bluuebunny/crossref_metadata_2025_split huggingface dataset:
scEccDNAdb: an integrated single-cell eccDNA resource for human and mouse
Authors: Wang Wenqing , Zhao Xinyu , Ma Tianyu , Zhong Tengwei , Zheng Junnuo , Yang Yi , Guo Yuanbiao , Guo Zhiyun 
Published: July 2024

AbstractExtrachromosomal circular DNA (eccDNA), an extrachromosomal circular structured DNA, is extensively found in eukaryotes. Exploring eccDNA at the single-cell level contributes to understanding heterogeneity, evolution, development, and specific functions within cells. Nevertheless, the high-throughput identification methods for single-cell eccDNA are complex, and currently mature and widely applicable technologies are lacking. Those factors have led to a scarcity of resources for studying eccDNA at the single-cell level. Therefore, using available single-cell whole-genome sequencing (WGS) data, we have constructed a comprehensive eccDNA database named scEccDNAdb (https://lcbb.swjtu.edu.cn/scEccDNAdb/). Presently, scEccDNAdb comprises 3,195,464 single-cell eccDNA entries from both disease/health human and mouse samples, which provides comprehensive annotations including oncogenes, typical enhancers, super-enhancers, CTCF binding sites, SNPs, chromatin accessibility, eQTLs, transcription factor binding sites, motifs, and SVs. Additionally, it provides nine online analysis and visualization tools, facilitating the generation of publication-quality figures for eccDNA analysis through the upload of customized files. Overall, scEccDNAdb represents the first comprehensive database known to us for exploring and analyzing single-cell eccDNA data in diverse cell types, tissues, and species.Graphical abstract
Surfing beta burst waveforms to improve motor imagery-based BCI
Authors: Papadopoulos S. , Darmet L. , Szul M.J. , Congedo M. , Bonaiuto J.J. , Mattout J. 
Published: July 2024

AbstractOur understanding of motor-related, macroscale brain processes has been significantly shaped by the description of the event-related desynchronization (ERD) and synchronization (ERS) phenomena in the mu and beta frequency bands prior to, during and following movement. The demonstration of reproducible, spatially-and band-limited signal power changes has, consequently, attracted the interest of non invasive brain-computer interface (BCI) research for a long time. BCIs often rely on motor imagery (MI) experimental paradigms that are expected to generate brain signal modulations analogous to movement-related ERD and ERS. However, a number of recent neuroscience studies has questioned the nature of these phenomena. Beta band activity has been shown to occur, on a single-trial level, in short, transient and heterogeneous events termed bursts rather than sustained oscillations. In a previous study, we established that an analysis of hand MI binary classification tasks based on beta bursts can be superior to beta power in terms of classification score. In this article we elaborate on this idea, proposing a signal processing algorithm that is comparable to-and compatible with state-of-the-art techniques. Our pipeline filters brain recordings by convolving them with kernels extracted from beta bursts and then applies spatial filtering before classification. This data-driven filtering allowed for a simple and efficient analysis of signals from multiple sensors thus being suitable for online applications. By adopting a time-resolved decoding approach we explored MI dynamics and showed the specificity of the new classification features. In accordance with previous results, beta bursts improved classification performance compared to beta band power, while often increasing information transfer rate compared to state-of-the-art approaches.Significance statementPatterns of waveform-specific burst rate comprise an alternative, neurophysiology-informed way of analyzing beta band activity during motor imagery (MI) tasks. By testing this method on multiple electroencephalography datasets and comparing its corresponding classification scores against those of conventional power-based features, this work demonstrates that brain-computer interface applications could benefit from utilizing beta burst activity. This activity gives access to a reliable decoding performance often requiring short recordings. As such, this study shows that waveform-specific beta burst rates encode information related to imagined (and presumably real) movements and serves as the first step for a real-time implementation of the proposed methodology.
Brain responses to predictable structure in auditory sequences: From complex regular patterns to tone repetition
Authors: Southwell Rosy , Tufo Candida , Chait Maria 
Published: July 2024

