bluuebunny/crossref_metadata_2025_split huggingface dataset:
Echinochloa crus-galli seedlings surviving florpyrauxifen-benzyl applications have a greater potential to produce resistant seeds
Authors: Chen Guoqi , Zhuang Xiangxin , Masoom Aatiqa , Chen Yang , Gu Yunhua , Zhang Jiahao 
Published: November 2023

Abstract
Florpyrauxifen-benzyl (FPB) is an important postemergence rice herbicide. This study tested the potential for seed production in an FPB-resistant barnyardgrass population. A barnyardgrass population (NL) collected from a rice field in eastern China was highly resistant to FPB with a GR50 dose (the FPB dose causing a 50% reduction in fresh weight of aboveground parts) of 50.2 g ai ha−1. No significant differences in the percentages of surviving seedlings after treatment with different doses of the herbicide were found between F1 lines collected from F0 plants surviving a 36 g ai ha−1 FPB treatment and those collected from nontreated control F0 plants. Additionally, no significant differences were found in the rate of surviving seedlings after treatment with varying doses of FPB among the F2 lines collected from F1 plants that survived varying doses of FPB. At a constant temperature of 30 C, seeds from different F1 and F2 lines showed germination percentages of 85% to 92.0% and 68.3% to 89.0%, respectively. In the absence of competition, plants from the NL population surviving 0–144 g ai ha−1 FPB showed no significant differences in plant height, dry weight of aboveground parts, effective accumulated temperature (EAT) from sowing to seed maturation, seed production per plant, or 1,000-seed weight. In the susceptible population (HJ), plants surviving 18 g ai ha−1 FPB showed no significant differences compared to the nontreated control plants of the same population for the above variables. This is the first report of FPB-resistant barnyardgrass in China. Barnyardgrass seedlings that survived FPB application showed a higher potential for accumulating in the soil seedbank and negatively affecting rice.
Differences Between the CMIP5 and CMIP6 Antarctic Sea Ice Concentration Budgets
Authors: Nie Yafei , Lin Xia , Yang Qinghua , Liu Jiping , Chen Dake , Uotila Petteri 
Published: November 2023

AbstractCompared to the Coupled Model Intercomparison Project Phase 5 (CMIP5) climate models, the Antarctic sea ice area (SIA) has been improved in Phase 6 (CMIP6). However, the lack of knowledge about the reliability of sea ice dynamic and thermodynamic processes in the CMIP6 models still limits the accuracy of Antarctic sea ice projections. Here, by using a novel and systematic statistical metric, the performance of CMIP5 and CMIP6 models with near‐realistic SIAs was assessed. We found improvements in CMIP6 models relative to CMIP5. Moreover, forcing the sea ice‐ocean model with atmospheric reanalysis led to excessive ice convergence compared to the fully coupled ocean‐sea ice‐atmosphere model, although the SIA bias could be much smaller. This prevalent insufficient ice divergence in the models is highly correlated with the negative ice thickness bias, highlighting the importance of ice thickness in the correct simulation of sea ice dynamics.
The mitochondrial NADH shuttle system is a targetable vulnerability for Group 3 medulloblastoma in a hypoxic microenvironment
Authors: Contenti J. , Guo Y. , Mazzu A. , Irondelle M. , Rouleau M. , Lago C. , Leva G. , Tiberi L. , Ben-Sahra I. , Bost F. , Mazure N. M. 
Published: November 2023

