bluuebunny/crossref_metadata_2025_split huggingface dataset:
Residential exposure to green and blue spaces over childhood and cardiometabolic health outcomes: The Generation XXI birth cohort
Authors: Valente Berta , Araújo B. , Pereira Rita , Ribeiro Ana Isabel , Barros Henrique , Santos Susana 
Published: October 2024

AbstractBackgroundEvidence on the effects of exposure to green and blue spaces on childhood cardiometabolic health is inconsistent, limited and mostly cross-sectional.ObjectivesTo assess the associations of exposure to green and blue spaces, at birth, 4, 7, and 10 years (to identify vulnerable periods of exposure) and as longitudinal trajectories (to identify the longitudinal effect over time), with cardiometabolic health outcomes at 10 years.MethodsParticipants are from Generation XXI, a population-based birth cohort from Porto Metropolitan Area, Portugal (n=4669). Residential normalized difference vegetation index (NDVI) and Euclidian distance to the nearest urban green and blue space were assessed at birth, 4, 7 and 10 years using geographic information systems and standardized by dividing the observed value by the standard deviation. Longitudinal trajectories of exposures from birth to 10 years were derived using latent class mixed models. At 10 years, we measured body mass index, fat mass index and android-to-gynoid fat ratio, blood pressure, and metabolic outcomes. We defined overweight/obesity by the World Health Organization, high blood pressure by the American Academy of Pediatrics and metabolic syndrome by the IDEFICS study.ResultsNo significant associations were observed between natural spaces exposure and body mass index, body fat content and distribution. We found an inverse association between distance to nearest blue space at birth and systolic blood pressure z-scores, and a positive association between distance to nearest green space at 7 and 10 years and metabolic syndrome score (p-values<0.05). Also, compared to children in the high stable trajectory of NDVI500m, those in the descending trajectory of NDVI500m presented a lower diastolic blood pressure z-score and metabolic syndrome score (p-values<0.05). However, after multiple testing correction, all associations lost statistical significance.DiscussionThis study did not find robust associations between the exposure to natural spaces over key developmental periods and cardiometabolic health.
“Evaluating the Impact of Artificial Intelligence on Vaccine Development: Lessons Learned from the COVID-19 Pandemic”
Authors: Farahani Arshia Farmahini , Kasraei Nika 
Published: October 2024

AbstractThe integration of artificial intelligence (AI) into the field of vaccine development has revolutionized the discovery and production processes, particularly during the COVID-19 pandemic. AI technologies played an instrumental role in accelerating the identification of viable vaccine candidates, optimizing clinical trial designs, and expediting regulatory approvals. This review critically examines the impact of AI-driven approaches on the development of COVID-19 vaccines, highlighting case studies such as the Pfizer-BioNTech and Moderna vaccines. By employing machine learning algorithms and sophisticated data analytics, AI significantly reduced traditional vaccine development timelines from years to mere months, all while enhancing precision, safety, and efficacy.Our analysis reveals that AI facilitated real-time monitoring of clinical trial data, improving patient stratification, and dynamically addressing adverse events, leading to faster approvals without compromising regulatory standards. Furthermore, AI-powered models optimized vaccine distribution strategies, overcoming logistical challenges associated with global deployment during the pandemic. This review also explores the ethical and technical challenges posed by AI, such as algorithmic biases, data privacy concerns, and the need for transparent governance frameworks. The lessons drawn from the COVID-19 pandemic underscore the transformative potential of AI in accelerating future vaccine research and pandemic preparedness. We conclude that continued interdisciplinary collaboration between AI experts, immunologists, and public health authorities will be essential in shaping the future of vaccine innovation.
The Impact of the Temperature on Extracting Information From Clinical Trial Publications Using Large Language Models
Authors: Windisch Paul , Dennstädt Fabio , Koechli Carole , Schröder Christina , Aebersold Daniel M. , Förster Robert , Zwahlen Daniel R. 
Published: October 2024

