bluuebunny/crossref_metadata_2025_split huggingface dataset:
A knowledge-enabled approach for user experience-driven product improvement at the conceptual design stage
Authors: Li Jun , Guo Xin , Zhang Kai , Zhao Wu 
Published: August 2023

Abstract
Improving existing products plays a vital role in enhancing customer satisfaction and coping with changes in the market. Analyzing user experience (UX) to find the deficiencies of existing products and establishing improved schemes is the key to UX-driven product improvement, especially at the conceptual design stage. Although some tools used in conceptual design, such as requirements analysis and knowledge reasoning, have advanced recently, they lack targeted goals and sufficient efficiency in identifying insufficient product attributes and improving existing functions and structures. The challenge lies in considering the influence imposed on design activities by the original product features (including attributes, functions, and structure). In this study, a knowledge-enabled approach and framework that integrates the conceptual design process, online reviews for UX, and knowledge is proposed to support product improvement. Specifically, a decision-making algorithm based on UX analysis is proposed to identify to-be-improved product attributes. Then, through optimizing the previous knowledge application model from knowledge requirement transformation, knowledge modeling, and knowledge reasoning, a smart knowledge reasoning model is established to push knowledge for functional solving of the to-be-improved attributes. A knowledge configuration method is used to modify product features to generate an improved scheme. To demonstrate the feasibility of the proposed approach, a case study of improving an agricultural sprayer is conducted. Through discussion, this study can help to regulate design activities for product improvement, enhance data and knowledge application, and promote divergent thinking during scheme modification.
Transboundary Rainfall Estimation Using Commercial Microwave Links
Authors: Blettner Nico , Fencl Martin , Bareš Vojtěch , Kunstmann Harald , Chwala Christian 
Published: August 2023

AbstractUnlike actual rainfall, the spatial extent of rainfall maps is often determined by administrative and political boundaries. Similarly, data from commercial microwave links (CMLs) is usually acquired on a national basis and exchange among countries is limited. Up to now, this has prohibited the generation of transboundary CML‐based rainfall maps despite the great extension of networks across the world. We present CML based transboundary rainfall maps for the first time, using independent CML data sets from Germany and the Czech Republic. We show that straightforward algorithms used for quality control strongly reduce anomalies in the results. We find that, after quality control, CML‐based rainfall maps can be generated via joint and consistent processing, and that these maps allow to seamlessly visualize rainfall events traversing the German‐Czech border. This demonstrates that quality control represents a crucial step for large‐scale (e.g., continental) CML‐based rainfall estimation.
Renaissance for magnetotactic bacteria in astrobiology
Authors: Shen Jianxun , Paterson Greig A , Wang Yinzhao , Kirschvink Joseph L , Pan Yongxin , Lin Wei 
Published: August 2023

Abstract
Capable of forming magnetofossils similar to some magnetite nanocrystals observed in the Martian meteorite ALH84001, magnetotactic bacteria (MTB) once occupied a special position in the field of astrobiology during the 1990s and 2000s. This flourish of interest in putative Martian magnetofossils faded from all but the experts studying magnetosome formation, based on claims that abiotic processes could produce magnetosome-like magnetite crystals. Recently, the rapid growth in our knowledge of the extreme environments in which MTB thrive and their phylogenic heritage, leads us to advocate for a renaissance of MTB in astrobiology. In recent decades, magnetotactic members have been discovered alive in natural extreme environments with wide ranges of salinity (up to 90 g L−1), pH (1–10), and temperature (0–70 °C). Additionally, some MTB populations are found to be able to survive irradiated, desiccated, metal-rich, hypomagnetic, or microgravity conditions, and are capable of utilizing simple inorganic compounds such as sulfate and nitrate. Moreover, MTB likely emerged quite early in Earth’s history, coinciding with a period when the Martian surface was covered with liquid water as well as a strong magnetic field. MTB are commonly discovered in suboxic or oxic-anoxic interfaces in aquatic environments or sediments similar to ancient crater lakes on Mars, such as Gale crater and Jezero crater. Taken together, MTB can be exemplary model microorganisms in astrobiology research, and putative ancient Martian life, if it ever occurred, could plausibly have included magnetotactic microorganisms. Furthermore, we summarize multiple typical biosignatures that can be applied for the detection of ancient MTB on Earth and extraterrestrial MTB-like life. We suggest transporting MTB to space stations and simulation chambers to further investigate their tolerance potential and distinctive biosignatures to aid in understanding the evolutionary history of MTB and the potential of magnetofossils as an extraterrestrial biomarker.
TRIM26 inhibited osteosarcoma progression through destabilizing RACK1 and thus inactivation of MEK/ERK signaling
Authors: Xia Kezhou , Zheng Di , Wei Zhun , Liu Wenda , Guo Weichun 
Published: August 2023

