bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autonomous biogenesis of the entire protein translation machinery excluding ribosomes
Authors: Schwarz-Schilling Matthaeus , Dupin Aurore , Avidan Noa , Barak Yoav , Shimizu Yoshihiro , Daube Shirley S. , Bar-Ziv Roy H. 
Published: October 2024

AbstractRecreating the conditions for autonomous biogenesis of the protein translation machinery is fundamental to our understanding of living systems and is essential for the assembly of minimal cell models. All components of the translation machinery, including the ribosomes, translation factors and aminoacyl tRNA synthetases, are made of proteins and are therefore involved in their own synthesis, posing a unique challenge for self-biogenesis. Here, we created physicochemical conditions for autonomous biogenesis of all the translation machinery, excluding the ribosome. We surface-immobilized synthetic genes coding for all thirty components as densely packed DNA brushes forming a reaction center that localizes, concentrates and catalyzes their simultaneous synthesis. To demonstrate their activity, we first determined empirically the minimal critical concentration of each translation protein required to initiate its own self-biogenesis in bulk solution. We then assembled a minimal gene expression reaction with all translation proteins at their critical concentrations. Under these dilute conditions, reporter proteins were not synthesized unless the DNA brushes encoded all the translation proteins, thereby demonstrating their co-synthesis, functionality and engagement in their own synthesis. This scenario of a complex biochemical process that amplifies itself can be generalized and extended to impact our understanding toward the design of autonomous self-replicating biological system.
Ten-Fold Expansion MALDI Mass Spectrometry Imaging of Tissues and Cells at 500 nm Resolution
Authors: Xie Chengyi , Wang Jianing , Diao Xin , Guo Lei , Lam Thomas Ka-Yam , Li Ruxin , Chen Yanyan , Zhang Yue , Wang Xiaoxiao , Fang Jiacheng , Cai Zongwei 
Published: October 2024

AbstractAchieving high spatial resolution in matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is crucial for detailed molecular mapping in biological tissues and cells. However, conventional MALDI-MSI platforms are typically limited to spatial resolutions of 5-20 μm, restricting their ability to visualize fine subcellular structures. Here, we present a novel ten-fold expansion MALDI-MSI (10X ExMSI) method that attains 500 nm spatial resolution without the need for specialized optics or customized instrumentation. By physically expanding biological samples using a swellable hydrogel matrix, our method maintains high retention and broadens the detection range of lipids, ensuring comprehensive lipid profiling. We demonstrated the effectiveness of 10X ExMSI by visualizing intricate subcellular structures within mouse brain tissues, including individual nuclei, astrocytes, Purkinje cells, and, notably, dendritic arborizations-features previously unresolvable using mass spectrometry imaging. Applying 10X ExMSI to single-cell analysis of cultured cells revealed detailed spatial distributions of lipids at the subcellular to organelle level. Notably, the method is fully compatible with standard commercial MALDI-MSI platforms, enabling widespread adoption without significant additional investment. The 10X ExMSI offers a transformative tool for high-resolution molecular imaging, opening new avenues for molecular analysis in diverse biological and biomedical fields, including neuroscience, pathology, and cellular biology.
An attention-based deep neural network model to detect cis-regulatory elements at the single-cell level from multi-omics data
Authors: Murakami Ken , Iida Keita , Okada Mariko 
Published: October 2024

AbstractCis-regulatory elements (cREs) play a crucial role in regulating gene expression and determining cell differentiation and state transitions. To capture the heterogeneous transitions of cell states associated with these processes, detecting cRE activity at the single-cell level is essential. However, current analytical methods can only capture the average behavior of cREs in cell populations, thereby obscuring cell-specific variations. To address this limitation, we proposed an attention-based deep neural network framework that integrates DNA sequences, genomic distances, and single-cell multi-omics data to detect cREs and their activities in individual cells. Our model shows higher accuracy in identifying cREs within single-cell multi- omics data from healthy human peripheral blood mononuclear cells than other existing methods. Furthermore, it clusters cells more precisely based on predicted cRE activities, enabling a finer differentiation of cell states. When applied to publicly available single-cell data from patients with glioma, the model successfully identified tumor-specific SOX2 activity. Additionally, it revealed the heterogeneous activation of the ZEB1 transcription factor, a regulator of epithelial-to-mesenchymal transition-related genes, which conventional methods struggle to detect. Overall, our model is a powerful tool for detecting cRE regulation at the single-cell level, which may contribute to revealing drug resistance mechanims in cell sub- populations.
Dorsal-caudal and ventral hippocampus target different cell populations in the medial frontal cortex in rodents
Authors: Alemán-Andrade Paola , Witter Menno P. , Tsutsui Ken-Ichiro , Ohara Shinya 
Published: October 2024

