bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of nirmatrelvir/ritonavir in children and adolescents aged 12–17 years following SARS-CoV-2 Omicron infection: A target trial emulation
Authors: Wong Carlos K. H. , Lau Kristy T. K. , Au Ivan C. H. , Chan Sophelia H. S. , Lau Eric H. Y. , Cowling Benjamin J. , Leung Gabriel M. 
Published: June 2024

AbstractCurrently there is a lack of randomized trial data examining the use of the antiviral nirmatrelvir/ritonavir in paediatric patients with SARS-CoV-2 infection. This target trial emulation study aims to address this gap by evaluating the use of nirmatrelvir/ritonavir in non-hospitalized paediatric patients aged 12–17 years with SARS-CoV-2 Omicron variant infection. Among paediatric patients diagnosed between 16th March 2022 and 5th February 2023, exposure was defined as outpatient nirmatrelvir/ritonavir treatment within 5 days of symptom onset or COVID-19 diagnosis. Primary outcome was 28 day all-cause mortality or all-cause hospitalization, while secondary outcomes were 28 day in-hospital disease progression, 28 day COVID-19-specific hospitalization, multisystem inflammatory syndrome in children (MIS-C), acute liver injury, acute renal failure, and acute respiratory distress syndrome. Overall, 49,378 eligible paediatric patients were included. Nirmatrelvir/ritonavir treatment was associated with reduced 28 day all-cause hospitalization (absolute risk reduction = 0.23%, 95%CI = 0.19%–0.31%; relative risk = 0.66, 95%CI = 0.56–0.71). No events of mortality, in-hospital disease progression, or adverse clinical outcomes were observed among nirmatrelvir/ritonavir users. The findings confirmed the effectiveness of nirmatrelvir/ritonavir in reducing all-cause hospitalization risk among non-hospitalized pediatric patients with SARS-CoV-2 Omicron variant infection.
The Legionella collagen-like protein employs a distinct binding mechanism for the recognition of host glycosaminoglycans
Authors: Rehman Saima , Antonovic Anna Katarina , McIntire Ian E. , Zheng Huaixin , Cleaver Leanne , Baczynska Maria , Adams Carlton O. , Portlock Theo , Richardson Katherine , Shaw Rosie , Oregioni Alain , Mastroianni Giulia , Whittaker Sara B-M. , Kelly Geoff , Lorenz Christian D. , Fornili Arianna , Cianciotto Nicholas P. , Garnett James A. 
Published: June 2024

AbstractBacterial adhesion is a fundamental process which enables colonisation of niche environments and is key for infection. However, in Legionella pneumophila, the causative agent of Legionnaires’ disease, these processes are not well understood. The Legionella collagen-like protein (Lcl) is an extracellular peripheral membrane protein that recognises sulphated glycosaminoglycans on the surface of eukaryotic cells, but also stimulates bacterial aggregation in response to divalent cations. Here we report the crystal structure of the Lcl C-terminal domain (Lcl-CTD) and present a model for intact Lcl. Our data reveal that Lcl-CTD forms an unusual trimer arrangement with a positively charged external surface and negatively charged solvent exposed internal cavity. Through molecular dynamics simulations, we show how the glycosaminoglycan chondroitin-4-sulphate associates with the Lcl-CTD surface via distinct binding modes. Our findings show that Lcl homologs are present across both the Pseudomonadota and Fibrobacterota-Chlorobiota-Bacteroidota phyla and suggest that Lcl may represent a versatile carbohydrate-binding mechanism.
Emergent digital bio-computation through spatial diffusion and engineered bacteria
Authors: Fedorec Alex J. H. , Treloar Neythen J. , Wen Ke Yan , Dekker Linda , Ong Qing Hsuan , Jurkeviciute Gabija , Lyu Enbo , Rutter Jack W. , Zhang Kathleen J. Y. , Rosa Luca , Zaikin Alexey , Barnes Chris P. 
Published: June 2024

