bluuebunny/crossref_metadata_2025_split huggingface dataset:
A One Health approach metagenomic study on the antimicrobial resistance traits of canine saliva
Authors: Tóth Adrienn Gréta , Tóth Darinka Lilla , Remport Laura , Tóth Imre , Németh Tibor , Dubecz Attila , Patai Árpád V. , Makrai László , Solymosi Norbert 
Published: January 2024

ABSTRACTAccording to the One Health concept, physical proximity among pets and their owners facilitates the spread of various bacteria. Interspecies bacterial transfer media include canine saliva that can be transmitted by licking and biting. Antimicrobial resistance genes (ARGs) are the natural constituents of the bacterial genome. However, human activity can increase the prominence of ARGs. To assess factors that may affect the resistome of the canine oral cavity, the shotgun metagenomic sequencing dataset of 1830 canine saliva samples was bioinformatically analyzed and supplemented with survey results of the physical and behavioral traits of the dogs. Bacteriome and resistome associated with the canine saliva samples were described throughout the analysis. Moreover, the subset of higher public health ARGs and ESKAPE pathogen-related (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) higher public health ARGs were also collected. Further on, the set and subsets of ARGs were studied considering the surveyed traits of the sampled dogs. Overall, 318 ARG types reached sufficiently high detection rates. These ARGs can affect 31 antibiotic drug classes by various resistance mechanisms. ARGs against tetracyclines and cephalosporins appeared in the highest number of samples. However, surprisingly, another CIA group, peptides were represented by ARGs in the third-highest number of samples. Considering further ARG appearance rates in the samples, Critically Important Antimicrobials (CIAs, WHO), such as aminoglycosides, fluoroquinolones, or macrolides, were among the most frequently affected drug classes by higher public health risk ARGs and ESKAPE pathogen related higher public health risk ARGs. Bacteria in the saliva of white and diluted (merle, gray) color dogs and dogs characterized with decreased activity and decreased aggression more often harbored ARGs. Reduced playfulness could have been specifically associated with higher public health risk ARG presence. Even though the oral microbiome of the owners is unknown, One Health and public health implications of the close human-pet bonds and factors potentially underlying the rise in salivary ARG numbers should be considered, mostly in the light of the presence of ARGs affecting critically important drugs for human medicine.
Integrative genomic analysis identifies unique immune environments associated with immunotherapy response in diffuse large B cell lymphoma
Authors: Tumuluru Sravya , Godfrey James K. , Cooper Alan , Yu Jovian , Chen Xiufen , MacNabb Brendan W. , Venkataraman Girish , Zha Yuanyuan , Pelzer Benedikt , Song Joo , Duns Gerben , Sworder Brian J. , Bolen Christopher , Penuel Elicia , Postovalova Ekaterina , Kotlov Nikita , Bagaev Aleksander , Fowler Nathan , Smith Sonali M. , Alizadeh Ash A. , Steidl Christian , Kline Justin 
Published: January 2024

AbstractMost diffuse large B-cell lymphoma (DLBCL) patients treated with bispecific antibodies (BsAb) or chimeric antigen receptor (CAR) T cells fail to achieve durable treatment responses, underscoring the need for a deeper understanding of mechanisms that regulate the immune environment and response to treatment. Here, an integrative, multi-omic approach was employed to characterize DLBCL immune environments, which effectively segregated DLBCLs into four quadrants – termed DLBCL-immune quadrants (IQ) - defined by cell-of-origin and immune-related gene set expression scores. Recurrent genomic alterations were enriched in each IQ, suggesting that lymphoma cell-intrinsic alterations contribute to orchestrating unique DLBCL immune environments. In relapsed/refractory DLBCL patients, DLBCL-IQ assignment correlated significantly with clinical benefit with the CD20 x CD3 BsAb, mosunetuzumab, but not with CD19-directed CAR T cells. DLBCL-IQ provides a new framework to conceptualize the DLBCL immune landscape and uncovers the differential impact of the endogenous immune environment on outcomes to BsAb and CAR T cell treatment.
Chromosome 7 to the rescue: overcoming chromosome 10 loss in gliomas
Authors: Nair Nishanth Ulhas , Schäffer Alejandro A. , Gertz E. Michael , Cheng Kuoyuan , Zerbib Johanna , Sahu Avinash Das , Leor Gil , Shulman Eldad D. , Aldape Kenneth D. , Ben-David Uri , Ruppin Eytan 
Published: January 2024

