signaling is compromised. Whereas neither Mad RNAi nor its hypomorphic mutation led to ISC loss, inactivation of Numb in these backgrounds resulted in stem cell loss due to precocious ISC-to-EB differentiation. Furthermore, we find thatnumbmutations resulted in stem cell loss during midgut regeneration in response to epithelial damage that causes fluctuation in BMP pathway activity, suggesting that the asymmetrical segregation of Numb into the future ISC may provide a fail-save mechanism for ISC self-renewal by offsetting BMP pathway fluctuation, which is important for ISC maintenance in regenerative guts.
A sensitive period for the development of episodic-like memory in mice
Authors: Ramsaran Adam I , Ventura Silvia , Gallucci Julia , De Snoo Mitchell L , Josselyn Sheena A , Frankland Paul W
Published: November 2024

Episodic-like memory is a later-developing cognitive function supported by the hippocampus. In mice, the formation of extracellular perineuronal nets in subfield CA1 of the dorsal hippocampus controls the emergence of episodic-like memory during the fourth postnatal week (Ramsaran et al., 2023). Whether the timing of episodic-like memory onset is hard-wired, or flexibly set by early-life experiences during a critical or sensitive period for hippocampal maturation, is unknown. Here, we show that the trajectories for episodic-like memory development vary for mice given different sets of experiences spanning the second and third postnatal weeks. Specifically, episodic-like memory precision developed later in mice that experienced early-life adversity, while it developed earlier in mice that experienced early-life enrichment. Moreover, we demonstrate that early-life experiences set the timing of episodic-like memory development by modulating the pace of perineuronal net formation in dorsal CA1. These results indicate that the hippocampus undergoes a sensitive period during which early-life experiences determine the timing for episodic-like memory development.
The acoustic properties, syllable structure, and syllable sequences of ultrasonic vocalizations (USVs) during neonatal opioid withdrawal in FVB/N mouse substrains
Authors: Wingfield Kelly K. , Misic Teodora , Miracle Sophia A. , McDermott Carly S. , Jain Kaahini , Abney Nalia M. , Richardson Kayla T. , Rubman Mia B. , Beierle Jacob A. , Wachman Elisha M. , Bryant Camron D.
Published: November 2024

Concomitant with the opioid epidemic, there has been a rise in pregnant women diagnosed with opioid use disorder and cases of infants born with neonatal opioid withdrawal syndrome (NOWS). NOWS refers to signs and symptoms following cessation of prenatal opioid exposure that comprise neurological, gastrointestinal, and autonomic system dysfunction. A critical indicator of NOWS severity is excessive, high-pitched crying. However, NOWS evaluation is, in large part, subjective, and additional cry features may not be easily recognized during clinical assessment. Thus, there is a need for more objective measures to determine NOWS severity. We used a third trimester-approximate opioid exposure paradigm to model NOWS traits in genetically similar inbred substrains of FVB/N mice (NJ, NCrl, NHsd, and NTac). Pups were injected twice daily from postnatal day 1 (P1) to P14 with morphine (10 mg/kg, s.c.) or saline (20 ml/g, s.c.). Because there were only very minor substrain differences in spontaneous withdrawal-induced ultrasonic vocalization (USV) profiles, we collapsed across substrains to evaluate the effects of morphine withdrawal on additional USV properties. We identified syllable sequences unique to morphine-withdrawn and saline-control FVB/N pups on P7 and P14. We also observed an effect of spontaneous morphine withdrawal on the acoustic properties of USVs and specific syllables on P7 and P14. Multiple withdrawal traits correlated with some acoustic properties of USVs and syllable type emission in morphine-withdrawn FVB/N pups on P7 and P14. These data provide an in-depth investigation of mouse USV syllable profiles and acoustic features during spontaneous neonatal opioid withdrawal in mice.
Unifying Subicular Function: A Predictive Map Approach
Authors: Bennett Lauren , de Cothi William , Muessig Laurenz , Rodrigues Fábio R , Cacucci Francesca , Wills Tom J , Sun Yanjun , Giocomo Lisa M , Lever Colin , Poulter Steven , Barry Caswell
Published: November 2024

