bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does acute cannabidiol (CBD) use impair performance? A meta-analysis and comparison with placebo and delta-9-tetrahydrocannabinol (THC)
Authors: Lo Lindsay A. , Christiansen April L. , Strickland Justin C. , Pistawka Carly A. , Eadie Lauren , Vandrey Ryan , MacCallum Caroline A. 
Published: March 2024

AbstractCannabidiol (CBD) is widely used and believed to be non-intoxicating, lacking acute performance effects (e.g., non-impairing). However, a synthesis of data has not evaluated this. This meta-analysis synthesized data from controlled human laboratory studies that evaluated if acute CBD use impairs performance. Performance on objective and subjective measures of cognitive and psychomotor function were used as markers for potential performance changes and impairment. Studies were identified through systematic database searches. Adult clinical trials measuring acute CBD effects (within 0–8 h of administration) were included. The primary outcome was the peak mean difference in performance measures between CBD and placebo. A secondary analysis utilizing delta-9-tetrahydrocannabinol (Δ9-THC) as a positive control for comparison to CBD was completed. Pooled Hedges’ g estimates were calculated using robust variance estimation (RVE) meta-regression. The omnibus RVE meta-analysis indicated a statistically significant, but small effect size (Hedge’s g < 0.2) for impaired performance following acute CBD consumption compared to placebo (N = 16 trials, Hedges’ g = 0.122, 95% CI: 0.023–0.221, p = 0.019). Measure type was a significant moderator with larger mean differences between CBD and placebo when subjective measures, specifically self-reported sedation, were used versus objective performance tasks (Hedges’ gSubjective = 0.288 versus Hedges’ gObjective = 0.048). Δ9-THC had a significantly greater magnitude of impairment compared to CBD (N = 8, Hedges’ g = 0.416, 95% CI: 0.017–0.816, p = 0.043). In summary, acute CBD consumption was associated with a small increase in subjective ratings of sedation, but no difference from placebo was observed across multiple domains of objectively assessed cognitive or psychomotor performance. These findings suggest that acute CBD alone is unlikely to significantly impair daily functioning or workplace performance.
Harnessing innate immune pathways for therapeutic advancement in cancer
Authors: Hu Ankang , Sun Li , Lin Hao , Liao Yuheng , Yang Hui , Mao Ying 
Published: March 2024

AbstractThe innate immune pathway is receiving increasing attention in cancer therapy. This pathway is ubiquitous across various cell types, not only in innate immune cells but also in adaptive immune cells, tumor cells, and stromal cells. Agonists targeting the innate immune pathway have shown profound changes in the tumor microenvironment (TME) and improved tumor prognosis in preclinical studies. However, to date, the clinical success of drugs targeting the innate immune pathway remains limited. Interestingly, recent studies have shown that activation of the innate immune pathway can paradoxically promote tumor progression. The uncertainty surrounding the therapeutic effectiveness of targeted drugs for the innate immune pathway is a critical issue that needs immediate investigation. In this review, we observe that the role of the innate immune pathway demonstrates heterogeneity, linked to the tumor development stage, pathway status, and specific cell types. We propose that within the TME, the innate immune pathway exhibits multidimensional diversity. This diversity is fundamentally rooted in cellular heterogeneity and is manifested as a variety of signaling networks. The pro-tumor effect of innate immune pathway activation essentially reflects the suppression of classical pathways and the activation of potential pro-tumor alternative pathways. Refining our understanding of the tumor’s innate immune pathway network and employing appropriate targeting strategies can enhance our ability to harness the anti-tumor potential of the innate immune pathway and ultimately bridge the gap from preclinical to clinical application.
Kdm6a-CNN1 axis orchestrates epigenetic control of trauma-induced spinal cord microvascular endothelial cell senescence to balance neuroinflammation for improved neurological repair
Authors: Li Chengjun , Qin Tian , Zhao Jinyun , Jin Yuxin , Qin Yiming , He Rundong , Wu Tianding , Duan Chunyue , Jiang Liyuan , Yuan Feifei , Lu Hongbin , Cao Yong , Hu Jianzhong 
Published: March 2024

