bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world data on long-acting intramuscular maintenance therapy with cabotegravir and rilpivirine mirror Phase 3 results
Authors: Serris Alexandra , Ferre Valentine Marie , Le Hingrat Quentin , Bachelard Antoine , Charpentier Charlotte , Exarchopoulos Marina , Damond Florence , Phung Bao-Chau , Landman Roland , Yazdanpanah Yazdan , Descamps Diane , Joly Véronique , Peytavin Gilles , Ghosn Jade 
Published: September 2024

Abstract

Introduction
Cabotegravir, an integrase strand transfer inhibitor, and rilpivirine, an NNRTI, constitute the first long-acting (LA), injectable, two-drug ART regimen approved for the maintenance of virological suppression in persons living with HIV-1 (PLHIV). The aim of this study was to assess clinical effectiveness and tolerability of LA cabotegravir/rilpivirine in a real-world setting.

Patients and methods
We conducted a retrospective, single centre study, including all PLHIV receiving LA cabotegravir/rilpivirine as standard-of-care in our tertiary centre even if initiated in clinical trials.

Results
Between 2014 and 2022, 126 PLHIV initiated LA cabotegravir/rilpivirine. All were ART-experienced, and 98.4% had a viral load (VL) of &lt;50 copies/mL before LA cabotegravir/rilpivirine initiation. Median BMI at cabotegravir/rilpivirine initiation was 24 IQR (23–28). During a median follow-up of 9 months IQR (7–24), 27 patients discontinued cabotegravir/rilpivirine: 5 because of virological failure, 6 for adverse events, 11 for personal reasons unrelated to treatment tolerance and 5 for other reasons. Virological failure was not associated with a higher BMI, nor with weight gain during LA intramuscular (IM) cabotegravir/rilpivirine treatment, inadequate cabotegravir and rilpivirine concentrations, VL blips or the use of oral lead-in (OLI) or not. No drug resistance-associated mutation emerged. Adverse events leading to treatment interruption were injection-site pain (n = 3) and neuropsychological side effects (n = 3). A correlation between BMI and both cabotegravir and rilpivirine concentrations at 1 month post-initiation of LA-IM cabotegravir/rilpivirine was observed, with no impact of OLI.

Conclusions
Data from this real-world cohort of PLHIV who received cabotegravir/rilpivirine LA injections suggest that this regimen is effective and well tolerated. Virological failures were not associated with the acquisition of resistance mutations.
Genome analysis of tigecycline-resistant Acinetobacter baumannii reveals nosocomial lineage shifts and novel resistance mechanisms
Authors: Qian Changrui , Hu Panjie , Guo Wenhui , Han Yijia , Yu Pingting , Zhang Yi , Ma Zhexiao , Chen Lijiang , Zhou Tieli , Cao Jianming 
Published: September 2024

Abstract

Objectives
To investigate the characteristics and clonal dynamics of tigecycline-resistant Acinetobacter baumannii (TRAB) isolates from a Chinese hospital from 2016 to 2021.

Methods
A total of 64 TRAB isolates were screened and WGS was performed. Phylogenetic analysis and non-polymorphic mutation analysis were used to analyse their clonal dynamics and tigecycline resistance-related mutations. RT-PCR was used to analyse the expression of the resistance-nodulation cell-division (RND) efflux pump genes adeB and adeJ. Gene cloning was used to explore the effect of tet(39) variants on tigecycline resistance.

Results
Most TRAB isolates were found to be MDR, with 95% (61/64) of the isolates showing resistance to carbapenems. These TRAB isolates were classified into three primary genetic clusters based on core-genome SNPs. The KL2 cluster persisted throughout the study period, whereas the KL7 cluster emerged in 2019 and became the dominant clone. The KL7 cluster carried more antimicrobial resistance genes than the other two clusters. The predominant tigecycline resistance mechanism of the KL2 cluster and KL7 cluster was IS insertion in adeN (82.1%, 23/28) and genetic alterations in adeS (76.2%, 16/21), respectively. Eleven novel AdeS mutations were identified associated with elevated AdeB expression and tigecycline resistance. Moreover, we characterized a plasmid-borne tet(39) variant with an Ala-36-Thr substitution that synergizes with the RND efflux pump to confer high-level tigecycline resistance.

