bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct pulmonary and systemic effects of dexamethasone in severe COVID-19
Authors: Neyton Lucile P. A. , Patel Ravi K. , Sarma Aartik ,   UCSF COMET Consortium, Ansel K. Mark , Christenson Stephanie , Adkisson Michael , Eckalbar Walter , Maliskova Lenka , Schroeder Andrew , Bueno Raymund , Gordon Gracie , Hartoularos George , Kushnoor Divya , Lee David , McCarthy Elizabeth , Ogorodnikov Anton , Spitzer Matthew , Hiam Kamir , Song Yun S. , Sun Yang , Tumurbaatar Erden , van der Wijst Monique , Whatley Alexander , Jones Chayse , Caldera Saharai , DeVoe Catherine , Serpa Paula Hayakawa , Love Christina , Mick Eran , Phelps Maira , Tsitsiklis Alexandra , Leroux Carolyn , Rashid Sadeed , Rodriguez Nicklaus , Tang Kevin , Altamirano Luz Torres , Leligdowicz Aleksandra , Matthay Michael , Wilson Michael , Ye Jimmie , Chak Suzanna , Ghale Rajani , Jauregui Alejandra , Lee Deanna , Nguyen Viet , Sigman Austin , Kangelaris Kirsten N. , Asthana Saurabh , Collins Zachary , Patel Ravi , Rao Arjun , Samad Bushra , Shaw Cole , Lea Tasha , Ward Alyssa , Jones Norman , Milush Jeff , Chan Vincent , Chew Nayvin , Combes Alexis , Courau Tristan , Hu Kenneth , Huang Billy , Kumar Nitasha , Mahboob Salman , Muñoz-Sandoval Priscila , Parada Randy , Reeder Gabriella , Shen Alan , Tsui Jessica , Zha Shoshana , Zhu Wandi S. , Willmore Andrew , Haller Sidney C. , Kangelaris Kirsten N. , Eckalbar Walter L. , Erle David J. , Krummel Matthew F. , Hendrickson Carolyn M. , Woodruff Prescott G. , Langelier Charles R. , Calfee Carolyn S. , Fragiadakis Gabriela K. 
Published: July 2024

AbstractDexamethasone is the standard of care for critically ill patients with COVID-19, but the mechanisms by which it decreases mortality and its immunological effects in this setting are not understood. Here we perform bulk and single-cell RNA sequencing of samples from the lower respiratory tract and blood, and assess plasma cytokine profiling to study the effects of dexamethasone on both systemic and pulmonary immune cell compartments. In blood samples, dexamethasone is associated with decreased expression of genes associated with T cell activation, including TNFSFR4 and IL21R. We also identify decreased expression of several immune pathways, including major histocompatibility complex-II signaling, selectin P ligand signaling, and T cell recruitment by intercellular adhesion molecule and integrin activation, suggesting these are potential mechanisms of the therapeutic benefit of steroids in COVID-19. We identify additional compartment- and cell- specific differences in the effect of dexamethasone that are reproducible in publicly available datasets, including steroid-resistant interferon pathway expression in the respiratory tract, which may be additional therapeutic targets. In summary, we demonstrate compartment-specific effects of dexamethasone in critically ill COVID-19 patients, providing mechanistic insights with potential therapeutic relevance. Our results highlight the importance of studying compartmentalized inflammation in critically ill patients.
Nickel-catalyzed asymmetric hydrogenation for the preparation of α-substituted propionic acids
Authors: Li Bowen , Wang Zhiling , Luo Yicong , Wei Hanlin , Chen Jianzhong , Liu Delong , Zhang Wanbin 
Published: July 2024