AbstractBiological computing is a promising field with potential applications in biosafety, environmental monitoring, and personalized medicine. Here we present work on the design of bacterial computers using spatial patterning to process information in the form of diffusible morphogen-like signals. We demonstrate, mathematically and experimentally, that single, modular, colonies can perform simple digital logic, and that complex functions can be built by combining multiple colonies, removing the need for further genetic engineering. We extend our experimental system to incorporate sender colonies as morphogen sources, demonstrating how one might integrate different biochemical inputs. Our approach will open up ways to perform biological computation, with applications in bioengineering, biomaterials and biosensing. Ultimately, these computational bacterial communities will help us explore information processing in natural biological systems.
Waning-and-waxing shape changes in ionic nanoplates upon cation exchange
Authors: Li Zhanzhao , Saruyama Masaki , Asaka Toru , Teranishi Toshiharu 
Published: June 2024

AbstractFlexible control of the composition and morphology of nanocrystals (NCs) over a wide range is an essential technology for the creation of functional nanomaterials. Cation exchange (CE) is a facile method by which to finely tune the compositions of ionic NCs, providing an opportunity to obtain complex nanostructures that are difficult to form using conventional chemical synthesis procedures. However, due to their robust anion frameworks, CE cannot typically be used to modify the original morphology of the host NCs. In this study, we report an anisotropic morphological transformation of Cu1.8S NCs during CE. Upon partial CE of Cu1.8S nanoplates (NPLs) with Mn2+, the hexagonal NPLs are transformed into crescent-shaped Cu1.8S–MnS NPLs. Upon further CE, these crescent-shaped NPLs evolve back into completely hexagonal MnS NPLs. Comprehensive characterization of the intermediates reveals that this waxing-and-waning shape-evolution process is due to dissolution, redeposition, and intraparticle migration of Cu+ and S2−. Furthermore, in addition to Mn2+, this CE-induced transformation process occurs with Zn2+, Cd2+ and Fe3+. This finding presents a strategy by which to create heterostructured NCs with various morphologies and compositions under mild conditions.
LDL receptor in alphavirus entry: structural analysis and implications for antiviral therapy
Authors: Wang Ningning , Merits Andres , Veit Michael , Lello Laura Sandra , Kong Shuhan , Jiao Houqi , Chen Jie , Wang Yu , Dobrikov Georgi , Rey Félix A. , Su Shuo 
Published: June 2024

AbstractVarious low-density lipoprotein receptors (LPRs) have been identified as entry factors for alphaviruses, and structures of the corresponding virion-receptor complexes have been determined. Here, we analyze the similarities and differences in the receptor binding modes of multiple alphaviruses to understand their ability to infect a wide range of hosts. We further discuss the challenges associated with the development of broad-spectrum treatment strategies against a diverse range of alphaviruses.
DOS-3 mediates cell-non-autonomous DAF-16/FOXO activity in antagonizing age-related loss of C. elegans germline stem/progenitor cells
Authors: Zhang Zhifei , Yang Haiyan , Fang Lei , Zhao Guangrong , Xiang Jun , Zheng Jialin C. , Qin Zhao 
Published: June 2024

AbstractAge-related depletion of stem cells causes tissue degeneration and failure to tissue regeneration, driving aging at the organismal level. Previously we reported a cell-non-autonomous DAF-16/FOXO activity in antagonizing the age-related loss of germline stem/progenitor cells (GSPCs) in C. elegans, indicating that regulation of stem cell aging occurs at the organ system level. Here we discover the molecular effector that links the cell-non-autonomous DAF-16/FOXO activity to GSPC maintenance over time by performing a tissue-specific DAF-16/FOXO transcriptome analysis. Our data show that dos-3, which encodes a non-canonical Notch ligand, is a direct transcriptional target of DAF-16/FOXO and mediates the effect of the cell-non-autonomous DAF-16/FOXO activity on GSPC maintenance through activating Notch signaling in the germ line. Importantly, expression of a human homologous protein can functionally substitute for DOS-3 in this scenario. As Notch signaling controls the specification of many tissue stem cells, similar mechanisms may exist in other aging stem cell systems.
Artificial cellulosic leaf with adjustable enzymatic CO2 sequestration capability
Authors: Zhu Xing , Du Chenxi , Gao Bo , He Bin 
Published: June 2024