Conclusions
This work provides important insights into the diverse mechanisms associated with tigecycline resistance in A. baumannii, highlighting a pressing need for further monitoring of ST2-KL7 A. baumannii in clinical settings.
COVID-19 in patients receiving treatment at an outpatient chemotherapy unit
Authors: Kinoshita Shiori , Takemoto Masashi , Asaoka Minami , Haraguchi Yoko , Adachi Tamami , Iida Shinsuke , Komatsu Hirokazu 
Published: September 2024

Abstract
During the COVID-19 pandemic period, many patients who required outpatient chemotherapy developed COVID-19, requiring chemotherapy interruption. However, there are no clear guidelines regarding the safe timing for restarting chemotherapy. We conducted a retrospective study to assess when such patients can safely recommence chemotherapy. Of the 40 patients included in this study, 34 restarted anticancer drug therapy after COVID-19 infection. Six patients, four with multiple myeloma, and one each with follicular lymphoma and glioma, remained SARS-CoV-2 antigen positive &gt;20 days after COVID-19 onset. Multiple myeloma patients recorded significantly higher frequencies of SARS-CoV-2 antigen positivity &gt;20 days after COVID-19 onset compared with solid tumor patients, with no significant differences in the frequency of SARS-CoV-2 positivity during 5–20 days from COVID-19 onset between them. According to our data, most solid tumor patients achieved SARS-CoV-2 antigen negativity after 20 days from COVID-19 onset. On the other hand, multiple myeloma patients might need serial antigen tests before restarting anticancer therapy in the outpatient chemotherapy setting.
A Bayesian complex-valued latent variable model applied to functional magnetic resonance imaging
Authors: Sakitis Chase J , Brown D Andrew , Rowe Daniel B 
Published: September 2024

Abstract
In linear regression, the coefficients are simple to estimate using the least squares method with a known design matrix for the observed measurements. However, real-world applications may encounter complications such as an unknown design matrix and complex-valued parameters. The design matrix can be estimated from prior information but can potentially cause an inverse problem when multiplying by the transpose as it is generally ill-conditioned. This can be combat by adding regularizers to the model but does not always mitigate the issues. Here, we propose our Bayesian approach to a complex-valued latent variable linear model with an application to functional magnetic resonance imaging (fMRI) image reconstruction. The complex-valued linear model and our Bayesian model are evaluated through extensive simulations and applied to experimental fMRI data.
Investigating temporary capture in the Sun–Jupiter three-body system via Lagrangian coherent structures
Authors: Li Zhenyu , Qiao Dong , Li Xiangyu 
Published: September 2024

ABSTRACT
The temporary capture (TC) of Jupiter-family objects has long been a pivotal focus in celestial mechanics research. This study investigates the TC of objects near Jupiter within the context of the planar circular restricted three-body problem (PCRTBP), employing Lagrangian coherent structures (LCSs) and periapsis Poincaré maps. Initially, LCSs are identified via periapsis Poincaré maps and applied to segment the phase space. Parameter scanning enables a detailed analysis, classifying the orbital behaviours of objects in the proximity of Jupiter into three distinct categories: TC, low-energy flyby, and collision, each designating specific regions in phase space. Subsequently, a novel method for screening potential TC objects within the Jupiter system is proposed and validated, informed by the dynamic characteristics of TC motions. The efficacy of this method is illustrated by the re-identification of six known TC comets and the prediction of a prospective TC asteroid, 2002 GV28. Within the framework of the PCRTBP, analogous TC trajectories for these comets and asteroids are identified, offering novel insights into the dynamics of TC events.
Functional Characterization Supports Multiple Evolutionary Origins of Pheromone Receptors in Bark Beetles
Authors: Biswas Twinkle , Sims Cassie , Yuvaraj Jothi Kumar , Roberts Rebecca E , Löfstedt Christer , Andersson Martin N 
Published: September 2024