AbstractOsteosarcoma is a highly aggressive malignant tumor that is common in the pediatric population and has a high rate of disability and mortality. Recent studies have suggested that the tripartite motif-containing family genes (TRIMs) play critical roles in oncogenesis in several cancers. TRIM26, one of the TRIMs family genes, was more frequently reported to exert a tumor-suppressive role, while its detailed functional roles in the osteosarcoma progression were still unknown and require further investigation. Herein, we found that TRIM26 was markedly downregulated in osteosarcoma tissues and cells. Survival analysis revealed that higher expression of TRIM26 was associated with better prognosis and its expression was an independent protective factor in osteosarcoma. Functional analysis demonstrated that overexpression of TRIM26 inhibited osteosarcoma cell proliferation and invasion via inhibiting the EMT process and MEK/ERK signaling. In contrast, the silence of TRIM26 caused the opposite effect. RACK1, a member of the Trp-Asp repeat protein family, was identified as a novel target of TRIM26. TRIM26 could interact with RACK1 and accelerate the degradation of RACK1, thus inactivation of MEK/ERK signaling. Overexpression of RACK1 could attenuate the inhibitory effect of TRIM26 overexpression on p-MEK1/2 and p-ERK1/2, and silence of RACK1 could partly impair the effect of TRIM26 knockdown-induced upregulation of p-MEK1/2 and p-ERK1/2. Further, a series of gain- and loss-of-function experiments showed that decreased malignant behaviors including cell proliferation and invasion in TRIM26-upregulated cells were reversed when RACK1 was overexpressed, whereas RACK1 knockdown diminished the increased malignant phenotypes in TRIM26-silenced osteosarcoma cells. In conclusion, our study indicated that TRIM26 inhibited osteosarcoma progression via promoting proteasomal degradation of RACK1, thereby resulting in inactivation of MEK/ERK signaling, and impeding the EMT process.
MenT nucleotidyltransferase toxins extend tRNA acceptor stems and can be inhibited by asymmetrical antitoxin binding
Authors: Xu Xibing , Usher Ben , Gutierrez Claude , Barriot Roland , Arrowsmith Tom J. , Han Xue , Redder Peter , Neyrolles Olivier , Blower Tim R. , Genevaux Pierre 
Published: August 2023

AbstractMycobacterium tuberculosis, the bacterium responsible for human tuberculosis, has a genome encoding a remarkably high number of toxin-antitoxin systems of largely unknown function. We have recently shown that the M. tuberculosis genome encodes four of a widespread, MenAT family of nucleotidyltransferase toxin-antitoxin systems. In this study we characterize MenAT1, using tRNA sequencing to demonstrate MenT1 tRNA modification activity. MenT1 activity is blocked by MenA1, a short protein antitoxin unrelated to the MenA3 kinase. X-ray crystallographic analysis shows blockage of the conserved MenT fold by asymmetric binding of MenA1 across two MenT1 protomers, forming a heterotrimeric toxin-antitoxin complex. Finally, we also demonstrate tRNA modification by toxin MenT4, indicating conserved activity across the MenT family. Our study highlights variation in tRNA target preferences by MenT toxins, selective use of nucleotide substrates, and diverse modes of MenA antitoxin activity.
Single-cell genomics improves the discovery of risk variants and genes of atrial fibrillation
Authors: Selewa Alan , Luo Kaixuan , Wasney Michael , Smith Linsin , Sun Xiaotong , Tang Chenwei , Eckart Heather , Moskowitz Ivan P. , Basu Anindita , He Xin , Pott Sebastian 
Published: August 2023