ABSTRACTThe co-occurrence of chromosome 10 loss and chromosome 7 gain in gliomas is the most frequent loss-gain co-aneuploidy pair in human cancers, a phenomenon that has been investigated without resolution since the late 1980s. Expanding beyond previous gene-centric studies, we investigate the co-occurrence in a genome-wide manner taking an evolutionary perspective. First, by mining large tumor aneuploidy data, we predict that the more likely order is 10 loss followed by 7 gain. Second, by analyzing extensive genomic and transcriptomic data from both patients and cell lines, we find that this co-occurrence can be explained by functional rescue interactions that are highly enriched on 7, which can possibly compensate for any detrimental consequences arising from the loss of 10. Finally, by analyzing transcriptomic data from normal, non-cancerous, human brain tissues, we provide a plausible reason why this co-occurrence happens preferentially in cancers originating in certain regions of the brain.
Takakiapossesses a key marker of embryophyte sporopollenin
Authors: Suh Dae-Yeon , Sraan Damanpreet K , Ashton Neil W 
Published: January 2024

AbstractThe enigmatic moss,Takakia lepidozioides, possesses a particular type III polyketide synthase, ASCL (Anther-Specific Chalcone synthase-Like), that is an identifying marker for genuine sporopollenin in the walls of embryophyte spores and pollen grains. By contrast, a survey of all algae with sequenced genomes confirms that they do not possess ASCL and, therefore, their spore walls are not composed of sporopollenin.
Genome-Wide Association Insights into the Genomic Regions Controlling Oil Production Traits inAcrocomia aculeata(neotropical native palm)
Authors: Couto Evellyn Giselly de Oliveira , Morales-Marroquín Jonathan , Alves-Pereira Alessandro , Fernandes Samuel B. , Colombo Carlos Augusto , Adelino de Azevedo Filho Joaquim , Carvalho Cassia Regina Limonta , Zucchi Maria Imaculada 
Published: January 2024

ABSTRACTMacauba (Acrocomia aculeata) is a non-domesticated neotropical palm that has been attracting attention for economical use due to its great potential for oil production comparable to the commercially used oil palm (Elaeis guineenses). The discovery of associations between quantitative trait loci and economically important traits represents an advance toward macauba domestication. Pursuing this advance, this study performs single-trait and multi-trait GWAS models to identify candidate genes related to oil production traits in macauba. We randomly selected 201 palms from a natural population and analysed 13 traits related to fruit production, processing, and oil content. Genotyping was performed following the genotyping-by- sequencing protocol. SNP calling was performed using three strategies since macauba doesn’t have a reference genome: using i) de novo pipeline, ii)Elaeis guineensesJacq. reference genome, and iii) transcriptome ofAcrocomia aculeata. Single-trait analysis was fitted using five models from GAPIT, while multi-trait analysis was fitted using a multivariate stepwise method implemented in the software TASSEL. Multi-trait analyses were conducted in all pairwise trait combinations. Results showed statistically significant differences in all phenotypic traits studied, and heritability values ranged from 0.63 to 0.95. Gene annotation detected 15 candidate genes in seven traits in the single-trait GWAS and four candidate genes in 10 trait combinations in the multi-trait GWAS. We provide new insights on genomic regions that mapped candidate genes involved in macauba oil production phenotypes. Associated markers to the traits of interest may be valuable resources for the development of marker-assisted selection in macauba for both domestication and pre-breeding purposes.
JAK/STAT Signaling Predominates in Human and Murine Fungal Post-infectious Inflammatory Response Syndrome
Authors: Hargarten Jessica C. , Ssebambulidde Kenneth , Anjum Seher H. , Vaughan Malcolm J. , Xu Jintao , Song Brian , Ganguly Anutosh , Park Yoon-dong , Scott Terri , Hammoud Dima A. , Olszewski Michal A. , Williamson Peter R. 
Published: January 2024