Abstract
Chemical communication using pheromones is thought to have contributed to the diversification and speciation of insects. The species-specific pheromones are detected by specialized pheromone receptors (PRs). Whereas the evolution and function of PRs have been extensively studied in Lepidoptera, only a few PRs have been identified in beetles, which limits our understanding of their evolutionary histories and physiological functions. To shed light on these questions, we aimed to functionally characterize potential PRs in the spruce bark beetle Ips typographus (“Ityp”) and explore their evolutionary origins and molecular interactions with ligands. Males of this species release an aggregation pheromone comprising 2-methyl-3-buten-2-ol and (4S)-cis-verbenol, which attracts both sexes to attacked trees. Using two systems for functional characterization, we show that the highly expressed odorant receptor (OR) ItypOR41 responds specifically to (4S)-cis-verbenol, with structurally similar compounds eliciting minor responses. We next targeted the closely related ItypOR40 and ItypOR45. Whereas ItypOR40 was unresponsive, ItypOR45 showed an overlapping response profile with ItypOR41, but a broader tuning. Our phylogenetic analysis shows that these ORs are present in a different OR clade as compared to all other known beetle PRs, suggesting multiple evolutionary origins of PRs in bark beetles. Next, using computational analyses and experimental validation, we reveal two amino acid residues (Gln179 and Trp310) that are important for ligand binding and pheromone specificity of ItypOR41 for (4S)-cis-verbenol, possibly via hydrogen bonding to Gln179. Collectively, our results shed new light on the origins, specificity, and ligand binding mechanisms of PRs in beetles.
Genomic Signatures of Domestication in a Fungus Obligately Farmed by Leafcutter Ants
Authors: A Leal-Dutra Caio , Vizueta Joel , Baril Tobias , Kooij Pepijn W , Rødsgaard-Jørgensen Asta , Conlon Benjamin H , Croll Daniel , Shik Jonathan Z 
Published: September 2024

Abstract
The naturally selected fungal crop (Leucoagaricus gongylophorus) farmed by leafcutter ants shows striking parallels with artificially selected plant crops domesticated by humans (e.g., polyploidy, engorged nutritional rewards, dependence on cultivation). To date, poorly resolved L. gongylophorus genome assemblies based on short-read sequencing have constrained hypotheses about how millions of years under cultivation by ants shaped the fungal crop genome and potentially drove domestication. We use PacBio HiFi sequencing of L. gongylophorus from the leafcutter ant Atta colombica to identify 18 putatively novel biosynthetic gene clusters that likely cemented life as a cultivar (e.g., plant fragment degradation, ant-farmer communication, antimicrobial defense). Comparative analyses with cultivated and free-living fungi showed genomic signatures of stepwise domestication transitions: 1) free-living to ant-cultivated: loss of genes conferring stress response and detoxification, 2) hyphal food to engorged nutritional rewards: expansions of genes governing cellular homeostasis, carbohydrate metabolism, and siderophore biosynthesis, and 3) detrital provisioning to freshly cut plant fragments: gene expansions promoting cell wall biosynthesis, fatty acid metabolism, and DNA repair. Comparisons across L. gongylophorus fungi farmed by three leafcutter ant species highlight genomic signatures of exclusively vertical clonal propagation and widespread transposable element activity. These results show how natural selection can shape domesticated cultivar genomes towards long-term ecological resilience of farming systems that have thrived across millennia.
Maturational competence of equine oocytes is associated with alterations in their ‘cumulome’
Authors: Walter Jasmin , Colleoni Silvia , Lazzari Giovanna , Fortes Claudia , Grossmann Jonas , Roschitzki Bernd , Laczko Endre , Naegeli Hanspeter , Bleul Ulrich , Galli Cesare 
Published: September 2024

Abstract
Assisted reproductive technologies are an emerging field in equine reproduction, with species-dependent peculiarities, such as the low success rate of conventional IVF. Here, the ‘cumulome’ was related to the developmental capacity of its corresponding oocyte. Cumulus–oocyte complexes collected from slaughterhouse ovaries were individually matured, fertilized by ICSI, and cultured. After maturation, the cumulus was collected for proteomics analysis using label-free mass spectrometry (MS)-based protein profiling by nano-HPLC MS/MS and metabolomics analysis by UPLC-nanoESI MS. Overall, a total of 1671 proteins and 612 metabolites were included in the quantifiable ‘cumulome’. According to the development of the corresponding oocytes, three groups were compared with each other: not matured (NM; n = 18), cleaved (CV; n = 15), and blastocyst (BL; n = 19). CV and BL were also analyzed together as the matured group (M; n = 34). The dataset revealed a closer connection within the two M groups and a more distinct separation from the NM group. Overrepresentation analysis detected enrichments related to energy metabolism as well as vesicular transport in the M group. Functional enrichment analysis found only the KEGG pathway ‘oxidative phosphorylation’ as significantly enriched in the NM group. A compound attributed to ATP was observed with significantly higher concentrations in the BL group compared with the NM group. Finally, in the NM group, proteins related to degradation of glycosaminoglycans were lower and components of cumulus extracellular matrix were higher compared to the other groups. In summary, the study revealed novel pathways associated with the maturational and developmental competence of oocytes.
4CAC: 4-class classifier of metagenome contigs using machine learning and assembly graphs
Authors: Pu Lianrong , Shamir Ron 
Published: September 2024

