bluuebunny/crossref_metadata_2025_split huggingface dataset:
New palaeoproterozoic palaeomagnetic data from Central and Northern Finland indicate a long-lived stable position for Fennoscandia
Authors: Luoto T , Salminen J , Mertanen S , Elming S-Å , Pesonen L J 
Published: June 2023

SUMMARYThe Svecofennian gabbro intrusions coincide temporally with the global 2100–1800 Ma orogens related to the amalgamation of the Mesoproterozoic supercontinent Nuna. We provide a new reliable 1891–1875 Ma palaeomagnetic pole for Fennoscandia based on rock magnetic and palaeomagnetic studies on the Svecofennian intrusions in central Finland to fill gaps in the Palaeoproterozoic palaeomagnetic record. By using the new pole together with other global high-quality data, we propose a new palaeogeographic reconstruction at 1885 Ma. This, together with previous data, supports a long-lived relatively stable position of Fennoscandia at low to moderate latitudes at 1890–1790 Ma. Similar stable pole positions have also been obtained for Kalahari at 1880–1830 Ma, Siberia at 1880–1850 Ma, and possibly India at 1980–1775 Ma. A new reconstruction at the beginning of this period indicates the convergence of several cratons at 1885 Ma in the initial stages of the amalgamation of the Nuna supercontinent at low to moderate latitudes. The close proximity of cratons at low to moderate latitudes is further supported by global and regional palaeoclimatic indicators. Stable position of several cratons could indicate a global period of minimal apparent drift at ca. 1880–1830 Ma. Before this period, the global palaeomagnetic record indicates large back-and-forth swings, most prominently seen in the high-resolution 2020–1870 Ma Coronation loops of the Slave craton. These large back-and-forth movements have been explained as resulting from an unstable geomagnetic field or basin- or local-scale vertical-axis rotations. However, the most likely explanation is inertial interchange true polar wander (IITPW) events, which is in line with the suggestion of large amplitude true polar wander events during the formation of the supercontinent.
Integrating GWAS summary statistics, individual-level genotypic and omic data to enhance the performance for large-scale trait imputation
Authors: Ren Jingchen , Lin Zhaotong , Pan Wei 
Published: June 2023

Abstract
Recently, a non-parametric method has been proposed to impute the genetic component of a trait for a large set of genotyped individuals based on a separate genome-wide association study (GWAS) summary dataset of the same trait (from the same population). The imputed trait may contain linear, non-linear and epistatic effects of genetic variants, thus can be used for downstream linear or non-linear association analyses and machine learning tasks. Here, we propose an extension of the method to impute both genetic and environmental components of a trait using both single nucleotide polymorphism (SNP)–trait and omics–trait association summary data. We illustrate an application to a UK Biobank subset of individuals (n ≈ 80K) with both body mass index (BMI) GWAS data and metabolomic data. We divided the whole dataset into two equally sized and non-overlapping training and test datasets; we used the training data to build SNP– and metabolite–BMI association summary data and impute BMI on the test data. We compared the performance of the original and new imputation methods. As by the original method, the imputed BMI values by the new method largely retained SNP–BMI association information; however, the latter retained more information about BMI–environment associations and were more highly correlated with the original observed BMI values.
Metabolic liver cancer: associations of rare and common germline variants in one-carbon metabolism and DNA methylation genes
Authors: Antwi Samuel O , Heckman Michael , White Launia , Yan Irene , Sarangi Vivekananda , Lauer Kimberly P , Reddy Joseph , Ahmed Fowsiyo , Veliginti Swathi , Mejías Febres Ellis D , Hatia Rikita I , Chang Ping , Izquierdo-Sanchez Laura , Boix Loreto , Rojas Angela , Banales Jesus M , Reig Maria , Stål Per , Gómez Manuel Romero , Singal Amit G , Li Donghui , Hassan Manal M , Roberts Lewis R , Patel Tushar 
Published: June 2023