AbstractGenome-wide association studies (GWAS) have linked hundreds of loci to cardiac diseases. However, in most loci the causal variants and their target genes remain unknown. We developed a combined experimental and analytical approach that integrates single cell epigenomics with GWAS to prioritize risk variants and genes. We profiled accessible chromatin in single cells obtained from human hearts and leveraged the data to study genetics of Atrial Fibrillation (AF), the most common cardiac arrhythmia. Enrichment analysis of AF risk variants using cell-type-resolved open chromatin regions (OCRs) implicated cardiomyocytes as the main mediator of AF risk. We then performed statistical fine-mapping, leveraging the information in OCRs, and identified putative causal variants in 122 AF-associated loci. Taking advantage of the fine-mapping results, our novel statistical procedure for gene discovery prioritized 46 high-confidence risk genes, highlighting transcription factors and signal transduction pathways important for heart development. In summary, our analysis provides a comprehensive map of AF risk variants and genes, and a general framework to integrate single-cell genomics with genetic studies of complex traits.
Combinatorial expression of neurexins and LAR-type phosphotyrosine phosphatase receptors instructs assembly of a cerebellar circuit
Authors: Sclip Alessandra , Südhof Thomas C. 
Published: August 2023

AbstractSynaptic adhesion molecules (SAMs) shape the structural and functional properties of synapses and thereby control the information processing power of neural circuits. SAMs are broadly expressed in the brain, suggesting that they may instruct synapse formation and specification via a combinatorial logic. Here, we generate sextuple conditional knockout mice targeting all members of the two major families of presynaptic SAMs, Neurexins and leukocyte common antigen-related-type receptor phospho-tyrosine phosphatases (LAR-PTPRs), which together account for the majority of known trans-synaptic complexes. Using synapses formed by cerebellar Purkinje cells onto deep cerebellar nuclei as a model system, we confirm that Neurexins and LAR-PTPRs themselves are not essential for synapse assembly. The combinatorial deletion of both neurexins and LAR-PTPRs, however, decreases Purkinje-cell synapses on deep cerebellar nuclei, the major output pathway of cerebellar circuits. Consistent with this finding, combined but not separate deletions of neurexins and LAR-PTPRs impair motor behaviors. Thus, Neurexins and LAR-PTPRs are together required for the assembly of a functional cerebellar circuit.
A deep learning method for replicate-based analysis of chromosome conformation contacts using Siamese neural networks
Authors: Al-jibury Ediem , King James W. D. , Guo Ya , Lenhard Boris , Fisher Amanda G. , Merkenschlager Matthias , Rueckert Daniel 
Published: August 2023

AbstractThe organisation of the genome in nuclear space is an important frontier of biology. Chromosome conformation capture methods such as Hi-C and Micro-C produce genome-wide chromatin contact maps that provide rich data containing quantitative and qualitative information about genome architecture. Most conventional approaches to genome-wide chromosome conformation capture data are limited to the analysis of pre-defined features, and may therefore miss important biological information. One constraint is that biologically important features can be masked by high levels of technical noise in the data. Here we introduce a replicate-based method for deep learning from chromatin conformation contact maps. Using a Siamese network configuration our approach learns to distinguish technical noise from biological variation and outperforms image similarity metrics across a range of biological systems. The features extracted from Hi-C maps after perturbation of cohesin and CTCF reflect the distinct biological functions of cohesin and CTCF in the formation of domains and boundaries, respectively. The learnt distance metrics are biologically meaningful, as they mirror the density of cohesin and CTCF binding. These properties make our method a powerful tool for the exploration of chromosome conformation capture data, such as Hi-C capture Hi-C, and Micro-C.
Gabapentinoid consumption in 65 countries and regions from 2008 to 2018: a longitudinal trend study
Authors: Chan Adrienne Y. L. , Yuen Andrew S. C. , Tsai Daniel H. T. , Lau Wallis C. Y. , Jani Yogini H. , Hsia Yingfen , Osborn David P. J. , Hayes Joseph F. , Besag Frank M. C. , Lai Edward C. C. , Wei Li , Taxis Katja , Wong Ian C. K. , Man Kenneth K. C. 
Published: August 2023

AbstractRecent studies raised concerns about the increasing use of gabapentinoids in different countries. With their potential for misuse and addiction, understanding the global consumption of gabapentinoids will offer us a platform to examine the need for any interventional policies. This longitudinal trend study utilised pharmaceutical sales data from 65 countries and regions across the world to evaluate the global trends in gabapentinoid consumption between 2008-2018. The multinational average annual percentage change of gabapentinoid consumption was +17.20%, increased from 4.17 defined daily dose per ten thousand inhabitants per day (DDD/TID) in 2008 to 18.26 DDD/TID in 2018. High-income countries had the highest pooled gabapentinoid consumption rate (39.92 DDD/TID) in 2018, which was more than six times higher than the lower-middle income countries (6.11 DDD/TID). The study shows that despite differences in healthcare system and culture, a consistent increase in gabapentinoid consumption is observed worldwide, with high-income countries remaining the largest consumers.
Randomized, double-blind, placebo-controlled trial of rapamycin in amyotrophic lateral sclerosis
Authors: Mandrioli Jessica , D’Amico Roberto , Zucchi Elisabetta , De Biasi Sara , Banchelli Federico , Martinelli Ilaria , Simonini Cecilia , Lo Tartaro Domenico , Vicini Roberto , Fini Nicola , Gianferrari Giulia , Pinti Marcello , Lunetta Christian , Gerardi Francesca , Tarlarini Claudia , Mazzini Letizia , De Marchi Fabiola , Scognamiglio Ada , Sorarù Gianni , Fortuna Andrea , Lauria Giuseppe , Bella Eleonora Dalla , Caponnetto Claudia , Meo Giuseppe , Chio Adriano , Calvo Andrea , Cossarizza Andrea 
Published: August 2023