AbstractMedulloblastoma is a cancerous brain tumor that affects mostly children. Among the four groups defined by molecular characteristics, Group 3, the least well characterized, is also the least favorable, with a survival rate of 50%. Current treatments, based on surgery, radiotherapy, and chemotherapy, are not adequate and the lack of understanding of the different molecular features of Group 3 tumor cells makes the development of effective therapies challenging. In this study, the problem of medulloblastoma is approached from a metabolic standpoint in a low oxygen microenvironment. We establish that Group 3 cells use both the mitochondrial glycerol-3 phosphate (G3PS) and malate-aspartate shuttles (MAS) to produce NADH. Small molecules that target G3PS and MAS show a greater ability to decrease cell proliferation and induce apoptosis specifically of Group 3 cells. In addition, as Group 3 cells show improved respiration in hypoxia, the use of Phenformin, a mitochondrial complex 1 inhibitor, alone or in combination, induced significant cell death. Furthermore, inhibition of the cytosolic NAD+ recycling enzyme lactate dehydrogenase A (LDHA), enhanced the effects of the NADH shuttle inhibitors. In a 3D model using Group 3 human cerebellar organoids, tumor cells also underwent apoptosis upon treatment with NADH shuttle inhibitors. Our study demonstrates metabolic heterogeneity depending on oxygen concentrations and provides potential therapeutic solutions for patients in Group 3 whose tumors are the most aggressive.
Clinical proof of concept for anti-FGF2 therapy in exudative age-related macular degeneration (nAMD): phase 2 trials in treatment-naïve and anti-VEGF pretreated patients
Authors: Pereira Daniel S. , Maturi Raj K. , Akita Kazumasa , Mahesh Vinaya , Bhisitkul Robert B. , Nishihata Toshiaki , Sakota Eri , Ali Yusuf , Nakamura Emiko , Bezwada Padma , Nakamura Yoshikazu 
Published: November 2023

Abstract
Background/Objective
Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents are the first-line treatment for exudative age-related macular degeneration (nAMD). Due to the limitations of these standard therapies, targeting alternative mechanisms of action may be helpful for treatment of this very common disease. Here, we investigated an anti-fibroblast growth factor-2 (FGF2) aptamer, umedaptanib pegol, a next generation therapeutic for the treatment of nAMD.

Methods
Three phase 2 studies were designed. First, a multicentre, randomized, double-masked TOFU study assessed the efficacy of intravitreal injections of umedaptanib pegol monotherapy or in combination with aflibercept, compared to aflibercept monotherapy in 86 subjects with anti-VEGF pretreated nAMD. Second, 22 subjects who had exited the TOFU study received 4 monthly intravitreal injections of umedaptanib pegol (extension, RAMEN study). Third, as an investigator-sponsored trial (TEMPURA study), a single-center, open-label, 4-month study was designed to evaluate the safety and treatment efficacy of umedaptanib pegol in five naïve nAMD patients who had not received any prior anti-VEGF treatment.

Results
The TOFU study demonstrated that umedaptanib pegol alone or in combination with aflibercept did not improve best-corrected visual acuity (BCVA) and central subfield thickness (CST) over aflibercept alone. However, the change in BCVA and CST at primary endpoint was marginal in all the three treatment groups, suggesting that umedaptanib pegol is effective to prevent the disease progression. The RAMEN study confirmed the cessation of disease progression. In the TEMPURA study, naïve nAMD patients showed improvement and no further macular degeneration, with striking improvement of visual acuity and central subfield thickness in some of the patients.

Conclusions
These results demonstrate, for the first time, clinical proof of concept for aptamer based anti-FGF2 therapy of nAMD.
Wake slow waves in focal human epilepsy impact network activity and cognition
Authors: Sheybani Laurent , Vivekananda Umesh , Rodionov Roman , Diehl Beate , Chowdhury Fahmida A. , McEvoy Andrew W. , Miserocchi Anna , Bisby James A. , Bush Daniel , Burgess Neil , Walker Matthew C. 
Published: November 2023

AbstractSlow waves of neuronal activity are a fundamental component of sleep that are proposed to have homeostatic and restorative functions. Despite this, their interaction with pathology is unclear and there is only indirect evidence of their presence during wakefulness. Using intracortical recordings from the temporal lobe of 25 patients with epilepsy, we demonstrate the existence of local wake slow waves (LoWS) with key features of sleep slow waves, including a down-state of neuronal firing. Consistent with a reduction in neuronal activity, LoWS were associated with slowed cognitive processing. However, we also found that LoWS showed signatures of a homeostatic relationship with interictal epileptiform discharges (IEDs): exhibiting progressive adaptation during the build-up of network excitability before an IED and reducing the impact of subsequent IEDs on network excitability. We therefore propose an epilepsy homeostasis hypothesis: that slow waves in epilepsy reduce aberrant activity at the price of transient cognitive impairment.
Delineating the interplay between oncogenic pathways and immunity in anaplastic Wilms tumors
Authors: Su Xiaoping , Lu Xiaofan , Bazai Sehrish Khan , Dainese Linda , Verschuur Arnauld , Dumont Benoit , Mouawad Roger , Xu Li , Cheng Wenxuan , Yan Fangrong , Irtan Sabine , Lindner Véronique , Paillard Catherine , Le Bouc Yves , Coulomb Aurore , Malouf Gabriel G. 
Published: November 2023

