bluuebunny/crossref_metadata_2025_split huggingface dataset:
A fast transition: A case study of patients' experiences during the diagnostic and surgical treatment phase of an accelerated brain cancer pathway
Authors: Vedelø Tina Wang , Sørensen Jens Christian H. , Hall Elisabeth O. C. , Delmar Charlotte 
Published: March 2024

AbstractBackgroundPatients receiving a brain cancer diagnosis may face cognitive decline and a poor prognosis. In addition, they suffer from a high symptom burden in a complex cancer pathway. The aim of this study was to investigate the early hospital experiences of brain tumour patients during the diagnostic and surgical treatment phase.MethodsA descriptive longitudinal single‐case study design was used, and data were analysed via systematic text condensation.ResultsThe patients' experiences of being diagnosed with and treated for brain cancer were interpreted in terms of the central theme: a fast transition into an unknown journey. This theme consisted of the following subthemes: emotionally overwhelmed, putting life on hold and an unfamiliar dependency.ConclusionsPatients diagnosed with brain cancer struggle with overwhelming emotions due to this sudden life‐threatening diagnosis, their fear of brain surgery and their progressing dependence. Patients did not voice their feelings, fears or needs, so these may easily be overlooked and unmet. A proactive and continuous care approach throughout the diagnostic phase is needed to support these patients.
Erecting monuments and making meanings: Analysis of the Statue of Peace using actor‐network theory
Authors: Yun Jieheerah 
Published: March 2024

AbstractObjectiveThis article analyzes the monument‐building and meaning‐making processes in the construction of the Statues of Peace erected to commemorate the Korean “Comfort Women.” The tensions surrounding the erection of the Statues of Peace did not stop with their installation, as people then started to place different objects on the statues. This article uses actor‐network theory (ANT) to shed light on the formation that this has involved of a new representational and cultural politics.MethodsFirst, archival research was conducted to understand current issues involving both ANT and the Statues of Peace. Participant observations and semistructured interviews with NGOs were conducted.ResultsI look at the afterlife of the Statues of Peace in cases involving not only destruction or restoration but also smaller acts of support or subversion. New material quality and meanings were formed by these actions.ConclusionI show that ANT is a useful framework for understanding the representational complexity surrounding public monuments and their reception.
Cable Path Analysis and Kinematic Control of a Cable-Driven Parallel Robot Allowing Cables to Wrap on Cylinders or Spheres
Authors: Xiong Hao , Xu Yuchen , Yu Yuanjie , Lou Yunjiang 
Published: March 2024

Abstract
Scholars have proposed to allow cables to wrap on the base, the end-effector, or obstacles to expand the workspace of a cable-driven parallel robot (CDPR) in recent years. However, it is not entirely clear whether the path of a cable wrapped on the surface of different rigid bodies can or cannot be solved analytically. To this end, this paper analyzes the statics of a cable wrapped on a general surface and proposes necessary conditions for a path of a cable wrapped on a general frictionless surface. This paper shows that only the path of a cable wrapped on a frictionless surface included in a handful of surfaces, including cylinders and spheres, can be solved analytically. Then, the cable path and inverse velocity kinematics of a CDPR with cables, every of which wraps on a frictionless cylinder or a frictionless sphere, are solved. A CDPR demonstrator with cables wrapped on cylinders fixed to the base and a CDPR demonstrator with cables wrapped on a spherical end-effector are established. The kinematics-based control of the CDPR demonstrators is achieved.
Design of a Novel Linkage for Electronic Parking Brake Transmission Systems
Authors: Quaglia Giuseppe , Pepe Fortunato , Toccaceli Lorenzo , Colucci Giovanni 
Published: March 2024

Abstract
This paper presents a novel mechanical transmission for pulling-cable electronic parking brakes (EPBs). The system is interposed between the brake electric actuator and the brake pads, and it exploits a 2DOF planar linkage to provide the requested brake force and ensure the correct vehicle standstill. This paper describes the working principles and main component of the adopted architecture, and compares it with the EPB state of the art. Thereafter, the paper focuses on the system requirements and consequent functional design. A first prototype of the presented mechanical transmission is then presented to discuss the role of a mechanical engagement within the system to ensure its proper behavior. In conclusion, the EPB drive motor assessment is discussed on the basis of a simplified drive chain dynamic model.
Multiphysics Missing Data Synthesis: A Machine Learning Approach for Mitigating Data Gaps and Artifacts
Authors: Steuben J. C. , Geltmacher A. B. , Rodriguez S. N. , Graber B. D. , Iliopoulos A. P. , Michopoulos J. G. 
Published: March 2024

