bluuebunny/crossref_metadata_2025 huggingface dataset:
N‐fold Darboux transformation of the discrete PT‐symmetric nonlinear Schrödinger equation and new soliton solutions over the nonzero background
Authors: Xu Tao , An Li‐Cong , Li Min , Xu Chuan‐Xin
Published: March 2024

For the discrete PT‐symmetric nonlinear Schrödinger (dPTNLS) equation, this paper gives a rigorous proof of the N‐fold Darboux transformation (DT) and especially verifies the PT‐symmetric relation between transformed potentials in the Lax pair. Meanwhile, some determinant identities are developed in completing the proof. When the tanh‐function solution is directly selected as a seed for the focusing case, the onefold DT yields a three‐soliton solution that exhibits the solitonic behavior with a wide range of parameter regimes. Moreover, it is shown that the solution contains three pairs of asymptotic solitons, and that each asymptotic soliton can display both the dark and antidark soliton profiles or vanish as . It indicates that the focusing dPTNLS equation admits a rich variety of soliton interactions over the nonzero background, behaving like those in the continuous counterpart.
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

Background

Patients 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.

Methods

A descriptive longitudinal single‐case study design was used, and data were analysed via systematic text condensation.

Results

The 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.

Conclusions

Patients 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

Objective

This 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.

Methods

First, 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.

Results

I 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.

Conclusion

I show that ANT is a useful framework for understanding the representational complexity surrounding public monuments and their reception.
The novel HLA‐B*44:387 allele shows a ‐21 methionine residue in the signal peptide
Authors: Balas Antonio , Moreno‐Hidalgo Miguel‐Ángel , Alenda Raquel , García‐Sánchez Félix , Vicario José L.
Published: March 2024

Characterization of the novel HLA‐B*44:387 allele.
Writing Woes of ESL Learners: Can Dynamic Assessment Be the Solution?
Authors: Kumar Aakash , Rupley William H. , Paige David , McKeown Debra
Published: March 2024

AbstractThis study explores the effectiveness of dynamic assessment (DA) in addressing grammatical writing difficulties in Pakistani English as a Second Language (ESL) learners' writing. Adopting an interactionist approach to DA, the research observes mediational moves by a teacher during the writing assessment process. The study employs a qualitative case study design, examining the interactional patterns and outcomes of DA for three higher secondary-level Pakistani ESL learners over an eight-week period. The findings indicate that the interactionist approach to DA is a promising method for improving the grammatical accuracy of Pakistani ESL learners, particularly in areas such as tenses, pronouns, and subject-verb agreement. The results of this study have significant implications for writing instruction in ESL contexts. Dynamic assessment can support the development of writing skills by providing ESL writers with opportunities to engage in distributive practice and receive feedback on their writing, resulting in a tailored and effective approach to writing instruction.
There are at most finitely many singular moduli that are S-units
Authors: Herrero Sebastián , Menares Ricardo , Rivera-Letelier Juan
Published: March 2024

We show that for every finite set of prime numbers $S$, there are at most finitely many singular moduli that are $S$-units. The key new ingredient is that for every prime number $p$, singular moduli are $p$-adically disperse. We prove analogous results for the Weber modular functions, the $\lambda$-invariants and the McKay–Thompson series associated with the elements of the monster group. Finally, we also obtain that a modular function that specializes to infinitely many algebraic units at quadratic imaginary numbers must be a weak modular unit.
Negligencia dental en la primera infancia: Perspectiva de docentes de odontología de dos universidades colombianas
Authors: Lafaurie V María Mercedes , Díaz Cárdenas Shyley , Castelblanco Retrepo Martha Helena
Published: March 2024