AbstractWilms tumors are highly curable in up to 90% of cases with a combination of surgery and radio-chemotherapy, but treatment-resistant types such as diffuse anaplastic Wilms tumors pose significant therapeutic challenges. Our multi-omics profiling unveils a distinct desert-like diffuse anaplastic Wilms tumor subtype marked by immune/stromal cell depletion, TP53 alterations, and cGAS-STING pathway downregulation, accounting for one-third of all diffuse anaplastic cases. This subtype, also characterized by reduced CD8 and CD3 infiltration and active oncogenic pathways involving histone deacetylase and DNA repair, correlates with poor clinical outcomes. These oncogenic pathways are found to be conserved in anaplastic Wilms tumor cell models. We identify histone deacetylase and/or WEE1 inhibitors as potential therapeutic vulnerabilities in these tumors, which might also restore tumor immunogenicity and potentially enhance the effects of immunotherapy. These insights offer a foundation for predicting outcomes and personalizing treatment strategies for aggressive pediatric Wilms tumors, tailored to individual immunological landscapes.
Bile proteome reveals biliary regeneration during normothermic preservation of human donor livers
Authors: Thorne Adam M. , Wolters Justina C. , Lascaris Bianca , Bodewes Silke B. , Lantinga Veerle A. , van Leeuwen Otto B. , de Jong Iris E. M. , Ustyantsev Kirill , Berezikov Eugene , Lisman Ton , Kuipers Folkert , Porte Robert J. , de Meijer Vincent E. 
Published: November 2023

AbstractNormothermic machine perfusion (NMP) after static cold storage is increasingly used for preservation and assessment of human donor livers prior to transplantation. Biliary viability assessment during NMP reduces the risk of post-transplant biliary complications. However, understanding of molecular changes in the biliary system during NMP remains incomplete. We performed an in-depth, unbiased proteomics analysis of bile collected during sequential hypothermic machine perfusion, rewarming and NMP of 55 human donor livers. Longitudinal analysis during NMP reveals proteins reflective of cellular damage at early stages, followed by upregulation of secretory and immune response processes. Livers with bile chemistry acceptable for transplantation reveal protein patterns implicated in regenerative processes, including cellular proliferation, compared to livers with inadequate bile chemistry. These findings are reinforced by detection of regenerative gene transcripts in liver tissue before machine perfusion. Our comprehensive bile proteomics and liver transcriptomics data sets provide the potential to further evaluate molecular mechanisms during NMP and refine viability assessment criteria.
Explainable machine learning for profiling the immunological synapse and functional characterization of therapeutic antibodies
Authors: Shetab Boushehri Sayedali , Essig Katharina , Chlis Nikolaos-Kosmas , Herter Sylvia , Bacac Marina , Theis Fabian J. , Glasmacher Elke , Marr Carsten , Schmich Fabian 
Published: November 2023

AbstractTherapeutic antibodies are widely used to treat severe diseases. Most of them alter immune cells and act within the immunological synapse; an essential cell-to-cell interaction to direct the humoral immune response. Although many antibody designs are generated and evaluated, a high-throughput tool for systematic antibody characterization and prediction of function is lacking. Here, we introduce the first comprehensive open-source framework, scifAI (single-cell imaging flow cytometry AI), for preprocessing, feature engineering, and explainable, predictive machine learning on imaging flow cytometry (IFC) data. Additionally, we generate the largest publicly available IFC dataset of the human immunological synapse containing over 2.8 million images. Using scifAI, we analyze class frequency and morphological changes under different immune stimulation. T cell cytokine production across multiple donors and therapeutic antibodies is quantitatively predicted in vitro, linking morphological features with function and demonstrating the potential to significantly impact antibody design. scifAI is universally applicable to IFC data. Given its modular architecture, it is straightforward to incorporate into existing workflows and analysis pipelines, e.g., for rapid antibody screening and functional characterization.
A colloidal viewpoint on the sausage catastrophe and the finite sphere packing problem
Authors: Marín-Aguilar Susana , Camerin Fabrizio , van der Ham Stijn , Feasson Andréa , Vutukuri Hanumantha Rao , Dijkstra Marjolein 
Published: November 2023