Abstract
The presence of gaps and spurious nonphysical artifacts in datasets is a nearly ubiquitous problem in many scientific and engineering domains. In the context of multiphysics numerical models, data gaps may arise from lack of coordination between modeling elements and limitations of the discretization and solver schemes employed. In the case of data derived from physical experiments, the limitations of sensing and data acquisition technologies, as well as myriad sources of experimental noise, may result in the generation of data gaps and artifacts. In the present work, we develop and demonstrate a machine learning (ML) meta-framework for repairing such gaps in multiphysics datasets. A unique “cross-training” methodology is used to ensure that the ML models capture the underlying multiphysics of the input datasets, without requiring training on datasets free of gaps/artifacts. The general utility of this approach is demonstrated by the repair of gaps in a multiphysics dataset taken from hypervelocity impact simulations. Subsequently, we examine the problem of removing scan artifacts from X-ray computed microtomographic (XCMT) datasets. A unique experimental methodology for acquiring XCMT data, wherein articles are scanned multiple times under different conditions, enables the ready identification of artifacts, their removal from the datasets, and the filling of the resulting gaps using the ML framework. This work concludes with observations regarding the unique features of the developed methodology, and a discussion of potential future developments and applications for this technology.
Integration of Febio as an Instructional Tool in the Undergraduate Biomechanics Curriculum
Authors: Jiang David , Grainger David W. , Weiss Jeffrey A. , Timmins Lucas H. 
Published: March 2024

Abstract
Computer simulations play an important role in a range of biomedical engineering applications. Thus, it is important that biomedical engineering students engage with modeling in their undergraduate education and establish an understanding of its practice. In addition, computational tools enhance active learning and complement standard pedagogical approaches to promote student understanding of course content. Herein, we describe the development and implementation of learning modules for computational modeling and simulation (CM&S) within an undergraduate biomechanics course. We developed four CM&S learning modules that targeted predefined course goals and learning outcomes within the febio studio software. For each module, students were guided through CM&S tutorials and tasked to construct and analyze more advanced models to assess learning and competency and evaluate module effectiveness. Results showed that students demonstrated an increased interest in CM&S through module progression and that modules promoted the understanding of course content. In addition, students exhibited increased understanding and competency in finite element model development and simulation software use. Lastly, it was evident that students recognized the importance of coupling theory, experiments, and modeling and understood the importance of CM&S in biomedical engineering and its broad application. Our findings suggest that integrating well-designed CM&S modules into undergraduate biomedical engineering education holds much promise in supporting student learning experiences and introducing students to modern engineering tools relevant to professional development.
MbovP0725, a secreted serine/threonine phosphatase, inhibits the host inflammatory response and affects metabolism in
Mycoplasma bovis
Authors: Zhang Hui , Zhang Yiqiu , Lu Doukun , Chen Xi , Chen Yingyu , Hu Changmin , Guo Aizhen 
Published: March 2024

ABSTRACT

Mycoplasma
species are able to produce and release secreted proteins, such as toxins, adhesins, and virulence-related enzymes, involved in bacteria adhesion, invasion, and immune evasion between the pathogen and host. Here, we investigated a novel secreted protein, MbovP0725, from
Mycoplasma bovis
encoding a putative haloacid dehalogenase (HAD) hydrolase function of a key serine/threonine phosphatase depending on Mg
2+
for the dephosphorylation of its substrate
pNPP,
and it was most active at pH 8 to 9 and temperatures around 40°C. A transposon insertion mutant strain of
M. bovis
HB0801 that lacked the protein MbovP0725 induced a stronger inflammatory response but with a partial reduction of adhesion ability. Using transcriptome sequencing and quantitative reverse transcription polymerase chain reaction analysis, we found that the mutant was upregulated by the mRNA expression of genes from the glycolysis pathway, while downregulated by the genes enriched in ABC transporters and acetate kinase–phosphate acetyltransferase pathway. Untargeted metabolomics showed that the disruption of the
Mbov_0725
gene caused the accumulation of 9-hydroxyoctadecadienoic acids and the consumption of cytidine 5′-monophosphate, uridine monophosphate, and adenosine monophosphate. Both the exogenous and endogenous MbvoP0725 protein created by purification and transfection inhibited lipopolysaccharide (LPS)-induced IL-1β, IL-6, and TNF-α mRNA production and could also attenuate the activation of MAPK-associated pathways after LPS treatment. A pull-down assay identified MAPK p38 and ERK as potential substrates for MbovP0725. These findings define metabolism- and virulence-related roles for a HAD family phosphatase and reveal its ability to inhibit the host pro-inflammatory response.