AbstractDeveloping artificial leaves to address the environmental burden of CO2 is pivotal for advancing our Net Zero Future. In this study, we introduce EcoLeaf, an artificial leaf that closely mimics the characteristics of natural leaves. It harnesses visible light as its sole energy source and orchestrates the controlled expansion and contraction of stomata and the exchange of petiole materials to govern the rate of CO2 sequestration from the atmosphere. Furthermore, EcoLeaf has a cellulose composition and mechanical strength similar to those of natural leaves, allowing it to seamlessly integrate into the ecosystem during use and participate in natural degradation and nutrient cycling processes at the end of its life. We propose that the carbon sequestration pathway within EcoLeaf is adaptable and can serve as a versatile biomimetic platform for diverse biogenic carbon sequestration pathways in the future.
Development of deaminase-free T-to-S base editor and C-to-G base editor by engineered human uracil DNA glycosylase
Authors: Tong Huawei , Wang Haoqiang , Wang Xuchen , Liu Nana , Li Guoling , Wu Danni , Li Yun , Jin Ming , Li Hengbin , Wei Yinghui , Li Tong , Yuan Yuan , Shi Linyu , Yao Xuan , Zhou Yingsi , Yang Hui 
Published: June 2024

AbstractDNA base editors enable direct editing of adenine (A), cytosine (C), or guanine (G), but there is no base editor for direct thymine (T) editing currently. Here we develop two deaminase-free glycosylase-based base editors for direct T editing (gTBE) and C editing (gCBE) by fusing Cas9 nickase (nCas9) with engineered human uracil DNA glycosylase (UNG) variants. By several rounds of structure-informed rational mutagenesis on UNG in cultured human cells, we obtain gTBE and gCBE with high activity of T-to-S (i.e., T-to-C or T-to-G) and C-to-G conversions, respectively. Furthermore, we conduct parallel comparison of gTBE/gCBE with those recently developed using other protein engineering strategies, and find gTBE/gCBE show the outperformance. Thus, we provide several base editors, gTBEs and gCBEs, with corresponding engineered UNG variants, broadening the targeting scope of base editors.
SOD3 suppresses early cellular immune responses to parasite infection
Authors: Li Qilong , Lv Kunying , Jiang Ning , Liu Tong , Hou Nan , Yu Liying , Yang Yixin , Feng Anni , Zhang Yiwei , Su Ziwei , Sang Xiaoyu , Feng Ying , Chen Ran , Xu Wenyue , Cui Liwang , Cao Yaming , Chen Qijun 
Published: June 2024

AbstractHost immune responses are tightly controlled by various immune factors during infection, and protozoan parasites also manipulate the immune system to evade surveillance, leading to an evolutionary arms race in host‒pathogen interactions; however, the underlying mechanisms are not fully understood. We observed that the level of superoxide dismutase 3 (SOD3) was significantly elevated in both Plasmodium falciparum malaria patients and mice infected with four parasite species. SOD3-deficient mice had a substantially longer survival time and lower parasitemia than control mice after infection, whereas SOD3-overexpressing mice were much more vulnerable to parasite infection. We revealed that SOD3, secreted from activated neutrophils, bound to T cells, suppressed the interleukin-2 expression and concomitant interferon-gamma responses crucial for parasite clearance. Overall, our findings expose active fronts in the arms race between the parasites and host immune system and provide insights into the roles of SOD3 in shaping host innate immune responses to parasite infection.
Solvent engineering for scalable fabrication of perovskite/silicon tandem solar cells in air
Authors: Zheng Xuntian , Kong Wenchi , Wen Jin , Hong Jiajia , Luo Haowen , Xia Rui , Huang Zilong , Luo Xin , Liu Zhou , Li Hongjiang , Sun Hongfei , Wang Yurui , Liu Chenshuaiyu , Wu Pu , Gao Han , Li Manya , Bui Anh Dinh , Mo Yi , Zhang Xueling , Yang Guangtao , Chen Yifeng , Feng Zhiqiang , Nguyen Hieu T. , Lin Renxing , Li Ludong , Gao Jifan , Tan Hairen 
Published: June 2024