AbstractIt is commonly believed that the most efficient way to pack a finite number of equal-sized spheres is by arranging them tightly in a cluster. However, mathematicians have conjectured that a linear arrangement may actually result in the densest packing. Here, our combined experimental and simulation study provides a physical realization of the finite sphere packing problem by studying arrangements of colloids in a flaccid lipid vesicle. We map out a state diagram displaying linear, planar, and cluster conformations of spheres, as well as bistable states which alternate between cluster-plate and plate-linear conformations due to membrane fluctuations. Finally, by systematically analyzing truncated polyhedral packings, we identify clusters of 56 ≤ N ≤ 70 number of spheres, excluding N = 57 and 63, that pack more efficiently than linear arrangements.
Lattice distortion SnS2 piezoelectric self-Fenton system for efficient degradation and detoxification of pollutants
Authors: Jiang Runren , Lu Guanghua , Wang Min , Chen Yufang , Liu Jianchao , Yan Zhenhua , Xie Haijiao 
Published: November 2023

AbstractBoth piezoelectricity and self-Fenton catalysis are effective ways to degrade water pollution, but little research has combined them to construct a more efficient water pollution treatment method. Here, a Fe-doped SnS2 (Sn1-xFexS2) piezoelectric self-Fenton system was constructed, which shows superior water treatment performance. The best piezoelectric properties of the Sn0.97Fe0.03S2 system were verified by degrading rhodamine B (RhB). The toxicity analysis of degradation intermediates and solutions confirmed that the toxicity of RhB decreased after degradation. In addition, Kelvin probe force microscopy and photoelectrochemical analysis confirmed the better piezoelectric properties of Sn0.97Fe0.03S2. It has demonstrated the enhancement of systematic piezoelectricity by Fe lattice defects and the formation of self-Fenton by Fe as an active center in the degradation of RhB. In this work, an efficient piezoelectric and self-Fenton technology is constructed to remove organic pollutants from water, which is significant for developing water treatment technology.
High-dimensional multi-pass flow cytometry via spectrally encoded cellular barcoding
Authors: Kwok Sheldon J. J. , Forward Sarah , Fahlberg Marissa D. , Assita Emane Rose , Cosgriff Sean , Lee Seung Hyung , Abbott Geoffrey R. , Zhu Han , Minasian Nicolas H. , Vote A. Sean , Martino Nicola , Yun Seok-Hyun 
Published: November 2023

AbstractAdvances in immunology, immuno-oncology, drug discovery and vaccine development demand improvements in the capabilities of flow cytometry to allow it to measure more protein markers per cell at multiple timepoints. However, the size of panels of fluorophore markers is limited by overlaps in fluorescence-emission spectra, and flow cytometers typically perform cell measurements at one timepoint. Here we describe multi-pass high-dimensional flow cytometry, a method leveraging cellular barcoding via microparticles emitting near-infrared laser light to track and repeatedly measure each cell using more markers and fewer colours. By using live human peripheral blood mononuclear cells, we show that the method enables the time-resolved characterization of the same cells before and after stimulation, their analysis via a 10-marker panel with minimal compensation for spectral spillover and their deep immunophenotyping via a 32-marker panel, where the same cells are analysed in 3 back-to-back cycles with 10–13 markers per cycle, reducing overall spillover and simplifying marker-panel design. Cellular barcoding in flow cytometry extends the utility of the technique for high-dimensional multi-pass single-cell analyses.
Isoform-level transcriptome-wide association uncovers genetic risk mechanisms for neuropsychiatric disorders in the human brain
Authors: Bhattacharya Arjun , Vo Daniel D. , Jops Connor , Kim Minsoo , Wen Cindy , Hervoso Jonatan L. , Pasaniuc Bogdan , Gandal Michael J. 
Published: November 2023