AbstractPost-infection inflammatory syndromes have been increasingly recognized as a cause of host damage in a variety of infectious diseases including tuberculosis, bacterial meningitis, and COVID-19. Recently, a post-infectious inflammatory response syndrome (PIIRS) was described in non-HIV-infected cryptococcal fungal meningoencephalitis (CM) as a major cause of mortality. Inflammatory syndromes are particularly severe in neurological infections due to the skull’s rigid structure which limits unchecked tissue expansion from inflammatory-induced edema. In the present studies, neurologic transcriptional pathway analysis utilizing a murine PIIRS model demonstrated a predominance of Janus kinase/signal transducer and activator of transcription (JAK/STAT) activation. JAK/STAT inhibitor treatment resulted in improvements in CNS damage markers, reductions in intrathecal CD44hiCD62loCD4+effector CD4+T-cells and MHC II+inflammatory myeloid cells, and weight gains in mice, the latter after treatment with antifungals. Based on these data, pathway-driven steroid-sparing human treatment for steroid-refractory PIIRS was initiated using short courses of the JAK/STAT inhibitor ruxolitinib. These were well tolerated and reduced activated HLA-DR+CD4+and CD8+cells and inflammatory monocytes as well as improved brain imaging. Together, these findings support the role of JAK/STAT in PIIRS as well as further study of JAK/STAT inhibitors as potential adjunctive therapy for PIRS and other neural inflammatory syndromes.
Monitoring Report: GLP-1 RA Prescribing Trends - September 2024 Data
Authors: Gratzl Samuel , Rodriguez Patricia J , Cartwright Brianna M Goodwin , Baker Charlotte , Stucky Nicholas L 
Published: January 2024

AbstractBackgroundLimited recent data exist on prescribing patterns and patient characteristics for glucagon-like peptide 1 receptor agonists (GLP-1 RAs), an important drug class used as anti-diabetic medication (ADM) for patients with type 2 diabetes mellitus (T2D) and/or anti-obesity medication (AOM) in patients with overweight or obesity.For brevity, we use the term GLP-1 RA to refer to both GLP-1 RA and dual GLP-1 RA/GIP medications.ObjectiveTo describe recent trends in prescribing and dispensing of GLP-1-based medications in the US.MethodsUsing a subset of real-world electronic health record (EHR) data from Truveta, a growing collective of health systems that provide more than 18% of all daily clinical care in the US, we identified people who were prescribed a GLP-1-based medication between January 01, 2018 and September 30, 2024. We describe prescribing volumes and patient characteristics over time, by medication, and by FDA-labeled use. Among the subset of patients for whom post-prescription dispensing data is available, we describe the proportion and characteristics of patients who were and were not dispensed a GLP-1 RA following their prescription.Results1,449,442 patients were prescribed a GLP-1 RA between January 2018 and September 2024, with 6,341,367 total prescriptions during this period. Among first-time prescriptions for which use could be established, ADMs accounted for 80.3% and AOMs accounted for 19.7%. The most common first-time medication was semaglutide (n = 821,890). Among those with available data, 69.5% of first-time ADM prescriptions overall and 70.6% in June 2024 had a fill within 60 days. By comparison, 45.4% of first-time AOM prescriptions overall and 50.1% in June 2024 had a fill within 60 days.
Routes of importation and spatial dynamics of SARS-CoV-2 variants during localised interventions in Chile
Authors: Gutierrez Bernardo , Tsui Joseph L.-H. , Pullano Giulia , Mazzoli Mattia , Gangavarapu Karthik , Inward Rhys P.D. , Bajaj Sumali , Evans Pena Rosario , Busch-Moreno Simon , Suchard Marc A. , Pybus Oliver G. , Dunner Alejandra , Puentes Rodrigo , Ayala Salvador , Fernandez Jorge , Araos Rafael , Ferres Leo , Colizza Vittoria , Kraemer Moritz U.G. 
Published: January 2024