Introducción: la negligencia dental se presenta cuando se descuidan y no se atienden oportunamente por parte de sus cuidadores los problemas de salud oral de los niños. Objetivos: identificar la perspectiva de odontólogos, docentes de las áreas de salud pública y comunitaria de las facultades de odontología de dos universidades colombianas, sobre la negligencia dental que afecta a la primera infancia. Metodología: estudio cualitativo fenomenológico-descriptivo. Se realizaron dos grupos focales online con 11 odontólogos, docentes de las áreas de salud pública y comunitaria, con experiencia en primera infancia. Se realizó análisis temático con apoyo del software Atlas ti 22. Resultados: los participantes coinciden en que la negligencia dental afecta la salud oral y el desarrollo físico y emocional de los niños. Implica caries, dolor, infecciones y pérdida dental. A menudo no es deliberada, siendo difícil de identificar; puede responder a falencias educativas en los padres; supera la responsabilidad familiar, incluyendo al Estado e instituciones de salud y educación. Es frecuente en contextos de desigualdad social y en familias vulnerables donde se delega la responsabilidad del cuidado parental. El desconocimiento de la importancia de la dentición temporal y barreras culturales inciden en este fenómeno. Conclusiones: acorde a la perspectiva de los participantes, la negligencia dental en la primera infancia constituye una problemática compleja frente a la cual se requiere mejorar la capacidad de cuidadores familiares e institucionales para comprender el qué, cómo y por qué del cuidado de la dentición temporal. El odontólogo requiere ser formado para reconocerla, prevenirla y actuar oportunamente.
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

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

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

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

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.
Interrupted mosaic speech revisited: Gain and loss in intelligibility by stretching
Authors: Ueda Kazuo , Hashimoto Masashi , Takeichi Hiroshige , Wakamiya Kohei
Published: March 2024

Our previous investigation on the effect of stretching spectrotemporally degraded and temporally interrupted speech stimuli showed remarkable intelligibility gains [Udea, Takeichi, and Wakamiya (2022). J. Acoust. Soc. Am. 152(2), 970–980]. In this previous study, however, gap durations and temporal resolution were confounded. In the current investigation, we therefore observed the intelligibility of so-called mosaic speech while dissociating the effects of interruption and temporal resolution. The intelligibility of mosaic speech (20 frequency bands and 20 ms segment duration) declined from 95% to 78% and 33% by interrupting it with 20 and 80 ms gaps. Intelligibility improved, however, to 92% and 54% (14% and 21% gains for 20 and 80 ms gaps, respectively) by stretching mosaic segments to fill silent gaps (n = 21). By contrast, the intelligibility was impoverished to a minimum of 9% (7% loss) when stretching stimuli interrupted with 160 ms gaps. Explanations based on auditory grouping, modulation unmasking, or phonemic restoration may account for the intelligibility improvement by stretching, but not for the loss. The probability summation model accounted for “U”-shaped intelligibility curves and the gain and loss of intelligibility, suggesting that perceptual unit length and speech rate may affect the intelligibility of spectrotemporally degraded speech stimuli.
Experimental demonstration of rainbow trapping of elastic waves in two-dimensional axisymmetric phononic crystal plates
Authors: Ellouzi Chadi , Zabihi Ali , Gormley Louis , Aghdasi Farhood , Stojanoska Katerina , Miri Amir , Jha Ratneshwar , Shen Chen
Published: March 2024

Structures with specific graded geometries or properties can cause spatial separation and local field enhancement of wave energy. This phenomenon is called rainbow trapping, which manifests itself as stopping the propagation of waves at different locations according to their frequencies. In acoustics, most research on rainbow trapping has focused on wave propagation in one dimension. This research examined the elastic wave trapping performance of a two-dimensional (2D) axisymmetric grooved phononic crystal plate structure. The performance of the proposed structure is validated using numerical simulations based on finite element analysis and experimental measurements using a laser Doppler vibrometer. It is found that rainbow trapping within the frequency range of 165–205 kHz is achieved, where elastic waves are trapped at different radial distances in the plate. The results demonstrate that the proposed design is capable of effectively capturing elastic waves across a broad frequency range of interest. This concept could be useful in applications such as filtering and energy harvesting by concentrating wave energy at different locations in the structure.
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

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

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

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

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

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

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.
Does extremely early expression of colostrum after very preterm birth improve mother’s own milk quantity? A cohort study
Authors: Levene Ilana , Quigley Maria A , Fewtrell Mary , O’Brien Frances
Published: March 2024

Objective

Assess the relationship of time to first expression after very preterm birth and mothers’ own milk quantity.

Design

A cohort study (nested within a randomised trial).

Setting

Four neonatal units in the UK.

Patients

132 mothers of single or twin infants born at 23+0 to 31+6 weeks postmenstrual age.

Exposures

Time to the first attempt to express after birth.

Primary outcomes

24-hour mother’s own milk yield on days 4, 14 and 21 after birth.

