bluuebunny/crossref_metadata_2025_split huggingface dataset:
Duvelisib for Critically Ill Patients With Coronavirus Disease 2019: An Investigator-Initiated, Randomized, Placebo-Controlled, Double-Blind Pilot Trial
Authors: Goldsmith Scott R , Covut Fahrettin , Fiala Mark , Xiang Zhifu , Iqbal Zahid , Moore Nathan , Bradtke Elizabeth , Christen Brandon , Rettig Michael P , Christ Stephanie , Gehrs Leah , Street Emily , Wallace Nicholas , Ritchey Julie , Gao Feng , Pachter Jonathan , Parikh Bijal , Dubberke Erik R , DiPersio John F 
Published: October 2023

Abstract

Background
Despite improvements in prevention and treatment, severe coronavirus disease 2019 (COVID-19) is associated with high mortality. Phosphoinositide 3-kinase (PI3K) pathways contribute to cytokine and cell-mediated lung inflammation. We conducted a randomized, placebo-controlled, double-blind pilot trial to determine the feasibility, safety, and preliminary activity of duvelisib, a PI3Kδγ inhibitor, for the treatment of COVID-19 critical illness.

Methods
We enrolled adults aged ≥18 years with a primary diagnosis of COVID-19 with hypoxic respiratory failure, shock, and/or new cardiac disease, without improvement after at least 48 hours of corticosteroid. Participants received duvelisib (25 mg) or placebo for up to 10 days. Participants had daily semi-quantitative viral load measurements performed. Dose modifications were protocol driven due to adverse events (AEs) or logarithmic change in viral load. The primary endpoint was 28-day overall survival (OS). Secondary endpoints included hospital and intensive care unit length of stay, 60-day OS, and duration of critical care interventions. Safety endpoints included viral kinetics and AEs. Exploratory endpoints included serial cytokine measurements and cytometric analysis.

Results
Fifteen patients were treated in the duvelisib cohort, and 13 in the placebo cohort. OS at 28 days was 67% (95% confidence interval [CI], 38%–88%) compared to 62% (95% CI, 32%–86%) for placebo (P = .544). Sixty-day OS was 60% versus 46%, respectively (hazard ratio, 0.66 [95% CI, .22–1.96]; P = .454). Other secondary outcomes were comparable. Duvelisib was associated with lower inflammatory cytokines.

Conclusions
In this pilot study, duvelisib did not significantly improve 28-day OS compared to placebo for severe COVID-19. Duvelisib appeared safe in this critically ill population and was associated with reduction in cytokines implicated in COVID-19 and acute respiratory distress syndrome, supporting further investigation.

Clinical Trials Registration
NCT04372602.
Beetles and lichens: tracing the origins and evolution of lichenophagy within the darkling beetle tribe Helopini (Coleoptera: Tenebrionidae)
Authors: Ntatsopoulos Konstantinos , Nabozhenko Maxim V , Jelinscaia Lagou Loudmila , Chigray Ivan A , Gagarina Ludmila V , Alpagut Keskin Nurşen , Keskin Bekir , Papadopoulou Anna 
Published: October 2023

Abstract
Although the complex evolutionary history of lichen-forming fungi has gained considerable attention, particularly regarding the long-debated role of these organisms in shaping early terrestrial ecosystems, the evolution of lichenivory and its potential impact on the diversification of lichenophages have been largely neglected. With &gt; 800 described species worldwide and a broad geographical distribution, the tribe Helopini (Coleoptera: Tenebrionidae) represents a diverse, yet poorly studied, group of predominantly lichenophagous beetles. Using a dataset of 52 ingroup taxa and five gene fragments, a first phylogenetic hypothesis of the tribe was generated, which was subsequently used for reconstructing the ancestral state of the trophic and habitat associations of the beetles and for estimating a time frame of diversification. Our phylogenetic reconstruction sheds light on the higher-level systematics of the tribe, supporting the current subtribal division of the group while also providing a framework for understanding the intergeneric relationships within subtribes. The results also indicate an Early Cretaceous origin of the tribe, highlighting the close association between Helopini and lichen-forming fungi since the emergence of the group. Nevertheless, at least seven independent switches from lichenophagy to alternative feeding habits have occurred since the middle Eocene, which can be linked temporally to transitions from forests to open habitats.
Photobacterium obscurum sp. nov., a marine bacterium isolated from the coast of Qingdao
Authors: Hong Wen , Wang Xiaolei , Yuan Yalin , Liu Ronghua , Zhao Wenbin , Xue Chun-Xu , Zhang Xiao-Hua 
Published: October 2023