Abstract
Animal studies implicate one-carbon metabolism and DNA methylation genes in hepatocellular carcinoma (HCC) development in the setting of metabolic perturbations. Using human samples, we investigated the associations between common and rare variants in these closely related biochemical pathways and risk for metabolic HCC development in a multicenter international study. We performed targeted exome sequencing of 64 genes among 556 metabolic HCC cases and 643 cancer-free controls with metabolic conditions. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for multiple comparisons. Gene-burden tests were used for rare variant associations. Analyses were performed in the overall sample and among non-Hispanic whites. The results show that among non-Hispanic whites, presence of rare functional variants in ABCC2 was associated with 7-fold higher risk of metabolic HCC (OR = 6.92, 95% CI: 2.38–20.15, P = 0.0004), and this association remained significant when analyses were restricted to functional rare variants observed in ≥2 participants (cases 3.2% versus controls 0.0%, P = 1.02 × 10−5). In the overall multiethnic sample, presence of rare functional variants in ABCC2 was nominally associated with metabolic HCC (OR = 3.60, 95% CI: 1.52–8.58, P = 0.004), with similar nominal association when analyses were restricted to functional rare variants observed in ≥2 participants (cases 2.9% versus controls 0.2%, P = 0.006). A common variant in PNPLA3 (rs738409[G]) was associated with higher HCC risk in the overall sample (P = 6.36 × 10−6) and in non-Hispanic whites (P = 0.0002). Our findings indicate that rare functional variants in ABCC2 are associated with susceptibility to metabolic HCC in non-Hispanic whites. PNPLA3-rs738409 is also associated with metabolic HCC risk.
Insights into energy balance dysregulation from a mouse model of methylmalonic aciduria
Authors: Lucienne Marie , Gerlini Raffaele , Rathkolb Birgit , Calzada-Wack Julia , Forny Patrick , Wueest Stephan , Kaech Andres , Traversi Florian , Forny Merima , Bürer Céline , Aguilar-Pimentel Antonio , Irmler Martin , Beckers Johannes , Sauer Sven , Kölker Stefan , Dewulf Joseph P , Bommer Guido T , Hoces Daniel , Gailus-Durner Valerie , Fuchs Helmut , Rozman Jan , Froese D Sean , Baumgartner Matthias R , de Angelis Martin Hrabě 
Published: June 2023

Abstract
Inherited disorders of mitochondrial metabolism, including isolated methylmalonic aciduria, present unique challenges to energetic homeostasis by disrupting energy-producing pathways. To better understand global responses to energy shortage, we investigated a hemizygous mouse model of methylmalonyl-CoA mutase (Mmut)–type methylmalonic aciduria. We found Mmut mutant mice to have reduced appetite, energy expenditure and body mass compared with littermate controls, along with a relative reduction in lean mass but increase in fat mass. Brown adipose tissue showed a process of whitening, in line with lower body surface temperature and lesser ability to cope with cold challenge. Mutant mice had dysregulated plasma glucose, delayed glucose clearance and a lesser ability to regulate energy sources when switching from the fed to fasted state, while liver investigations indicated metabolite accumulation and altered expression of peroxisome proliferator–activated receptor and Fgf21-controlled pathways. Together, these shed light on the mechanisms and adaptations behind energy imbalance in methylmalonic aciduria and provide insight into metabolic responses to chronic energy shortage, which may have important implications for disease understanding and patient management.
Elevated Levels of Interleukin-1β and Interleukin-10 Are Associated With Faster Lung Function Decline in People With Well-Treated Human Immunodeficiency Virus
Authors: Thudium Rebekka F , Arentoft Nicoline S , Hoel Hedda , Afzal Shoaib , von Stemann Jakob H , Forman Julie L , Wilcke Jon T , Benfield Thomas , Trøseid Marius , Borges Álvaro H , Ostrowski Sisse R , Vestbo Jørgen , Kunisaki Ken M , Jensen Jens-Ulrik S , Nielsen Susanne D 
Published: June 2023

Abstract

Background
People with human immunodeficiency virus (PWH) have an increased risk of chronic lung diseases and chronic inflammation. We aimed to investigate if inflammatory markers and monocyte activation are associated with faster lung function decline in PWH.

Methods
We included 655 PWH from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study. Eligible participants were aged ≥25 years and had 2 spirometries separated by &gt;2 years. Inflammatory markers (interleukin [IL]–1β, IL-2, IL-6, IL-10, tumor necrosis factor–α, and interferon-γ) were measured at baseline by Luminex, and soluble CD14 and soluble CD163 by enzyme-linked immunosorbent assay. Using linear mixed models, we investigated whether elevated cytokine levels were associated with faster lung function decline.

Results
The majority of PWH were males (85.2%) with undetectable viral replication (95.3%). We found a faster decline in forced expiratory volume in 1 second (FEV1) in PWH with elevated IL-1β and IL-10, with an additional decline of 10.3 mL/year (95% confidence interval [CI], 2.1–18.6; P = .014) and 10.0 mL/year (95% CI, 1.8–18.2; P = .017), respectively. We found no interaction between smoking and IL-1β or IL-10 on FEV1 decline.