AbstractTransition metal-catalyzed asymmetric hydrogenation is one of the most efficient methods for the preparation of chiral α-substituted propionic acids. However, research on this method, employing cleaner earth-abundant metal catalysts, is still insufficient in both academic and industrial contexts. Herein, we report an efficient nickel-catalyzed asymmetric hydrogenation of α-substituted acrylic acids affording the corresponding chiral α-substituted propionic acids with up to 99.4% ee (enantiomeric excess) and 10,000 S/C (substrate/catalyst). In particular, this method can be used to obtain (R)-dihydroartemisinic acid with 99.8:0.2 dr (diastereomeric ratio) and 5000 S/C, which is an essential intermediate for the preparation of the antimalarial drug Artemisinin. The reaction mechanism has been investigated via experiments and DFT (Density Functional Theory) calculations, which indicate that the protonolysis of the C-Ni bond of the key intermediate via an intramolecular proton transfer from the carboxylic acid group of the substrate, is the rate-determining step.
Epigenetic alterations affecting hematopoietic regulatory networks as drivers of mixed myeloid/lymphoid leukemia
Authors: Mulet-Lazaro Roger , van Herk Stanley , Nuetzel Margit , Sijs-Szabo Aniko , Díaz Noelia , Kelly Katherine , Erpelinck-Verschueren Claudia , Schwarzfischer-Pfeilschifter Lucia , Stanewsky Hanna , Ackermann Ute , Glatz Dagmar , Raithel Johanna , Fischer Alexander , Pohl Sandra , Rijneveld Anita , Vaquerizas Juan M. , Thiede Christian , Plass Christoph , Wouters Bas J. , Delwel Ruud , Rehli Michael , Gebhard Claudia 
Published: July 2024

AbstractLeukemias with ambiguous lineage comprise several loosely defined entities, often without a clear mechanistic basis. Here, we extensively profile the epigenome and transcriptome of a subgroup of such leukemias with CpG Island Methylator Phenotype. These leukemias exhibit comparable hybrid myeloid/lymphoid epigenetic landscapes, yet heterogeneous genetic alterations, suggesting they are defined by their shared epigenetic profile rather than common genetic lesions. Gene expression enrichment reveals similarity with early T-cell precursor acute lymphoblastic leukemia and a lymphoid progenitor cell of origin. In line with this, integration of differential DNA methylation and gene expression shows widespread silencing of myeloid transcription factors. Moreover, binding sites for hematopoietic transcription factors, including CEBPA, SPI1 and LEF1, are uniquely inaccessible in these leukemias. Hypermethylation also results in loss of CTCF binding, accompanied by changes in chromatin interactions involving key transcription factors. In conclusion, epigenetic dysregulation, and not genetic lesions, explains the mixed phenotype of this group of leukemias with ambiguous lineage. The data collected here constitute a useful and comprehensive epigenomic reference for subsequent studies of acute myeloid leukemias, T-cell acute lymphoblastic leukemias and mixed-phenotype leukemias.
Designing highly efficient interlocking interactions in anisotropic active particles
Authors: Riedel Solenn , Hoffmann Ludwig A. , Giomi Luca , Kraft Daniela J. 
Published: July 2024

AbstractCluster formation of microscopic swimmers is key to the formation of biofilms and colonies, efficient motion and nutrient uptake, but, in the absence of other interactions, requires high swimmer concentrations to occur. Here we experimentally and numerically show that cluster formation can be dramatically enhanced by an anisotropic swimmer shape. We analyze a class of model microswimmers with a shape that can be continuously tuned from spherical to bent and straight rods. In all cases, clustering can be described by Michaelis-Menten kinetics governed by a single scaling parameter that depends on particle density and shape only. We rationalize these shape-dependent dynamics from the interplay between interlocking probability and cluster stability. The bent rod shape promotes assembly in an interlocking fashion even at vanishingly low particle densities and we identify the most efficient shape to be a semicircle. Our work provides key insights into how shape can be used to rationally design out-of-equilibrium self-organization, key to creating active functional materials and processes that require two-component assembly with high fidelity.
Humid heat environment causes anxiety-like disorder via impairing gut microbiota and bile acid metabolism in mice
Authors: Weng Huandi , Deng Li , Wang Tianyuan , Xu Huachong , Wu Jialin , Zhou Qinji , Yu Lingtai , Chen Boli , Huang Li’an , Qu Yibo , Zhou Libing , Chen Xiaoyin 
Published: July 2024

