bluuebunny/crossref_metadata_2025 huggingface dataset:
Stability of Thermal Convection in Two Superimposed Miscible Viscous Fluids Under Gravitational Modulation
Authors: Echchadli Mourad , Aniss Saïd
Published: October 2024

The thermal stability of a system of two superimposed miscible viscous fluid layers, under gravitational modulation, is investigated using linear stability analysis. It is well known in the literature that in the absence of gravitational modulation, there exist two convection regimes depending on the buoyancy number: the single-cell regime, where convection is oscillating and occupies the entire volume of the two fluid layers, and the stratified regime where stationary convection occurs in each fluid layer. Using Chebyshev's spectral collocation method and Floquet's theory, the numerical results show that under gravitational modulation, single-cell convection oscillates at half the frequency of the external oscillation (subharmonic threshold), while the stratified regime oscillates at a frequency equal to that of the forcing (harmonic threshold). The critical buoyancy number corresponding to the transition between the two convection regimes depends, in addition to the viscosity ratio and the depth of the two layers, on certain dimensionless frequencies permeating this transition and also on the amplitude of oscillation via the Froude number. In the plane of the critical Rayleigh number versus dimensionless modulation frequency, the branch associated with stratified convection does not depend on the buoyancy number for equal viscosities whereas this is the case for the whole-convection regime. For different viscosities, both convection regimes depend on the buoyancy number. At last, in the stratified regime (harmonic threshold), the critical value of the viscosity contrast, corresponding to the passage from an active layer to a passive layer and vice versa, increases with the modulation frequency.
An Actuator-Disk Model Augmentation for Low-Pressure Axial Fan Simulation
Authors: Venter Adam J. , Owen Michael T. F. , Muiyser Jacques
Published: October 2024

Actuator-disk rotor models are important simulation tools for cost-effective industrial axial fan system analysis. Actuator-disk fan model performance, however, is constrained by the conventional use of two-dimensional airfoil coefficient input data, which limits the accuracy of the models to a narrow operating range free from significant radial blade flow. Radial blade flow is characteristic of off-design fan operation, which is often unavoidable within typical industrial fan system environments, so the enhancement of actuator-disk model performance for these conditions is desired. This paper accordingly presents a new means of robustly determining actuator-disk model coefficient inputs that are suitable for a wide range of fan operating conditions. The proposed augmented actuator-disk method (AADM) capitalizes on new insights into the unique aerodynamic behavior of low-pressure axial fan rotors. The performance of the AADM is evaluated for two different industrial cooling fans and is shown to outperform existing actuator-disk coefficient formulations through computational fluid dynamics simulations. The AADM is shown to better predict key fan performance metrics, spanwise blade force distributions, and to produce flow fields that are more physically representative (an important feature for industrial heat exchanger studies where the AADM is anticipated to be commonly applied). The AADM has been developed to be easily adopted in generic industrial fan analyses and is expected to serve as a valuable springboard for future actuator-disk fan model developments.
Study on the Surface Texture-Microparticles Synergistic Lubrication Mechanism of Artificial Joint
Authors: Liu Qi , Shentu Jun , Yang Daolong , Ni Yuquan , Yuan Hengdi , Guo Junde , Dong Guangneng , Wang Guanghong
Published: October 2024

After total joint replacement surgery, frequent injection of lubricating substances is required due to lubrication failure caused by the absorption of lubricants by the human body, which will cause serious physiological and psychological burdens on patients. In this study, with the help of surface texture aggregation of particles, gelatin microgel particles with a diameter of about 4 μm were used as lubricating substances to achieve aggregation in the texture, thus improving the friction environment under low-concentration lubricants. The study found that the rectangular cross-sectional texture demonstrated the most effective anti-friction properties, resulting in a 26% reduction in friction coefficient compared to non-textured surfaces. Additionally, utilizing comsol for particle flow simulation, researchers observed the motion behavior of particles within the texture and clarified the mechanism of particle aggregation and the improvement of lubrication on the surface. This article confirms the beneficial effects of combining surface texture and particles on lubrication, thus providing valuable insight for improving lubrication in dilute particle solutions.
Ultrasonic Corner Wave Imaging for Crack Characterization in Nozzle-To-Vessel Welds
Authors: Xu Xintao , Jin Haoran , Yu Zhenyang , Yang Keji
Published: October 2024