The successor representation has emerged as a powerful model for understanding mammalian navigation and memory; explaining the spatial coding properties of hippocampal place cells and entorhinal grid cells. However, the diverse spatial responses of subicular neurons, the primary output of the hippocampus, have eluded a unified account. Here, we demonstrate that incorporating rodent behavioural biases into the successor representation successfully reproduces the heterogeneous activity patterns of subicular neurons. This framework accounts for the emergence of boundary and corner cells; neuronal types absent in upstream hippocampal regions. We provide evidence that subicular firing patterns are more accurately described by the successor representation than a purely spatial or boundary vector cell model of subiculum. Our work offers a unifying theory of subicular function that positions the subiculum, more than other hippocampal regions, as a predictive map of the environment.
A Prefrontal Cortex Map based on Single Neuron Activity
Authors: Le Merre Pierre , Heining Katharina , Slashcheva Marina , Jung Felix , Moysiadou Eleni , Guyon Nicolas , Yahya Ram , Park Hyunsoo , Wernstal Fredrik , Carlén Marie
Published: November 2024

The intrinsic organization underlying the central cognitive role of the prefrontal cortex (PFC) is poorly understood. The work to date has been dominated by cytoarchitecture as a canvas for studies on the PFC, constraining concepts, analyses, results, and their interpretations to pre-configured delimitations that might not be relevant to function. We approached organization by profiling the activity and spatial location of >23,000 neurons recorded in awake mice. Regularly firing neurons were over-represented in most PFC subregions, yet a fine-grained activity map of the PFC did not align with cytoarchitecturally defined subregions. Instead, we observed a robust relationship between spontaneous activity patterns and intra-PFC hierarchy, suggesting internal organization principles transcending cytoarchitecture. Single neuron responses to sounds did not reflect intra-PFC hierarchy but were linked to spontaneous firing rate, indicating that responsiveness increases with excitability and is decoupled from the PFC’s intrinsic operational structure. Our data-driven approach provides a scalable roadmap to explore functional organizations in diverse brain regions and species, opening avenues to link activity, structure, and function in the brain.
Comparative Analysis of Neural Crest Development in the Chick and Mouse
Authors: Morrison JA , Pushel I , McLennan R , McKinney MC , Gogol MM , Scott A , Krumlauf R , Kulesa PM
Published: November 2024

A core framework of the gene regulatory network (GRN) governing neural crest (NC) cell development has been generated by integrating separate inputs from diverse model organisms rather than direct comparison. This has limited insights into the diversity of genes in the NC cell GRN and extent of conservation of newly identified transcriptional signatures in cell differentiation and invasion. Here, we address this by leveraging the strengths and accessibility of the avian embryo to precise developmental staging by egg incubation and use an integrated analysis of chick (HH13) and mouse (E9.5) embryo tissue samples collected during NC cell migration into pharyngeal arches 1-2 (PA1 and PA2). We successfully identify a cluster of NC cells containing both mouse and chick cells that share expression ofLmo4,Tfap2B,Sox10, andTwist1, and distinct genes that lack known conserved roles in NC. Importantly, we discovered a cluster of cells exhibiting a conserved transcriptional signature associated with the NC cell migratory wavefront in both mouse and chick, including KAZALD1, BAMBI, DES, and GPC3. We confirm their expression is restricted to leader mouse NCs by multiplexed FISH. Together, these data offer novel insights into the transcriptional programs that underlie NC cell migration and establish the foundation for future comparative functional analyses.
Alternative Import-Channels And Destinations Of Mitochondrial PINK1 Controlled By Trans-Membrane-Domain Structural Plasticity
Authors: Lorriman James S. , Grieve Adam G. , Corey Robin A. , Collinson Ian
Published: November 2024