A Gram-stain-negative, facultative anaerobic, rod-shaped strain, named SDRW27T, was isolated from offshore seawater collected near Qingdao. Strain SDRW27T was able to grow at 16–37 °C (optimum, 28 °C), pH 6.0–9.0 (optimum, pH 6.0) and in the presence of 1–7 % (w/v) NaCl (optimum, 3 %). Phylogenetic analysis using 16S rRNA gene sequences indicated that strain SDRW27T was most closely related to

Photobacterium toruni

H01100410BT (97.89 % sequence similarity),

Photobacterium andalusiense

H01100409BT (97.89 %) and

Photobacterium leiognathi

ATCC 25521T (97.82 %). The predominant fatty acids were summed feature 3 (C16 : 1 ω7c and/or iso-C15 : 0 2-OH), summed feature 8 (C18 : 1
ω7c and/or C18 : 1
ω6c) and C16 : 0. The polar lipids of strain SDRW27T comprised phosphatidylglycerol, phosphatidylinositol dimannoside, phosphatidylcholine, phosphatidylethanolamine and three unidentified lipids. The major respiratory quinone was ubiquinone-8. The G+C content was 47.71 mol%. The genome size was 5.84 Mbp, including 85 contigs with an N50 value of 223 542. The average nucleotide identity (ANI) values of SDRW27T with its three most similar strains,

P. toruni

H01100410BT,

P. andalusiense

H01100409BT and

P. leiognathi

ATCC 25521T, were 71.36, 71.58 and 72.23 %, respectively (all lower than the 95–96 % ANI threshold), and the DNA–DNA hybridization (DDH) values were 20.4, 20.8 and 20.4 % (all lower than the 70 % DDH threshold). The obtained results of polyphasic analysis demonstrate that strain SDRW27T represents a novel species, for which the name Photobacterium obscurum sp. nov. is proposed. The type strain is SDRW27T (=MCCC 1K06286T=KCTC 82892T).
OMEinfo: Global Geographic Metadata for -omics Experiments
Authors: Crown Matthew , Bashton Matthew 
Published: October 2023

AbstractMicrobiome studies increasingly associate geographical features like rurality and climate types with microbiomes. However, microbiologists/bioinformaticians often struggle to access and integrate rich geographical metadata from sources such as GeoTIFFs; and inconsistent definitions of rurality, for example, can hinder cross-study comparisons. To address this, we present OMEinfo, a Python-based tool for automated retrieval of consistent geographical metadata from user-provided location data. OMEinfo leverages open data sources such as the Global Human Settlement Layer, Köppen-Geiger climate classification models, and Open-Data Inventory for Anthropogenic Carbon dioxide, to ensure metadata accuracy and provenance. OMEinfo’s Dash application enables users to visualise their sample metadata on an interactive map and to investigate the spatial distribution of metadata features, which is complemented by data visualisation to analyse patterns and trends in the geographical data before further analysis. The tool is available as a Docker container, providing a portable, lightweight solution for researchers. Through its standardised metadata retrieval approach and incorporation of FAIR and Open data principles, OMEinfo promotes reproducibility and consistency in microbiome metadata. To demonstrate its utility, OMEinfo is utilised to replicate the results of a previous study linking population density to soil sample alpha diversity. As the field continues to explore the relationship between microbiomes and geographical features, tools like OMEinfo will prove vital in developing a robust, accurate, and interconnected understanding of these interactions, whilst having applicability beyond this field to any studies utilising location-based metadata. Finally, we release the OMEinfo annotation dataset, a collection of 5.3 million OMEinfo annotated samples from the ENA, for use in a retrospective analysis of sequencing samples, and highlight a number of ways researchers and sequencing read repositories can improve the quality of underlying metadata submitted to these public stores.AvailabilityOMEinfo is freely available and released under an MIT licence. OMEinfo source code is available athttps://github.com/m-crown/OMEinfo/Contactmatthew.crown@northumbria.ac.uk,matthew.bashton@northumbria.ac.uk
Genotype-specific nonphotochemical quenching responses to nitrogen deficit are linked to chlorophyll a to b ratios
Authors: Sahay Seema , Grzybowski Marcin , Schnable James C. , Głowacka Katarzyna 
Published: October 2023