IMPORTANCE

Mycoplasma bovis
(
M. bovis
) infection is characterized by chronic pneumonia, otitis, arthritis, and mastitis, among others, and tends to involve the suppression of the immune response via multiple strategies to avoid host cell immune clearance. This study found that MbovP0725, a haloacid dehalogenase (HAD) family phosphatase secreted by
M. bovis
, had the ability to inhibit the host pro-inflammatory response induced by lipopolysaccharide. Transcriptomic and metabolomic analyses were used to identify MbovP0725 as an important phosphatase involved in glycolysis and nucleotide metabolism. The
M. bovis
transposon mutant strain T8.66 lacking MbovP0725 induced a higher inflammatory response and exhibited weaker adhesion to host cells. Additionally, T8.66 attenuated the phosphorylation of MAPK P38 and ERK and interacted with the two targets. These results suggested that MbovP0725 had the virulence- and metabolism-related role of a HAD family phosphatase, performing an anti-inflammatory response during
M. bovis
infection.
Construction of an infectious clone for enterovirus A89 and mutagenesis analysis of viral infection and cell binding
Authors: Yan Jingjing , Wang Min , Li Xiaohong , Fan Jun , Yu Rui , Kang Miaomiao , Zhang Yong , Xu Jianqing , Zhang Xiaoyan , Zhang Shuye 
Published: March 2024

ABSTRACT

Enterovirus A89 (EV-A89) is an unconventional strain belonging to the
Enterovirus A
species. Limited research has been conducted on EV-A89, leaving its biological and pathogenic properties unclear. Developing reverse genetic tools for EV-A89 would help to unravel its infection mechanisms and aid in the development of vaccines and anti-viral drugs. In this study, an infectious clone for EV-A89 was successfully constructed and recombinant enterovirus A89 (rEV-A89) was generated. The rEV-A89 exhibited similar characteristics such as growth curve, plaque morphology, and dsRNA expression with parental strain. Four amino acid substitutions were identified in the EV-A89 capsid, which were found to enhance viral infection. Mechanistic studies revealed that these substitutions increased the virus’s cell-binding ability. Establishing reverse genetic tools for EV-A89 will significantly contribute to understanding viral infection and developing anti-viral strategies.

IMPORTANCE

Enterovirus A
species contain many human pathogens and have been classified into conventional cluster and unconventional cluster. Most of the research focuses on various conventional members, while understanding of the life cycle and infection characteristics of unconventional viruses is still very limited. In our study, we constructed the infectious cDNA clone and single-round infectious particles for the unconventional EV-A89, allowing us to investigate the biological properties of recombinant viruses. Moreover, we identified key amino acids residues that facilitate EV-A89 infection and elucidate their roles in enhancing viral binding to host cells. The establishment of the reverse genetics system will greatly facilitate future study on the life cycle of EV-A89 and contribute to the development of prophylactic vaccines and anti-viral drugs.
Sequence signatures within the genome of SARS-CoV-2 can be used to predict host source
Authors: Rudar Josip , Kruczkiewicz Peter , Vernygora Oksana , Golding G. Brian , Hajibabaei Mehrdad , Lung Oliver 
Published: March 2024