Abstract
Microbial communities usually harbor a mix of bacteria, archaea, plasmids, viruses and microeukaryotes. Within these communities, viruses, plasmids, and microeukaryotes coexist in relatively low abundance, yet they engage in intricate interactions with bacteria. Moreover, viruses and plasmids, as mobile genetic elements, play important roles in horizontal gene transfer and the development of antibiotic resistance within microbial populations. However, due to the difficulty of identifying viruses, plasmids, and microeukaryotes in microbial communities, our understanding of these minor classes lags behind that of bacteria and archaea. Recently, several classifiers have been developed to separate one or more minor classes from bacteria and archaea in metagenome assemblies. However, these classifiers often overlook the issue of class imbalance, leading to low precision in identifying the minor classes. Here, we developed a classifier called 4CAC that is able to identify viruses, plasmids, microeukaryotes, and prokaryotes simultaneously from metagenome assemblies. 4CAC generates an initial four-way classification using several sequence length-adjusted XGBoost models and further improves the classification using the assembly graph. Evaluation on simulated and real metagenome datasets demonstrates that 4CAC substantially outperforms existing classifiers and combinations thereof on short reads. On long reads, it also shows an advantage unless the abundance of the minor classes is very low. 4CAC runs 1–2 orders of magnitude faster than the other classifiers. The 4CAC software is available at https://github.com/Shamir-Lab/4CAC.
Crystal structure and nucleic acid binding mode of CPV NSP9: implications for viroplasm in Reovirales
Authors: Wang Yeda , Guo Hangtian , Lu Yuhao , Yang Wanbin , Li Tinghan , Ji Xiaoyun 
Published: September 2024

Abstract
Cytoplasmic polyhedrosis viruses (CPVs), like other members of the order Reovirales, produce viroplasms, hubs of viral assembly that shield them from host immunity. Our study investigates the potential role of NSP9, a nucleic acid-binding non-structural protein encoded by CPVs, in viroplasm biogenesis. We determined the crystal structure of the NSP9 core (NSP9ΔC), which shows a dimeric organization topologically similar to the P9-1 homodimers of plant reoviruses. The disordered C-terminal region of NSP9 facilitates oligomerization but is dispensable for nucleic acid binding. NSP9 robustly binds to single- and double-stranded nucleic acids, regardless of RNA or DNA origin. Mutagenesis studies further confirmed that the dimeric form of NSP9 is critical for nucleic acid binding due to positively charged residues that form a tunnel during homodimerization. Gel migration assays reveal a unique nucleic acid binding pattern, with the sequential appearance of two distinct complexes dependent on protein concentration. The similar gel migration pattern shared by NSP9 and rotavirus NSP3, coupled with its structural resemblance to P9-1, hints at a potential role in translational regulation or viral genome packaging, which may be linked to viroplasm. This study advances our understanding of viroplasm biogenesis and Reovirales replication, providing insights into potential antiviral drug targets.
Constitutional mosaicism of pathogenic variants in SMARCB1 in a subset of patients with sporadic rhabdoid tumors
Authors: Fleischmann Lara S , Nemes Karolina , Glaser Selina , Kouroukli Alexandra G , Boros Matej , Bens Susanne , Dahlum Sonja , Kretzmer Helene , Oyen Florian , Gerss Joachim , Hasselblatt Martin , Frühwald Michael C , Siebert Reiner 
Published: September 2024

Abstract

Background
Malignant rhabdoid tumors (RT) are aggressive malignancies predominantly affecting very young children. The characteristic genetic alteration is the biallelic inactivation of SMARCB1. In approximately 30% of patients, one SMARCB1 allele is constitutionally altered conferring a particularly unfavorable prognosis. Constitutional mosaicism for pathogenic SMARCB1 mutations has recently been reported in distinct cases of allegedly sporadic RT. We aimed to systematically investigate the frequency and clinical impact of constitutional mosaicism in patients with sporadic RT included in the EU-RHAB registry.