Conclusions
Elevated IL-1β and IL-10 were independently associated with faster lung function decline in PWH, suggesting that dysregulated systemic inflammation may play a role in the pathogenesis of chronic lung diseases.
Safety and Immunogenicity of an Andes Virus DNA Vaccine by Needle-Free Injection: A Randomized, Controlled Phase 1 Study
Authors: Paulsen Grant C , Frenck Robert , Tomashek Kay M , Alarcon Rodolfo M , Hensel Elizabeth , Lowe Ashley , Brocato Rebecca L , Kwilas Steve A , Josleyn Matthew D , Hooper Jay W 
Published: June 2023

Abstract

Background
Andes virus (ANDV), a rodent-borne hantavirus, causes hantavirus pulmonary syndrome (HPS). The safety and immunogenicity of a novel ANDV DNA vaccine was evaluated.

Methods
Phase 1, double-blind, dose-escalation trial randomly assigned 48 healthy adults to placebo or ANDV DNA vaccine delivered via needle-free jet injection. Cohorts 1 and 2 received 2 mg of DNA or placebo in a 3-dose (days 1, 29, 169) or 4-dose (days 1, 29, 57, 169) schedule, respectively. Cohorts 3 and 4 received 4 mg of DNA or placebo in the 3-dose and 4-dose schedule, respectively. Subjects were monitored for safety and neutralizing antibodies by pseudovirion neutralization assay (PsVNA50) and plaque reduction neutralization test (PRNT50).

Results
While 98% and 65% of subjects had at least 1 local or systemic solicited adverse event (AE), respectively, most AEs were mild or moderate; no related serious AEs were detected. Cohorts 2, 3, and 4 had higher seroconversion rates than cohort 1 and seropositivity of at least 80% by day 197, sustained through day 337. PsVNA50 geometric mean titers were highest for cohort 4 on and after day 197.

Conclusions
This first-in-human candidate HPS vaccine trial demonstrated that an ANDV DNA vaccine was safe and induced a robust, durable immune response.
Clinical Trials Registration. NCT03682107.
The Mucin-Like Domain of the Ebola Glycoprotein Does Not Impact Virulence or Pathogenicity in Ferrets
Authors: Halfmann Peter J , Borisevich Viktoriya , Levine Corri B , Mire Chad E , Fenton Karla A , Geisbert Thomas W , Kawaoka Yoshihiro , Cross Robert W 
Published: June 2023

Abstract

Background
Ebola virus (EBOV) is considered among the most dangerous viruses with case fatality rates approaching 90% depending on the outbreak. While several viral proteins (VPs) including VP24, VP35, and the soluble glycoprotein are understood to contribute to virulence, less is known of the contribution of the highly variable mucin-like domain (MLD) of EBOV. Early studies have defined a potential role in immune evasion of the MLD by providing a glycan shield to critical glycoprotein residues tied to viral entry. Nonetheless, little is known as to what direct role the MLD plays in acute EBOV disease (EVD).

Methods
We generated an infectious EBOV clone that lacks the MLD and assessed its virulence in ferrets compared with wild-type (WT) virus.

Results
No differences in growth kinetics were observed in vitro, nor were there any differences in time to death, viremia, or clinical picture in ferrets infected with recombinant EBOV (rEBOV)–WT or rEBOV-Δmucin.

Conclusions
The EBOV MLD does not play a critical role in acute pathogenesis of EVD in ferrets.
Orthopoxvirus-Specific T-Cell Responses in Convalescent Mpox Patients
Authors: Traut Caroline C , Jones Joyce L , Sanders Renata A , Clark Laura R , Hamill Matthew M , Stavrakis Georgia , Sop Joel , Beckey Tyler P , Keller Sara C , Gilliams Elizabeth A , Cochran Willa V , Laeyendecker Oliver , Manabe Yukari C , Mostafa Heba H , Thomas David L , Hansoti Bhakti , Gebo Kelly A , Blankson Joel N 
Published: June 2023

Abstract
Orthopoxvirus-specific T-cell responses were analyzed in 10 patients who had recovered from Mpox including 7 people with human immunodeficiency virus (PWH). Eight participants had detectable virus-specific T-cell responses, including a PWH who was not on antiretroviral therapy and a PWH on immunosuppressive therapy. These 2 participants had robust polyfunctional CD4+ T-cell responses to peptides from the 121L vaccinia virus (VACV) protein. T-cells from 4 of 5 HLA-A2–positive participants targeted at least 1 previously described HLA-A2–restricted VACV epitope, including an epitope targeted in 2 participants. These results advance our understanding of immunity in convalescent Mpox patients.
Using copula graphical models to detect the impact of drought stress on maize and wheat yield
Authors: Hermes Sjoerd , van Heerwaarden Joost , Behrouzi Pariya 
Published: June 2023

