bluuebunny/crossref_metadata_2025_split huggingface dataset:
Verification, Validation, and Calibration Through a Causal Lens
Authors: Gonzales Ronald , Mandelli Diego , Wang Congjian , Abdo Mohammad , Balestra Paolo , Qin Sunming , Welker Zachary , Petrov Victor , Manera Annalisa 
Published: June 2024

Abstract
While typical validation and verification approaches focus on identifying the associations between data elements using statistical and machine learning methods, the novel methods in this paper focus instead on identifying causal relationships between data elements. Statistical and machine-learning-based approaches are strictly data-driven, meaning that they provide quantitative comparison measures between data sets without explicitly considering the hypotheses behind them. This can lead to the erroneous conclusion that, if two data sets are close enough, the models that generated them are similar. In addition, when experimental and simulated data differ to an extent that fails to meet the acceptance criteria, calibration techniques are used to tweak simulation model parameters to reduce the gap between the two types of data. This produces the false expectation that a simulation model will match reality. The methods presented in this paper move away from these strictly data-driven methods for validation and calibration toward more robust, model-driven methods based on causal inference. Causal inference aims to identify the possible mechanisms that might have generated data. Thus, this analysis targets the prediction of the effects when one (or more) of the identified mechanisms are altered. There are many approaches to identify, quantify, and illustrate causal relationships. For the scope of this paper, directed graphs are employed as causal models. If the directed graph lacks cycles, it is known as a directed acyclic graph. A node in such a graph represents an observed data element while a directed edge connecting two nodes represents a causal relationship between two variables. The developed causal methods are designed to extract causal models from simulation models and experimental data. Causal models capture the causal relationships between data elements (e.g., simulated and experimental data). In this context, validation and verification are performed by comparing causal models. The proposed approach does not only inform system analysts on how a simulation model matches real-world data, but also identifies elements of the simulation model that should be revised when discrepancies between simulation and experimental data are observed. Through these causal methods, analysts can identify the portion of the model equation(s) that are behind an edge connecting two variables. Hence, once the structural differences between causal models have been determined, model calibration can occur by changing only those model parameters that impact the identified causal relationships.
Solution Verification of CFD Simulations of a Drowning Body at Sea
Authors: Silva S. Ribeiro e , Eça L. 
Published: June 2024

Abstract
This works aims at evaluating the ability of assessing drifting of a drowning body at sea using Computational Fluid Dynamics (CFD). This paper is focused on the evaluation of the numerical accuracy of the CFD simulations performed with the Simerics-MP flow solver, i.e., solution verification. The main goal of the paper is to illustrate the challenges found when using a commercial CFD package.
The study of the drift of a drowning body at sea involves the simulation of incompressible, two-phase (air and water) flows around a bluff body and so the simplest mathematical model to tackle it is the Reynolds-averaged Navier-Stokes equations using ensemble average to define the mean flow and to average mass and momentum balances. This leads to unsteady flow problems that require integration in space and time. Therefore, numerical errors include contributions from the round-off, iterative, discretization (time and space) and statistical errors.
Two simple situations to address the difficulties of estimating numerical uncertainties in the simulation of the drift of a drowning body at sea have been selected: (i) current induced drag forces, no wind and no waves; (ii) wind induced drag forces, no current and no waves. Grid/time refinement studies are performed for the two selected conditions to determine numerical uncertainties of the three selected quantities of interest: the resistance/drag force and the trim (pitch) and sinkage (heave) of the drowning body. It is clear that “default settings” cannot be used for such exercise and that there are small details that may have a significant influence on the estimated uncertainties. Nonetheless, the results show that it is not easy to obtain negligible numerical uncertainties in this type of simulations and so the planned comparison of simulations and experiments to determine the modelling error of CFD will be affected by a significant validation uncertainty.
Long-Term Evaluation of Lipid Profile Changes in Olympic Athletes
Authors: Di Gioia Giuseppe , Buzzelli Lorenzo , Maestrini Viviana , Squeo Maria Rosaria , Lemme Erika , Monosilio Sara , Serdoz Andrea , Fiore Roberto , Zampaglione Domenico , Segreti Andrea , Pelliccia Antonio 
Published: June 2024