AbstractIntroductionThe application of natural language processing (NLP) for extracting data from biomedical research has gained momentum with the advent of large language models (LLMs). However, the effect of different LLM parameters, such as temperature settings, on biomedical text mining remains underexplored and a consensus on what settings can be considered “safe” is missing. This study evaluates the impact of temperature settings on LLM performance for a named-entity recognition and a classification task in clinical trial publications.MethodsTwo datasets were analyzed using GPT-4o and GPT-4o-mini models at nine different temperature settings (0.00–2.00). The models were used to extract the number of randomized participants and classified abstracts as randomized controlled trials (RCTs) and/or as oncology-related. Different performance metrics were calculated for each temperature setting and task.ResultsBoth models provided correctly formatted predictions for more than 98.7% of abstracts across temperatures from 0.00 to 1.50. While the number of correctly formatted predictions started to decrease afterwards with the most notable drop between temperatures 1.75 and 2.00, the other performance metrics remained largely stable.ConclusionTemperature settings at or below 1.50 yielded consistent performance across text mining tasks, with performance declines at higher settings. These findings are aligned with research on different temperature settings for other tasks, suggesting stable performance within a controlled temperature range across various NLP applications.
Detecting Potential Mediators of the Causal Effect of Education Level on The Risk of Stroke: A Two-Step, Two-Sample Multivariable Mendelian Randomization Study
Authors: Ken C , Ying Z , Zheng W , Ying Y 
Published: October 2024

AbstractBackgroundThe effect of education level on the risk of stroke is not fully understood. The present study aimed to reveal the genetic and modifiable mediators for the effect of education level on the risk of stroke.MethodsSummary-level genetic data were obtained from GWAS consortia. Two-sample Mendelian Randomization (MR) analysis was performed to uncover the causal effect of education level on the risk of stroke, and regression-based multivariable MR (MVMR) analyses were used to explore potential mediators.ResultsGenome-wide MR analyses showed that genetically determined higher education level was associated with reduced risk of stroke (Odds ratio (OR) per standard deviation (SD) increase: 0.74[95% confidence interval (CI): 0.58 to 0.94]; p = 0.013). We found instant coffee intake, never smoking status, body mass index (BMI), waist circumference (WC), waist-hip- ratio (WHR), Type-2 diabetes mellitus (T2DM), Diastolic pressure (DBP), Systolic pressure (SBP), Alanine aminotransferase (ALT), Platelet (PLT) and CTRP-1 (complement c1q tumor necrosis factor-related protein 1) had significant mediation roles in the effect of education level on the risk of stroke. The proportion of total effect mediated by these modifiable factors was 79%.ConclusionWe found many modifiable mediators had essential mediation roles in the effect of education level on the risk of stroke. Intervention on these mediators might have protective effect on the risk of stroke, which highlighted novel therapeutic targets.
Expression of sex steroid receptors and sex differences of Otp glutamatergic neurons of the medial extended amygdala
Authors: González-Alonso Alba , Morales Lorena , Sanz Elisenda , Medina Loreta , Desfilis Ester 
Published: October 2024

AbstractThe medial extended amygdala (EAme) is part of the social behavior network and its subdivisions show expression of sex steroid receptors, which participate in the regulation of sexually dimorphic behaviors. However, EAme subdivisions are highly heterogeneous in terms of neuron subtypes, with different subpopulations being involved in regulation of different aspects of social and non-social behaviors. To further understand the role of the different EAme neurons and their contribution to sexual differences, here we studied one of its major subtypes of glutamatergic neurons, those derived from the telencephalon-opto-hypothalamic domain that coexpressOtpandFoxg1genes during development. Our results showed that the vast majority of the Otp glutamatergic neurons of the medial amygdala and BSTM in both sexes expressAr,Esr1 (ERα)andEsr2 (ERβ) mRNA. Moreover, the high percentage of receptors expression in the Otp neurons (between 93 and 100%) indicates that probably the majority of the Otp neurons of EAme are coexpressing the three receptors. In addition, Otp neurons of the posterodorsal medial amygdala have a larger soma and occupy more space in males than in females. These and other features of the Otp neurons regarding their expression of sex steroid receptors likely contribute to some of the sexually-dimorphic behaviors regulated by EAme.
Rewired type I IFN signaling is linked to age-dependent differences in COVID-19
Authors: Petrov Lev , Brumhard Sophia , Wisniewski Sebastian , Georg Philipp , Hillus David , Hiller Anna , Astaburuaga-García Rosario , Blüthgen Nils , Wyler Emanuel , Vogt Katrin , Dey Hannah-Philine , von Stillfried Saskia , Iwert Christina , Bülow Roman D. , Märkl Bruno , Maas Lukas , Langner Christine , Meyer Tim , Loske Jennifer , Eils Roland , Lehmann Irina , Ondruschka Benjamin , Ralser Markus , Trimpert Jakob , Boor Peter , Bedoui Sammy , Meisel Christian , Mall Marcus A. , Corman Victor M. , Sander Leif Erik , Röhmel Jobst , Sawitzki Birgit 
Published: October 2024