Methods
We selected 29 patients with RT displaying at least one pathogenic small variant in SMARCB1 in the tumor DNA and the absence of a germline mutation. We re-screened blood-derived patients and controlled DNA for the respective small variant by polymerase chain reaction with unique molecular identifiers and ultra-deep next-generation sequencing. Clinical data in patients with and without mosaicism and 174 EU-RHAB controls were compared.

Results
Employing an ultra-deep sequencing approach, we detected tumor-associated SMARCB1 variants in blood-derived DNA in 9/29 patients. In 6/29 patients (21%), whose variant allele frequency (VAF) exceeded 2%, constitutional mosaicism was assumed whereas tumor DNA contamination was documented in 1/3 of patients with VAF below 1%. No significant differences were observed between 6 mosaic-positive and 20 -negative patients regarding age at diagnosis, presence of metastases, event-free or overall survival.

Conclusions
Constitutional mosaicism for pathogenic small SMARCB1 variants is recurrent in patients with allegedly sporadic RT. The clinical implications of such variants need to be determined in larger, prospective cohorts also including detection of structural variants of SMARCB1.
Global decline in microbial-derived carbon stocks with climate warming and its future projections
Authors: Liang Yuting , Hu Han , Crowther Thomas W , Jörgensen Rainer Georg , Liang Chao , Chen Ji , Sun Yishen , Liu Chaoyang , Ding Jixian , Huang Aidi , Zhou Jizhong , Zhang Jiabao 
Published: September 2024

ABSTRACT
Soil organic carbon (SOC) represents the largest terrestrial pool of organic carbon and is indispensable for mitigating climate change and sustaining soil fertility. As a major component of stable SOC, microbial-derived carbon (MDC) accounts for approximately half of the total SOC and has repercussions on climate feedback. However, our understanding of the spatial and temporal dynamics of MDC stocks is limited, hindering assessments of the long-term impacts of global warming on persistent SOC sequestration in the soil‒atmosphere carbon cycle. Here, we compiled an extensive global dataset and employed ensemble machine learning techniques to forecast the spatial-temporal dynamics of MDC stocks across 93.4% of the total global land area from 1981 to 2018. Our findings revealed that for every 1°C increase in temperature, there was a global decrease of 6.7 Pg in the soil MDC stock within the predictable areas, equivalent to 1.4% of the total MDC stock or 0.9% of the atmospheric C pool. Tropical regions experienced the most substantial declines in MDC stocks. We further projected future MDC stocks for the next century based on shared socioeconomic pathways, showing a global decline in MDC stocks with a potential 6–37 Pg reduction by 2100 depending on future pathways. We recommend integrating the response of MDC stocks to warming into socioeconomic models to enhance confidence in selecting sustainable pathways.
Grasslands in the Northern Prairie region support a diverse assemblage of migrant birds and facilitate fattening during migratory stopover
Authors: West Amy C , Swanson David L 
Published: September 2024

ABSTRACT
Grasslands have been reduced as a result of conversion to agriculture and other anthropogenic uses. Consequently, grassland migrant birds may have limited options for migration stopover. In addition, the simple presence of birds in grassland fragments during migration periods does not imply that the habitat is providing the food resources necessary for birds to replenish fat stores and continue migration. We examined (1) the diversity of birds using grasslands during migration stopovers in southeastern South Dakota and (2) whether a reconstructed prairie can provide the resources necessary for a successful stopover. To accomplish these goals, we conducted line transect surveys on plots dominated by either cool- (primarily non-native) or warm-season (primarily native) grasses and captured birds on a reconstructed tallgrass prairie to determine plasma levels of triglycerides, an indicator of fat deposition, and β-hydroxybutyrate, an indicator of fat depletion. Grassland, woodland/shrub, and habitat generalist bird species were all present in the study grasslands during spring and fall migration seasons. Overall, species-richness tended to be greater at warm-season dominated sites during spring migration, but richness differences between sites varied by year during fall migration. Overall bird densities, however, were roughly similar between the 2 habitat types in both seasons, although some differences for individual bird species occurred. Plasma triglyceride and β-hydroxybutyrate levels of migrant birds using the reconstructed tallgrass prairie were consistent with those from birds in known high-quality stopover habitats. These findings suggest that grasslands that have a diversity of plant species and structural heterogeneity may be important for stopover sites for a variety of migratory birds using grasslands as stopover sites, including declining grassland species. These data further suggest that the creation and management of restored and reconstructed prairies throughout the migratory routes for grassland birds may provide quality stopovers for these species.