Entry of the PINK1-kinase into the mitochondrial inner-membrane results in cleavage by the rhomboid-protease PARL, followed by retro-translocation back to the outer-membrane and proteasomal-degradation. Failure of this process, in compromised mitochondria, leads to kinase activation at the surface, and ultimately mitophagy. Analysis of PINK1-import within intact cells reveals an alternative pathway into the matrix. Structural modelling predicts that PINK1’s trans-membrane-domain (TMD) forms either an α-helix or α/β-hybrid at the interface between Tim17, of the TIM23-core-complex, and, respectively, either Romo1 or PARL. These mutually exclusive interactions both encapsulate a hydrated protein-channel. The α-helical-TMD form adopts a pose suggestive of translocation through the Romo1/Tim17-channel, while the α/β-hybrid-TMD is retracted into PARL’s active-site for cleavage, presumably after import through the adjacent rhomboid/Tim17-channel. We propose structural plasticity of the PINK1-TMD underlies alternative destinies for full-length matrix-import or cleavage/retro-translocation. The results reveal new insights of PINK1’s role in mitochondrial function, quality-control and early-onset Parkinson’s disease.
Membrane asymmetry facilitates murine norovirus entry and persistent enteric infection
Authors: Stewart Brittany M. , Pierce Linley R. , Olson Mikayla C. , Orchard Robert C.
Published: November 2024

Norovirus, the leading cause of gastroenteritis worldwide, is a non-enveloped virus whose tropism is determined in part by the expression patterns of entry receptors. However, the contribution of cellular lipids to viral entry is not well understood. Here, we determined that the asymmetrical distribution of lipids within membrane bilayers is required for murine norovirus (MNV) replication. Specifically, TMEM30a, an essential subunit of lipid flippases, is required for MNV replication in vitro. Disruption of TMEM30a in mouse intestinal epithelial cells prevents persistent, enteric infection by MNV in vivo. Mechanistically, TMEM30a facilitates MNV binding and entry. Surprisingly, exoplasmic phosphatidylserine (PS), a typical marker of dying cells, does not inhibit MNV infection. Rather, TMEM30a maintains a lipid ordered state that impacts membrane fluidity that is necessary for the low affinity, high avidity binding of MNV to cells. Our data provides a new role for lipid asymmetry in promoting non-enveloped virus infectionin vitroand norovirus persistence in vivo.
“Randomized controlled clinical trial with a multifaceted cognitive training program using video games in childhood cancer survivors”
Authors: González-Pérez Carlos , Fernández-Jiménez Eduardo , Morán Elena , Melero Helena , Malpica Norberto , Álvarez-Linera Juan , Puig Mario Alonso , Plaza Diego , Pérez-Martínez Antonio
Published: November 2024

1

This randomized controlled trial aims to evaluate the efficacy of a cognitive training program using video games in improving neuropsychological, neurological, immunological, and inflammatory parameters in childhood cancer survivors. This study will recruit 56 patients aged 8-17 years who have completed cancer treatment 1-7 years prior to enrollment. Participants will be randomized to either the video game intervention or waiting group. The primary objectives are analyzing potential changes in neuropsychological tests covering all neurocognitive domains, neuroimaging tests (structural, diffusion, and functional imaging), and immune and inflammatory biomarker levels after video game intervention. The secondary objectives are to define the prevalence of neurocognitive deficits in the study population, analyze psychological and emotional self-perception and parental perception after the intervention, and assess the feasibility of implementing this new intervention methodology. The inclusion criteria comprise specific diagnoses (CNS cancer, hematologic malignancies, extracranial solid tumors, and nonmalignant hematological diseases requiring allogeneic hematopoietic progenitor transplantation) and treatments (CNS surgery, radiotherapy, intrathecal/intraventricular chemotherapy, neurotoxic systemic chemotherapy, and hematopoietic stem cell transplantation). Patients with active disease, relapse, or prior neurological or psychiatric pathology will be excluded. This study will improve the understanding and management of neurocognitive sequelae in childhood cancer survivors and ultimately enhance their quality of life.
Recurrent Connectivity Shapes Spatial Coding in Hippocampal CA3 Subregions
Authors: Kong Eunji , Zabeh Erfan , Liao Zhenrui , Mihaila Tiberiu S. , Wilson Caroline , Santhirasegaran Charan , Peterka Darcy S. , Losonczy Attila , Geiller Tristan
Published: November 2024