AbstractMethods integrating genetics with transcriptomic reference panels prioritize risk genes and mechanisms at only a fraction of trait-associated genetic loci, due in part to an overreliance on total gene expression as a molecular outcome measure. This challenge is particularly relevant for the brain, in which extensive splicing generates multiple distinct transcript-isoforms per gene. Due to complex correlation structures, isoform-level modeling from cis-window variants requires methodological innovation. Here we introduce isoTWAS, a multivariate, stepwise framework integrating genetics, isoform-level expression and phenotypic associations. Compared to gene-level methods, isoTWAS improves both isoform and gene expression prediction, yielding more testable genes, and increased power for discovery of trait associations within genome-wide association study loci across 15 neuropsychiatric traits. We illustrate multiple isoTWAS associations undetectable at the gene-level, prioritizing isoforms of AKT3, CUL3 and HSPD1 in schizophrenia and PCLO with multiple disorders. Results highlight the importance of incorporating isoform-level resolution within integrative approaches to increase discovery of trait associations, especially for brain-relevant traits.
AlphaFold predictions are valuable hypotheses and accelerate but do not replace experimental structure determination
Authors: Terwilliger Thomas C. , Liebschner Dorothee , Croll Tristan I. , Williams Christopher J. , McCoy Airlie J. , Poon Billy K. , Afonine Pavel V. , Oeffner Robert D. , Richardson Jane S. , Read Randy J. , Adams Paul D. 
Published: November 2023

AbstractArtificial intelligence-based protein structure prediction methods such as AlphaFold have revolutionized structural biology. The accuracies of these predictions vary, however, and they do not take into account ligands, covalent modifications or other environmental factors. Here, we evaluate how well AlphaFold predictions can be expected to describe the structure of a protein by comparing predictions directly with experimental crystallographic maps. In many cases, AlphaFold predictions matched experimental maps remarkably closely. In other cases, even very high-confidence predictions differed from experimental maps on a global scale through distortion and domain orientation, and on a local scale in backbone and side-chain conformation. We suggest considering AlphaFold predictions as exceptionally useful hypotheses. We further suggest that it is important to consider the confidence in prediction when interpreting AlphaFold predictions and to carry out experimental structure determination to verify structural details, particularly those that involve interactions not included in the prediction.
Explained predictions of strong eastern Pacific El Niño events using deep learning
Authors: Rivera Tello Gerardo A. , Takahashi Ken , Karamperidou Christina 
Published: November 2023

AbstractGlobal and regional impacts of El Niño-Southern Oscillation (ENSO) are sensitive to the details of the pattern of anomalous ocean warming and cooling, such as the contrasts between the eastern and central Pacific. However, skillful prediction of such ENSO diversity remains a challenge even a few months in advance. Here, we present an experimental forecast with a deep learning model (IGP-UHM AI model v1.0) for the E (eastern Pacific) and C (central Pacific) ENSO diversity indices, specialized on the onset of strong eastern Pacific El Niño events by including a classification output. We find that higher ENSO nonlinearity is associated with better skill, with potential implications for ENSO predictability in a warming climate. When initialized in May 2023, our model predicts the persistence of El Niño conditions in the eastern Pacific into 2024, but with decreasing strength, similar to 2015–2016 but much weaker than 1997–1998. In contrast to the more typical El Niño development in 1997 and 2015, in addition to the ongoing eastern Pacific warming, an eXplainable Artificial Intelligence analysis for 2023 identifies weak warm surface, increased sea level and westerly wind anomalies in the western Pacific as precursors, countered by warm surface and southerly wind anomalies in the northern Atlantic.
Evidence of cochlear neural degeneration in normal-hearing subjects with tinnitus
Authors: Vasilkov Viacheslav , Caswell-Midwinter Benjamin , Zhao Yan , de Gruttola Victor , Jung David H. , Liberman M. Charles , Maison Stéphane F. 
Published: November 2023

AbstractTinnitus, reduced sound-level tolerance, and difficulties hearing in noisy environments are the most common complaints associated with sensorineural hearing loss in adult populations. This study aims to clarify if cochlear neural degeneration estimated in a large pool of participants with normal audiograms is associated with self-report of tinnitus using a test battery probing the different stages of the auditory processing from hair cell responses to the auditory reflexes of the brainstem. Self-report of chronic tinnitus was significantly associated with (1) reduced cochlear nerve responses, (2) weaker middle-ear muscle reflexes, (3) stronger medial olivocochlear efferent reflexes and (4) hyperactivity in the central auditory pathways. These results support the model of tinnitus generation whereby decreased neural activity from a damaged cochlea can elicit hyperactivity from decreased inhibition in the central nervous system.