bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of Cannabis Legalization with Cannabis Positive Drug Screening in US Veterans
Authors: Fink David S. , Samples Hillary , Malte Carol A. , Olfson Mark , Wall Melanie M. , Alschuler Daniel M. , Saxon Andrew J. , Hasin Deborah S. 
Published: December 2023

AbstractBackgroundAlthough cannabis legalization is associated with increases in self-report cannabis use, biological measures of cannabis use are needed to address potential bias introduced by improved self-reporting of cannabis use in states enacting medical cannabis laws (MCL) and recreational cannabis laws (RCL).ObjectiveQuantify the role of MCL and RCL enactment in cannabis positive urine drug screen (UDS) prevalence among Veterans Health Administration (VHA) emergency department (ED) patients from 2008 to 2019.DesignStaggered-adoption difference-in-difference analysis were used to estimate the role of MCL and RCL in cannabis positive UDS data, fitting adjusted linear binomial regression models to estimate the association between MCL and RCL enactment and prevalence of cannabis positive UDS.ParticipantsVHA enrolled veterans aged 18-75 years with ≥1 ED visit in a given year from 2008 to 2019.Main MeasuresReceipt of ≥1 cannabis positive UDS during an ED visit were analyzed.Key ResultsFrom 2008 to 2019, adjusted cannabis positive UDS prevalences increased from 16.4% to 25.6% in states with no cannabis law, 16.6% to 27.6% in MCL-only enacting states, and 18.2% to 33.8% in RCL-enacting states. MCL-only and MCL/RCL enactment was associated with a 0.8% (95% CI, 0.4-1.0) and 2.9% (95% CI, 2.5-3.3) absolute increase in cannabis positive UDS, respectively. Significant effect sizes were found for MCL and RCL, such that 7.0% and 18.5% of the total increase in cannabis positive UDS prevalence in MCL-only and RCL states could be attributed to MCLs and RCLs.ConclusionsIn this study of VHA ED patients, MCL and RCL enactment played a significant role in the overall increases in cannabis positive UDS. The increase in a biological measure of cannabis use reduces concerns that previously documented increases in self-reported cannabis use from surveys are due to changes in patient willingness to report use as it becomes more legal.
Comprehensive analysis of differentially expressed miRNAs in Hepatocellular carcinoma: prognostic significance and pathway insights
Authors: Smith Kayleigh , Beach Dan , Silva Roger , Balazs Gyorffy , Salani Francesca , Crea Francesco 
Published: December 2023

AbstractRobust prognostic and predictive factors for hepatocellular carcinoma, a leading cause of cancer-related deaths worldwide, have not yet been identified. Previous studies have identified potential HCC determinants such as genetic mutations, epigenetic alterations, and pathway dysregulation. However the clinical significance of these molecular alterations remains elusive. MicroRNAs are major regulators of protein expression. MiRNA functions are frequently altered in cancer. In this study, we aimed to explore the prognostic value of differentially expressed miRNAs in HCC and elucidate their associated pathways. To this aim, bioinformatics techniques and clinical dataset analyses were employed to identify differentially expressed miRNAs in HCC compared to normal hepatic tissue. We validated known associations and identified novel miRNAs with potential prognostic significance and proposed new targeting pathways based on our comprehensive analysis.
BDNF signaling requires Matrix Metalloproteinase-9 during structural synaptic plasticity
Authors: Legutko Diana , Kuźniewska Bożena , Kalita Katarzyna , Yasuda Ryohei , Kaczmarek Leszek , Michaluk Piotr 
Published: December 2023