Results

Median time to first expression attempt was 6 hours. 51.7% expressed within 6 hours of birth (62/120) and 48.3% expressed more than 6 hours after birth (58/120). Expressing within 6 hours of birth was associated with higher milk yield on day 4 (88.3 g, 95% CI 7.1 to 169.4) and day 14 (155.7 g, 95% CI 12.2 to 299.3) but not on day 21 (73.6 g, 95% CI −91.4 to 238.7). There was an interaction between expressing frequency and time to first expression (p<0.005), with increased expressing frequency being associated with higher yield only in those who expressed within 6 hours. Expressing within 2 hours of birth was not associated with further milk yield increase.

Conclusions

Mothers who expressed within 6 hours of birth had higher milk yield, and a greater yield per expressing session, in the first 3 weeks after birth. This information will be highly motivating for families and the clinicians supporting them. There was no evidence of further benefit of extremely early expression (first 2 hours after birth).

Trial registration number

ISRCTN 16356650.
Endometriosis-associated spontaneous major haemoperitoneum in pregnancy
Authors: Mondelli Benedetto , Balais George , Erritty Matthew , Minas Vasileios
Published: March 2024

Spontaneous haemoperitoneum in pregnancy (SHiP) related to endometriosis is a rare and life-threatening complication. We report a case of a patient presenting to our department with major haemoperitoneum at 23+3 weeks of gestation due to a large rectovaginal endometriotic nodule. The patient required a midline laparotomy to evacuate 1 L of haemoperitoneum and achieve haemostasis. A large rectovaginal nodule was seen bleeding and was packed with haemostatic material and a large swab. After 24 hours, the swab was removed and haemostasis was confirmed. The patient was monitored very closely by a multidisciplinary team and the pregnancy was allowed to continue to try and achieve a better outcome for the baby and at 28 weeks of gestation, a girl was delivered in good condition via caesarean section.
Mycobacterium bovisinfection of the appendix: a case of appendiceal tuberculosis in rural England
Authors: Miles Esther Lucy , Spellar Kayleigh , Williams David
Published: March 2024

Appendiceal tuberculosis is a rare mimic of acute appendicitis, demonstrated by several case reports of patients from tuberculosis endemic countries. On literature review, there are few cases reported of appendiceal tuberculosis in urban England, and no reports from rural England. This case describes a patient with primary appendiceal tuberculosis from a remote district hospital in England who underwent a diagnostic laparoscopy for suspected acute appendicitis. Intraoperatively, an abnormal appearance with extensive intra-abdominal adhesions was seen in addition to appendicitis, making the diagnosis dubious. Histology of the appendix was positive for acid-fast bacilli and culture of the intra-abdominal fluid revealed a diagnosis ofMycobacterium bovisinfection. The mode of infection was thought to be reactivation of latent bovine tuberculosis from drinking unpasteurised milk in adolescence. Taking a focused history, particularly in those with a farming background, and intraoperative sampling for histology and culture are vital in the diagnosis of appendiceal tuberculosis.
Postpartum ovarian vein thrombosis with left renal venous infarction after vaginal delivery
Authors: Cheung Wingman , Stegwee Sanne , van Hamont Dennis , Visser Jantien
Published: March 2024

A primipara in her late 20s presented with abdominal pain and pain in the left flank 14 days after a ventouse delivery. She was treated with antibiotics, antiemetics and analgesics with the initial differential diagnosis of cystitis, pyelonephritis or nephrolithiasis. Despite the treatment, the patient experienced increased colic pain and nausea. An ultrasound showed an enlarged left kidney, suggesting pyelonephritis, and thereby, the antibiotic treatment was adjusted accordingly. Despite additional pain medication, pain relief could not be achieved. The diagnosis of ovarian venous thrombosis was considered, and an abdominal CT scan confirmed the diagnosis. The patient was treated with anticoagulant therapy. Hypercoagulability work-up revealed a heterozygous mutation of the Factor V Leiden. Our patient awaits a haematologic follow-up.
National COVID-19 preparedness and response plans: a global review from the perspective of services for maternal, newborn, child and adolescent health and older people
Authors: Czerniewska Alexandra , Sharkey Alyssa , Portela Anayda , Drapkin Sarah , Mustafa Saqif
Published: March 2024

Introduction

Infectious disease outbreaks have historically led to widespread disruptions in routine essential health services. Disruptions due to COVID-19 responses led to excess deaths, including among women and children. This review builds on earlier reviews of essential health services in national COVID-19 response and preparedness plans, focusing specifically on maternal, newborn, child, adolescent and ageing health (MNCAAH) in the context of renewed global emphasis on monitoring, recovering and strengthening these services.