SUMMARYDirect projections from the ventral hippocampus (vHPC) to the medial frontal cortex (MFC) play crucial roles in memory and emotional regulation. Using anterograde transsynaptic tracing andin vitroelectrophysiology in mice, we document a previously unexplored pathway that parallels the established vHPC-MFC connectivity. This pathway connects the dorsal-caudal hippocampus (dcHPC) to specific subregions of the ventral MFC, in particular the dorsal peduncular cortex. Notably, this pathway exerts a strong inhibitory influence on ventral MFC by targeting a substantial proportion of inhibitory neurons. Retrograde transsynaptic tracing in rats indicated that ventral MFC subregions project disynaptically back to vHPC. These results, altogether, suggest the existence of a remarkable functional circuit connecting distinct functional areas: the cognition-related dcHPC with the emotion-related ventral MFC and vHPC. These findings further provide valuable insights in the cognitive and emotional abnormalities associated with the HPC-MFC connectivity in neurological and psychiatric disorders.
Wartime food availability in the Gaza Strip, October 2023 to August 2024: a retrospective analysis
Authors: Checchi Francesco , Ververs Mija-Tesse , Jamaluddine Zeina 
Published: October 2024

AbstractBackgroundThe Israeli operation in the Gaza Strip has damaged much of the territory’s food system, exposing vulnerable population groups to poor nutrition. We retrospectively estimated food availability per capita and the contribution of different food sources and categories during the first ten months of the war.MethodsWe described the composition and caloric value of food trucked into Gaza based on United Nations data over the period 7 October 2023 to 31 August 2024 and compared these with the Israeli government’s. We supplemented trucking data with information on baseline stocks, agricultural output, air or seaborne deliveries, population denominators and pre-war caloric intake estimates into a probabilistic simulation to estimate caloric availability in both northern and south-central governorates.ResultsBetween October 2023 and April 2024, food trucks entering Gaza remained below pre-war levels. Israeli data offered higher estimates of food weight trucked in but appeared to feature extreme approximation. Following Israel’s takeover of crossings in May 2024, United Nations data likely featured underreporting, though even Israeli data indicated declining deliveries. The share of food categories changed little during the period analysed, but trucked-in food’s caloric value was lowest just as food was scarcest (February-March 2024). Trucks accounted for three-fourths of food in south-central Gaza, but <20% in the north; air and sea deliveries made up a small percentage. During at least 12 weeks in northern and 4 weeks in south-central Gaza, per-capita caloric availability was below the recommended intake.ConclusionsIsrael, as occupying power, did not ensure sufficient food availability throughout the analysis period, and its data appear unreliable. Existing stocks probably mitigated caloric deficits resulting from insufficient deliveries, but air and sea routes added little. Strengthened coordination of food deliveries may be warranted to optimise caloric quantity and dietary diversity despite aid restrictions.
Cost-effectiveness analysis of 21-valent pneumococcal conjugated vaccine among adults in Canada
Authors: Ximenes Raphael , Simmons Alison E. , Gebretekle Gebremedhin B. , Nam Austin , Wong Eva , Salvadori Marina I. , Golden Alyssa R. , Sander Beate , Hildebrand Kyla J. , Tunis Matthew , Tuite Ashleigh R. 
Published: October 2024