AbstractCellular senescence assumes pivotal roles in various diseases through the secretion of proinflammatory factors. Despite extensive investigations into vascular senescence associated with aging and degenerative diseases, the molecular mechanisms governing microvascular endothelial cell senescence induced by traumatic stress, particularly its involvement in senescence-induced inflammation, remain insufficiently elucidated. In this study, we present a comprehensive demonstration and characterization of microvascular endothelial cell senescence induced by spinal cord injury (SCI). Lysine demethylase 6A (Kdm6a), commonly known as UTX, emerges as a crucial regulator of cell senescence in injured spinal cord microvascular endothelial cells (SCMECs). Upregulation of UTX induces senescence in SCMECs, leading to an amplified release of proinflammatory factors, specifically the senescence-associated secretory phenotype (SASP) components, thereby modulating the inflammatory microenvironment. Conversely, the deletion of UTX in endothelial cells shields SCMECs against senescence, mitigates the release of proinflammatory SASP factors, and promotes neurological functional recovery after SCI. UTX forms an epigenetic regulatory axis by binding to calponin 1 (CNN1), orchestrating trauma-induced SCMECs senescence and SASP secretion, thereby influencing neuroinflammation and neurological functional repair. Furthermore, local delivery of a senolytic drug reduces senescent SCMECs and suppresses proinflammatory SASP secretion, reinstating a local regenerative microenvironment and enhancing functional repair after SCI. In conclusion, targeting the UTX-CNN1 epigenetic axis to prevent trauma-induced SCMECs senescence holds the potential to inhibit SASP secretion, alleviate neuroinflammation, and provide a novel treatment strategy for SCI repair.
Evaluation of a two-step model of opportunistic genomic screening
Authors: Martyn Melissa , Lee Ling , Jan Alli , Lynch Elly , Weerasuriya Rona , Kanga-Parabia Anaita , Gaff Clara 
Published: March 2024

AbstractIncreasing use of diagnostic genomic sequencing is pushing health services to confront the issue of opportunistic genomic screening (OGS). To date, OGS has been offered concomitant with diagnostic testing. In contrast, we piloted a service offering OGS after return of diagnostic testing results. Evaluation was designed to provide insights for future models of service and included patient surveys at three time points, semi-structured interviews with genetic counsellors (GCs) and a focus group with medical scientists. Uptake was relatively low: 83 of 200 patients approached (42%) attended the OGS service, with 81 accepting OGS. Whilst many who declined to attend the service cited practical barriers, others gave reasons that indicated this was a considered decision. Despite specific genetic counselling, one third of patients did not understand the scope of re-analysis. Yet after post-test counselling, all respondents with novel pathogenic additional findings (AF) understood the implications and reported relevant follow-up. Recall was high: five months after last contact, 75% recalled being offered OGS without prompting. GC interviews and patient survey responses provide insights into complexities that influence patient support needs, including diagnostic status and AF result type. There was no consensus among patients or professionals about when to offer OGS. There was a clear preference for multiple, flexible methods of information provision; achieving this whilst balancing patient support needs and resource requirements is a challenge requiring further investigation. Decisions about whether, when and how to offer OGS are complex; our study shows the two-step approach warrants further exploration.
Phosphonate-based iron complex for a cost-effective and long cycling aqueous iron redox flow battery
Authors: Nambafu Gabriel S. , Hollas Aaron M. , Zhang Shuyuan , Rice Peter S. , Boglaienko Daria , Fulton John L. , Li Miller , Huang Qian , Zhu Yu , Reed David M. , Sprenkle Vincent L. , Li Guosheng 
Published: March 2024

AbstractA promising metal-organic complex, iron (Fe)-NTMPA2, consisting of Fe(III) chloride and nitrilotri-(methylphosphonic acid) (NTMPA), is designed for use in aqueous iron redox flow batteries. A full-cell testing, where a concentrated Fe-NTMPA2 anolyte (0.67 M) is paired with a Fe-CN catholyte, demonstrates exceptional cycling stability over 1000 charge/discharge cycles, and noteworthy performances, including 96% capacity utilization, a minimal capacity fade rate of 0.0013% per cycle (1.3% over 1,000 cycles), high Coulombic efficiency and energy efficiency near 100% and 87%, respectively, all achieved under a current density of 20 mA·cm-². Furthermore, density functional theory unveils two potential coordination structures for Fe-NTMPA2 complexes, improving the understanding between the ligand coordination environment and electron transfer kinetics. When paired with a high redox potential Fe-Dcbpy/CN catholyte, 2,2′-bipyridine-4,4′-dicarboxylic (Dcbpy) acid and cyanide (CN) ligands, Fe-NTMPA2 demonstrates a notably elevated cell voltage of 1 V, enabling a practical energy density of up to 9 Wh/L.
Field-scale crop water consumption estimates reveal potential water savings in California agriculture
Authors: Boser Anna , Caylor Kelly , Larsen Ashley , Pascolini-Campbell Madeleine , Reager John T. , Carleton Tamma 
Published: March 2024