ABSTRACTIn classical studies of auditory pattern learning, neuronal responses exhibit repetition suppression, where sequences of repeated tones show a reduced evoked response. This may be due in part to adaptation, but is also hypothesized to indicate suppression of expected stimuli. Repetition suppression is thought to form a building block of regularity learning, and is the paradigmatic example of predictive coding in humans and other animals.However, stimuli with more complex patterns appear to show the opposite effect. Predictable regular (REG) patterns distributed over a range of frequencies show a strongly enhanced sustained brain response compared to frequency-matched random (RAND) sequences, sitting at odds with the usual reduced evoked responses to predictable stimuli. A limiting factor in reconciling these findings is that they are obtained using different stimuli and analysis methods.This human EEG study (N=20) brings together auditory sequence predictability and repetition in a single paradigm, based on rapidly unfolding tone pip patterns, incorporating sequences consisting of exactly repeating tones at a single frequency, alongside REG and RAND of varying complexity. We demonstrate that regularity is associated with increased sustained responses, offset responses, tone locked responses and cycle-locked responses. We further show that both repetition suppression and repetition enhancement occur over different timescales, and that sustained brain responses to simple repetition show qualitatively different effects than to more complex regularities during automatic tracking of stimulus statistics. Our results indicate a system for automatic monitoring of predictability in the auditory environment, which is distinct from, but concurrent with, repetition suppression.NEW & NOTEWORTHYWe investigate how human brain response patterns evolve as auditory patterns become progressively simplified, focusing on the impact of sequence structure on various aspects of EEG responses, both evoked and induced. By contrasting EEG responses across different phases of the stimulus—onset, sustained, and offset—we uncover the interplay between repetition suppression and predictability. This approach allows us to discern how the brain processes and adapts to changing regularities in sensory input.
Encoding of cerebellar dentate neuron activity during visual attention in rhesus macaques
Authors: Flierman Nico A. , Koay Sue Ann , van Hoogstraten Willem S. , Ruigrok Tom J.H. , Roelfsema Pieter R. , Badura Aleksandra , De Zeeuw Chris I. 
Published: July 2024

AbstractThe role of cerebellum in controlling eye movements is well established, but its contribution to more complex forms of visual behavior has remained elusive. To study cerebellar activity during visual attention we recorded extracellular activity of dentate nucleus (DN) neurons in two non-human primates (NHPs). NHPs were trained to read the direction indicated by a peripheral visual stimulus while maintaining fixation at the center, and report the direction of the cue by performing a saccadic eye movement into the same direction following a delay. We found that single unit DN neurons modulated spiking activity over the entire time-course of the task, and that their activity often bridged temporally separated intra-trial events, yet in a heterogeneous manner. To better understand the heterogeneous relationship between task structure, behavioral performance and neural dynamics, we constructed a behavioral, an encoding and a decoding model. Both NHPs showed different behavioral strategies, which influenced the performance. Activity of the DN neurons reflected the unique strategies, with the direction of the visual stimulus frequently being encoded long before an upcoming saccade. Moreover, the latency of the ramping activity of DN neurons following presentation of the visual stimulus was shorter in the better performing NHP. Labeling with the retrograde tracer CTB in the recording location in the DN indicated that these neurons predominantly receive inputs from Purkinje cells in the D1 and D2 zones of the lateral cerebellum as well as neurons of the principal olive and medial pons, all regions known to connect with neurons in the prefrontal cortex contributing to planning of saccades. Together, our results highlight that DN neurons can dynamically modulate their activity during a visual attention task, comprising not only sensorimotor but also cognitive attentional components.
Label-free multiphoton imaging reveals volumetric shifts across development in sensory-related brain regions of a miniature transparent vertebrate
Authors: Tatarsky Rose L. , Akbari Najva , Wang Ke , Xu Chris , Bass Andrew H. 
Published: July 2024