AbstractBackgroundA 21-valent pneumococcal conjugate vaccine (PCV21) was recently authorized in Canada to protect adults against invasive pneumococcal disease (IPD).ObjectiveTo assess the cost-effectiveness of PCV21 compared to current Canadian vaccination recommendations for adults of different age and risk groups.MethodsWe used a static cohort model to estimate lifetime incremental cost-effectiveness ratios (ICERs), in 2023 Canadian dollars per quality-adjusted life year (QALY), discounted at 1.5%, in population cohorts aged 33 (midpoint of the 18-49 year age group), 50, and 65 years from the health system and societal perspectives. The primary analysis used 2022 serotype distributions for IPD cases. Additional analyses incorporated indirect effects from pediatric vaccination and used IPD serotype distributions from 2015-2019, to explore the impact of changes over time observed in some age groups.ResultsFor population groups currently recommended to receive PCV20 in Canada (65 years and older, 50-64 years with additional risk factors for IPD, or 18-49 years with immunocompromising conditions), PCV21 was cost-effective at a $50,000 per QALY threshold and dominated PCV20 in most scenarios when PCV21 serotypes were more prevalent. When PCV20 serotypes were equally or more prevalent than PCV21 serotypes, results were more sensitive to assumptions about indirect effects and serotype replacement. For groups not currently recommended a conjugate vaccine (50-64 years without additional IPD risk factors and 18-49 years with chronic medical conditions or unhoused populations), use of a higher-valency conjugate vaccine was a cost-effective intervention compared to no vaccination, with the optimal vaccine dependent on the proportion of IPD attributable to PCV20 and PCV21 serotypes in the population of interest. Results were sensitive to vaccine price in most scenarios.InterpretationThe use of PCV21 may be cost-effective in some populations, depending on the prevalence of IPD serotypes covered by PCV20 and PCV21.
On-scalp magnetoencephalography based on optically pumped magnetometers to investigate temporal lobe epilepsy
Authors: Feys Odile , Wens Vincent , Depondt Chantal , Rikir Estelle , Gaspard Nicolas , Paesschen Wim Van , Aeby Alec , Bodart Olivier , Carrette Evelien , Holmes Niall , Brookes Matthew , Ferez Maxime , Corvilain Pierre , Tiège Xavier De 
Published: October 2024

AbstractCryogenic magnetoencephalography (MEG) has a lower yield in temporal lobe epilepsy (TLE) than in extra-TLE (ETLE). The advent of optically pumped magnetometers (OPMs) might change this thanks to on-scalp MEG, which allows sensors to be placed closer to the brain and the design of bespoke sensor arrays to target specific brain regions. This study aims to investigate the detection and localization accuracy of interictal epileptiform discharges (IEDs) using on-scalp MEG in TLE and the added-value of face-OPMs for temporal IED detection/localization.Eleven patients underwent a 1-h MEG recording with OPMs placed both on the scalp (flexible cap, scalp-OPMs) and on the face (3D-printed glass-like structure, face-OPMs). Nine patients also underwent cryogenic MEG. IEDs were visually detected, averaged and localized using distributed source reconstruction. On-scalp MEG IED amplitude and signal-to-noise (SNR) were assessed and compared with cryogenic MEG when more than 10 IEDs were detected. Neural sources with and without face-OPMs were compared. The correlation between face- and scalp-OPMs was assessed.A mean of 13 IEDs/patient was detected using on-scalp MEG (mean amplitude: 3.3pT, mean SNR: 9.4) and localized in the (medial, anterior, basal, lateral or posterior) temporal lobe. Three patients had >10 IEDs in on-scalp and cryogenic MEG signals with amplitude and SNR that were either higher or similar for the on-scalp MEG recording compared with cryogenic MEG, and sources were separated by 8-11 mm. In two other patients, on-scalp MEG source locations were confirmed by gold-standard methods (surgical resection cavity, n=1; stereo-electroencephalography, n=1). Face-OPMs had a clear added-value (i.e., IED detection and localization) in one patient with antero-medial TLE. Face-OPM signals were correlated with scalp-OPM signals in most patients, showing that face-OPMs recorded brain activity.This study shows that on-scalp MEG is able to detect and localize IEDs in TLE and to discriminate irritative zones from different key (medial, anterior, basal, lateral or postero-lateral) temporal areas with similar or enhanced SNR than cryogenic MEG. Face-OPMs have a clear added-value in patients with anterior/medial TLE and increase the spatial coverage of the temporal lobe. This study paves the way for the future use of on-scalp MEG in patients with refractory TLE or with other brain disorders affecting the temporal lobe such as, e.g., Alzheimer’s disease.
Parental income and psychiatric disorders from age 10 to 40: a genetically informative population study
Authors: Sunde Hans Fredrik , Eilertsen Espen Moen , Kinge Jonas Minet , Kleppesto Thomas H. , Nordmo Magnus , Caspi Avshalom , Moffitt Terrie E. , Torvik Fartein Ask 
Published: October 2024