AbstractAdvanced age is the most important risk factor for severe disease or death from COVID-19, but a thorough mechanistic understanding of the molecular and cellular underpinnings is lacking. Multi-omics analysis of samples from SARS-CoV-2 infected persons aged 1 to 84 years, revealed a rewiring of type I interferon (IFN) signaling with a gradual shift from signal transducer and activator of transcription 1 (STAT1) to STAT3 activation in monocytes, CD4+T cells and B cells with increasing age. Diversion of interferon IFN signaling was associated with increased expression of inflammatory markers, enhanced release of inflammatory cytokines, and delayed contraction of infection-induced CD4+T cells. A shift from IFN-responsive germinal center B (GCB) cells towards CD69highGCB and atypical B cells corresponded to the formation of IgA in children while complement fixing IgG was dominant in adults. Our data provide a mechanistic basis for inflammation-prone responses to infections and associated pathology during aging.Abstract Figure
Synaptic vesicle endocytosis deficits underlie GBA-linked cognitive dysfunction in Parkinson’s disease and Dementia with Lewy bodies
Authors: Vidyadhara D J , Bäckström David , Chakraborty Risha , Ruan Jiapeng , Park Jae-Min , Mistry Pramod K. , Chandra Sreeganga. S. 
Published: October 2024

AbstractGBAis the major risk gene for Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB), two common α-synucleinopathies with cognitive deficits. We investigated the role of mutantGBAin cognitive decline by utilizing Gba (L444P) mutant, SNCA transgenic (tg), and Gba-SNCA double mutant mice. Notably, Gba mutant mice showed early cognitive deficits but lacked PD-like motor deficits or α-synuclein pathology. Conversely, SNCA tg mice displayed age-related motor deficits, without cognitive abnormalities. Gba-SNCA mice exhibited both cognitive decline and exacerbated motor deficits, accompanied by greater cortical phospho-α-synuclein pathology, especially in layer 5 neurons. Single-nucleus RNA sequencing of the cortex uncovered synaptic vesicle (SV) endocytosis defects in excitatory neurons of Gba mutant and Gba-SNCA mice, via robust downregulation of genes regulating SV cycle and synapse assembly. Immunohistochemistry and electron microscopy validated these findings. Our results indicate that Gba mutations, while exacerbating pre-existing α-synuclein aggregation and PD-like motor deficits, contribute to cognitive deficits through α-synuclein-independent mechanisms, involving dysfunction in SV endocytosis.
Spontaneous alpha-band lateralization extends persistence of visual information in iconic memory by modulating cortical excitability
Authors: Smith Paul J.C. , Busch Niko A. 
Published: October 2024

AbstractPre-stimulus alpha oscillations in the visual cortex modulate neuronal excitability, influencing sensory processing and decision-making. While this relationship has been demonstrated mostly in detection tasks with low-visibility stimuli, interpretations of such effects can be ambiguous due to biases, making it difficult to clearly distinguish between perception-related and decision-related effects. In this study, we investigated how spontaneous fluctuations in pre-stimulus alpha power affect iconic memory, a high-capacity, ultra-short visual memory store. Data from 49 healthy adults (34 female and 15 male) was analyzed. We employed a partial report task, where a brief display of six stimuli was followed by a report cue indicating the target stimulus. In this paradigm, accuracy at short stimulus-cue onset asynchronies (SOAs) is typically high, reflecting the initial availability of sensory information, but it rapidly declines at intermediate SOAs due to the decay of the iconic memory trace, stabilizing at a low asymptote at long SOAs, representing the limited capacity of short-term memory. Crucially, performance in this task is constrained by the temporal persistence of sensory information, not by low visibility or response bias. We found that strong pre-stimulus alpha power enhanced performance by amplifying initial stimulus availability without affecting the speed of iconic decay. This effect was driven predominantly by stronger pre-stimulus alpha power in the hemisphere ipsilateral to the to-be-reported target, likely suppressing neuronal excitability of neurons coding irrelevant stimuli. Our findings underscore the role of alpha oscillations in modulating neuronal excitability and visual perception, independent of decision-making strategies implicated in prior studies.
A GABA-A receptor response to CBD followingstatus epilepticusin the medial entorhinal cortex of the rat
Authors: Henley Benjamin S. , Walsh Richard , Greenhill Stuart , Woodhall Gavin 
Published: October 2024