Abstract
Improving crop yields is one of the main goals of agronomy. However, yield is determined by a complex interplay between Genotypic, Environmental and Management factors (G$\times$E$\times$M), which varies across time and space. Therefore, identifying the fundamental relations underlying yield variation is a principal aim of agricultural research. A narrow, and not necessarily appropriate, set of statistical methods tends to be used in the study of such relations, which is why we aim to introduce a diverse audience of agronomists, production ecologists, plant breeders and others interested in explaining yield variation to the use of graphical models. More specifically, we wish to demonstrate the usefulness of copula graphical models for heterogeneous mixed data. This new statistical learning technique provides a graphical representation of conditional independence relationships within data that is not necessarily normally distributed and consists of multiple groups for environments, management decisions, genotypes or abiotic stresses such as drought. This article introduces some basic graphical model terminology and theory, followed by an application on Ethiopian maize and wheat yield undergoing drought stress. The proposed method is accompanied with the R package heteromixgm https://CRAN.R-project.org/package=heteromixgm.
Validating a novel three-times-weekly post-hemodialysis ceftriaxone regimen in infected Indigenous Australian patients—a population pharmacokinetic study
Authors: Tsai Danny , Zam Betty B , Tongs Carleigh , Chiong Fabian , Sajiv Cherian , Pawar Basant , Ashok Aadith , Cooper Brynley P , Tong Steven Y C , Janson Sonja , Wallis Steven C , Roberts Jason A , Parker Suzanne L 
Published: June 2023

Abstract

Objectives
To describe the total and unbound population pharmacokinetics of a 2 g three-times-weekly post-dialysis ceftriaxone regimen in Indigenous Australian patients requiring hemodialysis.

Methods
A pharmacokinetic study was carried out in the dialysis unit of a remote Australian hospital. Adult Indigenous patients on intermittent hemodialysis (using a high-flux dialyzer) and treated with a 2 g three-times-weekly ceftriaxone regimen were recruited. Plasma samples were serially collected over two dosing intervals and assayed using validated methodology. Population pharmacokinetic analysis and Monte Carlo simulations were performed using Pmetrics in R. The probability of pharmacokinetic/pharmacodynamic target attainment (unbound trough concentrations ≥1 mg/L) and toxicity [trough concentrations (total)  ≥100 mg/L] were simulated for various dosing strategies.

Results
Total and unbound concentrations were measured in 122 plasma samples collected from 16 patients (13 female) with median age 57 years. A two-compartment model including protein-binding adequately described the data, with serum bilirubin concentrations associated (inversely) with ceftriaxone clearance. The 2 g three-times-weekly regimen achieved 98% probability to maintain unbound ceftriaxone concentrations ≥1 mg/L for a serum bilirubin of 5 µmol/L. Incremental accumulation of ceftriaxone was observed in those with bilirubin concentrations &gt;5 µmol/L. Three-times-weekly regimens were less probable to achieve toxic exposures compared with once-daily regimens. Ceftriaxone clearance was increased by &gt;10-fold during dialysis.

Conclusions
A novel 2 g three-times-weekly post-dialysis ceftriaxone regimen can be recommended for a bacterial infection with an MIC ≤1 mg/L. A 1 g three-times-weekly post-dialysis regimen is recommended for those with serum bilirubin ≥10 µmol/L. Administration of ceftriaxone during dialysis is not recommended.
Use of marine microorganisms in designing anti-infective strategies for sustainable aquaculture production
Authors: Hamza Faseela , Zinjarde Smita 
Published: June 2023