Dyslipidemia is a major contributor to the development of atherosclerotic cardiovascular disease. Despite high level of physical activity, athletes are not immune from dyslipidemia, but longitudinal data on the variation of lipids are currently lacking. We sought to assess lipid profile changes over time in Olympic athletes practicing different sports disciplines (power, skills, endurance, and mixed). We enrolled 957 consecutive athletes evaluated from London 2012 to Beijing 2022 Olympic Games. Dyslipidemia was defined as low-density lipoprotein (LDL) ≥115 mg/dl, high-density lipoprotein (HDL) <40 mg/dl for males, or HDL <50 mg/dl for females. Hypertriglyceridemia was defined as triglycerides >150 mg/dl. At the follow-up, a variation of ±40 mg/dl for LDL, ±6 mg/dl for HDL, and ±50 mg/dl for triglycerides was considered relevant. Athletes with follow-up <10 months or taking lower lipid agents were excluded. Follow-up was completed in 717 athletes (74.9%), with a mean duration of 55.6 months. Mean age was 27.2 ± 4.8 years old, 54.6% were male (n = 392). Overall, 19.8% (n = 142) athletes were dyslipidemic at both blood tests, being older, practicing nonendurance sports, and predominantly male. In 69.3% (n = 129) of those with elevated LDL at t0, altered values were confirmed at follow-up, while the same occurred in 36.5% (n = 15) with hypo-HDL and 5.3% (n = 1) in those with elevated triglycerides. Weight and fat mass percentage modifications did not affect lipid profile variation. LDL hypercholesterolemia tends to persist over time especially among male, older, and nonendurance athletes. LDL hypercholesterolemia detection in athletes should prompt early preventive intervention to reduce the risk of future development of atherosclerotic disease.
Exogenous putrescine plays a switch-like influence on the pH stress adaptability of biofilm-based activated sludge
Authors: Jiang Guanyu , Wang Can , Wang Yongchao , Wang Jiayi , Xue Yimei , Lin Yuting , Hu Xurui , Lv Yahui 
Published: June 2024

ABSTRACT

Microbial community adaptability to pH stress plays a crucial role in biofilm formation. This study aims to investigate the regulatory mechanisms of exogenous putrescine on pH stress, as well as enhance understanding and application for the technical measures and molecular mechanisms of biofilm regulation. Findings demonstrated that exogenous putrescine acted as a switch-like distributor affecting microorganism pH stress, thus promoting biofilm formation under acid conditions while inhibiting it under alkaline conditions. As pH decreases, the protonation degree of putrescine increases, making putrescine more readily adsorbed. Protonated exogenous putrescine could increase cell membrane permeability, facilitating its entry into the cell. Subsequently, putrescine consumed intracellular H
+
by enhancing the glutamate-based acid resistance strategy and the γ-aminobutyric acid metabolic pathway to reduce acid stress on cells. Furthermore, putrescine stimulated ATPase expression, allowing for better utilization of energy in H
+
transmembrane transport and enhancing oxidative phosphorylation activity. However, putrescine protonation was limited under alkaline conditions, and the intracellular H
+
consumption further exacerbated alkali stress and inhibits cellular metabolic activity. Exogenous putrescine promoted the proportion of fungi and acidophilic bacteria under acidic stress and alkaliphilic bacteria under alkali stress while having a limited impact on fungi in alkaline biofilms. Increasing
Bdellovibrio
under alkali conditions with putrescine further aggravated the biofilm decomposition. This research shed light on the unclear relationship between exogenous putrescine, environmental pH, and pH stress adaptability of biofilm. By judiciously employing putrescine, biofilm formation could be controlled to meet the needs of engineering applications with different characteristics.

IMPORTANCE
The objective of this study is to unravel the regulatory mechanism by which exogenous putrescine influences biofilm pH stress adaptability and understand the role of environmental pH in this intricate process. Our findings revealed that exogenous putrescine functioned as a switch-like distributor affecting the pH stress adaptability of biofilm-based activated sludge, which promoted energy utilization for growth and reproduction processes under acidic conditions while limiting biofilm development to conserve energy under alkaline conditions. This study not only clarified the previously ambiguous relationship between exogenous putrescine, environmental pH, and biofilm pH stress adaptability but also offered fresh insights into enhancing biofilm stability within extreme environments. Through the modulation of energy utilization, exerting control over biofilm growth and achieving more effective engineering goals could be possible.
Circular metagenome-assembled genome of
Candidatus
Cloacimonadota recovered from anaerobic digestion sludge
Authors: Sakurai Riku , Fukuda Yasuhiro , Tada Chika 
Published: June 2024