ABSTRACTAnimals integrate information from different sensory modalities as they mature and perform increasingly complex behaviors. This may parallel differential investment in specific brain regions depending on the demands of changing sensory inputs. To investigate developmental changes in the volume of canonical sensory integration brain regions, we used third harmonic generation imaging for morphometric analysis of forebrain and midbrain regions from 5 to 90 days post fertilization (dpf) inDanionella dracula, a transparent, miniature teleost fish whose brain is optically accessible throughout its lifespan. Relative to whole brain volume, increased volume or investment in telencephalon, a higher order sensory integration center, and torus longitudinalis (TL), a midbrain visuomotor integration center, is relatively consistent from 5 to 30 dpf, until it increases at 60 dpf, followed by another increase at 90 dpf, as animals reach adulthood. In contrast, investment in midbrain optic tectum (TeO), a retinal-recipient target, progressively decreases from 30-90 dpf, whereas investment is relatively consistent across all stages for the midbrain torus semicircularis (TS), a secondary auditory and mechanosensory lateral line center, and the olfactory bulb (OB), a direct target of the olfactory epithelium. In sum, increased investment in higher order integration centers (telencephalon, TL) occurs as juveniles reach adulthood and exhibit more complex cognitive tasks, whereas investment in modality-dominant regions occurs in earlier stages (TeO) or is relatively consistent across development (TS, OB). Complete optical access throughoutDanionella’s lifespan provides a unique opportunity to investigate how changing brain structure over development correlates with changes in connectivity, microcircuitry, or behavior.
Self-avoidance dominates the selection of hippocampal replay
Authors: Mallory Caitlin S , Widloski John , Foster David J 
Published: July 2024

AbstractSpontaneous neural activity sequences are generated by the brain in the absence of external input1–12, yet how they are produced remains unknown. During immobility, hippocampal replay sequences depict spatial paths related to the animal’s past experience or predicted future13. By recording from large ensembles of hippocampal place cells14in combination with optogenetic manipulation of cortical input in freely behaving rats, we show here that the selection of hippocampal replay is governed by a novel self-avoidance principle. Following movement cessation, replay of the animal’s past path is strongly avoided, while replay of the future path predominates. Moreover, when the past and future paths overlap, early replays avoid both and depict entirely different trajectories. Further, replays avoid self-repetition, on a shorter timescale compared to the avoidance of previous behavioral trajectories. Eventually, several seconds into the stopping period, replay of the past trajectory dominates. This temporal organization contrasts with established and recent predictions9,10,15,16but is well-recapitulated by a symmetry-breaking attractor model of sequence generation in which individual neurons adapt their firing rates over time26–35. However, while the model is sufficient to produce avoidance of recently traversed or reactivated paths, it requires an additional excitatory input into recently activated cells to produce the later window of past-dominance. We performed optogenetic perturbations to demonstrate that this input is provided by medial entorhinal cortex, revealing its role in maintaining a memory of past experience that biases hippocampal replay. Together, these data provide specific evidence for how hippocampal replays are generated.
Detection of pneumococcal carriage in asymptomatic healthcare workers
Authors: Waghela Pari , Davis Raechel , Campbell Melissa , Datta Rupak , Hislop Maikel S. , Vega Noel J. , Wurst Loren , Yolda-Carr Devyn , Couch Luke , Hernandez Michael , Grant Lindsay R. , Alexander-Parrish Ronika , Arguedas Adriano , Gessner Bradford D. , Martinello Richard A. , Weinberger Daniel M. , Wyllie Anne L. 
Published: July 2024