AbstractBackgroundLower parental income is associated with more psychiatric disorders among offspring, but it is unclear if this association reflects effects of parental income (social causation) or shared risk factors (social selection). Prior research finds contradictory results, which may be due to age differences between the studied offspring.MethodsHere, we studied the entire Norwegian population aged 10 to 40 between 2006 and 2018 (N = 2,468,503). By linking tax registries to administrative health registries, we describe prevalence rates by age, sex, and parental income rank. Next, we used kinship-based models with extended families of twins and siblings to distinguish direct effects of parents from shared genetic and environmental risk factors.ResultsWe show that lower parental income rank was associated with more psychiatric disorders at all ages from age 10 to 40 (rbetween −.06 and −.15). The kinship-based models indicated that direct effects of parental income played a large role (38%) in explaining the parent-offspring correlation among adolescents, while shared risk factors accounted for the entire parent-offspring correlation among adults.ConclusionOur findings indicate that social causation plays a significant role during adolescence, while social selection fully explains the parent-offspring association in adulthood.
Deciphering the dynamic clinical patterns inSCN8A-related disorders using real-world data
Authors: Magielski Jan H. , Cohen Stacey , Kaufman Michael C. , Parthasarathy Shridhar , Xian Julie , Brimble Elise , Fitter Nasha , Furia Francesca , Gardella Elena , Møller Rikke S. , Helbig Ingo , McKee Jillian L. 
Published: October 2024

AbstractBackground and ObjectivesSCN8A-related disorders encompass a range of neurodevelopmental and epilepsy phenotypes. However, despite representing one of the most common epilepsy-associated channelopathies, the longitudinal progression of its clinical features remains largely uncharacterized.MethodsHere, we harmonized electronic medical record data of 82 individuals withSCN8A-related disorders. Clinical data was mapped to the standardized language of the Human Phenotype Ontology to reconstruct the natural history ofSCN8A-related disorders in comparison to a cohort of 2,833 individuals with known or presumed genetic epilepsies.ResultsCompared to other known or presumed genetic epilepsies, those withSCN8A-related disorders had earlier generalized seizures, including a ten-fold risk for generalized-onset seizures at 9 months (P= 4.98 × 10−17, OR 10.65, CI 6.07-18.77) and >40-fold risk bilateral tonic-clonic seizures at 1 year (P= 1.76 × 10−8, OR 46.09, CI 10.72-275.01). Individuals carrying gain-of-functionSCN8Avariants had particularly high generalized seizure risk at 9 months (P= 0.005, OR 3.85, CI 1.35-11.55), as well as an increased risk for global developmental delay as early as 3 months (P= 0.002, OR 5.67, CI 1.74-20.23) when compared to the broaderSCN8Acohort. Individuals with loss-of-function variants were more likely to experience absence seizures, most prominently at 4.25 years (P= 0.013, OR 32.71, CI 1.44-2193.51). Compared to the widerSCN8Acohort, individuals with the recurrent p.Arg850Gln variant were more likely to have infantile spasms at 6 months (P= 0.016, OR 12.02, CI 1.20-164.23), those with variants at the p.Arg1872Trp/Gln/Leu hotspot were more likely to have neonatal seizures (P= 0.025, OR 16.84, CI 0.99-291.58). Individuals with the recurrent p.Gly1475Arg variant were more likely to have active epilepsy after 5 years of age. Focal seizures in later childhood were more prominent in individuals with the recurrent p.Arg1617Gln variant.DiscussionSCN8A-related disorders distinguish themselves from other genetic epilepsies by the frequent generalized-onset seizures in infancy, prominent early epileptic and developmental features in gain-of-function variant carriers, and unique seizure phenotypes in those with recurrent variants. Our study provides a longitudinal perspective on this genetic condition, paving the way for the future precision medicine approaches.
Mendelian randomisation with proxy exposures: challenges and opportunities
Authors: Rahu Ida , Tambets Ralf , Fauman Eric B. , Alasoo Kaur 
Published: October 2024