AbstractPerovskite/silicon tandem solar cells hold great promise for realizing high power conversion efficiency at low cost. However, achieving scalable fabrication of wide-bandgap perovskite (~1.68 eV) in air, without the protective environment of an inert atmosphere, remains challenging due to moisture-induced degradation of perovskite films. Herein, this study reveals that the extent of moisture interference is significantly influenced by the properties of solvent. We further demonstrate that n-Butanol (nBA), with its low polarity and moderate volatilization rate, not only mitigates the detrimental effects of moisture in air during scalable fabrication but also enhances the uniformity of perovskite films. This approach enables us to achieve an impressive efficiency of 29.4% (certified 28.7%) for double-sided textured perovskite/silicon tandem cells featuring large-size pyramids (2–3 μm) and 26.3% over an aperture area of 16 cm2. This advance provides a route for large-scale production of perovskite/silicon tandem solar cells, marking a significant stride toward their commercial viability.
Pure estrogen receptor antagonists potentiate capecitabine activity in ESR1-mutant breast cancer
Authors: Grinshpun Albert , Russo Douglas , Ma Wen , Verma Ana , Hermida-Prado Francisco , Sherman Shira , Gaglia Giorgio , Kabraji Sheheryar , Kirkner Gregory , Hughes Melissa E. , Lin Nancy U. , Sandusky Zachary , Nardone Agostina , Guarducci Cristina , Nguyen Quang-De , Santagata Sandro , Nagy Zsuzsanna , Jeselsohn Rinath 
Published: June 2024

AbstractThe ESR1 ligand binding domain activating mutations are the most prevalent genetic mechanism of acquired endocrine resistance in metastatic hormone receptor-positive breast cancer. These mutations confer endocrine resistance that remains estrogen receptor (ER) dependent. We hypothesized that in the presence of the ER mutations, continued ER blockade with endocrine therapies that target mutant ER is essential for tumor suppression even with chemotherapy treatment. Here, we conducted comprehensive pre-clinical in vitro and in vivo experiments testing the efficacy of adding fulvestrant to fluorouracil (5FU) and the 5FU pro-drug, capecitabine, in models of wild-type (WT) and mutant ER. Our findings revealed that while this combination had an additive effect in the presence of WT-ER, in the presence of the Y537S ER mutation there was synergy. Notably, these effects were not seen with the combination of 5FU and selective estrogen receptor modulators, such as tamoxifen, or in the absence of intact P53. Likewise, in a patient-derived xenograft (PDX) harboring a Y537S ER mutation the addition of fulvestrant to capecitabine potentiated tumor suppression. Moreover, multiplex immunofluorescence revealed that this effect was due to decreased cell proliferation in all cells expressing ER and was not dependent on the degree of ER expression. Taken together, these results support the clinical investigation of the combination of ER antagonists with capecitabine in patients with metastatic hormone receptor-positive breast cancer who have experienced progression on endocrine therapy and targeted therapies, particularly in the presence of an ESR1 activating mutation.
Ocular perfusion pressure is not reduced in response to lower body negative pressure
Authors: Hall Eric A. , Whittle Richard S. , Diaz-Artiles Ana 
Published: June 2024