AbstractIn preclinical studies rapamycin was found to target neuroinflammation, by expanding regulatory T cells, and affecting autophagy, two pillars of amyotrophic lateral sclerosis (ALS) pathogenesis. Herein we report a multicenter, randomized, double-blind trial, in 63 ALS patients who were randomly assigned in a 1:1:1 ratio to receive rapamycin 2 mg/m2/day,1 mg/m2/day or placebo (EUDRACT 2016-002399-28; NCT03359538). The primary outcome, the number of patients exhibiting an increase >30% in regulatory T cells from baseline to treatment end, was not attained. Secondary outcomes were changes from baseline of T, B, NK cell subpopulations, inflammasome mRNA expression and activation status, S6-ribosomal protein phosphorylation, neurofilaments; clinical outcome measures of disease progression; survival; safety and quality of life. Of the secondary outcomes, rapamycin decreased mRNA relative expression of the pro-inflammatory cytokine IL-18, reduced plasmatic IL-18 protein, and increased the percentage of classical monocytes and memory switched B cells, although no corrections were applied for multiple tests. In conclusion, we show that rapamycin treatment is well tolerated and provides reassuring safety findings in ALS patients, but further trials are necessary to understand the biological and clinical effects of this drug in ALS.
Genomic analysis and clinical correlations of non-small cell lung cancer brain metastasis
Authors: Skakodub Anna , Walch Henry , Tringale Kathryn R. , Eichholz Jordan , Imber Brandon S. , Vasudevan Harish N. , Li Bob T. , Moss Nelson S. , Hei Yu Kenny Kwok , Mueller Boris A. , Powell Simon , Razavi Pedram , Yu Helena A. , Reis-Filho Jorge S. , Gomez Daniel , Schultz Nikolaus , Pike Luke R. G. 
Published: August 2023

AbstractUp to 50% of patients with non-small cell lung cancer (NSCLC) develop brain metastasis (BM), yet the study of BM genomics has been limited by tissue access, incomplete clinical data, and a lack of comparison with paired extracranial specimens. Here we report a cohort of 233 patients with resected and sequenced (MSK-IMPACT) NSCLC BM and comprehensive clinical data. With matched samples (47 primary tumor, 42 extracranial metastatic), we show CDKN2A/B deletions and cell cycle pathway alterations to be enriched in the BM samples. Meaningful clinico-genomic correlations are noted, namely EGFR alterations in leptomeningeal disease (LMD) and MYC amplifications in multifocal regional brain progression. Patients who developed early LMD frequently have had uncommon, multiple, and persistently detectable EGFR driver mutations. The distinct mutational patterns identified in BM specimens compared to other tissue sites suggest specific biologic underpinnings of intracranial progression.
A critical role of a eubiotic microbiota in gating proper immunocompetence in Arabidopsis
Authors: Paasch Bradley C. , Sohrabi Reza , Kremer James M. , Nomura Kinya , Cheng Yu Ti , Martz Jennifer , Kvitko Brian , Tiedje James M. , He Sheng Yang 
Published: August 2023