Stable and flexible neural representations of space in the hippocampus are crucial for navigating complex environments. However, how these distinct representations emerge from the underlying local circuit architecture remains unknown. Using two-photon imaging of CA3 subareas during active behavior, we reveal opposing coding strategies within specific CA3 subregions, with proximal neurons demonstrating stable and generalized representations and distal neurons showing dynamic and context-specific activity. We show in artificial neural network models that varying the recurrence level causes these differences in coding properties to emerge. We confirmed the contribution of recurrent connectivity to functional heterogeneity by characterizing the representational geometry of neural recordings and comparing it with theoretical predictions of neural manifold dimensionality. Our results indicate that local circuit organization, particularly recurrent connectivity among excitatory neurons, plays a key role in shaping complementary spatial representations within the hippocampus.
SMAS: Structural MRI-Based AD Score using Bayesian VAE
Authors: Nemali A. , Bernal J. , Yakupov R. , Singh D. , Dyrba M. , Incesoy E.I. , Mukherjee S. , Peters O. , Hellmann-Regen J. , Ersözlü E. , Preis L. , Priller J. , Spruth E. , Altenstein S. , Lohse A. , Schneider A. , Fliessbach K. , Kimmich O. , Wiltfang J. , Hansen N. , Schott B. , Rostamzadeh A. , Glanz W. , Butryn M. , Buerger K. , Janowitz D. , Ewers M. , Perneczky R. , Rauchmann B. , Teipel S. , Kilimann I. , Goerss D. , Laske C. , Sodenkamp S. , Spottke A. , Coenjaerts M. , Brosseron F. , Lüsebrink F. , Dechent P. , Scheffler K. , Hetzer S. , Kleineidam L. , Stark M. , Jessen F. , Duzel E. , Ziegler G.
Published: November 2024

This study introduces the Structural MRI-based Alzheimer’s Disease Score (SMAS), a novel index intended to quantify Alzheimer’s Disease (AD)-related morphometric patterns using a deep learning Bayesian-supervised Variational Autoencoder (Bayesian-SVAE). SMAS index was constructed using baseline structural MRI data from the DELCODE study and evaluated longitudinally in two independent cohorts: DEL-CODE (n=415) and ADNI (n=190). Our findings indicate that SMAS has strong associations with cognitive performance (DELCODE: r=-0.83; ADNI: r=-0.62), age (DEL-CODE: r=0.50; ADNI: r=0.28), hippocampal volume (DEL-CODE: r=-0.44; ADNI: r=-0.66), and total grey matter volume (DELCODE: r=-0.42; ADNI: r=-0.47), suggesting its potential as a biomarker for AD-related brain atrophy. Moreover, our longitudinal studies suggest that SMAS may be useful for early identification and tracking of AD. The model demonstrated significant predictive accuracy in distinguishing cognitively healthy individuals from those with AD (DELCODE: AUC=0.971 at baseline, 0.833 at 36 months; ADNI: AUC=0.817 at baseline, improving to 0.903 at 24 months). Notably, over a 36-month period, SMAS index outperformed existing measures such as SPARE-AD and hippocampal volume. Relevance map analysis revealed significant morphological changes in key AD-related brain regions—including the hippocampus, posterior cingulate cortex, precuneus, and lateral parietal cortex—highlighting that SMAS is a sensitive and interpretable biomarker of brain atrophy, suitable for early AD detection and longitudinal monitoring of disease progression.
Axonal injury signaling is restrained by a spared synaptic branch
Authors: Smithson Laura J. , Zang Juliana , Junginger Lucas , Waller Thomas J. , Jankowiak Reilly , Khan Sophia , Li Ye , Cai Dawen , Collins Catherine A.
Published: November 2024