ABSTRACT

This study reports a circular metagenome-assembled genome (cMAG) of
Candidatus
Cloacimonadota recovered from a mesophilic full-scale food waste treatment plant. The cMAG spans 2,298,113 bp, with 980× coverage and 1 contig.
Complete genome sequences of
Edwardsiella ictaluri
strains isolated from ayu (
Plecoglossus altivelis altivelis
) in the Kagami and Shimanto Rivers, Kochi, Japan
Authors: Imajoh Masayuki , Yukawa Akane , Kawahara Miyu , Daibata Masanori 
Published: June 2024

ABSTRACT

The complete genome sequences of seven
Edwardsiella ictaluri
strains, isolated from the kidneys of dead ayu (
Plecoglossus altivelis altivelis
) in Kochi’s Kagami and Shimanto Rivers, Japan, were determined. Multilocus sequencing typing revealed that their genotypes were sequence-type ST26.
The dynamics of the female microbiome: unveiling abrupt changes of microbial domains across body sites from prepartum to postpartum phases
Authors: Neumann Charlotte J. , Pausan Manuela-Raluca , Haid Victoria , Weiss Eva-Christine , Kolovetsiou-Kreiner Vassiliki , Amtmann Bettina , Winkler Petra , Mahnert Alexander , Jantscher-Krenn Evelyn , Moissl-Eichinger Christine 
Published: June 2024

ABSTRACT

The microbial ecosystem of women undergoes enormous changes during pregnancy and the perinatal period. Little is known about the extent of changes in the maternal microbiome beyond the vaginal cavity and its recovery after birth. In this study, we followed pregnant women [maternal prepartum (mpre),
n
= 30] into the postpartum period [1 month postpartum, maternal postpartum (mpost),
n
= 30]. We profiled their oral, urinary, and vaginal microbiome; archaeome; mycobiome; and urinary metabolome and compared them with those of nonpregnant (np) women (
n
= 29). Overall, pregnancy status (np, mpre, and mpost) had a smaller effect on the microbiomes than body site, but massive transitions were observed for the oral and urogenital (vaginal and urinary) microbiomes. While the oral microbiome fluctuates during pregnancy but stabilizes rapidly within the first month postpartum, the urogenital microbiome is characterized by a major remodeling caused by a massive loss of
Lactobacillus
and thus a shift from Vaginal Community State Type (CST) I (40% of women) to CST IV (85% of women). The urinary metabolome rapidly reached an np-like composition after delivery, apart from lactose and oxaloacetic acid, which were elevated during active lactation. Fungal and archaeal profiles were indicative of pregnancy status.
Methanobacterium
signatures were found mainly in np women, and
Methanobrevibacter
showed an opposite behavior in the oral cavity (increased) and vagina (decreased) during pregnancy. Our findings suggest that the massive remodeling of the maternal microbiome and metabolome needs more attention and that potential interventions could be envisioned to optimize recovery and avoid long-term effects on maternal health and subsequent pregnancies.

IMPORTANCE
The perinatal microbiome is of specific interest for the health of the mother and infant. We therefore investigate the dynamics of the female microbiome from nonpregnant over prepartum to the postpartum period in urine and the oral and vaginal cavities. A specific focus of this study is put not only on the bacterial part of the microbiome but also on the underinvestigated contribution of fungi and archaea. To our knowledge, we present the first study highlighting those aspects. Our findings suggest that the massive remodeling of the maternal microbiome and metabolome needs more attention and that potential interventions could be envisioned to optimize recovery and avoid long-term effects on maternal health and subsequent pregnancies.
Evaluation of the Allplex HPV assay’s adherence to international guidelines for cervical cancer screening in clinician-collected samples
Authors: Chung Pui Yan Jenny , Dhillon Sharonjit K. , Cortoos Selina , Hamerlinck Hannelore , Pereira Rita , Padalko Elizaveta , Vanden Broeck Davy , Arbyn Marc 
Published: June 2024