AbstractSouth America suffered large SARS-CoV-2 epidemics between 2020 and 2022 caused by multiple variants of interest and concern, some causing substantial morbidity and mortality. However, their transmission dynamics are poorly characterised. The epidemic situation in Chile enables us to investigate differences in the distribution and spread of variants Alpha, Gamma, Lambda, Mu and Delta. Chile implemented non-pharmaceutical interventions and an integrated genomic and epidemiological surveillance system that included airport and community surveillance to track SARS-CoV-2 variants. Here we combine viral genomic data and anonymised human mobility data from mobile phones to characterise the routes of importation of different variants into Chile, the relative contributions of airport-based importations to viral diversity versus land border crossings and test the impact of the mobility network on the diffusion of viral lineages within the country. We find that Alpha, Lambda and Mu were identified in Chile via airport surveillance six, four and five weeks ahead of their detection via community surveillance, respectively. Further, some variants that originated in South America were imported into Chile via land rather than international air travel, most notably Gamma. Different variants exhibited similar trends of viral dissemination throughout the country following their importation, and we show that the mobility network predicts the time of arrival of imported lineages to different Chilean comunas. Higher stringency of local NPIs was also associated with fewer domestic viral importations. Our results show how genomic surveillance combined with high resolution mobility data can help predict the multi-scale geographic expansion of emerging infectious diseases.Significance statementGlobal preparedness for pandemic threats requires an understanding of the global variations of spatiotemporal transmission dynamics. Regional differences are important because the local context sets the conditions for the unfolding of local epidemics, which in turn affect transmission dynamics at a broader scale. Knowledge gaps from the SARS-CoV-2 pandemic remain for regions like South America, where distinct sets of viral variants emerged and spread from late 2020 onwards, and where changes in human behaviour resulted in epidemics which differed from those observed in other regions. Our interdisciplinary analysis of the SARS-CoV-2 epidemic in Chile provides insights into the spatiotemporal trends of viral diffusion in the region which shed light on the drivers that can influence future epidemic waves and pandemics.
Speedy benthi: Elongated photoperiods reduce generation times of the model plant speciesNicotiana benthamiana
Authors: Castle Matthew , Lüdke Daniel 
Published: January 2024

AbstractNicotiana benthamianais increasingly gaining prominence as a model plant species with recently published high-quality genome assemblies, which will further enable forward and reverse genetic approaches (Bally et al., 2018; Derevnina et al., 2019; Kourelis et al., 2019; Ranawaka et al., 2023; Vollheyde et al., 2023). However, the generation time ofN. benthamianaposes a bottleneck in the creation of mutant and transgenic plant lines. Speed breeding (SB), by extended photoperiods and adjustments to growth parameters, is an efficient way to reduce generation times for many crop and model plant species (Ghosh et al., 2018; Watson et al., 2018; Hickey et al., 2019; Varshney et al., 2021). We hypothesized that an extended photoperiod could reduce the seed to seed generation time ofN. benthamiana. We tested this hypothesis by comparing generation times under SB conditions to traditionally used photoperiods in growth chambers and green house settings. We found that a 22h photoperiod reduced the generation time ofN. benthamianaby approximately 2 weeks (16-22%). Fertilization in combination with a far-red light spectrum did not yield a further reduction in generation time when combined with SB conditions. Our findings further contribute to the establishment ofN. benthamianaas an important model organism for plant research.
Development of a metabolic engineering technology to simultaneously suppress the expression of multiple genes in yeast and application in carotenoid production
Authors: Yamada Ryosuke , Yamamoto Chihiro , Sakaguchi Rumi , Matsumoto Takuya , Ogino Hiroyasu 
Published: January 2024

AbstractIn yeast metabolic engineering, there is a need for technologies that simultaneously suppress and regulate the expression of multiple genes and improve the production of target chemicals. In this study, we aimed to develop a novel technology that simultaneously suppresses the expression of multiple genes by combining RNA interference with global metabolic engineering technology (GMES). Furthermore, using β-carotene as the target chemical, we attempted to improve its production by using the technology. First, we developed a technology to suppress the expression of the target genes with various strengths using RNA interference. Using this technology, total carotenoid production was successfully improved by suppressing the expression of a single gene out of 10 candidate genes. Then, using this technology, RNA interference strain targeting 10 candidate genes for simultaneous suppression was constructed. The total carotenoid production of the constructed RNA interference strain was 1.7 times compared with the parental strain. In the constructed strain, the expression of eight out of the 10 candidate genes was suppressed. We developed a novel technology that can simultaneously suppress the expression of multiple genes at various intensities and succeeded in improving carotenoid production in yeast. Because this technology can suppress the expression of any gene, even essential genes, using only gene sequence information, it is considered a useful technology that can suppress the formation of by-products during the production of various target chemicals by yeast.
Dissecting the membrane association mechanism of aerolysin pore at femtomolar concentrations using water as a probe
Authors: Roesel Tereza , Cao Chan , Juarez Juan F. Bada , Dal Peraro Matteo , Roke Sylvie 
Published: January 2024