The intrinsic ability of injured neurons to degenerate and regenerate their axons facilitates nervous system repair, however this ability is not engaged in all neurons and injury locations. Here we investigate the regulation of a conserved axonal injury response pathway with respect to the location of damage in branched motoneuron axons inDrosophilalarvae. The dileucine zipper kinase DLK, (also known as MAP3K12 in mammals and Wallenda (Wnd) inDrosophila), is a key regulator of diverse responses to axonal injury. In three different populations of motoneurons, we observed the same striking result that Wnd/DLK signaling becomes activated only in response to injuries that remove all synaptic terminals. Injuries that spare even a small part of a synaptic terminal fail to activate Wnd/DLK signaling, despite the presence of extensive axonal degeneration. The regulation of injury-induced Wnd/DLK signaling occurs independently of its previously known regulator, the Hiw/PHR ubiquitin ligase. We propose that Wnd/DLK signaling regulation is linked to the trafficking of a synapse-to-nucleus axonal cargo and that this mechanism enables neurons to respond to impairments in synaptic connectivity.
Exploring structure-function relationships in engineered receptor performance using computational structure prediction
Authors: Corcoran William K. , Cosio Amparo , Edelstein Hailey I. , Leonard Joshua N.
Published: November 2024

Engineered receptors play increasingly important roles in transformative cell-based therapies. However, the structural mechanisms that drive differences in performance across receptor designs are often poorly understood. Recent advances in protein structural prediction tools have enabled the modeling of virtually any user-defined protein, but how these tools might build understanding of engineered receptors has yet to be fully explored. In this study, we employed structural modeling tools to perform post hoc analyses to investigate whether predicted structural features might explain observed functional variation. We selected a recently reported library of receptors derived from natural cytokine receptors as a case study, generated structural models, and from these predictions quantified a set of structural features that plausibly impact receptor performance. Encouragingly, for a subset of receptors, structural features explained considerable variation in performance, and trends were largely conserved across structurally diverse receptor sets. This work indicates potential for structure prediction-guided synthetic receptor engineering.
Motional-state analysis of a trapped ion by ultranarrowband composite pulses
Authors: Mallweger Marion , Guevara-Bertsch Milena , Torosov Boyan T. , Thomm Robin , Kuk Natalia , Parke Harry , Roos Christan F. , Higgins Gerard , Hennrich Markus , Vitanov Nikolay V.
Published: November 2024

In this work, we present a method for measuring the motional state of a two-level system coupled to a harmonic oscillator. Our technique uses ultranarrowband composite pulses on the blue sideband transition to scan through the populations of the different motional states. Our approach does not assume any previous knowledge of the motional state distribution and is easily implemented. It is applicable both inside and outside of the Lamb-Dicke regime. For higher phonon numbers especially, the composite pulse sequence can be used as a filter for measuring phonon number ranges. We demonstrate this measurement technique using a single trapped ion and show good detection results with the numerically evaluated pulse sequence.

Published by the American Physical Society
2024
Topological magnon in exchange frustration driven incommensurate spin spiral of kagome-lattice
YMn6Sn6
Authors: Sadhukhan Banasree , Bergman Anders , Thunström Patrik , Lopez Manuel Pereiro , Eriksson Olle , Delin Anna
Published: November 2024

YMn6Sn6 consists of two types of Mn-based kagome planes stacked along the c-axis having a complex magnetic interaction. We report a spin reconstruction in YMn6Sn6 from ferromagnetic (FM) into a combination of two incommensurate spin spirals (SSs) originating from two different types of Mn kagome planes driven by frustrated magnetic exchanges along the c-axis with the inclusion of the Hubbard U. The pitch angle and wave vector of the incommensurate SSs are ∼89.3∘ and ∼ (0 0 0.248), respectively, which are in excellent agreement with the experiment. We employ an effective model Hamiltonian constructed out of exchange interactions to capture the experimentally observed nonequivalent nature of the two incommensurate SSs which also explain the FM-SS crossover due to antiferromagntic spin exchange with correlation. We further report the existence of a topological magnon with spin-orbit coupling in the incommensurate SS phase of YMn6Sn6 by calculating the topological invariants and Berry curvature profile. The location of the Dirac magnon in the energy landscape at 73 meV matches with another experimental report. We demonstrate the accuracy of our results by highlighting the experimental features in YMn6Sn6.