AbstractSynaptic plasticity underlies learning and memory processes as well as contributes, in its aberrant form, to neuropsychiatric disorders. One of its major forms is structural long-term potentiation (sLTP), an activity-dependent growth of dendritic spines that harbor excitatory synapses. The process depends on the release of brain-derived neurotrophic factor (BDNF), and activation of its receptor, TrkB. Matrix metalloproteinase-9 (MMP-9), an extracellular protease is essential for many forms of neuronal plasticity engaged in physiological as well as pathological processes. Here, we utilized two-photon microscopy and two-photon glutamate uncaging to demonstrate that MMP-9 activity is essential for sLTP and is rapidly (∼seconds) released from dendritic spines in response to synaptic stimulation. Moreover, we show that either chemical or genetic inhibition of MMP-9 impairs TrkB activation, as measured by fluorescence lifetime imaging microscopy of FRET sensor. Furthermore, we provide evidence for a cell-free cleavage of proBDNF into mature BDNF by MMP-9. Our findings point to the autocrine mechanism of action of MMP-9 through BDNF maturation and TrkB activation during sLTP.
Size photometry and fluorescence imaging of immobilized immersed extracellular vesicles
Authors: Wallucks Andreas , DeCorwin-Martin Philippe , Shen Molly L. , Ng Andy , Juncker David 
Published: December 2023

ABSTRACTImmunofluorescence analysis of individual extracellular vesicles (EVs) in common fluorescence microscopes is gaining popularity due to its accessibility and high fluorescence sensitivity, however, EV number and size are only measurable using fluorescent stains requiring extensive sample manipulations. Here we introduce highly sensitive label-free EV size photometry (SP) based on interferometric scattering (iSCAT) imaging of immersed EVs immobilized on a glass coverslip. We implement SP on a common inverted epifluorescence microscope with LED illumination and a simple 50:50 beamsplitter, permitting seamless integration of SP with fluorescence imaging (SPFI). We present a high-throughput SPFI workflow recording >10,000 EVs in 7 min over multiple fields of view, pre- and post-incubation imaging to suppress background, along with automated image alignment, aberration correction, spot detection, and EV sizing. We identify the upper sizing limit of SP with 440 nm illumination and extend EVs sizing from ∼37 nm in diameter to >200 nm with dual 440 nm and 740 nm illumination. We benchmark SP to flow cytometry using calibrated silica nanoparticles and demonstrate superior, label-free sensitivity. We showcase SPFI’s potential for EV analysis by experimentally distinguishing surface and volumetric EV dyes, observing the deformation of EVs adsorbed to a surface, and by uncovering distinct subpopulations in <100 nm-in-diameter EVs with fluorescently tagged membrane proteins.
Ultrasound programmable hydrogen-bonded organic frameworks for sono-chemogenetics
Authors: Wang Wenliang , Shi Yanshu , Chai Wenrui , Kevin Tang Kai Wing , Pyatnitskiy Ilya , Xie Yi , Liu Xiangping , He Weilong , Jeong Jinmo , Hsieh Ju-Chun , Lozano Anakaren Romero , Artman Brinkley , Henkelman Graeme , Chen Banglin , Wang Huiliang 
Published: December 2023

AbstractThe precise control of mechanochemical activation within deep tissues via non-invasive ultrasound holds profound implications for advancing our understanding of fundamental biomedical sciences and revolutionizing disease treatments. However, a theory-guided mechanoresponsive materials system with well-defined ultrasound activation has yet to be explored. Here we present the concept of using porous hydrogen-bonded organic frameworks (HOFs) as toolkits for focused ultrasound programmably triggered drug activation to control specific cellular events in the deep brain, through on-demand scission of the supramolecular interactions. A theoretical model is developed to visualize the mechanochemical scission and ultrasound mechanics, providing valuable guidelines for the rational design of mechanoresponsive materials at the molecular level to achieve programmable and spatiotemporal activation control. To demonstrate the practicality of this approach, we encapsulate designer drug clozapine N-oxide (CNO) into the optimal HOF nanoparticles for FUS gated release to activate engineered G-protein-coupled receptors in the mice and rat ventral tegmental area (VTA), and hence achieved targeted neural circuits modulation even at depth 9 mm with a latency of seconds. This work demonstrates the capability of ultrasound to precisely control molecular interaction and develops ultrasound programmable HOFs to minimally invasive and spatiotemporally control cellular events, thereby facilitating the establishment of precise molecular therapeutic possibilities. We anticipate that this research could serve as a source of inspiration for precise and non-invasive molecular manipulation techniques, potentially applicable in programming molecular robots to achieve sophisticated control over cellular events in deep tissues.
New insights into the dynamics ofde novogene origin
Authors: Blair Logan , Cridland Julie , Luo Yige , Begun David , Kopp Artyom 
Published: December 2023