AbstractEfficiently managing agricultural irrigation is vital for food security today and into the future under climate change. Yet, evaluating agriculture’s hydrological impacts and strategies to reduce them remains challenging due to a lack of field-scale data on crop water consumption. Here, we develop a method to fill this gap using remote sensing and machine learning, and leverage it to assess water saving strategies in California’s Central Valley. We find that switching to lower water intensity crops can reduce consumption by up to 93%, but this requires adopting uncommon crop types. Northern counties have substantially lower irrigation efficiencies than southern counties, suggesting another potential source of water savings. Other practices that do not alter land cover can save up to 11% of water consumption. These results reveal diverse approaches for achieving sustainable water use, emphasizing the potential of sub-field scale crop water consumption maps to guide water management in California and beyond.
The Persian plateau served as hub for Homo sapiens after the main out of Africa dispersal
Authors: Vallini Leonardo , Zampieri Carlo , Shoaee Mohamed Javad , Bortolini Eugenio , Marciani Giulia , Aneli Serena , Pievani Telmo , Benazzi Stefano , Barausse Alberto , Mezzavilla Massimo , Petraglia Michael D. , Pagani Luca 
Published: March 2024

AbstractA combination of evidence, based on genetic, fossil and archaeological findings, indicates that Homo sapiens spread out of Africa between ~70-60 thousand years ago (kya). However, it appears that once outside of Africa, human populations did not expand across all of Eurasia until ~45 kya. The geographic whereabouts of these early settlers in the timeframe between ~70-60 to 45 kya has been difficult to reconcile. Here we combine genetic evidence and palaeoecological models to infer the geographic location that acted as the Hub for our species during the early phases of colonisation of Eurasia. Leveraging on available genomic evidence we show that populations from the Persian Plateau carry an ancestry component that closely matches the population that settled the Hub outside Africa. With the paleoclimatic data available to date, we built ecological models showing that the Persian Plateau was suitable for human occupation and that it could sustain a larger population compared to other West Asian regions, strengthening this claim.
Direct observation of phase transitions in truncated tetrahedral microparticles under quasi-2D confinement
Authors: Doan David , Kulikowski John , Gu X. Wendy 
Published: March 2024

AbstractColloidal crystals are used to understand fundamentals of atomic rearrangements in condensed matter and build complex metamaterials with unique functionalities. Simulations predict a multitude of self-assembled crystal structures from anisotropic colloids, but these shapes have been challenging to fabricate. Here, we use two-photon lithography to fabricate Archimedean truncated tetrahedrons and self-assemble them under quasi-2D confinement. These particles self-assemble into a hexagonal phase under an in-plane gravitational potential. Under additional gravitational potential, the hexagonal phase transitions into a quasi-diamond two-unit basis. In-situ imaging reveal this phase transition is initiated by an out-of-plane rotation of a particle at a crystalline defect and causes a chain reaction of neighboring particle rotations. Our results provide a framework of studying different structures from hard-particle self-assembly and demonstrates the ability to use confinement to induce unusual phases.
Single drop cytometry onboard the International Space Station
Authors: Rea Daniel J. , Miller Rachael S. , Crucian Brian E. , Valentine Russell W. , Cristoforetti Samantha , Bearg Samuel B. , Sipic Zlatko , Cheng Jamie , Yu Rebecca , Calaway Kimesha M. , Eames Dexter , Nelson Emily S. , Lewandowski Beth E. , Perusek Gail P. , Chan Eugene Y. 
Published: March 2024