Published by the American Physical Society
2024
Ferromagnetic ferroelectricity due to the Kugel-Khomskii mechanism of orbital ordering assisted by atomic Hund's second rule effects
Authors: Solovyev I. V. , Ono R. , Nikolaev S. A.
Published: November 2024

The exchange interactions in insulators depend on the orbital state of magnetic ions, obeying certain phenomenological principles, known as Goodenough-Kanamori-Anderson rules. Particularly, the ferro order of alike orbitals tends to stabilize antiferromagnetic interactions, while the antiferro order of unlike orbitals favors ferromagnetic interactions. The Kugel-Khomskii theory provides a universal view on such coupling between spin and orbital degrees of freedom, based on the superexchange processes: namely, for a given magnetic order, the occupied orbitals tend to arrange in a way to further minimize the exchange energy. Then, if two magnetic sites are connected by the spatial inversion, the antiferro orbital order should lead to the ferromagnetic coupling break the inversion symmetry. This constitutes the basic idea of our work, which provides a pathway for designing ferromagnetic ferroelectrics: the rare but fundamentally and practically important multiferroic materials. After illustrating the basic idea on toy-model examples, we propose that such behavior can be indeed realized in the van der Waals ferromagnet VI3, employing for this analysis the realistic model derived from first-principles calculations for magnetic 3d bands. We argue that the intra-atomic interactions responsible for Hund's second rule, acting against the crystal field, tend to restore the orbital degeneracy of the ionic d2 state in VI3 and, thus, provide a necessary flexibility for activating the Kugel-Khomskii mechanism of the orbital ordering. In the honeycomb lattice, this orbital ordering breaks the inversion symmetry, stabilizing the ferromagnetic-ferroelectric ground state. The symmetry breaking leads to the canting of magnetization, which can be further controlled by the magnetic field, producing a huge change of electric polarization.

Published by the American Physical Society
2024
Influence of dynamical screening of four-quarks interaction on the chiral phase diagram
Authors: Szymański Michał , Lo Pok Man , Redlich Krzysztof , Sasaki Chihiro
Published: November 2024

We investigate the effect of screening of the four-quarks contact interactions by the ring diagram at finite temperature and density in an effective chiral model inspired by QCD in the Coulomb gauge. As a consequence, a medium-dependent coupling naturally emerges which, in a class of chiral models, brings the chiral crossover temperature down to the value calculated in lattice QCD at low net-baryon density. Furthermore, it implies a stronger divergence of the chiral susceptibility at the critical point compared to the mean-field dynamics. At high densities, the screening induces a substantial instability region and its size depends on the regularization schemes. We discuss the properties of an effective potential for a class of models described by momentum-independent gap equations. In particular, we introduce the method to construct an approximate effective potential from the gap equations to determine the location of the first-order phase transition.

Published by the American Physical Society
2024
Production mechanism of the hidden charm pentaquark states
Pcc¯
Authors: Clymton Samson , Kim Hyun-Chul , Mart Terry
Published: November 2024

We investigate hidden charm pentaquark states using an off-shell coupled-channel formalism involving heavy meson and singly heavy baryon scattering. Our approach utilizes an effective Lagrangian to construct the kernel amplitudes, which respect both heavy quark symmetry and hidden local symmetry. After solving the coupled integral equations, we obtain the transition amplitudes for J/ψN scattering and various heavy meson and singly heavy baryon scattering processes. We identify seven distinct peaks related to molecular states of heavy mesons D¯ (D¯*) and singly heavy baryons Σc (Σc*). Four of these peaks can be associated with the known Pcc¯ states: Pcc¯(4312), Pcc¯(4380), Pcc¯(4440), and Pcc¯(4457). We predict two additional resonances with masses around 4.5 GeV, which we interpret as D¯*Σc* molecular states, and identify one cusp structure. Additionally, we predict two P-wave pentaquark states with positive parity, which may be candidates for genuine pentaquark configurations. Notably, these pentaquark states undergo significant modifications in the J/ψN elastic channel, with some even disappearing due to interference from the positive parity channel. The present investigation may provide insight into the absence of pentaquark states in J/ψ photoproduction observed by the GlueX Collaboration.