ABSTRACT

Clinically validated human papillomavirus (HPV) assays are crucial in cervical cancer screening. In this study, we evaluated the Allplex HPV HR Detection assay (Seegene, SouthKorea) for its clinical accuracy and reproducibility according to the international criteria, using the RealTime High Risk HPV m2000 assay (Abbott, USA) as standard comparator. The Allplex HPV HR assay exhibits significant non-inferior sensitivity to detect cervical intraepithelial neoplasia grade (CIN) 2 or worse (CIN2+) with a ratio of 1.00 (95% CI: 0.97–1.03,
P
= 0.006), insignificant non-inferior sensitivity to detect CIN3+ with a ratio of 1.00 (95% CI: 0.88–1.13,
P
= 0.098), and non-inferior specificity to exclude CIN2+ with a ratio of 0.99 (95% CI: 0.99–1.00,
P
< 0.001) compared to the standard comparator. In addition, the assay shows an excellent reproducibility within the same laboratory [96.5% (95% CI: 94.6–97.9) with a kappa value of 0.91 (95% CI: 0.87–0.95)] and between laboratories [96.7% (95% CI: 94.8–98.0) with a kappa value of 0.91 (95% CI: 0.87–0.95)] for overall high-risk HPV positivity as well as for each individual HPV type. Pooling our study data with those of another independent study supports the consistency of our findings. We conclude that both the clinical accuracy to detect cervical precancer and the reproducibility of Allplex HPV HR Detection assay fulfill the international validation criteria of use in cervical cancer screening.

IMPORTANCE
The clinical validation of human papillomavirus (HPV) assays in accordance with well-established international guidelines is crucial to ensure that only validated assays are used in the context of screening (Meijer et al., Int J Cancer, 2009). The guidelines, developed by an international consortium, require that a novel HPV assay has non-inferior accuracy against a standard comparator test for the detection of cervical intraepithelial neoplasia grade (CIN) 2 or worse (CIN2+). Additionally, a new HPV assay should meet specific criteria for both intra- and inter-laboratory reproducibility to ensure the assay consistently exhibits technical precision and robust performance. Pooling our study data with those of another independent study supports the consistency of our findings. In conclusion, both the clinical accuracy to detect cervical precancer and the reproducibility of Allplex HPV HR Detection assay fulfill the international validation criteria of use in cervical cancer screening.
Absolute quantification of viral proteins from pseudotyped VSV-GP using UPLC-MRM
Authors: Basu Rajeswari , Dambra Richard , Jiang Di , Schätzlein Sophia A. , Njiyang Shu , Ashour Joseph , Chiramel Abhilash I. , Vigil Adam , Papov Vladimir V. 
Published: June 2024

ABSTRACT

The rapidly developing field of oncolytic virus (OV) therapy necessitates the development of new and improved analytical approaches for the characterization of the virus during production and development. Accurate monitoring and absolute quantification of viral proteins are crucial for OV product characterization and can facilitate the understanding of infection, immunogenicity, and development stages of viral replication. Targeted mass spectrometry methods like multiple reaction monitoring (MRM) offer a robust way to directly detect and quantify specific targeted proteins represented by surrogate peptides. We have leveraged the power of MRM by combining ultra-high performance liquid chromatography (UPLC) with a Sciex 6500 triple-stage quadrupole mass spectrometer to develop an assay that accurately and absolutely quantifies the structural proteins of a pseudotyped vesicular stomatitis virus (VSV) intended for use as a new biotherapeutic (designated hereafter as VSV-GP to differentiate it from native VSV). The new UPLC-MRM method provides absolute quantification with the use of heavy-labeled reference standard surrogate peptides. When added in known exact amounts to standards and samples, the reference standards normalize and account for any small perturbations during sample preparation and/or instrument performance, resulting in accurate and precise quantification. Because of the multiplexed nature of MRM, all targeted proteins are quantified at the same time. The optimized assay has been enhanced to quantify the ratios of the processed GP1 and GP2 proteins while simultaneously measuring any remaining or unprocessed form of the envelope protein GP complex (GPC; full-length GPC).

IMPORTANCE
The development of oncolytic viral therapy has gained considerable momentum in recent years. Vesicular stomatitis virus glycoprotein (VSV-GP) is a new biotherapeutic emerging in the oncolytic viral therapy platform. Novel analytical assays that can accurately and precisely quantify the viral proteins are a necessity for the successful development of viral vector as a biotherapeutic. We developed an ultra-high performance liquid chromatography multiple reaction monitoring-based assay to quantify the absolute concentrations of the different structural proteins of VSV-GP. The complete processing of GP complex (GPC) is a prerequisite for the infectivity of the virus. The assay extends the potential for quantifying full-length GPC, which provides an understanding of the processing of GPC (along with the quantification of GP1 and GP2 separately). We used this assay in tracking GPC processing in HEK-293-F production cell lines infected with VSV-GP.
Mechanisms of gastrointestinal toxicity in neuromyelitis optica spectrum disorder patients treated with mycophenolate mofetil: insights from a mouse model and human study
Authors: Li Gong , Xia Li-Juan , Shu Ya-Qing , Wan Lei , Huang Qiao , Ma Xiao-Yu , Zhang Hai-Yi , Zheng Zi-Jian , Wang Xi-Ran , Zhou Shi-Ying , Gao Ang , Ren Hao , Lian Xin-Lei , Xu Dan , Tang Sheng-Qiu , Liao Xiao-Ping , Qiu Wei , Sun Jian 
Published: June 2024