AbstractThe evolution of genesde novofrom ancestrally nongenic sequences is a significant mechanism of gene origin. Many studies have focused on distant evolutionary comparisons, which bias the sample ofde novogenes towards older genes that have acquired important functions and have been refined by selection. In this report, we focus on the earliest steps inde novogene origin by identifying young, polymorphic transcripts that may be missed by other study designs. To accomplish this, we sequenced tissue-specific transcriptomes from a much larger sample of genotypes than have been used in previous analyses ofde novogenes inDrosophila melanogaster. We identified 90 potential species-specificde novogenes expressed in the male accessory glands of 29D melanogasterlines derived from the same natural population. We find that most young, unannotated transcripts are both rare in the population and transcribed at low abundance. Improved sampling of both ingroup and outgroup genotypes reveals that many young genes are polymorphic in more than one species, resulting in substantial uncertainty about the age and phylogenetic distribution ofde novogenes. Among the genes expressed in the same tissue, gene age correlates with proximity to other tissue-specific genes, with the youngest genes being least likely to occur near established tissue-specific genes. This and other lines of evidence suggest thatde novogenes do not commonly evolve by simply reutilizing pre-existing regulatory elements. Together, these results provide new insights into the origin and early evolution ofde novogenes.Author SummaryGenes may be born and lost without any lasting evidence of their existence. The typical longevity may be especially limited forde novogenes – that is, genes that originate from ancestrally non-genic, untranscribed sequences, since most genomic regions are not expected to be beneficial when transcribed. To better capture the population biology of nascentde novogenes at points close to their origin, we sequenced tissue-specific transcriptomes from a large number ofDrosophila melanogastergenotypes. Mostde novogenes were expressed in very few genotypes, consistent with the expectation of transience and rapid turnover. However, many young genes showed polymorphic transcription in multiple species, suggesting that the combination of low frequency with limited sampling can lead us to underestimate how longde novogenes persist in populations. We identified several features thatde novogenes come to share with established tissue-specific genes the longer they persist. This study highlights important challenges in reconstructingde novogene origin and helps elucidate why some transcripts may survive long enough to acquire selectable functions.
Brain encoding of naturalistic, continuous, and unpredictable tactile events
Authors: Castellani Nicolò , Federici Alessandra , Fantoni Marta , Ricciardi Emiliano , Garbarini Francesca , Bottari Davide 
Published: December 2023

AbstractStudies employing EEG to measure somatosensory responses have been typically optimized to compute event-related potentials in response to discrete events (ERPs). However, tactile interactions involve continuous processing of non-stationary inputs that change in location, duration, and intensity. To fill this gap, this study aims to demonstrate the possibility of measuring the neural tracking of continuous and unpredictable tactile information. Twenty-seven young adults (females = 15) were continuously and passively stimulated with a random series of gentle brushes on single fingers of each hand, which were covered from view. Thus, tactile stimulations were unique for each participant, and stimulated fingers. An encoding model measured the degree of synchronization between brain activity and continuous tactile input, generating a temporal response function (TRF). Brain topographies associated with the encoding of each finger stimulation showed a contralateral response at central sensors starting at 50 ms and peaking at about 140 ms of lag, followed by a bilateral response at about 240 ms. A series of analyses highlighted that reliable tactile TRF emerged after just 3 minutes of stimulation. Strikingly, topographical patterns of the TRF allowed discriminating digit lateralization across hands and digit representation within each hand. Our results demonstrated for the first time the possibility of using EEG to measure the neural tracking of a naturalistic, continuous, and unpredictable stimulation in the somatosensory domain. Crucially, this approach allows the study of brain activity following individualized, idiosyncratic tactile events to the fingers.Significant StatementThis study expands the current research conducted on neural tracking, opening the exploration of idiosyncratic tactile events and overcoming constraints of laboratory tasks that typically rely on discrete events. We validated a protocol for the ecological investigations of continuous, slow, tactile processing of the hands. The employed approach enriches the possible use of the EEG to characterize somatosensory neural representations of tactile events. Findings unravel coherent neural responses to continuous and naturalistic touch, with sensitivity for digit lateralization and representation.
Generating realistic artificial Human genomes using adversarial autoencoders
Authors: Burnard Callum , Mancheron Alban , Ritchie William 
Published: December 2023