Abstract
Aquaculture, a noteworthy food production sector, is confronted with disease occurrences. Treatment of aquaculture pathogens with antibiotics is often rendered ineffective due to biofilm formation and the development of resistant strains. Marine ecosystems encompass unusual microorganisms that produce novel bioactive compounds, including agents that could be used as alternatives to antibiotics. Moreover, biomass and/or biomolecules associated with these microorganisms could act as feed supplements to enhance the overall health of aquaculture species’ and improve water quality parameters. The present review summarizes the contents of studies on such marine microorganisms with the potential to be developed as agents for tackling bacterial diseases in the aquaculture segment. Bioactive compounds produced by marine bacteria are known to inhibit biofilm-associated infections mediated by their bactericidal properties (produced by Bacillus, Vibrio, Photobacterium, and Pseudoalteromonas species), surfactant activity (obtained from different species of Bacillus and Staphylococcus lentus), anti-adhesive activity (derived from Bacillus sp. and Brevibacterium sp.), and quorum sensing inhibition. Several marine fungal isolates capable of producing antibacterial agents have also been effective in inhibiting aquaculture-associated pathogens. Another strategy followed by investigators to reduce the severity of infections is the use of bacterial, yeast, and microalgae biomass as feed supplements, probiotics, and immunostimulants. In some cases, marine microalgae have been employed as sustainable alternatives to fish oil and fish meal without compromising on nutritional quality. Their inclusion in aquaculture feed has enhanced growth, favored better survival of cultured species, and improved water quality parameters. Marine microorganisms (by providing effective bioactive compounds and being used as feed supplements) could enable aquaculture practices to be more sustainable in the future.
A scoping review of the clinical application of machine learning in data-driven population segmentation analysis
Authors: Liu Pinyan , Wang Ziwen , Liu Nan , Peres Marco Aurélio 
Published: June 2023

AbstractObjectiveData-driven population segmentation is commonly used in clinical settings to separate the heterogeneous population into multiple relatively homogenous groups with similar healthcare features. In recent years, machine learning (ML) based segmentation algorithms have garnered interest for their potential to speed up and improve algorithm development across many phenotypes and healthcare situations. This study evaluates ML-based segmentation with respect to (1) the populations applied, (2) the segmentation details, and (3) the outcome evaluations.Materials and MethodsMEDLINE, Embase, Web of Science, and Scopus were used following the PRISMA-ScR criteria. Peer-reviewed studies in the English language that used data-driven population segmentation analysis on structured data from January 2000 to October 2022 were included.ResultsWe identified 6077 articles and included 79 for the final analysis. Data-driven population segmentation analysis was employed in various clinical settings. K-means clustering is the most prevalent unsupervised ML paradigm. The most common settings were healthcare institutions. The most common targeted population was the general population.DiscussionAlthough all the studies did internal validation, only 11 papers (13.9%) did external validation, and 23 papers (29.1%) conducted methods comparison. The existing papers discussed little validating the robustness of ML modeling.ConclusionExisting ML applications on population segmentation need more evaluations regarding giving tailored, efficient integrated healthcare solutions compared to traditional segmentation analysis. Future ML applications in the field should emphasize methods’ comparisons and external validation and investigate approaches to evaluate individual consistency using different methods.
Lnc-TRTMFS promotes milk fat synthesis via the miR-132x/RAI14/mTOR pathway in BMECs
Authors: Jia Hongru , Wu Zhangqing , Tan Jianbing , Wu Silin , Yang Chaoqun , Raza Sayed Haidar Abbas , Wang Meng , Song Guibing , Shi Yujie , Zan Linsen , Yang Wucai 
Published: June 2023

Abstract
As an important index to evaluate the quality of milk, milk fat content directly determines the nutrition and flavor of milk. Recently, growing evidence has suggested that long noncoding RNAs (lncRNAs) play important roles in bovine lactation, but little is known about the roles of lncRNAs in milk fat synthesis, particularly the underlying molecular processes. Therefore, the purpose of this study was to explore the regulatory mechanism of lncRNAs in milk fat synthesis. Based on our previous lncRNA-seq data and bioinformatics analysis, we found that Lnc-TRTMFS (transcripts related to milk fat synthesis) was upregulated in the lactation period compared to the dry period. In this study, we found that knockdown of Lnc-TRTMFS significantly inhibited milk fat synthesis, resulting in a smaller amount of lipid droplets and lower cellular triacylglycerol levels, and significantly decreased the expression of genes related to adipogenesis. In contrast, overexpression of Lnc-TRTMFS significantly promoted milk fat synthesis in bovine mammary epithelial cells (BMECs). In addition, Bibiserv2 analysis showed that Lnc-TRTMFS could act as a molecular sponge for miR-132x, and retinoic acid induced protein 14 (RAI14) was a potential target of miR-132x, which was further confirmed by dual-luciferase reporter assays, quantitative reverse transcription PCR, and western blots. We also found that miR-132x significantly inhibited milk fat synthesis. Finally, rescue experiments showed that Lnc-TRTMFS could weaken the inhibitory effect of miR-132x on milk fat synthesis and rescue the expression of RAI14. Taken together, these results revealed that Lnc-TRTMFS regulated milk fat synthesis in BMECs via the miR-132x/RAI14/mTOR pathway.