ABSTRACT

We conducted an
in silico
analysis to better understand the potential factors impacting host adaptation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in white-tailed deer, humans, and mink due to the strong evidence of sustained transmission within these hosts. Classification models trained on single nucleotide and amino acid differences between samples effectively identified white-tailed deer-, human-, and mink-derived SARS-CoV-2. For example, the balanced accuracy score of Extremely Randomized Trees classifiers was 0.984 ± 0.006. Eighty-eight commonly identified predictive mutations are found at sites under strong positive and negative selective pressure. A large fraction of sites under selection (86.9%) or identified by machine learning (87.1%) are found in genes other than the spike. Some locations encoded by these gene regions are predicted to be B- and T-cell epitopes or are implicated in modulating the immune response suggesting that host adaptation may involve the evasion of the host immune system, modulation of the class-I major-histocompatibility complex, and the diminished recognition of immune epitopes by CD8+ T cells. Our selection and machine learning analysis also identified that silent mutations, such as C7303T and C9430T, play an important role in discriminating deer-derived samples across multiple clades. Finally, our investigation into the origin of the B.1.641 lineage from white-tailed deer in Canada discovered an additional human sequence from Michigan related to the B.1.641 lineage sampled near the emergence of this lineage. These findings demonstrate that machine-learning approaches can be used in combination with evolutionary genomics to identify factors possibly involved in the cross-species transmission of viruses and the emergence of novel viral lineages.

IMPORTANCE
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible virus capable of infecting and establishing itself in human and wildlife populations, such as white-tailed deer. This fact highlights the importance of developing novel ways to identify genetic factors that contribute to its spread and adaptation to new host species. This is especially important since these populations can serve as reservoirs that potentially facilitate the re-introduction of new variants into human populations. In this study, we apply machine learning and phylogenetic methods to uncover biomarkers of SARS-CoV-2 adaptation in mink and white-tailed deer. We find evidence demonstrating that both non-synonymous and silent mutations can be used to differentiate animal-derived sequences from human-derived ones and each other. This evidence also suggests that host adaptation involves the evasion of the immune system and the suppression of antigen presentation. Finally, the methods developed here are general and can be used to investigate host adaptation in viruses other than SARS-CoV-2.
Emergence and spread of
Mycobacterium ulcerans
at different geographic scales
Authors: Briand Martial , Boccarossa Alexandra , Rieux Adrien , Jacques Marie-Agnès , Ganlanon Line , Johnson Christian , Eveillard Matthieu , Marsollier Laurent , Marion Estelle 
Published: March 2024

ABSTRACT

The classical lineage of
Mycobacterium ulcerans
is the most prevalent clonal group associated with Buruli ulcer in humans. Its reservoir is strongly associated with the environment. We analyzed together 1,045 isolates collected from 13 countries on two continents to define the evolutionary history and population dynamics of this lineage. We confirm that this lineage spread over 7,000 years from Australia to Africa with the emergence of outbreaks in distinct waves in the 18th and 19th centuries. In sharp contrast with its global spread over the last century, transmission chains are now mostly local, with little or no dissemination between endemic areas. This study provides new insights into the phylogeography and population dynamics of
M. ulcerans,
highlighting the importance of comparative genomic analyses to improve our understanding of pathogen transmission.

IMPORTANCE

Mycobacterium ulcerans
is an environmental mycobacterial pathogen that can cause Buruli ulcer, a severe cutaneous infection, mostly spread in Africa and Australia. We conducted a large genomic study of
M. ulcerans
, combining genomic and evolutionary approaches to decipher its evolutionary history and pattern of spread at different geographic scales. At the scale of villages in an endemic area of Benin, the circulating genotypes have been introduced in recent decades and are not randomly distributed along the river. On a global scale,
M. ulcerans
has been spreading for much longer, resulting in distinct and compartmentalized endemic foci across Africa and Australia.
Reverse transcription of plasma-derived HIV-1 RNA generates multiple artifacts through tRNA(Lys-3)-priming
Authors: Hardy Jarryt , Demecheleer Els , Schauvliege Marlies , Staelens Delfien , Mortier Virginie , Verhofstede Chris 
Published: March 2024