AbstractReal-time lab analysis is needed to support clinical decision making and research on human missions to the Moon and Mars. Powerful laboratory instruments, such as flow cytometers, are generally too cumbersome for spaceflight. Here, we show that scant test samples can be measured in microgravity, by a trained astronaut, using a miniature cytometry-based analyzer, the rHEALTH ONE, modified specifically for spaceflight. The base device addresses critical spaceflight requirements including minimal resource utilization and alignment-free optics for surviving rocket launch. To fully enable reduced gravity operation onboard the space station, we incorporated bubble-free fluidics, electromagnetic shielding, and gravity-independent sample introduction. We show microvolume flow cytometry from 10 μL sample drops, with data from five simultaneous channels using 10 μs bin intervals during each sample run, yielding an average of 72 million raw data points in approximately 2 min. We demonstrate the device measures each test sample repeatably, including correct identification of a sample that degraded in transit to the International Space Station. This approach can be utilized to further our understanding of spaceflight biology and provide immediate, actionable diagnostic information for management of astronaut health without the need for Earth-dependent analysis.
Fire suppression makes wildfires more severe and accentuates impacts of climate change and fuel accumulation
Authors: Kreider Mark R. , Higuera Philip E. , Parks Sean A. , Rice William L. , White Nadia , Larson Andrew J. 
Published: March 2024

AbstractFire suppression is the primary management response to wildfires in many areas globally. By removing less-extreme wildfires, this approach ensures that remaining wildfires burn under more extreme conditions. Here, we term this the “suppression bias” and use a simulation model to highlight how this bias fundamentally impacts wildfire activity, independent of fuel accumulation and climate change. We illustrate how attempting to suppress all wildfires necessarily means that fires will burn with more severe and less diverse ecological impacts, with burned area increasing at faster rates than expected from fuel accumulation or climate change. Over a human lifespan, the modeled impacts of the suppression bias exceed those from fuel accumulation or climate change alone, suggesting that suppression may exert a significant and underappreciated influence on patterns of fire globally. Managing wildfires to safely burn under low and moderate conditions is thus a critical tool to address the growing wildfire crisis.
Landslide topology uncovers failure movements
Authors: Bhuyan Kushanav , Rana Kamal , Ferrer Joaquin V. , Cotton Fabrice , Ozturk Ugur , Catani Filippo , Malik Nishant 
Published: March 2024

AbstractThe death toll and monetary damages from landslides continue to rise despite advancements in predictive modeling. These models’ performances are limited as landslide databases used in developing them often miss crucial information, e.g., underlying movement types. This study introduces a method of discerning landslide movements, such as slides, flows, and falls, by analyzing landslides’ 3D shapes. By examining landslide topological properties, we discover distinct patterns in their morphology, indicating different movements including complex ones with multiple coupled movements. We achieve 80-94% accuracy by applying topological properties in identifying landslide movements across diverse geographical and climatic regions, including Italy, the US Pacific Northwest, Denmark, Turkey, and Wenchuan in China. Furthermore, we demonstrate a real-world application on undocumented datasets from Wenchuan. Our work introduces a paradigm for studying landslide shapes to understand their underlying movements through the lens of landslide topology, which could aid landslide predictive models and risk evaluations.
Diverging co-translational protein complex assembly pathways are governed by interface energy distribution
Authors: Venezian Johannes , Bar-Yosef Hagit , Ben-Arie Zilberman Hila , Cohen Noam , Kleifeld Oded , Fernandez-Recio Juan , Glaser Fabian , Shiber Ayala 
Published: March 2024