AbstractNon-photochemical quenching (NPQ) protects plants from photodamage caused by excess light energy. The mechanism of NPQ appears to be conserved across flowering plants. However, substantial variation in NPQ has been reported within different genotypes of the same species grown under the environmental conditions. Individual maize genotypes from a diversity panel exhibited a range of responses to low nitrogen with some genotypes exhibiting increased NPQ between control and low nitrogen conditions and others exhibiting no change. These patterns were consistent for the same genotypes across multiple field seasons. NPQ increases under low nitrogen were correlated with shifts in the ratio of chlorophyllato chlorophyllbconsistent with a decrease in reaction centers. Both photosynthetic capacity and dry biomass accumulation decreased more in maize genotypes which were unable to maintain constant NPQ levels between control and low N conditions. Collectively these results suggest that the ability to maintain sufficient numbers of reaction centers under low nitrogen conditions and avoid dissipating a greater proportion of absorbed light energy via the NPQ pathway may play a key role in increasing carbon fixation and productivity in nitrogen-limited environments.HighlightsSubstantial variation in NPQ kinetics exists in maize on both low and control N.In early and late-vegetative stages a similar portion of genotypes increased, no-change or decreasedNPQmaxin response to low N while in the post-flowering stage substantially more genotypes decreasedNPQmax.In low nitrogen conditions, theNPQmaxstrongly correlates with shifts in Chla/Chlbratios.
Replication stress underlies genomic instability at CTCF/cohesin-binding sites in cancer
Authors: Faseela Elangoli Ebrahimkutty , Notani Dimple , Sabarinathan Radhakrishnan 
Published: October 2023

AbstractCCCTC-binding factor (CTCF) and cohesin play a significant role in the formation of chromatin loops and topologically associating domains (TADs), which influence gene expression and DNA replication. CTCF/cohesin-binding sites (CBSs) present at the loop anchors and TAD boundaries are frequently mutated in cancer; however, the molecular mechanisms underlying this remain unclear. Here, we investigate whether the binding of CTCF/cohesin on DNA imposes constraints on DNA replication, leading to replication stress and genomic instability. Our results reveal that CTCF and cohesin remain bound to DNA during replication (S phase) in cancer cells (HeLa). Further, examination of replication stress through imaging revealed colocalization of DNA damage response proteins (MRE11 and STN1) with CTCF/cohesin in the S phase. In addition, ChIP-seq of the DNA damage response/repair proteins (MRE11, STN1, γH2AX and RAD51) showed high enrichment of these proteins at CBSs (as compared to their immediate flanking regions and control sites) and positively correlated with the binding strength of CTCF/cohesin at CBSs in the S phase. Moreover, analysis of somatic mutations from cancer genomes supports that the enrichment of mutations at CBSs is significantly higher in samples harbouring somatic copy number deletion in MRE11 and STN1 compared to wild-type samples. Together, these results demonstrate that the binding of CTCF/cohesin on the DNA during the S phase causes replication stress and DNA strand breaks, and this could lead to genome instability at CBSs observed in cancer.
The rapid diversification of Boletales is linked to Early Eocene and Mid-Miocene Climatic Optima
Authors: Wu Gang , Wu Kui , Halling Roy E. , Horak Egon , Xu Jianping , Li Guang-Mei , Lee Serena , Pecoraro Lorenzo , Arzu Roberto Flores , Ndolo Ebika Sydney T. , Aouali Souhila , Persiani Anna Maria , Yorou Nourou S. , Xu Xin , Feng Bang , Li Yan-Chun , Yang Zhu-Liang 
Published: October 2023