ABSTRACT

In vitro
reverse transcription of full-length HIV-1 RNA extracted from the blood plasma of people living with HIV-1 remains challenging. Here, we describe the initiation of reverse transcription of plasma-derived viral RNA in the absence of an exogenous primer. Real-time PCR and Sanger sequencing were applied to identify the source and to monitor the outcome of this reaction. Results demonstrated that during purification of viral RNA from plasma, tRNA(Lys-3) is co-extracted in a complex with the viral RNA. In the presence of a reverse transcription enzyme, this tRNA(Lys-3) can induce reverse transcription, a reaction that is not confined to transcription of the 5’ end of the viral RNA. A range of cDNA products is generated, most of them indicative for the occurrence of
in vitro
strand transfer events that involve translocation of cDNA from the 5’ end to random positions on the viral RNA. This process results in the formation of cDNAs with large internal deletions. However, near full-length cDNA and cDNA with sequence patterns resembling multiple spliced HIV-1 RNA were also detected. Despite its potential to introduce significant bias in the interpretation of results across various applications, tRNA(Lys-3)-driven reverse transcription has been overlooked thus far. A more in-depth study of this tRNA-driven
in vitro
reaction may provide new insight into the complex process of
in vivo
HIV-1 replication.

IMPORTANCE

The use of silica-based extraction methods for purifying HIV-1 RNA from viral particles is a common practice, but it involves co-extraction of human tRNA(Lys-3) due to the strong interactions between these molecules. This co-extraction becomes particularly significant when the extracted RNA is used in reverse transcription reactions, as the tRNA(Lys-3) then serves as a primer. Reverse transcription from tRNA(Lys-3) is not confined to cDNA synthesis of the 5’ end of the viral RNA but extends across various regions of the viral genome through
in vitro
strand transfer events. Co-extraction of tRNA(Lys-3) has been overlooked thus far, despite its potential to introduce bias in downstream, reverse transcription-related applications. The observed events in the tRNA(Lys-3)-induced
in vitro
reverse transcription resemble
in vivo
replication processes. Therefore, these reactions may offer a unique model to better understand the replication dynamics of HIV-1.
Comparison of
tet
(X4)-containing contigs assembled from metagenomic sequencing data with plasmid sequences of isolates from a cohort of healthy subjects
Authors: Ding Yichen , Er Shuan , Tan Abel , Gounot Jean-Sebastien , Saw Woei-Yuh , Tan Linda Wei Lin , Teo Yik Ying , Nagarajan Niranjan , Seedorf Henning 
Published: March 2024

ABSTRACT

Recently discovered
tet
(X) gene variants have provided new insights into microbial antibiotic resistance mechanisms and their potential consequences for public health. This study focused on detection, analysis, and characterization of Tet(X4)-positive Enterobacterales from the gut microbiota of a healthy cohort of individuals in Singapore using cultivation-dependent and cultivation-independent approaches. Twelve Tet(X4)-positive Enterobacterales strains that were previously obtained from the cohort were fully genome-sequenced and comparatively analyzed. A metagenomic sequencing (MS) data set of the same samples was mined for contigs that harbored the
tet
(X4) resistance gene. The sequences of
tet
(X4)-containing contigs and plasmids sequences were compared. The presence of the resistance genes
floR
and
estT
(previously annotated as
catD
) was detected in the same cassette in 10 and 12 out of the 12
tet
(X4)-carrying plasmids, respectively. MS detected
tet
(X4)-containing contigs in 2 out of the 109 subjects, while cultivation-dependent analysis previously reported a prevalence of 10.1%. The
tet
(X4)-containing sequences assembled from MS data are relatively short (~14 to 33 kb) but show high similarity to the respective plasmid sequences of the isolates. Our findings show that MS can complement efforts in the surveillance of antibiotic resistance genes for clinical samples, while it has a lower sensitivity than a cultivation-based method when the target organism has a low abundance. Further optimization is required if MS is to be utilized in antibiotic resistance surveillance.

IMPORTANCE

The global rise in antibiotic resistance makes it necessary to develop and apply new approaches to detect and monitor the prevalence of antibiotic resistance genes in human populations. In this regard, of particular interest are resistances against last-resort antibiotics, such as tigecycline. In this study, we show that metagenomic sequencing can help to detect high abundance of the tigecycline resistance gene
tet
(X4) in fecal samples from a cohort of healthy human subjects. However, cultivation-based approaches currently remain the most reliable and cost-effective method for detection of antibiotic-resistant bacteria.