AbstractClimate and environmental changes threaten human mental health, but the impacts of specific environmental conditions on neuropsychiatric disorders remain largely unclear. Here, we show the impact of a humid heat environment on the brain and the gut microbiota using a conditioned housing male mouse model. We demonstrate that a humid heat environment can cause anxiety-like behaviour in male mice. Microbial 16 S rRNA sequencing analysis reveals that a humid heat environment caused gut microbiota dysbiosis (e.g., decreased abundance of Lactobacillus murinus), and metabolomics reveals an increase in serum levels of secondary bile acids (e.g., lithocholic acid). Moreover, increased neuroinflammation is indicated by the elevated expression of proinflammatory cytokines in the serum and cortex, activated PI3K/AKT/NF-κB signalling and a microglial response in the cortex. Strikingly, transplantation of the microbiota from mice reared in a humid heat environment readily recapitulates these abnormalities in germ-free mice, and these abnormalities are markedly reversed by Lactobacillus murinus administration. Human samples collected during the humid heat season also show a decrease in Lactobacillus murinus abundance and an increase in the serum lithocholic acid concentration. In conclusion, gut microbiota dysbiosis induced by a humid heat environment drives the progression of anxiety disorders by impairing bile acid metabolism and enhancing neuroinflammation, and probiotic administration is a potential therapeutic strategy for these disorders.
Directional integration and pathway enrichment analysis for multi-omics data
Authors: Slobodyanyuk Mykhaylo , Bahcheli Alexander T. , Klein Zoe P. , Bayati Masroor , Strug Lisa J. , Reimand Jüri 
Published: July 2024

AbstractOmics techniques generate comprehensive profiles of biomolecules in cells and tissues. However, a holistic understanding of underlying systems requires joint analyses of multiple data modalities. We present DPM, a data fusion method for integrating omics datasets using directionality and significance estimates of genes, transcripts, or proteins. DPM allows users to define how the input datasets are expected to interact directionally given the experimental design or biological relationships between the datasets. DPM prioritises genes and pathways that change consistently across the datasets and penalises those with inconsistent directionality. To demonstrate our approach, we characterise gene and pathway regulation inIDH-mutant gliomas by jointly analysing transcriptomic, proteomic, and DNA methylation datasets. Directional integration of survival information in ovarian cancer reveals candidate biomarkers with consistent prognostic signals in transcript and protein expression. DPM is a general and adaptable framework for gene prioritisation and pathway analysis in multi-omics datasets.
Engineered cytosine base editor enabling broad-scope and high-fidelity gene editing in Streptomyces
Authors: Wang Jian , Wang Ke , Deng Zhe , Zhong Zhiyu , Sun Guo , Mei Qing , Zhou Fuling , Deng Zixin , Sun Yuhui 
Published: July 2024

AbstractBase editing (BE) faces protospacer adjacent motif (PAM) constraints and off-target effects in both eukaryotes and prokaryotes. For Streptomyces, renowned as one of the most prolific bacterial producers of antibiotics, the challenges are more pronounced due to its diverse genomic content and high GC content. Here, we develop a base editor named eSCBE3-NG-Hypa, tailored with both high efficiency and -fidelity for Streptomyces. Of note, eSCBE3-NG-Hypa recognizes NG PAM and exhibits high activity at challenging sites with high GC content or GC motifs, while displaying minimal off-target effects. To illustrate its practicability, we employ eSCBE3-NG-Hypa to achieve precise key amino acid conversion of the dehydratase (DH) domains within the modular polyketide synthase (PKS) responsible for the insecticide avermectins biosynthesis, achieving domains inactivation. The resulting DH-inactivated mutants, while ceasing avermectins production, produce a high yield of oligomycin, indicating competitive relationships among multiple biosynthetic gene clusters (BGCs) in Streptomyces avermitilis. Leveraging this insight, we use eSCBE3-NG-Hypa to introduce premature stop codons into competitor gene cluster of ave in an industrial S. avermitilis, with the mutant Δolm exhibiting the highest 4.45-fold increase in avermectin B1a compared to the control. This work provides a potent tool for modifying biosynthetic pathways and advancing metabolic engineering in Streptomyces.
Hematopoietic stem and progenitor cell membrane-coated vesicles for bone marrow-targeted leukaemia drug delivery
Authors: Li Jinxin , Wu Honghui , Yu Zebin , Wang Qiwei , Zeng Xin , Qian Wenchang , Lu Siqi , Jiang Lingli , Li Jingyi , Zhu Meng , Han Yingli , Gao Jianqing , Qian Pengxu 
Published: July 2024