AbstractCannabidiol is a non-psychoactive phytocannabinoid that has been implicated as a potential therapeutic in numerous neurological diseases. Perhaps the most widespread therapeutic use of CBD has been in the form of Epidiolex, which is used to treat seizures associated with Lennox-Gastaut syndrome, Dravet syndrome and tuberous sclerosis. Whilst the effectiveness of CBD in seizure reduction is clear, its mechanism of action is complex, and reflects the wide range of pharmacodynamic targets that includes receptors, ion channels and enzymes. This study investigated the effects of action of cannabidiol (CBD) on GABAergic transmission in layer II of the medial entorhinal cortex in animals that had previously undergone a period ofstatus epilepticus (SE). Spontaneous post-synaptic currents were recorded from medial entorhinal cortex layer II pyramidal cells in animals 1-7 after SE and in age matched controls as well as in tissue resected from children with temporal lobe epilepsy (TLE). CBD enhanced GABAAR-mediated inhibition by increasing decay times and inhibitory charge transfer across the postsynaptic membrane in status epilepticus (SE) but did not alter GABAergic transmission in age-matched control rats. The SE-induced effects of CBD were blocked by ligands acting as inverse agonists at the benzodiazepine site of the GABAAR receptor and the effects of CBD were additive to low-doses of benzodiazepine and barbiturate agonists, consistent with allosteric actions on the GABAAR. Similar effects were observed in both SE rat and human layer II neurons. Overall, these data suggest CBD may act as a positive allosteric modulator (PAM) at postsynaptic GABAARs and this action appears to develop following SE.Key pointsCBD increases inhibition only poststatus epilepticus.This effect is blocked by benzodiazepine site inverse agonistsCBD is additive to low-dose zolpidem, suggesting an allosteric effect on the GABAARCBD was similarly effective inex vivohuman epileptic tissueThese results suggest CBD is a positive allosteric modulator at the GABAAR
Topography of putative bidirectional interaction between hippocampal sharp wave ripples and neocortical slow oscillations
Authors: Swanson Rachel , Chinigò Elisa , Levenstein Daniel , Vöröslakos Mihály , Mousavi Navid , Wang Xiao-Jing , Basu Jayeeta , Buzsáki György 
Published: October 2024

SummarySystems consolidation relies on coordination between hippocampal sharp-wave ripples (SWRs) and neocortical UP/DOWN states during sleep. However, whether this coupling exists across neocortex and the mechanisms enabling it remain unknown. By combining electrophysiology in mouse hippocampus (HPC) and retrosplenial cortex (RSC) with widefield imaging of dorsal neocortex, we found spatially and temporally precise bidirectional hippocampo-neocortical interaction. HPC multi-unit activity and SWR probability was correlated with UP/DOWN states in mouse default mode network, with highest modulation by RSC in deep sleep. Further, some SWRs were preceded by the high rebound excitation accompanying DMN DOWN→UP transitions, while large-amplitude SWRs were often followed by DOWN states originating in RSC. We explain these electrophysiological results with a model in which HPC and RSC are weakly coupled excitable systems capable of bi-directional perturbation and suggest RSC may act as a gateway through which SWRs can perturb downstream cortical regions via cortico-cortical propagation of DOWN states.
Nance-Horan Syndrome-like 1 interacts with endophilin and Ena/VASP proteins to promote fast endophilin-mediated endocytosis
Authors: Cope Jonathan F. W. , Law Ah-Lai , Juma Samina , Krause Matthias 
Published: October 2024