Methods

Using Google searches, we identified publicly available COVID-19 response and preparedness plans authored by a national government body or Public Health Institute from any country, territory and/or area, published between January 2020 and December 2022. We assessed whether each plan considered maintenance of MNCAAH services with related activities, costing or monitoring plans, and whether these considerations were integrated into the national incident management system for COVID-19.

Results

We identified plans from 110 countries, representing 56% of our sample, in 10 languages. Most plans came from low-income and middle-income countries. Three quarters of dated documents were published between February and April 2020. 22% of plans referenced the impact of COVID-19 on MNCAAH, but only 13% included a planned activity for monitoring or mitigating this impact and less than 5% included relevant indicators, costing or integration of services in the incident management system.

Conclusion

We propose that unless content specifically related to the services and needs of these populations is integrated, these services will suffer in a future disruptive event. The COVID-19 response demonstrated the need for an interdisciplinary response to address the unforeseen impacts that arose, yet plans continue to have a narrow focus and a generic approach which may be limiting.
Words matter: ‘enduring intolerable suffering’ and the provider-side peril of Medical Assistance in Dying in Canada
Authors: Lyon Christopher
Published: March 2024

Enduring intolerable suffering, an essential eligibility criterion in Medical Assistance in Dying (MAiD) in Canada and elsewhere, is a contradiction in terms, in that suffering must be tolerable to be endured. Cases of people who were approved for MAiD but who elected to die naturally, thus tolerating their suffering, bear out the unreliability of this central safeguard. The clinical assessment of intolerable suffering may be strengthened by adopting a definition of intolerable suffering centred on clinically evidenced physical and psychological decompensation. This argument also raises important questions about the risks of MAiD clinicians subjectively defining, approving and providing MAiD in ways that deviate from accepted legal and clinical concepts and ethics. Examples show some prolific clinicians describe MAiD in terminology that differs from such norms, as a personal mission, as personally pleasurable, and as a rights-based service. These alternative views are explored for their risks in assessing and providing MAiD for intolerable suffering. This further demonstrates the need for conceptual clarity in legislation, improved vetting and monitoring of clinicians, and a different assessment process to protect patients and clinicians.
Learning imaging in axial spondyloarthritis: more than just a matter of experience
Authors: Radny Felix , Ziegeler Katharina , Eshed Iris , Greese Juliane , Deppe Dominik , Stelbrink Carsten , Biesen Robert , Haibel Hildrun , Rios Rodriguez Valeria , Rademacher Judith , Protopopov Mikhail , Proft Fabian , Hermann Kay Geert A , Poddubnyy Denis , Diekhoff Torsten , Ulas Sevtap Tugce
Published: March 2024

Objective

Reliable interpretation of imaging findings is essential for the diagnosis of axial spondyloarthritis (axSpA) and requires a high level of experience. We investigated experience-dependent differences in diagnostic accuracies using X-ray (XR), MRI and CT.

Methods

This post hoc analysis included 163 subjects with low back pain. Eighty-nine patients had axSpA, and 74 patients had other conditions (mechanical, degenerative or non-specific low back pain). Final diagnoses were established by an experienced rheumatologist before the reading sessions. Nine blinded readers (divided into three groups with different levels of experience) scored the XR, CT and MRI of the sacroiliac joints for the presence versus absence of axSpA. Parameters for diagnostic performance were calculated using contingency tables. Differences in diagnostic performance between the reader groups were assessed using the McNemar test. Inter-rater reliability was assessed using Fleiss kappa.

Results

Diagnostic performance was highest for the most experienced reader group, except for XR. In the inexperienced and semi-experienced group, diagnostic performance was highest for CT&MRI (78.5% and 85.3%, respectively). In the experienced group, MRI showed the highest performance (85.9%). The greatest difference in diagnostic performance was found for MRI between the inexperienced and experienced group (76.1% vs 85.9%, p=0.001). Inter-rater agreement was best for CT in the experienced group with κ=0.87.