AbstractLower body negative pressure (LBNP) has been proposed as a countermeasure to mitigate the cephalad fluid shift occurring during spaceflight, which may be associated with the development of Spaceflight Associated Neuro-ocular Syndrome (SANS). This study quantifies the effect of LBNP on intraocular pressure (IOP), mean arterial pressure at eye level (MAPeye), and ocular perfusion pressure (OPP). Twenty-four subjects (12 male, 12 female) were subjected to graded LBNP in 0° supine and 15° head-down tilt (HDT) postures from 0 mmHg to –50 mmHg in 10 mmHg increments. IOP decreased significantly with LBNP pressure in 0° supine (by 0.7 ± 0.09 mmHg per 10 mmHg LBNP pressure,p < 0.001) and in 15° HDT (by 1.0 ± 0.095 mmHg per 10 mmHg of LBNP pressure,p < 0.001). MAPeyesignificantly decreased by 0.9 ± 0.4 mmHg per 10 mmHg of LBNP pressure in 0° supine (p = 0.016) but did not significantly change with LBNP in 15° HDT (p = 0.895). OPP did not significantly change with LBNP in 0° supine (p = 0.539) but it significantly increased in 15° HDT at 1.0 ± 0.3 mmHg per 10 mmHg of LBNP pressure (p = 0.010). Sex did not have a significant effect on OPP, MAPeye, or IOP in any condition. In 15° HDT, the reduction in IOP during increasing negative pressure, combined with the relatively constant MAPeye, led to the increase in OPP. Furthermore, results suggest that LBNP, while effective in reducing IOP, is not effective in reducing OPP across all postures investigated.
Differential long-term bivalent HPV vaccine cross-protection by variants in the Costa Rica HPV vaccine trial
Authors: Shing Jaimie Z. , Porras Carolina , Pinheiro Maísa , Herrero Rolando , Hildesheim Allan , Liu Danping , Gail Mitchell H. , Romero Byron , Schiller John T. , Zúñiga Michael , Mishra Sambit , Burdette Laurie , Jones Kristine , Schussler John , Ocampo Rebeca , Fang Jianwen , Liu Zhiwei , Lowy Douglas R. , Tsang Sabrina H. , Rodríguez Ana Cecilia , Schiffman Mark , Haas Cameron B. , Carvajal Loretto J. , Brown Jalen R. , Kreimer Aimée R. , Mirabello Lisa ,   Costa Rica HPV Vaccine Trial (CVT) Group, Cortés Bernal , González Paula , Herrero Rolando , Jiménez Silvia E. , Porras Carolina , Rodríguez Ana Cecilia , Hildesheim Allan , Kreimer Aimée R. , Lowy Douglas R. , Schiffman Mark , Schiller John T. , Sherman Mark , Wacholder Sholom , Pinto Ligia A. , Kemp Troy J. , Sidawy Mary K. , Quint Wim , van Doorn Leen-Jan , Struijk Linda , Palefsky Joel M. , Darragh Teresa M. , Stoler Mark H. 
Published: June 2024

AbstractThe AS04-adjuvanted human papillomavirus (HPV)16/18 vaccine, an L1-based vaccine, provides strong vaccine efficacy (VE) against vaccine-targeted type infections, and partial cross-protection to phylogenetically-related types, which may be affected by variant-level heterogeneity. We compared VE against incident HPV31, 33, 35, and 45 detections between lineages and SNPs in the L1 region among 2846 HPV-vaccinated and 5465 HPV-unvaccinated women through 11-years of follow-up in the Costa Rica HPV Vaccine Trial. VE was lower against HPV31-lineage-B (VE=60.7%;95%CI = 23.4%,82.8%) compared to HPV31-lineage-A (VE=94.3%;95%CI = 83.7%,100.0%) (VE-ratio = 0.64;95%CI = 0.25,0.90). Differential VE was observed at several lineage-associated HPV31-L1-SNPs, including a nonsynonymous substitution at position 6372 on the FG-loop, an important neutralization domain. For HPV35, the only SNP-level difference was at position 5939 on the DE-loop, with significant VE against nucleotide-G (VE=65.0%;95%CI = 28.0,87.8) but not for more the common nucleotide-A (VE=7.4%;95%CI = −34.1,36.7). Because of the known heterogeneity in precancer/cancer risk across cross-protected HPV genotype variants by race and region, our results of differential variant-level AS04-adjuvanted HPV16/18 vaccine efficacy has global health implications.
A Clinical Bacterial Dataset for Deep Learning in Microbiological Rapid On-Site Evaluation
Authors: Wang Xiuli , Shi Yinghan , Guo Shasha , Qu Xuzhong , Xie Fei , Duan Zhimei , Hu Ye , Fu Han , Shi Xin , Quan Tingwei , Wang Kaifei , Xie Lixin 
Published: June 2024