Published by the American Physical Society
2024
Irreducible cosmological backgrounds of a real scalar with a broken symmetry
Authors: D’Eramo Francesco , Tesi Andrea , Vaskonen Ville
Published: November 2024

We explore the irreducible cosmological implications of a singlet real scalar field. Our focus is on theories with an approximate and spontaneously broken Z2 symmetry where quasistable domain walls can form at early times. This seemingly simple framework bears a wealth of phenomenological implications that can be tackled by means of different cosmological and astrophysical probes. We elucidate the connection between domain wall dynamics and the production of dark matter and gravitational waves. In particular, we identify three main benchmark scenarios. The gravitational wave signal observed by pulsar timing arrays can be generated by the domain walls if the mass of the singlet is ms∼PeV. For lower masses, but with ms≳10  GeV, scalars produced in the annihilation of the domain walls can be dark matter with a distinctive feature in their power spectrum. Finally, the thermal bath provides an unavoidable source of unstable scalars via the freeze-in mechanism whose subsequent decays can be tested by their imprints on cosmological and terrestrial observables.

Published by the American Physical Society
2024
Phenomenological model of gravitational self-force enhanced tides in inspiraling binary neutron stars
Authors: Williams Natalie , Schmidt Patricia , Pratten Geraint
Published: November 2024

Gravitational waves from inspiraling binary neutron stars provide unique access to ultradense nuclear matter and offer the ability to constrain the currently unknown neutron star equation-of-state through tidal measurements. This, however, requires the availability of accurate and efficient tidal waveform models. In this paper we present henom, a new phenomenological tidal phase model for the inspiral of neutron stars in the frequency domain, which captures the gravitational self-force informed tidal contributions of the time-domain effective-one-body model esum. henom is highly faithful and computationally efficient, and by choosing a modular approach, it can be used in conjunction with frequency-domain binary black hole waveform model to generate the complete phase for a binary neutron star inspiral. henom is valid for neutron star binaries with unequal masses and mass ratios between 1 and 3, and dimensionless tidal deformabilities up to 5000. Furthermore, henom does not assume universal relations or parametrized equations of state, hence allowing for exotic matter analyses and beyond standard model physics investigations. We demonstrate the efficacy and accuracy of our model through comparisons against esum, numerical relativity waveforms and full Bayesian inference, including a reanalysis of the binary neutron star observation GW170817.

Published by the American Physical Society
2024
Gravitational form factors of pion from top-down holographic QCD
Authors: Fujii Daisuke , Iwanaka Akihiro , Tanaka Mitsuru
Published: November 2024

The gravitational form factors (GFFs) of pions are calculated from a top-down holographic quantum chromodynamics (QCD) approach with momentum transfer dependence for the first time. It is important because the GFFs of hadrons have information on the internal stress distribution that may provide insight into the mechanism of how QCD forms hadrons. The forward limit value of this GFFs, i.e., the D-term, was also obtained. Furthermore, in this approach, we observe the so-called glueball dominance, in which pions have gravitational interactions via infinite glueball spectra.

Published by the American Physical Society
2024
Separated reactant mix width across diffusion-dominated and hydrodynamically dominated interface mix in inertial confinement fusion implosions
Authors: Meaney K. D. , Kim Y. , Hoffman N. M. , Mohamed Z. L. , Taitano W. T. , Herrmann H. W. , Geppert-Kleinrath H. , Springstead M. P. , Zylstra A. B. , Leatherland A. , Wilson L. , Glebov V. Yu. , Forrest C.
Published: November 2024

Diffusion-dominated mix in inertial confinement fusion (ICF) is characterized where the majority of the mix occurs in the immediate fuel-shell interface while hydrodynamic-dominated mix pulls shell material from farther away into the central fuel. A thin (150 nm) separated reactants ICF mix platform is highly sensitive to the amount of mix from the first micron of shell-fuel interface. This fine-spatial resolution platform has revealed that material mix in moderate convergence (CR∼12) ICF implosions is dominated by a diffusion mechanism. This technique has now been expanded across a set of OMEGA ICF implosions, observing an increase in mix width and mix amount for cooler, slower, and more compressive implosions. Hydrodynamic simulations require a buoyancy-drag mix model to capture the increasing mix width, suggesting a transition between these two mix mechanisms.