ABSTRACT

Mycophenolate mofetil (MMF) is commonly utilized for the treatment of neuromyelitis optica spectrum disorders (NMOSD). However, a subset of patients experience significant gastrointestinal (GI) adverse effects following MMF administration. The present study aims to elucidate the underlying mechanisms of MMF-induced GI toxicity in NMOSD. Utilizing a vancomycin-treated mouse model, we compiled a comprehensive data set to investigate the microbiome and metabolome in the GI tract to elucidate the mechanisms of MMF GI toxicity. Furthermore, we enrolled 17 female NMOSD patients receiving MMF, who were stratified into non-diarrhea NMOSD and diarrhea NMOSD (DNM) groups, in addition to 12 healthy controls. The gut microbiota of stool samples was analyzed using 16S rRNA gene sequencing. Vancomycin administration prevented weight loss and tissue injury caused by MMF, affecting colon metabolomes and microbiomes. Bacterial β-glucuronidase from Bacteroidetes and Firmicutes was linked to intestinal tissue damage. The DNM group showed higher alpha diversity and increased levels of Firmicutes and Proteobacteria. The β-glucuronidase produced by Firmicutes may be important in causing gastrointestinal side effects from MMF in NMOSD treatment, providing useful information for future research on MMF.

IMPORTANCE
Neuromyelitis optica spectrum disorder (NMOSD) patients frequently endure severe consequences like paralysis and blindness. Mycophenolate mofetil (MMF) effectively addresses these issues, but its usage is hindered by gastrointestinal (GI) complications. Through uncovering the intricate interplay among MMF, gut microbiota, and metabolic pathways, this study identifies specific gut bacteria responsible for metabolizing MMF into a potentially harmful form, thus contributing to GI side effects. These findings not only deepen our comprehension of MMF toxicity but also propose potential strategies, such as inhibiting these bacteria, to mitigate these adverse effects. This insight holds broader implications for minimizing complications in NMOSD patients undergoing MMF therapy.
Anti-phase variation of long eccentricity and precipitation in inland Asia during the Middle Miocene Climatic Optimum
Authors: Zhang Zhongbao , Nie Junsheng , Licht Alexis , Cogne Nathan , Sarr Anta-Clarisse , Shen Tiantian , Liu Xingwan , Wang Weihang , Gao Peng , Li Lin , Poujol Marc , Guihou Abel , Deschamps Pierre , Hao Lewei 
Published: June 2024

Abstract
The mechanisms and pace of orbital forcing on precipitation in inland Asia during the Cenozoic remain poorly understood. Many previous studies using magnetic proxies for precipitation have shown a consistent signal of long eccentricity (405 kyr) in hydrological records of central China that are younger than ca. 11 Ma. Most studies suggest that variations in rainfall amount were controlled by Northern Hemisphere summer insolation, and the peak of precipitation is associated with eccentricity maxima. Here, we report multiple magnetic records dating back to the Middle Miocene Climatic Optimum (MMCO, ~14–17 m.y. ago), including a detailed record from a new section in the Qaidam Basin, which was dated using magnetostratigraphy, U-Pb geochronology, and apatite low-temperature thermochronology. Our records show the exact opposite: 405 kyr wet-dry cycles dominated, but the wetter intervals correspond to eccentricity minima and ice-volume maxima during the MMCO. Taken at face value, these results question the origin—monsoonal or westerly-derived—of the precipitation that reached central China during the middle Miocene and the mechanisms that enhanced monsoonal penetration of inland Asia. We also suggest that this anti-phase relationship could also reflect biases in magnetic proxies for precipitation during the wettest climatic phases, which can result in the dissolution of magnetic minerals and a significant underestimation of past rainfall.