AbstractMicrobiological Rapid On-Site Evaluation (M-ROSE) is based on smear staining and microscopic observation, providing critical references for the diagnosis and treatment of pulmonary infectious disease. Automatic identification of pathogens is the key to improving the quality and speed of M-ROSE. Recent advancements in deep learning have yielded numerous identification algorithms and datasets. However, most studies focus on artificially cultured bacteria and lack clinical data and algorithms. Therefore, we collected Gram-stained bacteria images from lower respiratory tract specimens of patients with lung infections in Chinese PLA General Hospital obtained by M-ROSE from 2018 to 2022 and desensitized images to produce 1705 images (4,912 × 3,684 pixels). A total of 4,833 cocci and 6,991 bacilli were manually labelled and differentiated into negative and positive. In addition, we applied the detection and segmentation networks for benchmark testing. Data and benchmark algorithms we provided that may benefit the study of automated bacterial identification in clinical specimens.
DustSCAN: A Five Year (2018-2022) Hourly Dataset of Dust Plumes From SEVIRI
Authors: AlNasser Faisal , Entekhabi Dara 
Published: June 2024

AbstractAirborne mineral dust significantly impacts air quality, human health, and the global climate. Due to sparse ground sensors, particularly in source regions, dust monitoring relies mainly on remote sensing through Aerosol Optical Depth (AOD) retrievals from polar-orbiting satellite optical instruments. These are valuable but lack the temporal resolution for precise plume tracking and source characterization. We introduce DustSCAN, a five-year, hourly dust plume dataset derived from the Spinning Enhanced Visible and InfraRed Imager (SEVIRI) images on geostationary-orbit Meteosat satellites. Using multi-channel infrared images, we detect atmospheric dust and track hourly dust-affected pixels. These are clustered into discrete plumes using the Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm. DustSCAN includes 9950 discrete plumes over 2018-2022 across the Sahara, the Arabian Desert, and Western and Central Asia. It complements existing resources and provides a framework for detailed analysis of dust sources, trajectories, and impacts. Its distinctive event-based and spatio-temporal detail offers an advancement in unraveling the complexities of dust storm dynamics.
A multivariate process quality correlation diagnosis method based on grouping technique
Authors: Niu Qing , Cheng Shujie , Qiu Zeyang 
Published: June 2024

AbstractCorrelation diagnosis in multivariate process quality management is an important and challenging issue. In this paper, a new diagnostic method based on quality component grouping is proposed. Firstly, three theorems describing the properties of the covariance matrix of multivariate process quality are established based on the statistical viewpoint of product quality, to prove the correlation decomposition theorem, which decomposes the correlation of all the quality components into a series of correlations of components pairs, and then by using the factor analysis method, all quality components are grouped in order to maximize the correlations in the same groups and minimize the ones between different groups. Finally, on the basis of correlations between different groups are ignored, T2 control charts of component pairs in the same groups are established to form the diagnostic model. Theoretical analysis and practice prove that for the multivariate process quality whose the correlations between different components vary considerably, the grouping technique enables the size of the correlation diagnostic model to be drastically reduced, thus allowing the proposed method can be used as a generalized theoretical model for the correlation diagnosis.