Published by the American Physical Society
2024
Conversion-Driven Leptogenesis: A Testable Theory of Dark Matter and Baryogenesis at the Electroweak Scale
Authors: Heisig Jan
Published: November 2024

The phenomena of dark matter and the baryon asymmetry pose two of the most pressing questions in today’s fundamental physics. Conversion-driven freeze-out has emerged as a successful mechanism to generate the observed dark matter relic density. It supports thermalization of dark matter despite its very weak couplings, aligning with the null results from direct and indirect detection experiments. In this Letter, we demonstrate that the departure from equilibrium of dark matter, induced by semi-efficient conversions, satisfies Sakharov’s conditions, providing a novel explanation for both dark matter and the baryon asymmetry. Specifically, for a leptophilic model, we establish the mechanism of conversion-driven leptogenesis. The scenario predicts dark matter masses close to the electroweak scale offering testable predictions, such as soft displaced leptons at the LHC and future colliders.

Published by the American Physical Society
2024
Survival Resonances during Fractional Killing of Cell Populations
Authors: Puccioni Francesco , Pausch Johannes , Piho Paul , Thomas Philipp
Published: November 2024

Fractional killing in response to drugs is a hallmark of nongenetic cellular heterogeneity. Yet how individual lineages evade drug treatment, as observed in bacteria and cancer cells, is not quantitatively understood. We study a stochastic population model with age-dependent division and death rates, allowing for persistence. In periodic drug environments, we discover peaks in the survival probabilities at division or death times that are multiples of the environment duration. The survival resonances are unseen in unstructured populations and are amplified by persistence.

Published by the American Physical Society
2024
Non-invasive nanoscale imaging of protein micro- and nanocrystals for screening crystallization conditions
Authors: Khakurel Krishna Prasad , Hosomi Kei , Inami Wataru , Yoshimasa Kawata
Published: November 2024

Crystallography has been the routine technique for studying high-resolution structures of proteins for over five decades. A major bottleneck in structure determination of macromolecules is obtaining crystals of a size and quality suitable for single-crystal X-ray crystallography experiments. Many challenging proteins either fail to grow into crystals or fail to grow into crystals of a size suitable for obtaining high-resolution structures using conventional X-ray crystallography. When it comes to smaller crystals, they can be used either for seeding to get larger crystals or for serial crystallography and electron diffraction for obtaining the structures. For both purposes, a limiting step is to non-invasively image such small crystals of sub-micrometre dimensions and to screen the conditions where such crystals prevail. Here we use cathodoluminescence-based (CL-based) nanoscopy to image protein nanocrystals. We show that crystals of micrometre and submicrometre dimensions can be non-invasively imaged by the CL-based nanoscope. The results presented here demonstrate the feasibility of non-invasive imaging of protein crystals with sub-100 nm resolution.
Complete classification of six-dimensional iso-edge domains
Authors: Dutour Sikirić Mathieu , van Woerden Wessel
Published: November 2024

In this paper, we report on the full classification of generic iso-edge subdivisions of six-dimensional translational lattices. We obtain a complete list of 55083357 affine types of iso-edge subdivisions. We report on the use of the method of canonical forms that allows us to apply hashing techniques used in modern databases.
Management information systems and organizational agility: a bibliometric analysis
Authors: Hameed Ibrahim Mohammed , Singla Jagdeep , Goel Ridhima
Published: November 2024

Purpose

This paper aims to complex relationship between management information systems (MIS) and organizational agility, identifying gaps and key themes to guide future research in this domain.

Design/methodology/approach

A systematic extraction of 578 relevant articles from the Scopus database was conducted to provide an in-depth bibliometric analysis of the evolving role of MIS in enhancing organizational agility. Data analysis and visualization were performed using R Studio and VOSviewer.

Findings

The analysis highlights significant publication trends and identifies leading countries, institutions and journals in MIS and organizational agility research. Collaborative efforts from nations such as the USA, China and the UK, were prominent, focusing on information technology alignment, strategic agility and big data analytics. This study delineates distinct research clusters and future research questions, offering a clear trajectory for ongoing exploration in the field.

Originality/value

To the best of the authors’ knowledge, this study is one of the first to provide a comprehensive bibliometric analysis of the intersection between MIS and organizational agility. It offers valuable insights into research trends and future directions while emphasizing the need for MIS deployment, thereby contributing to a comprehensive understanding of the field.