AbstractA publicly available human genome serves as both a valuable resource for researchers and a potential risk to the individual who provided the genome. Many actors with selfish intentions could exploit it to extract information about the donor’s health or that of their relatives. Recent efforts have employed artificial intelligence models to simulate genomic data, aiming to create synthetic datasets with scientific merit while preserving patient anonymity. However, a major challenge arises in dealing with the vast amount of data that constitutes a complete human genome and the resources required to process it.We have developed a dimension reduction method that combines artificial intelligence with our knowledge of in vivo mutation association mechanisms. This approach enables the processing of large amounts of data without significant computational resources. Our genome segmentation follows chromosomal recombination hotspots, closely resembling mutation transmission mechanisms. Training data is sourced from the 1000 Genomes Project, which catalogues over 2500 genomes from diverse ethnic groups. Variational autoencoders, utilising neural networks, serve as an extension to the generative model. Wasserstein Generative Adversarial Networks (WGAN) are a benchmark among generation methods for various data types.After optimisation of our data simulation strategy our pipeline allows the generation of a simulated population meeting several essential criteria. It demonstrates good diversity, closely resembling that found in the reference dataset. It is plausible, as newly generated combinations of mutations do not disrupt the linkage disequilibria found in humans. It also preserves donor anonymity by synthesising combinations of reference genomes that are distant from reference samples.
Diversity-disease relationships in natural microscopic nematode communities
Authors: van Himbeeck Robbert , Sowa Jessica N. , Jarkass Hala Tamim El , Wu Wenjia , Vrielink Job Oude , Riksen Joost A. G. , Reinke Aaron , van Sluijs Lisa 
Published: December 2023

AbstractBiodiversity can affect parasite prevalence, a phenomenon widely studied in macroscopic organisms. However, data from microscopic communities is lacking, despite their essential role in ecosystem functioning and the unique experimental opportunities microscopic organisms offer. Here, we study diversity-disease effects in wild nematode communities by profiting from the molecular tools available in the well-studied model nematodeCaenorhabditis elegans. Nanopore sequencing was used to characterize nematode community diversity and composition, whereas parasites were identified using nine distinct experimental assays based on fluorescent staining or fluorescent reporter strains. Our results indicate biotic stress is abundant in wild nematode communities. Moreover, in two assays, diversity-disease relations were observed: microsporidia and immune system activation were more often detected in relatively species-poor communities. Other assays, targeting different parasites, were without diversity-disease relations. Together, this study provides the first demonstration of diversity-disease effects in microbial communities and establishes the use of nematode communities as model systems for disease dilution.
Increasingly efficient chromatin binding of cohesin and CTCF supports chromatin architecture formation during zebrafish embryogenesis
Authors: Coßmann Jonas , Kos Pavel I. , Varamogianni-Mamatsi Vassiliki , Assenheimer Devin , Bischof Tobias , Kuhn Timo , Vomhof Thomas , Papantonis Argyris , Giorgetti Luca , Gebhardt J. Christof M. 
Published: December 2023

AbstractThe three-dimensional folding of chromosomes is essential for nuclear functions such as DNA replication and gene regulation. The emergence of chromatin architecture is thus an important process during embryogenesis. To shed light on the molecular and kinetic underpinnings of chromatin architecture formation, we characterized biophysical properties of cohesin and CTCF binding to chromatin and their changes upon cofactor depletion using single-molecule imaging in live developing zebrafish embryos. We found that chromatin-bound fractions of both cohesin and CTCF increased significantly between the 1000-cell and shield stages, which we could explain through changes in both their association and dissociation rates. Moreover, increasing binding of cohesin restricted chromatin motion, potentially via loop extrusion, and showed distinct stage-dependent nuclear distribution. Polymer simulations with experimentally derived parameters recapitulated the experimentally observed gradual emergence of chromatin architecture. Our findings suggest a kinetic framework of chromatin architecture formation during zebrafish embryogenesis.
Temporal Complexity of the BOLD-Signal In Preterm Versus Term Infants
Authors: Mella Allison Eve , Vanderwal Tamara , Miller Steven P , Weber Alexander Mark 
Published: December 2023