ABSTRACTAerolysin is a bacterial pore-forming toxin able to form transmembrane pores at the host plasma membrane of narrow internal diameter and great stability. These assets make it a highly promising nanopore for the detection of biopolymers such as nucleic acids and peptides. While much is known about aerolysin from a microbiological and structural side, its membrane association and pore-formation mechanism are not yet fully disclosed. Here, we studied the interaction of femtomolar concentrations of aerolysin and its mutants with liposomes in aqueous solution using angle-resolved second harmonic scattering (AR-SHS), in combination with single-channel current measurements. The measurements were so sensitive to detect electrostatic changes on the membrane-bound aerolysin induced by pH variation induced by the changes in the hydration shell of aerolysin. We reported for the first time the membrane binding affinity of aerolysin at different stages of the pore formation mechanism: while wt aerolysin has a binding affinity as high as 20 fM, the quasi-pore state and the prepore state show gradually decreasing membrane affinities, incomplete insertion and pore opening signature. Moreover, we quantitatively characterized the membrane affinity of mutants relevant for applications to nanopore sensing. This approach opens new possibilities to efficiently screen biological pores suitable for conducting molecular sensing and sequencing measurements, as well as to probe pore forming processes.
Pre-trained Maldi Transformers improve MALDI-TOF MS-based prediction
Authors: De Waele Gaetan , Menschaert Gerben , Vandamme Peter , Waegeman Willem 
Published: January 2024

AbstractFor the last decade, matrix-assisted laser desportion/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has been the reference method for species identification in clinical microbiology. Hampered by a historical lack of open data, machine learning research towards models specifically adapted to MALDI-TOF MS remains in its infancy. Given the growing complexity of available datasets (such as large-scale antimicrobial resistance prediction), a need for models that (1) are specifically designed for MALDI-TOF MS data, and (2) have high representational capacity, presents itself.Here, we introduce Maldi Transformer, an adaptation of the state-of-the-art transformer architecture to the MALDI-TOF mass spectral domain. We propose the first self-supervised pre-training technique specifically designed for mass spectra. The technique is based on shuffling peaks across spectra, and pre-training the transformer as a peak discriminator. Extensive benchmarks confirm the efficacy of this novel design. The final result is a model exhibiting state-of-the-art (or competitive) performance on downstream prediction tasks. In addition, we show that Maldi Transformer’s identification of noisy spectra may be leveraged towards higher predictive performance.All code supporting this study is distributed on PyPI and is packaged under:https://github.com/gdewael/maldi-nn
Metabolic responses to cold: thermal physiology of native common waxbills (Estrilda astrild)
Authors: Pacioni Cesare , Sentís Marina , Kerimov Anvar , Bushuev Andrey , Downs Colleen T. , Lens Luc , Strubbe Diederik 
Published: January 2024

AbstractEcophysiological studies of invasive species tend to focus on captive individuals and their invasive range. However, the importance of gaining a thorough understanding of their physiology in their native range, where autecological knowledge is limited, has played a crucial role in assessing species ecophysiological responses to the often novel environmental conditions encountered in their invasive range. Here, we investigated the ecophysiological characteristics of a population of the wild-caught common waxbill (Estrilda astrild), a successful global invader, in part of its native range (South Africa). We investigated how this species adjusts its resting metabolic rate over a range of temperatures to identify its thermoneutral zone (TNZ) as an indicator of a species’ thermal tolerance. The observed TNZ curve predominantly followed the classic Scholander-Irving model, with metabolic rates increasing linearly at temperatures outside the TNZ. However, we found an inflection point at moderately cold temperatures (16°C) where the common waxbill began to decrease its metabolic rate. This finding highlights the potential use of an energy-saving strategy as an adaptive response to cold, such as facultative hypothermic responses through a reduction in body temperature, which may explain their success as an invasive species. We argue that although metabolic infection points have been repeatedly identified in studies of TNZ, the specific mechanisms behind metabolic down-regulation at low temperatures remain underexplored in the literature. We therefore suggest that future research should focus on investigating body temperature variation, with particular emphasis on its potential contribution to metabolic adaptation in colder environments.