AbstractLeukemia is a kind of hematological malignancy originating from bone marrow, which provides essential signals for initiation, progression, and recurrence of leukemia. However, how to specifically deliver drugs to the bone marrow remains elusive. Here, we develop biomimetic vesicles by infusing hematopoietic stem and progenitor cell (HSPC) membrane with liposomes (HSPC liposomes), which migrate to the bone marrow of leukemic mice via hyaluronic acid-CD44 axis. Moreover, the biomimetic vesicles exhibit superior binding affinity to leukemia cells through intercellular cell adhesion molecule-1 (ICAM-1)/integrin β2 (ITGB2) interaction. Further experiments validate that the vesicles carrying chemotherapy drug cytarabine (Ara-C@HSPC-Lipo) markedly inhibit proliferation, induce apoptosis and differentiation of leukemia cells, and decrease number of leukemia stem cells. Mechanically, RNA-seq reveals that Ara-C@HSPC-Lipo treatment induces apoptosis and differentiation and inhibits the oncogenic pathways. Finally, we verify that HSPC liposomes are safe in mice. This study provides a method for targeting bone marrow and treating leukemia.
Stable and efficient CsPbI3 quantum-dot light-emitting diodes with strong quantum confinement
Authors: Li Yanming , Deng Ming , Zhang Xuanyu , Xu Ting , Wang Ximeng , Yao Zhiwei , Wang Qiangqiang , Qian Lei , Xiang Chaoyu 
Published: July 2024

AbstractEven though lead halide perovskite has been demonstrated as a promising optoelectronic material for next-generation display applications, achieving high-efficiency and stable pure-red (620~635 nm) emission to cover the full visible wavelength is still challenging. Here, we report perovskite light-emitting diodes emitting pure-red light at 628 nm achieving high external quantum efficiencies of 26.04%. The performance is attributed to successful synthesizing strongly confined CsPbI3 quantum dots with good stability. The strong binding 2-naphthalene sulfonic acid ligands are introduced after nucleation to suppress Ostwald ripening, meanwhile, ammonium hexafluorophosphate exchanges long chain ligands and avoids regrowth by strong binding during the purification process. Both ligands enhance the charge transport ability of CsPbI3 quantum dots. The state-of-the-art synthesis of pure red CsPbI3 quantum dots achieves 94% high quantum efficiency, which can maintain over 80% after 50 days, providing a method for synthesizing stable strong confined perovskite quantum dots.
Molecular and supramolecular adaptation by coupled stimuli
Authors: Dünnebacke Torsten , Niemeyer Niklas , Baumert Sebastian , Hochstädt Sebastian , Borsdorf Lorenz , Hansen Michael Ryan , Neugebauer Johannes , Fernández Gustavo 
Published: July 2024

AbstractAdaptation transcends scale in both natural and artificial systems, but delineating the causative factors of this phenomenon requires urgent clarification. Herein, we unravel the molecular requirements for adaptation and establish a link to rationalize adaptive behavior on a self-assembled level. These concepts are established by analyzing a model compound exhibiting both light- and pH-responsive units, which enable the combined or independent application of different stimuli. On a molecular level, adaptation arises from coupled stimuli, as the final outcome of the system depends on their sequence of application. However, in a self-assembled state, a single stimulus suffices to induce adaptation as a result of collective molecular behavior and the reversibility of non-covalent interactions. Our findings go beyond state-of-the-art (multi)stimuli-responsive systems and allow us to draw up design guidelines for adaptive behavior both at the molecular and supramolecular levels, which are fundamental criteria for the realization of intelligent matter.
Pedestrians' safety using projected time-to-collision to electric scooters
Authors: Jafari Alireza , Liu Yen-Chen 
Published: July 2024

AbstractSafety concern among electric scooter riders drives them onto sidewalks, endangering pedestrians and making them uncomfortable. Regulators’ solutions are inconsistent and conflicting worldwide. Widely accepted pedestrian safety metrics may lead to converging solutions. Adapting the time-to-collision from car traffic safety, we define projected time-to-collision and experimentally study pedestrians’ objective and subjective safety. We design isolated and crowd experiments using e-scooter-to-pedestrian interactions to assess the impact of various factors on objective safety. In addition, we conducted a pedestrian survey to relate the subjective safety and the metric. We report a strong correlation between subjective safety and the projected time-to-collision when agents face each other and no relation when the e-scooter overtakes a pedestrian. As a near-miss metric correlated with pedestrian comfort, projected time-to-collision is implementable in policy-making, urban architecture, and e-scooter design to enhance pedestrian safety.
Genetic diversity, determinants, and dissemination of Burkholderia pseudomallei lineages implicated in melioidosis in Northeast Thailand
Authors: Seng Rathanin , Chomkatekaew Chalita , Tandhavanant Sarunporn , Saiprom Natnaree , Phunpang Rungnapa , Thaipadungpanit Janjira , Batty Elizabeth M. , Day Nicholas P. J. , Chantratita Wasun , West T. Eoin , Thomson Nicholas R. , Parkhill Julian , Chewapreecha Claire , Chantratita Narisara 
Published: July 2024