SUMMARYInvestigating the mechanisms that underpin the diversity and distribution patterns of species is fundamental in ecology and evolution. However, the study of fungi, particularly the ectomycorrhizal group, has been relatively constrained in this field.We conducted a high-resolution phylogenomic analysis of Boletales, an ecologically and economically significant group of fungi, covering 83 genera across 15 families. We subsequently investigated its evolutionary history using sequences at four genes obtained from 984 species across 121 genera within 15 families.The findings unveiled that Boletales likely originated in Early Jurassic and underwent two remarkable episodes of rapid diversification, commencing in early Eocene (∼54 Mya) and early Miocene (∼17 Mya) epochs. The notable surges were predominantly driven by ectomycorrhizal clades, with a specific emphasis on East Asia and North America. These expansions were strongly correlated with the warm-humid paleoclimates during the Early Eocene Climatic Optimum and Mid-Miocene Climatic Optimum, as well as the rapid expansion of Fagales and Pinaceae hosts.This study provides novel insights into the spatiotemporal evolution of fungi, highlighting the synergistic impact of abiotic factors, such as warm and humid paleoclimates, and the biotic factor of rapid diversification of host plants on the fungal diversification.
Identification of CD44 as a key mediator of cell traction force generation in hyaluronic acid-rich extracellular matrices
Authors: Cheung Brian C. H. , Chen Xingyu , Davis Hannah J. , Nordmann Cassidy S. , Toth Joshua , Hodgson Louis , Segall Jeffrey E. , Shenoy Vivek B. , Wu Mingming 
Published: October 2023

AbstractMechanical properties of the extracellular matrix (ECM) critically regulate a number of important cell functions including growth, differentiation and migration. Type I collagen and glycosaminoglycans (GAGs) are two primary components of ECMs that contribute to mammalian tissue mechanics, with the collagen fiber network sustaining tension, and GAGs withstanding compression. The architecture and stiffness of the collagen network are known to be important for cell-ECM mechanical interactions via integrin cell surface adhesion receptors. In contrast, studies of GAGs in modulating cell-ECM interactions are limited. Here, we present experimental studies on the roles of hyaluronic acid (HA, an unsulfated GAG) in single tumor cell traction force generation using a recently developed 3D cell traction force microscopy method. Our work reveals that CD44, a cell surface adhesion receptor to HA, is engaged in cell traction force generation in conjunction with β1-integrin. We find that HA significantly modifies the architecture and mechanics of the collagen fiber network, decreasing tumor cells’ propensity to remodel the collagen network, attenuating traction force generation, transmission distance, and tumor invasion. Our findings point to a novel role for CD44 in traction force generation, which can be a potential therapeutic target for diseases involving HA rich ECMs such as breast cancer and glioblastoma.
TRILL: Orchestrating Modular Deep-Learning Workflows for Democratized, Scalable Protein Analysis and Engineering
Authors: Martinez Zachary A , Murray Richard M. , Thomson Matt W. 
Published: October 2023

AbstractDeep-learning models have been rapidly adopted by many fields, partly due to the deluge of data humanity has amassed. In particular, the petabases of biological sequencing data enable the unsupervised training of protein language models that learn the “language of life.” However, due to their prohibitive size and complexity, contemporary deep-learning models are often unwieldy, especially for scientists with limited machine learning backgrounds. TRILL (TRaining andInference using theLanguage ofLife) is a platform for creative protein design and discovery. Leveraging several state-of-the-art models such as ESM-2, DiffDock, and RFDiffusion, TRILL allows researchers to generate novel proteins, predict 3-D structures, extract high-dimensional representations of proteins, functionally classify proteins and more. What sets TRILL apart is its ability to enable complex pipelines by chaining together models and effectively merging the capabilities of different models to achieve a sum greater than its individual parts. Whether using Google Colab with one GPU or a supercomputer with hundreds, TRILL allows scientists to effectively utilize models with millions to billions of parameters by using optimized training strategies such as ZeRO-Offload and distributed data parallel. Therefore, TRILL not only bridges the gap between complex deep-learning models and their practical application in the field of biology, but also simplifies the orchestration of these models into comprehensive workflows, democratizing access to powerful methods. Documentation:https://trill.readthedocs.io/en/latest/home.html.
Allosteric Modulation of YAP/TAZ-TEAD Interaction by Palmitoylation and Small Molecule Inhibitors
Authors: Mills Kira R. , Misra Jyoti , Torabifard Hedieh 
Published: October 2023