Conclusion

Differences exist in the learnability of the imaging modalities for axSpA diagnosis. MRI requires more experience, while CT is more suitable for inexperienced radiologists. However, diagnosis relies on both clinical and imaging information.
Impact of cigarette price and tobacco control policies on youth smoking experimentation in Albania
Authors: Merkaj Elvina , Zhllima Edvin , Imami Drini , Gjika Irena , Guerrero-López Carlos Manuel , Drope Jeffrey
Published: March 2024

Background

Albania has one of the highest smoking prevalence in Europe especially among the youth. There is a lack of evidence in Albania, as well as in most of Eastern Europe and middle-income countries, regarding the effect of price on smoking experimentation.

Objective

The study aims to assess the effect of price and tobacco control policies on youth smoking experimentation in Albania.

Methods

We used microdata from the Global Youth Tobacco Survey in Albania for 2004, 2009, 2015 and 2020. We constructed a pseudo-longitudinal dataset and estimated a split-population model to assess the hazard of smoking experimentation.

Results

Price is a significant predictor of smoking experimentation among teenagers in Albania for both males and females (p<0.001). Being male increases the odds for smoking experimentation by more than 50% as compared with females (p<0.001), whereas females appear to be more price sensitive. Peer and parent smoking are also important determinants for smoking experimentation. Introducing penalties for smokers and legal entities violating smoke-free policies implemented in 2014 is also associated with a lower hazard of smoking experimentation.

Conclusion

Price is a significant predictor of smoking experimentation among teenagers in Albania for both males and females. A combination of increasing taxes and strengthening the rule of law to control tobacco use in public spaces, in addition to public awareness campaigns targeting both youth and smoking parents, could help to significantly reduce the probability of smoking experimentation.
Do serial troponins predict the need for cardiac evaluation in trauma patients after ground-level fall?
Authors: Bellini Alyssa R , Ross James T , Larson Madelyn , Pearson Skyler , Robles Anamaria J , Callcut Rachael A
Published: March 2024

Purpose

Troponin T levels are routinely checked in trauma patients after experiencing a ground-level fall to identify potential cardiac causes of syncope. An elevated initial troponin prompts serial testing until the level peaks. However, the high sensitivity of the test may lead to repeat testing that is of little clinical value. Here, we examine the role of serial troponins in predicting the need for further cardiac workup in trauma patients after sustaining a fall.

Methods

Retrospective review of all adult trauma activations for ground-level fall from January 1, 2021 to December 31, 2021 in patients who were hemodynamically and neurologically normal at presentation. Outcomes evaluated included need for cardiology consult, admission to cardiology service, outpatient cardiology follow-up, cardiology intervention and in-hospital mortality.

Results

There were 1555 trauma activations for ground-level fall in the study period. The cohort included 560 patients evaluated for a possible syncopal fall, hemodynamically stable, Glasgow Coma Scale score of 15, and with a troponin drawn at presentation. The initial median troponin was 20 ng/L (13–37). Second troponin values were drawn on 58% (median 33 ng/L (22–52)), with 42% of patients having an increase from first to second test. 29% of patients had a third troponin drawn (median 42 ng/L (26–67)). The initial troponin value was significantly associated with undergoing a subsequent echo (p=0.01), cardiology consult (p<0.01), admission for cardiac evaluation (p<0.01), cardiology follow-up (p<0.01), and in-hospital mortality (p=0.01); the initial troponin was not associated with cardiac intervention (p=0.91). An increase from the first to second troponin was not associated with any of outcomes of interest. Analysis was done with cut-off values of 30 ng/L, 50 ng/L, 70 ng/L, and 90 ng/L; a troponin T threshold of 19 ng/L was significant for cardiology consult (p=0.01) and cardiology follow-up (p=0.04). When the threshold was increased to 50 ng/L, it was also significant for admission for cardiac issue (p<0.01). When the threshold was increased to 90 ng/L, it was significant for the same three outcomes and in-hospital mortality (p=0.04).

Conclusion

The initial serum troponin has clinical value in identifying underlying cardiac disease in patients who present after ground-level fall; however, that serial testing is likely of little value. Further, using a cut-off of >50 ng/L as a threshold for further clinical evaluation would improve the utility of the test and likely reduce unnecessary hospital stays and costs for otherwise healthy patients.

Level of evidence

Level III.