AbstractMelioidosis is an often-fatal neglected tropical disease caused by an environmental bacterium Burkholderia pseudomallei. However, our understanding of the disease-causing bacterial lineages, their dissemination, and adaptive mechanisms remains limited. To address this, we conduct a comprehensive genomic analysis of 1,391 B. pseudomallei isolates collected from nine hospitals in northeast Thailand between 2015 and 2018, and contemporaneous isolates from neighbouring countries, representing the most densely sampled collection to date. Our study identifies three dominant lineages, each with unique gene sets potentially enhancing bacterial fitness in the environment. We find that recombination drives lineage-specific gene flow. Transcriptome analyses of representative clinical isolates from each dominant lineage reveal increased expression of lineage-specific genes under environmental conditions in two out of three lineages. This underscores the potential importance of environmental persistence for these dominant lineages. The study also highlights the influence of environmental factors such as terrain slope, altitude, and river direction on the geographical dispersal of B. pseudomallei. Collectively, our findings suggest that environmental persistence may play a role in facilitating the spread of B. pseudomallei, and as a prerequisite for exposure and infection, thereby providing useful insights for informing melioidosis prevention and control strategies.
Dataset for quantum-mechanical exploration of conformers and solvent effects in large drug-like molecules
Authors: Medrano Sandonas Leonardo , Van Rompaey Dries , Fallani Alessio , Hilfiker Mathias , Hahn David , Perez-Benito Laura , Verhoeven Jonas , Tresadern Gary , Kurt Wegner Joerg , Ceulemans Hugo , Tkatchenko Alexandre 
Published: July 2024

AbstractWe here introduce the Aquamarine (AQM) dataset, an extensive quantum-mechanical (QM) dataset that contains the structural and electronic information of 59,783 low-and high-energy conformers of 1,653 molecules with a total number of atoms ranging from 2 to 92 (mean: 50.9), and containing up to 54 (mean: 28.2) non-hydrogen atoms. To gain insights into the solvent effects as well as collective dispersion interactions for drug-like molecules, we have performed QM calculations supplemented with a treatment of many-body dispersion (MBD) interactions of structures and properties in the gas phase and implicit water. Thus, AQM contains over 40 global and local physicochemical properties (including ground-state and response properties) per conformer computed at the tightly converged PBE0+MBD level of theory for gas-phase molecules, whereas PBE0+MBD with the modified Poisson-Boltzmann (MPB) model of water was used for solvated molecules. By addressing both molecule-solvent and dispersion interactions, AQM dataset can serve as a challenging benchmark for state-of-the-art machine learning methods for property modeling and de novo generation of large (solvated) molecules with pharmaceutical and biological relevance.
A comprehensive city-level final energy consumption dataset including renewable energy for China, 2005–2021
Authors: Yang Guanglei , Zhang Guoxing , Cao Dongqin , Gao Xiulin , Wang Xiaojuan , Yang Shaowen , Jiang Pansong , Zha Donglan , Shan Yuli 
Published: July 2024

AbstractThe role of China is increasingly pivotal in climate change mitigation, and the formulation of energy conservation and emission reduction policies requires city-level information. The effectiveness of national policy implementation is contingent upon the support and involvement of local governments. Accurate data on final energy consumption is vital to formulate and implement city-level energy transitions and energy conservation and emission reduction policies. However, there is a dearth of data sources pertaining to China’s city-level final energy consumption. To address these gaps, we developed computational modeling techniques along with top-down and downscaling methods to estimate China’s city-level final energy consumption. In this way, we compiled a final energy consumption inventory for 331 Chinese cities from 2005 to 2021, covering seven economic sectors, 30 fossil fuels, and four clean power sources. Moreover, we discussed the validity of the estimation results from multiple perspectives to enhance estimation accuracy. This dataset can be utilized for analysis in various cutting-edge research fields such as energy transition dynamics, transition risk management strategies, and policy formulation processes.