AbstractProtein-protein interactions are at the heart of all cellular processes, with the ribosome emerging as a platform, orchestrating the nascent-chain interplay dynamics. Here, to study the characteristics governing co-translational protein folding and complex assembly, we combine selective ribosome profiling, imaging, and N-terminomics with all-atoms molecular dynamics. Focusing on conserved N-terminal acetyltransferases (NATs), we uncover diverging co-translational assembly pathways, where highly homologous subunits serve opposite functions. We find that only a few residues serve as “hotspots,” initiating co-translational assembly interactions upon exposure at the ribosome exit tunnel. These hotspots are characterized by high binding energy, anchoring the entire interface assembly. Alpha-helices harboring hotspots are highly thermolabile, folding and unfolding during simulations, depending on their partner subunit to avoid misfolding. In vivo hotspot mutations disrupted co-translational complexation, leading to aggregation. Accordingly, conservation analysis reveals that missense NATs variants, causing neurodevelopmental and neurodegenerative diseases, disrupt putative hotspot clusters. Expanding our study to include phosphofructokinase, anthranilate synthase, and nucleoporin subcomplex, we employ AlphaFold-Multimer to model the complexes’ complete structures. Computing MD-derived interface energy profiles, we find similar trends. Here, we propose a model based on the distribution of interface energy as a strong predictor of co-translational assembly.
Phenome-wide Mendelian randomisation analysis of 378,142 cases reveals risk factors for eight common cancers
Authors: Went Molly , Sud Amit , Mills Charlie , Hyde Abi , Culliford Richard , Law Philip , Vijayakrishnan Jayaram , Gockel Ines , Maj Carlo , Schumacher Johannes , Palles Claire , Kaiser Martin , Houlston Richard 
Published: March 2024

AbstractFor many cancers there are only a few well-established risk factors. Here, we use summary data from genome-wide association studies (GWAS) in a Mendelian randomisation (MR) phenome-wide association study (PheWAS) to identify potentially causal relationships for over 3,000 traits. Our outcome datasets comprise 378,142 cases across breast, prostate, colorectal, lung, endometrial, oesophageal, renal, and ovarian cancers, as well as 485,715 controls. We complement this analysis by systematically mining the literature space for supporting evidence. In addition to providing supporting evidence for well-established risk factors (smoking, alcohol, obesity, lack of physical activity), we also find sex steroid hormones, plasma lipids, and telomere length as determinants of cancer risk. A number of the molecular factors we identify may prove to be potential biomarkers. Our analysis, which highlights aetiological similarities and differences in common cancers, should aid public health prevention strategies to reduce cancer burden. We provide a R/Shiny app to visualise findings.
SKA2 regulated hyperactive secretory autophagy drives neuroinflammation-induced neurodegeneration
Authors: Hartmann Jakob , Bajaj Thomas , Otten Joy , Klengel Claudia , Ebert Tim , Gellner Anne-Kathrin , Junglas Ellen , Hafner Kathrin , Anderzhanova Elmira A. , Tang Fiona , Missig Galen , Rexrode Lindsay , Trussell Daniel T. , Li Katelyn X. , Pöhlmann Max L. , Mackert Sarah , Geiger Thomas M. , Heinz Daniel E. , Lardenoije Roy , Dedic Nina , McCullough Kenneth M. , Próchnicki Tomasz , Rhomberg Thomas , Martinelli Silvia , Payton Antony , Robinson Andrew C. , Stein Valentin , Latz Eicke , Carlezon William A. , Hausch Felix , Schmidt Mathias V. , Murgatroyd Chris , Berretta Sabina , Klengel Torsten , Pantazopoulos Harry , Ressler Kerry J. , Gassen Nils C. 
Published: March 2024

AbstractHigh levels of proinflammatory cytokines induce neurotoxicity and catalyze inflammation-driven neurodegeneration, but the specific release mechanisms from microglia remain elusive. Here we show that secretory autophagy (SA), a non-lytic modality of autophagy for secretion of vesicular cargo, regulates neuroinflammation-mediated neurodegeneration via SKA2 and FKBP5 signaling. SKA2 inhibits SA-dependent IL-1β release by counteracting FKBP5 function. Hippocampal Ska2 knockdown in male mice hyperactivates SA resulting in neuroinflammation, subsequent neurodegeneration and complete hippocampal atrophy within six weeks. The hyperactivation of SA increases IL-1β release, contributing to an inflammatory feed-forward vicious cycle including NLRP3-inflammasome activation and Gasdermin D-mediated neurotoxicity, which ultimately drives neurodegeneration. Results from protein expression and co-immunoprecipitation analyses of male and female postmortem human brains demonstrate that SA is hyperactivated in Alzheimer’s disease. Overall, our findings suggest that SKA2-regulated, hyperactive SA facilitates neuroinflammation and is linked to Alzheimer’s disease, providing mechanistic insight into the biology of neuroinflammation.