AbstractThe Hippo signaling pathway is a highly conserved signaling network that plays a central role in regulating cellular growth, proliferation, and organ size. This pathway consists of a kinase cascade that integrates various upstream signals to control the activation or inactivation of YAP/TAZ proteins. Phosphorylated YAP/TAZ is sequestered in the cytoplasm; however, when the Hippo pathway is deactivated, they translocate into the nucleus, where they associate with TEAD transcription factors. This partnership is instrumental in regulating the transcription of pro-growth and anti-apoptotic genes. Thus, in many cancers, aberrantly hyperactivated YAP/TAZ promotes oncogenesis by contributing to cancer cell proliferation, metastasis, and therapy resistance. Because YAP and TAZ exert their oncogenic effects by binding with TEAD, it is critical to understand this key interaction to develop cancer therapeutics. Previous research has indicated that TEAD undergoes an auto-palmitoylation at a conserved cysteine, and small molecules that inhibit TEAD palmitoylation disrupt effective YAP/TAZ binding. However, how exactly palmitoylation contributes to YAP/TAZ-TEAD interactions and how the TEAD palmitoylation inhibitors disrupt this interaction remains unknown. Utilizing molecular dynamics simulations, our investigation not only provides a detailed atomistic insight into the YAP/TAZ-TEAD dynamics but also unveils that the inhibitor studied influences YAP and TAZ binding to TEAD in distinct manners. This discovery holds significant implications for the design and deployment of future molecular interventions targeting this interaction.
Individual canopy tree species maps for the National Ecological Observatory Network
Authors: Weinstein Ben. G. , Marconi Sergio , Zare Alina , Bohlman Stephanie A. , Singh Aditya , Graves Sarah J. , Magee Lukas , Johnson Daniel J. , Record Sydne , Rubio Vanessa E. , Swenson Nathan G. , Townsend Philip , Veblen Thomas T. , Andrus Robert A. , White Ethan P. 
Published: October 2023

AbstractThe ecology of forest ecosystems depends on the composition of trees. Capturing fine-grained information on individual trees at broad scales provides a unique perspective on forest ecosystems, forest restoration and responses to disturbance. Individual tree data at wide extents promises to increase the scale of forest analysis, biogeographic research, and ecosystem monitoring without losing details on individual species composition and abundance. Computer vision using deep neural networks can convert raw sensor data into predictions of individual canopy tree species through labeled data collected by field researchers. Using over 40,000 individual tree stems as training data, we create landscape-level species predictions for over 100 million individual trees across 24 sites in the National Ecological Observatory Network. Using hierarchical multi-temporal models fine-tuned for each geographic area, we produce open-source data available as 1 km2shapefiles with individual tree species prediction, as well as crown location, crown area and height of 81 canopy tree species. Site-specific models had an average performance of 79% accuracy covering an average of six species per site, ranging from 3 to 15 species per site. All predictions are openly archived and have been uploaded to Google Earth Engine to benefit the ecology community and overlay with other remote sensing assets. We outline the potential utility and limitations of these data in ecology and computer vision research, as well as strategies for improving predictions using targeted data sampling.
The biochemical impact of extracting an embedded adenylate kinase domain using circular permutation
Authors: Coleman Tom , Shin John , Silberg Jonathan J. , Shamoo Yousif , Atkinson Joshua T. 
Published: October 2023

ABSTRACTAdenylate kinases (AKs) are phosphotransferases that are frequently employed as models to investigate protein structure-function relationships. Prior studies have shown that AK homologs of different stabilities retain cellular activity in cells following circular permutation that split the AMP binding domain into fragments coded at different ends of the primary structure, such that this domain was no longer embedded as a continuous polypeptide within the core domain. Herein, we show mesophilic and thermophilic AKs having this topological restructuring retain activity and substrate-binding characteristics of the parental AK. While permutation decreased the activity of both AK homologs at physiological temperatures, the catalytic activity of the thermophilic AK increased upon permutation when assayed >30°C below the melting temperature of the native AK. The thermostabilities of the permuted AKs were uniformly lower than native AKs, and they exhibited multi-phasic unfolding transitions, unlike the native AKs, which presented cooperative thermal unfolding. In addition, proteolytic digestion revealed that permutation destabilized each AK, and mass spectrometry suggested that the new termini within the AMP binding domain were responsible for the increased proteolysis sensitivity. These findings illustrate how changes in contact order can be used to tune enzyme activity and alter folding dynamics in multidomain enzymes.Graphical abstract