AbstractAlthough many studies have shown that microbes can ectopically stimulate or suppress plant immune responses, the fundamental question of whether the entire preexisting microbiota is indeed required for proper development of plant immune response remains unanswered. Using a recently developed peat-based gnotobiotic plant growth system, we found that Arabidopsis grown in the absence of a natural microbiota lacked age-dependent maturation of plant immune response and were defective in several aspects of pattern-triggered immunity. Axenic plants exhibited hypersusceptibility to infection by the bacterial pathogen Pseudomonas syringae pv. tomato DC3000 and the fungal pathogen Botrytis cinerea. Microbiota-mediated immunocompetence was suppressed by rich nutrient conditions, indicating a tripartite interaction between the host, microbiota and abiotic environment. A synthetic microbiota composed of 48 culturable bacterial strains from the leaf endosphere of healthy Arabidopsis plants was able to substantially restore immunocompetence similar to plants inoculated with a soil-derived community. In contrast, a 52-member dysbiotic synthetic leaf microbiota overstimulated the immune transcriptome. Together, these results provide evidence for a causal role of a eubiotic microbiota in gating proper immunocompetence and age-dependent immunity in plants.
Unconventional room-temperature carriers in the triangular-lattice Mott insulator TbInO3
Authors: Jung Taek Sun , Xu Xianghan , Kim Jaewook , Kim Beom Hyun , Shin Hyun Jun , Choi Young Jai , Moon Eun-Gook , Cheong Sang-Wook , Kim Jae Hoon 
Published: August 2023

AbstractThe strong correlations between electrons in Mott insulator materials may produce highly entangled many-body states with unconventional emergent excitations. The signatures of such excitations, if any, are commonly believed to be observable only at low temperatures. Here, we challenge this common belief and show using terahertz time-domain spectroscopy that exotic carriers exist even at room temperature in TbInO3, a candidate material for realizing a low-temperature quantum spin-liquid phase. In particular, over the entire temperature range of 1.5–300 K, we observe a quadratic frequency dependence in the real part of the in-plane optical conductivity as well as Fano asymmetry of an optical phonon mode strongly interacting with the excitation continuum. These features are robust even under external magnetic fields of up to 7 T. Our data confirm the presence of emergent charge carriers within the Mott charge gap of TbInO3, suggesting that it is possible to probe and manipulate highly entangled quantum many-body states at room temperature.
Alignment of spatial genomics data using deep Gaussian processes
Authors: Jones Andrew , Townes F. William , Li Didong , Engelhardt Barbara E. 
Published: August 2023

AbstractSpatially resolved genomic technologies have allowed us to study the physical organization of cells and tissues, and promise an understanding of local interactions between cells. However, it remains difficult to precisely align spatial observations across slices, samples, scales, individuals and technologies. Here, we propose a probabilistic model that aligns spatially-resolved samples onto a known or unknown common coordinate system (CCS) with respect to phenotypic readouts (for example, gene expression). Our method, Gaussian Process Spatial Alignment (GPSA), consists of a two-layer Gaussian process: the first layer maps observed samples’ spatial locations onto a CCS, and the second layer maps from the CCS to the observed readouts. Our approach enables complex downstream spatially aware analyses that are impossible or inaccurate with unaligned data, including an analysis of variance, creation of a dense three-dimensional (3D) atlas from sparse two-dimensional (2D) slices or association tests across data modalities.
Distortion of Mendelian segregation across the Angus cattle genome uncovering regions affecting reproduction
Authors: Id-Lahoucine S. , Casellas J. , Lu D. , Sargolzaei M. , Miller S. , Cánovas A. 
Published: August 2023

AbstractNowadays, the availability of genotyped trios (sire-dam-offspring) in the livestock industry enables the implementation of the transmission ratio distortion (TRD) approach to discover deleterious alleles in the genome. Various biological mechanisms at different stages of the reproductive cycle such as gametogenesis, embryo development and postnatal viability can induce signals of TRD (i.e., deviation from Mendelian inheritance expectations). In this study, TRD was evaluated using both SNP-by-SNP and sliding windows of 2-, 4-, 7-, 10- and 20-SNP across 92,942 autosomal SNPs for 258,140 genotyped Angus cattle including 7,486 sires, 72,688 dams and 205,966 offspring. Transmission ratio distortion was characterized using allelic (specific- and unspecific-parent TRD) and genotypic parameterizations (additive- and dominance-TRD). Across the Angus autosomal chromosomes, 851 regions were clearly found with decisive evidence for TRD. Among these findings, 19 haplotypes with recessive patterns (potential lethality for homozygote individuals) and 52 regions with allelic patterns exhibiting complete or quasi-complete absence for homozygous individuals in addition to under-representation (potentially reduced viability) of the carrier (heterozygous) offspring were found. In addition, 64 (12) and 20 (4) regions showed significant influence on the trait heifer pregnancy at p-value < 0.05 (after chromosome-wise false discovery rate) and 0.01, respectively, reducing the pregnancy rate up to 15%, thus, supporting the biological importance of TRD phenomenon in reproduction.