ABSTRACTBackgroundHealthcare workers are at increased risk of exposure to respiratory pathogens includingStreptococcus pneumoniae(pneumococcus). While little asymptomatic carriage has been reported in young-to-middle-aged adults, this may be due to non-sensitive diagnostic methods. The aim of the study was to investigate the rates of pneumococcal carriage in a large cohort of healthcare workers using saliva as a respiratory specimen.MethodsWe evaluated the prevalence of pneumococcal carriage in a convenience sample of saliva, self-collected from asymptomatic healthcare workers at Yale New Haven Hospital (CT, USA) who were testing for SARS-CoV-2 from March 30 to June 11, 2020. Samples were transported at ambient temperature and stored at −80°C within 12 hours. DNA extracted from the culture-enriched saliva was later tested using qPCR forpiaB, lytA, and serotype. Saliva samples were considered positive for pneumococcus when thepiaBCt value was <40.ResultsStudy participants were 22-74 years old (mean=38.5), 75% female, 75% white, with occupations including registered nurses (48%), medical doctors (23%), and patient care assistants (5%). Overall, 138/1241 (11%) samples from 86/392 (21%) individuals testedpiaB-positive for pneumococcus at some point during the 4-month study period, with 28 (33%) colonized individuals positive at multiple time points. Carriers reflected the overall study population. No significant demographic characteristics were associated with detection of pneumococcus. Colonized individuals primarily carried serotypes 19F (25%) and 3 (12%), however, we were unable to resolve a primary serotype for 31% of all pneumococcus-positive samples identified.ConclusionsDuring a period of mandatory masking, we identified a cumulative pneumococcal carriage prevalence of 21% among healthcare workers. This study highlights that healthcare workers may act as unrecognized reservoirs of pneumococcus in the population. Despite long-standing PCV7 and PCV13 pediatric immunization programs, vaccine serotypes continue to be prevalent among the adult population.
A Multi-Center Randomized, Double-Blind, Placebo Controlled, Parallel Group, Phase IIa Study to Evaluate the Efficacy, Safety and Tolerability of an Anthocyanin Rich Extract (ACRE) in Patients with Ulcerative Colitis
Authors: Biedermann Luc , Doulberis Michael , Schreiner Philipp , Nielsen Ole Haagen , The Frans Olivier , Brand Stephan , Burk Sabine , Hruz Petr , Juillerat Pascal , Krieger-Grübel Claudia , Leu Kristin , Leventhal Gabriel , Misselwitz Benjamin , Scharl Sylvie , Schoepfer Alain , Seibold Frank , Herfarth Hans , Rogler Gerhard 
Published: July 2024

AbstractBackgroundIn an open label pilot study dried bilberries were effective in inducing clinical, endoscopic and biochemical improvement in ulcerative colitis (UC) patients. Aim was the investigation of efficacy of anthocyanin rich extract (ACRE), the presumptive active ingredient of bilberries, in a controlled clinical trial in moderate-severe UC.MethodsWe performed a multicenter randomized, placebo-controlled, double-blind study (planned initially for 100 patients; premature termination due to COVID-19 pandemic). Patients had moderate-severe active UC at screening (Mayo-score 6-12, endoscopic sub-score at least 2) and were randomized at baseline (verum: placebo, 2:1). Continuation of all UC-directed stable medical therapy was allowed. Primary endpoint was clinical response at week 8 (reduction of total Mayo-score at least 3 points). Biochemical (fecal calprotectin) and centrally-read endoscopic response were amongst the secondary endpoints.ResultsOut of 48 patients screened in six Swiss trial centers, 34 were randomized. Eighteen ACRE and eight placebo patients could be analyzed in the Per-Protocol-Set. Half (9/18) of ACRE patients and 3/8 of placebo patients revealed clinical response at week 8 (CI 0.399-6.963; p=0.278). An improvement of the Mayo-score was observed in 77.8% of ACRE treated patients (62.5% of placebo). Fecal calprotectin dropped from 1049+/-1139 to 557+/-756μg/g feces in the ACRE but not in the placebo group (947+/-1039 to 1040+/-1179; p=0.035). Adverse events were rare.ConclusionsACRE therapy was not significantly superior to placebo at inducing a clinical response. However, placebo response was unusual high. Moreover, there was a significant calprotectin decrease at end of treatment, indicative of ACRE biochemical efficacy in UC.Study HighlightsWhat is knownDried bilberries have been reported to ameliorate active ulcerative colitis (UC) in an uncontrolled pilot trialAnthocyanins (flavonoids) are regarded to be the active anti-inflammatory compound of bilberriesAn anthocyanin rich extract (ACRE) of bilberries was reported to ameliorate colitis in mouse modelsWhat is new hereIn a multi-center randomized, double-blind, placebo controlled, parallel group study in patients with moderate to severe active UC, ACRE did not reach the statistical endpoint of clinical responseAn unusually high placebo response was observedACRE induced significant biochemical response with significant decrease in calprotectin levels
Analysis of B-cell receptor repertoire to evaluate the immunogenicity of SARS-CoV-2 RBD mRNA vaccine: MAFB-7256a (DS-5670d)
Authors: Ohji Goh , Funakoshi Yohei , Yakushijin Kimikazu , Matsutani Takaji , Sasaki Tomoki , Kusakabe Takahiro , Matsumoto Sakuya , Koyama Taiji , Nagatani Yoshiaki , Kurata Keiji , Kimbara Shiro , Kiyota Naomi , Minami Hironobu 
Published: July 2024

