bluuebunny/crossref_metadata_2025_split huggingface dataset:
Making the Exercise Experience More Pleasant: Effects of Open-Label Placebos on Affective Responses to Exercise Induced through Verbal Suggestions
Authors: Yue QIU , Dong-Ting YUN , Jiao LIU , Zhi-Xiong MAO 
Published: November 2024

AbstractObjectiveBy manipulating psychological factors—such as fostering positive expectations about exercise outcomes through verbal suggestions—it is possible to induce placebo effects without the use of traditional placebos, such as inert substances (closed-label placebos, CLPs). This can be achieved even when individuals are aware they are receiving a placebo through verbal suggestions (open-label placebo, OLP). This proof-of-principle study investigated whether the effects of OLPs on affective responses to exercise can be induced solely through verbal suggestions.MethodsEighty-nine healthy volunteers were randomized into three groups during a 30-minute session of moderate-intensity running. The first experimental group was informed that the running session would enhance their mood (CLP: positive verbal suggestion), the second experimental group was educated on the concept of an OLP and its anticipated effects during the running session (OLP: positive verbal suggestion), and the third control group received unrelated information about the study (no verbal suggestion). The primary study outcomes were self-reported affective valence during exercise and postexercise enjoyment. In addition, anticipated affect and remembered affect were assessed. Resting-state functional connectivity (RSFC) in the prefrontal cortex was objectively measured via functional near-infrared spectroscopy (fNIRS).ResultsCompared with the control group, both experimental groups presented increased affective valence during exercise, postexercise enjoyment, and anticipated affect, along with lower RSFC in the right prefrontal cortex, and the OLP intervention had a greater effect on remembered affect.ConclusionsThe results illustrate a potential role for OLPs in inducing affective response to exercise and suggest that further study of verbal suggestions through an extensive explanation of placebo effects might be promising for practice.
Vocal markers of schizophrenia: assessing the generalizability of machine learning models and their clinical applicability
Authors: Parola Alberto , Trenckner Jessen Emil , Rybner Astrid , Damsgaard Mortensen Marie , Nyhus Larsen Stine , Simonsen Arndis , Lin Jessica Mary , Zhou Yuan , Wang Huiling , Koelkebeck Katja , Sechidis Konstantinos , Bliksted Vibeke , Fusaroli Riccardo 
Published: November 2024

AbstractBackground and HypothesisMachine Learning (ML) models have been argued to reliably predict diagnosis and symptoms of schizophrenia based on voice data only. However, it is unclear to what extent such ML markers would generalize to different clinical samples and different languages, a crucial assessment to move towards clinical applicability. In this study, we systematically assessed the generalizability of ML models of vocal markers of schizophrenia across contexts and languages.Study DesignWe trained models relying on a large cross-linguistic dataset (Danish, German, Chinese) of 217 patients with schizophrenia and 221 controls, and used a conservative pipeline to minimize overfitting. We tested the models’ generalizability on: (i) new participants, speaking the same language; (ii) new participants, speaking a different language; (iii) further, we assessed whether training on data with multiple languages would improve generalizability using Mixture of Expert (MoE) and multilingual models.ResultsModel performance was comparable to state-of-the-art findings (F1-score ∼ 0.75) within the same language; however, models did not generalize well - showing a substantial decrease - when tested on new languages. The performance of MoE and multilingual models was also generally low (F1-score ∼ 0.50).ConclusionsOverall, the cross-linguistic generalizability of vocal markers of schizophrenia is limited. We argue that more emphasis should be placed on collecting large open cross- linguistic datasets to systematically test the generalizability of voice-based ML models, and on identifying more precise mechanisms of how the clinical features of schizophrenia are expressed in language and voice, and how different languages vary in that expression.
Assessing infant risk of cerebral palsy with video-based motion tracking
Authors: Segado Melanie , Prosser Laura , Duncan Andrea F. , Johnson Michelle J. , Kording Konrad P. 
Published: November 2024

AbstractCerebral Palsy (CP) is a common (about 1 in 500 children) health condition caused by abnormal brain development that affects the ability to control movement. Early risk assessment happens through the General Movements Assessment (GMA), a test administered by trained clinicians at 3-4 months of age that has high predictive value for CP. With recent improvements in video-based motion tracking, automated risk assessment for CP based on the GMA is being explored. However, studies generally have used small datasets or were limited in terms of methodological rigor. Here we acquired a large dataset (1060 infants) of videos from a clinical population with elevated CP risk. In a preregistered pipeline using a lock-box set that was not used before algorithm submission we find that our machine learning predictions are highly predictive of the clinician-assessed GMA (AUC=0.79). Given its low cost, our video-based approach may be useful for clinical screening applications, particularly in low-resource settings.
“A baby is like an empty USB. Whatever you do, they store it”: a qualitative study of caregiving practices and beliefs in Soweto, South Africa
Authors: Palmer Tom , Nkosi Nokuthula , Motlhatlhedi Molebogeng , Prost Audrey , Skordis Jolene , Gram Lu , Norris Shane A , Batura Neha , Draper Catherine E 
Published: November 2024

AbstractThe importance of nurturing care for children’s development has been emphasised in the global literature. Although societal risk factors which may hinder nurturing care in South Africa have been extensively documented, the goals, beliefs and practices of caregivers in infancy have received less attention in the literature. This qualitative study was conducted with mothers of children aged 6 to 10 months in Soweto. Data were collected during focus group discussions held in May 2023 with 26 mothers, then analysed using thematic analysis. We found that mothers view themselves as playing an active role in their children’s learning and development, and are broadly aware of the importance of nurturing care. Our findings also emphasise that nurturing care is bidirectional, and based on the relationship between caregivers and children, both of whom should be viewed as individuals. This study contributes to relatively limited literature on infancy in South Africa and can help to inform context-appropriate interventions to improve early childhood development in comparable settings.
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

ABSTRACTBackgroundDual-antiplatelet therapy (DAPT) is the standard of care for acute coronary syndromes, but uncertainty exists regarding the optimal regime for North American patients.MethodsThis 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.Results1,005 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.ConclusionsWhether 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

AbstractChronic 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

ABSTRACTJamestown 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

AbstractDNA 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

AbstractThe 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

ABSTRACTCXXC5 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

AbstractStem 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

ABSTRACTEpisodic-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.
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

AbstractThe 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

AbstractThe 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.