AbstractEndocytosis is crucial for various physiological processes, facilitating the uptake of membrane proteins and extracellular material. Fast endophilin-mediated endocytosis (FEME), driven by endophilin A (EndoA), enables clathrin-independent, ligand-induced receptor uptake at the leading edge of cells. Whilst F-actin polymerisation is essential for FEME, how actin dynamics are regulated at sites of FEME is unknown. NHSL1, a member of the Nance-Horan Syndrome protein family, localises to the leading edge of cells, where it regulates migration, and to vesicular puncta, where its function is undetermined. Here, we show that NHSL1 and its uncharacterised family member NHSL2 co-localise and engage in direct, multivalent interactions with EndoA. NHSL1 also binds Ena/VASP proteins, a family of actin elongators. NHSL1 promotes FEME in cells and its interactions with EndoA and Ena/VASP proteins are required for this function. Thus, NHSL1 may cooperate with EndoA and Ena/VASP proteins to control membrane invagination and actin polymerisation, thereby mediating FEME.
Effector selection precedes movement specification: evidence from repetition effects in motor planning
Authors: Seegelke Christian , Heed Tobias 
Published: October 2024

AbstractMotor performance is influenced by movements that were performed shortly prior. For example, reaction times (RTs) for successive movements are reduced when executed with the same effector, even if the specifics of the consecutive movements differ. These findings have been taken to support the notion that repetition effects in motor planning reflect the involvement of effector-specific motor plans. However, previous studies have confounded motor and visual aspects of repetition: movements have typically been instructed via visual cues, and movement repetition, therefore, implied repeating also the visual cue, so that the latter may be (at least partly) responsible for the observed RT effects. In the present study, participants performed two movements in succession, a prime and a probe action, either with their left or right hand and in one of two directions, inward or outward relative to the body midline. We used different cues for prime and probe actions, so that movement repetitions did not involve repetition of the visual cue. Participants initiated successive same-limb movements faster than different-limb movements, but this RT advantage was smaller than observed in previous work. Moreover, repeating movement direction also led to a decrease in RT, though only in combination with hand repetition. Whereas these findings imply that visual cue repetition can contribute to accelerated RTs in movement repetition, they confirm that the recent motor history affects motor planning. Furthermore, they support the idea of a hierarchical framework of motor planning in which effector selection precedes specification of motor parameters.
A common stay-on-goal mechanism in anterior cingulate cortex for information and effort choices
Authors: González Valeria V. , Malvaez Melissa , Yeghikian Alex , Wissing Sydney , Sharpe Melissa , Wassum Kate M. , Izquierdo Alicia 
Published: October 2024

AbstractHumans and non-humans alike often make choices to gain information, even when the information cannot be used to change the outcome. Prior research has shown the anterior cingulate cortex (ACC) is important for evaluating options involving reward-predictive information. Here we studied the role of ACC in information choices using optical inhibition to evaluate the contribution of this region during specific epochs of decision making. Rats could choose between an uninformative option followed by a cue that predicted reward 50% of the time vs. a fully informative option that signaled outcomes with certainty, but was rewarded only 20% of the time. Reward seeking during the informative S+ cue decreased following ACC inhibition, indicating a causal contribution of this region in supporting reward expectation to a cue signaling reward with certainty. Separately in a positive control experiment and in support of a known role for this region in sustaining high-effort behavior for preferred rewards, we observed reduced lever presses and lower breakpoints in effort choices following ACC inhibition. The lack of changes in reward latencies in both types of decisions indicate the motivational value of rewards remained intact, revealing instead a common role for ACC in maintaining persistence toward certain and valuable rewards.Graphical SummarySignificance StatementWe often make choices to gain information, even when the information cannot be used to change the outcome. Here we investigated the precise timing of the role of the anterior cingulate cortex (ACC) in decisions that involve seeking certain versus uncertain rewards. By optically inhibiting ACC neurons, we demonstrate that this region is crucial for maintaining persistence toward rewards signaled with certainty, without altering the motivational value of the reward itself. In a positive control experiment, we also confirm that ACC is important in effort-based choice. The findings reveal a common role for ACC in maintaining persistence toward certain and valuable rewards, necessary for making optimal decisions. These results have implications for understanding psychiatric disorders involving maladaptive reward-seeking behavior.