ABSTRACTA monovalent Omicron XBB.1.5 mRNA RBD analogue vaccine, MAFB-7256a (DS-5670d), was newly developed and approved in Japan in the Spring of 2024 for preventing COVID-19. However, clinical efficacy data for this vaccine are currently lacking. We previously established the Quantification of Antigen-specific Antibody Sequence (QASAS) method to assess the response to SARS-CoV-2 vaccination at the mRNA level using B-cell receptor (BCR) repertoire assays and the Coronavirus Antibody Database (CoV-AbDab). Here, we used this method to evaluate the immunogenicity of MAFB-7256a. We analyzed repeated blood samples using the QASAS method from three healthy volunteers before and after MAFB-7256a vaccination. BCR response increased rapidly one week post-vaccination and then decreased, as with conventional vaccine. Notably, the matched sequences after MAFB-7256a vaccination specifically bound to the receptor-binding domain (RBD), with no sequences binding to other epitopes. These results validate that MAFB-7256a is an effective vaccine that exclusively induces antibodies specific for the RBD, demonstrating its targeted immunogenic effect.
Blood metabolomic shift links diet and gut microbiota to multiple health outcomes among Hispanic/Latino immigrants in the U.S.
Authors: Li Yang , Peters Brandilyn A. , Yu Bing , Perreira Krista M. , Daviglus Martha , Chan Queenie , Knight Rob , Boerwinkle Eric , Isasi Carmen R. , Burk Robert , Kaplan Robert , Wang Tao , Qi Qibin 
Published: July 2024

SummaryImmigrants from less industrialized countries who are living in the U.S. often bear an elevated risk of multiple disease due to the adoption of a U.S. lifestyle. Blood metabolome holds valuable information on environmental exposure and the pathogenesis of chronic diseases, offering insights into the link between environmental factors and disease burden. Analyzing 634 serum metabolites from 7,114 Hispanics (1,141 U.S.-born, 5,973 foreign-born) in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we identified profound blood metabolic shift during acculturation. Machine learning highlighted the prominent role of non-genetic factors, especially food and gut microbiota, in these changes. Immigration-related metabolites correlated with plant-based foods and beneficial gut bacteria for foreign-born Hispanics, and with meat-based or processed food and unfavorable gut bacteria for U.S.-born Hispanics. Cardiometabolic traits, liver, and kidney function exhibited a link with immigration-related metabolic changes, which were also linked to increased risk of diabetes, severe obesity, chronic kidney disease, and asthma.Graphical abstractHighlightsA substantial proportion of identified blood metabolites differ between U.S.-born and foreign-born Hispanics/Latinos in the U.S.Food and gut microbiota are the major modifiable contributors to blood metabolomic difference between U.S.-born and foreign-born Hispanics/Latinos.U.S. nativity related metabolites collectively correlate with a spectrum of clinical traits and chronic diseases.