AbstractPreterm birth causes alterations in cerebral development. We calculated the Hurst exponent (H) - a measure of temporal complexity - from resting state functional magnetic resonance signal in preterm and term born infants. Anatomical, fMRI, and diffusion weighted imaging data from 716 neonates born between 23-43 weeks gestational age were obtained from the Developing Human Connectome Project. H was assessed in brain tissues and 13 resting state networks. H significantly increased with age, and earlier birth age contributed to lower H values. In most brain regions, H begins below 0.5 at preterm age and crosses 0.5 at term age. Motor and sensory networks demonstrated the greatest increase in H. Correlations between indirect measures of myelination and H were moderate. Overall, H appears to reflect developmental processes in the neonatal brain, as BOLD signal in the preterm infant transforms from anticorrelated to correlated but is reduced compared to term born infants.
NS2B-D55E and NS2B-E65D Variations are Responsible for Differences in NS2B-NS3 Protease Activities Between Japanese Encephalitis Virus Genotype I and III in Fluorogenic Peptide Model
Authors: Wahaab Abdul , Zhang Yan , Rasgon Jason L. , Kang Lei , Hameed Muddassar , Li Chenxi , Anwar Muhammad Naveed , Zhang Yanbing , Shoaib Anam , Liu Ke , Lee Beibei , Wei Jianchao , Qiu Yafeng , Ma Zhiyong 
Published: December 2023

AbstractJapanese Encephalitis Virus (JEV) NS2B-NS3 is a protein complex composed of NS3 proteases and a NS2B cofactor. The N-terminal protease domain (180 residues) of NS3 (NS3(pro)) interacts directly with a central 40-amino acid hydrophilic domain of NS2B (NS2B(H)) to form an active serine protease. In this study, the recombinant NS2B(H)-NS3(pro) proteases were prepared inE. coliand used to compare the enzymatic activity between genotype I (GI) and III (GIII) NS2B-NS3 proteases. The GI NS2B(H)-NS3(pro) was able to cleave the sites at internal C, NS2A/NS2B, NS2B/NS3 and NS3/NS4A junctions that were identical to the sites proteolytically processed by GIII NS2B(H)-NS3(pro). Analysis of the enzymatic activity of recombinant NS2B(H)-NS3(pro) proteases using a model of fluorogenic peptide substrate revealed that the proteolytical processing activity of GIII NS2B(H)-NS3(pro) was significantly higher than that of GI NS2B(H)-NS3(pro). There were eight amino acid variations between GI and GIII NS2B(H)-NS3(pro), which may be responsible for the difference in enzymatic activities between GI and GIII proteases. Therefore, recombinant mutants were generated by exchanging NS2B(H) and NS3(pro) domains between GI and GIII NS2B(H)-NS3(pro) and subjected to protease activity analysis. Substitution of NS2B(H) significantly altered the protease activities, as compared to the parental NS2B(H)-NS3(pro), suggesting that NS2B(H) played an essential role in regulation of NS3(pro) protease activity. To further identify the amino acids responsible for the difference in protease activities, multiple substitution mutants including the individual and combined mutations at the variant residue 55 and 65 of NS2B(H) were generated and subjected to protease activity analysis. Replacement of NS2B-55 and NS2B-65 of GI to GIII significantly increased the enzymatic activity of GI NS2B(H)-NS3(pro) protease, whereas mutation of NS2B-55 and NS2B-65 of GIII to GI remarkably reduced the enzymatic activity of GIII NS2B(H)-NS3(pro) protease. Overall, these data demonstrated that NS2B-55 and NS2B-65 variations in hydrophilic domain of NS2B co-contributed to the difference in NS2B(H)-NS3(pro) protease activities between GI and GIII. These observations gain an insight into the role of NS2B in regulation of NS3 protease activities, which is useful for understanding the replication of JEV GI and GIII viruses.