AbstractA key challenge in human genetics is the discovery of modifiable causal risk factors for complex traits and diseases. Mendelian randomisation (MR) using molecular traits as exposures is a particularly promising approach for identifying such risk factors. Despite early successes with the application of MR to biomarkers such as low-density lipoprotein cholesterol and C-reactive protein, recent studies have revealed a more nuanced picture, with widespread horizontal pleiotropy. Using data from the UK Biobank, we illustrate the issue of horizontal pleiotropy with two case studies, one involving glycolysis and the other involving vitamin D synthesis. We demonstrate that, although the measured metabolites (pyruvate or histidine, respectively) do not have a direct causal effect on the outcomes of interest (red blood cell count or vitamin D level), we can still use variant effects on these downstream metabolites to infer how they perturb protein function in different gene regions. This allows us to use variant effects on metabolite levels as proxy exposures in acis-MR framework, thus rediscovering the causal roles of histidine ammonia lyase (HAL) in vitamin D synthesis and glycolysis pathway in red blood cell survival. We also highlight the assumptions that need to be satisfied forcis-MR with proxy exposures to yield valid inferences and discuss the practical challenges of meeting these assumptions.
Mycobiome Dysbiosis and Genetic Predisposition for Elevated IL-17A Drive Fibrosis in MASLD
Authors: Thielemann Nadja , Siliceo Sara Leal , Rau Monika , Schöninger Annika , Reus Nathalie , Aldejohann Alexander M. , Shehata Aia , Behr Isabell S. , Nieuwenhuizen Natalie E. , Herz Michaela , Hermanns Heike M. , Mirhakkak Mohammad , Löffler Jürgen , Dandekar Thomas , Hünniger-Ast Kerstin , Martin Ronny , Panagiotou Gianni , Geier Andreas , Kurzai Oliver 
Published: October 2024

ABSTRACTMetabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease in Western countries. Progression to metabolic dysfunction-associated steatohepatitis (MASH) occurs when fat accumulation in the liver triggers Th17 activation and other inflammatory processes. In this study, we identify theIL17Ars2275913 minor allele variant as a risk factor for fibrosis progression in MASLD patients. In patients with advanced fibrosis, we also observed an increased abundance of fungal CTG species includingCandida albicansandDebaryomyces hansenii, which are potent triggers of Th17 responses. Integrating genetic risk-predisposition and mycobiome composition, we show inex vivoT cell stimulation assays, that donors carrying the minor allele variant ofIL17Ars2275913 secreted significantly higher IL-17A levels in response to CTG species. Additionally, MASH patients carrying theIL17Ars2275913 risk allele have elevated Th17/Treg ratios in peripheral blood. Taken together, our data indicate that genetic predisposition for enhanced Th17 responses in the context of mycobiome dysbiosis can trigger MASH progression and liver fibrosis.Graphical AbstractThis Graphical Abstract was created withBioRender.com.Brief summaryIncreased antifungal immune responses triggered by gut mycobiome dysbiosis in genetically predisposed patients can lead to severe stages of metabolic dysfunction-associated steatotic liver disease.
Insights into Diversity, Host-Range, and Temporal Stability ofBacteroidesandPhocaeicolaProphages
Authors: Stopnisek Nejc , Hedžet Stina , Accetto Tomaž , Rupnik Maja 
Published: October 2024

AbstractBackgroundPhages are critical components of the gut microbiome, influencing bacterial composition and function as predators, parasites, and modulators of bacterial phenotypes. Prophages, integrated forms of these phages, are prevalent in many bacterial genomes and play a role in bacterial adaptation and evolution. However, the diversity and stability of prophages within gut commensals, particularly in the generaBacteroidesandPhocaeicola, remain underexplored. This study aims to screen and characterize prophages in these genera, providing insights into their diversity, host range, and temporal dynamics in the human gut.ResultsUsing a combination of three bioinformatic tools—Cenote-Taker 3, Vibrant, and PHASTER—we conducted a comprehensive analysis of prophages inBacteroidesandPhocaeicola. Cenote-Taker 3 identified the most diverse set of prophages, with significant overlaps observed between the tools. After clustering high-quality prophages, we identified 22 unique viral operational taxonomic units (vOTUs). Notably, comparisons between prophages identified in isolated bacterial genomes, metaviromes, and large public gut virome databases revealed a broader host range than initially observed in single isolates. Certain prophages were consistent across time points and individuals, suggesting temporal stability. All identified prophages belonged to theCaudoviricetesclass and contained genes related to antibiotic resistance, toxin production, and metabolic processes.ConclusionsThe combined use of multiple prophage detection tools allowed for a more comprehensive assessment of prophage diversity inBacteroidesandPhocaeicola. The identified prophages were not only prevalent but also exhibited broad host ranges and temporal stability. The presence of antibiotic resistance and toxin genes suggests that these prophages may significantly influence bacterial community structure and function in the gut, with potential implications for human health. These findings highlight the importance of using diverse detection tools to accurately assess prophage diversity and dynamics.