Cracks are easily generated in nozzle-to-vessel welds owing to the difficulty of welding and the harsh operating conditions of the pressure vessels. The phased array ultrasonic testing method enables accurate and convenient weld inspection of in-service vessels, however, it is difficult to detect cracks in certain directions, such as cracks parallel to the weld surface, because the specular echoes cannot be received when the probe is placed from the outside. This paper proposes ultrasonic corner wave imaging by extending the multi-view plane wave imaging to include more ultrasonic ray paths. Utilizing the paths consisting of up to four successive reflections on the nozzle backwall and sidewall, the specular echoes from surface-parallel cracks can be received and imaged. Combining these multiple views enables accurate crack characterization. Simulation was performed using the CIVA UT software and experiments were conducted on steel reference blocks containing notches at different angles. The results show that all defects can be characterized along with position and sizing accuracy within 0.8 mm and an angle deviation below 2°. Artifacts induced by waves in other modes or paths were observed in the image, but they can be accurately identified, without affecting the detection results.
Harmonic Imaging of Local Plastic Regions in Metals By Mode Converted Transverse Wave and Longitudinal Thickness-Mode Local Resonance Techniques
Authors: Grimsley Thomas J , Kyotani Kazuhiro , Shirota Takeru , Kawashima Koichiro
Published: October 2024

In this work we present and compare two ultrasonic immersion scanning imaging techniques based on the nonlinear phenomenon of harmonic generation: harmonic imaging using 1) mode converted transverse waves (MCTW) and 2) excited longitudinal thickness-mode local resonances (LTR). Both techniques make use of harmonic generation, which refers to the harmonic distortion developed in a sinusoidal ultrasonic wave as it propagates through a material with a nonlinear response. The MCTW technique measures the relative harmonic content of wave packets that have travelled through the sample thickness with at least 1 trip as a transverse wave generated at a boundary reflection. In the local thickness-mode resonance (LTR) technique the frequency of the excitation applied to the transducer is chosen to correspond to one of the longitudinal thickness modes of the sample, and the duration is chosen such that a strong reverberation is developed in the sample. Results are shown for 1) aluminum alloy plates subjected to a maximum tensile plastic strain of 0.3%, and 2) a steel (SM400) plate subjected to tension-tension low-cycle fatigue. We find that both techniques are capable of imaging the plastic region. The MCTW technique is found to show the plastic regions more clearly than the LTR technique, which is very sensitive to sample thickness variation and boundary effects.
Simultaneous Ultrasound using Genetic Algorithm
Authors: Machado Victor H. R. , Burda Matheus A. , Prado Tatiana de A. , Brante Glauber , Passarin Thiago A. R. , Maia Joaquim M. , Pires Gustavo P. , Pipa Daniel R.
Published: October 2024

Reducing the acquisition time in nondestructive ultrasound inspection is always beneficial, especially during costly campaigns. The simultaneous emission of coded waveforms is a promising approach in this sense. However, coded sequences must have low auto-correlation sidelobes and low crosscorrelation to avoid artifacts in the resultant image. In addition, ultrasound systems usually employ a tri-state, pulse-width modulated ternary excitation scheme, which limits the waveforms that can be generated at the output of the transducer. Therefore, a joint strategy that considers both the hardware constraints and the correlation properties is crucial to obtaining good images. This paper addresses the problem of designing coded sequences with favorable auto- and cross-correlation properties for ultrasound systems that employ a tri-state excitation scheme. We implement an iterative framework resorting to a genetic algorithm with a cost function that combines auto- and cross-correlations metrics. Results show that the proposed method outperforms state-of-the-art approaches, resulting in lower auto-correlation sidelobes and low cross-correlation than the usual frequency-modulated chirps.
Guided Waves-Based Disbond Detection of Double-Layer Plates using LSTM Networks
Authors: Wang Junzhen , Qu Jianmin
Published: October 2024

Adhesively bonded structures are of great interest in a wide range of industries. However, such adhesive bonds are prone to interfacial defects like disbond and delamination during both the fabrication process and service life. In this paper, we propose a deep-learning (DL) approach to automatically localize and size the disbond in a double-layer plate using ultrasonic guided waves. This plate consists of an aluminum substrate with a stainless-steel coating layer. A guided wave active sensing procedure is used by implementing one transmitter-receiver configuration. Both guided wave pulse-echo and pitch-catch signals are simulated through finite element simulations under various disbond scenarios. To account for uncertainty and noise in the experimental measurements, Gaussian random noise is introduced in the numerically simulated data. The proposed DL model organically combines the convolutional neural network (CNN) with long short-term memory (LSTM). Once trained, the neural network is capable of outputting the location and length of the disbond between the transmitter and receiver. Not only the testing set but also the extended unseen dataset is accurately predicted by the well-trained neural network. These results demonstrate that the proposed method has tremendous potential for characterizing disbond in practical nondestructive evaluation (NDE) and structural health monitoring (SHM) applications.
A Web Application for Ultrasonic Nondestructive Testing Analysis
Authors: Guarneri Giovanni A. , Pegorini Vinicius , Pipa Daniel R. , Pires Gustavo P. , Nunes Maria Isabela S. , Forlin Felipe , Passarin Thiago A. R.
Published: October 2024

Identifying and mapping corrosion represents a significant challenge in maintaining oil production systems. Mechanical and chemical phenomena, such as abrasion and hydrogen attack, cause corrosion on the internal surface of pipes. Knowing the dimensions of corrosion enables technicians to make decisions about the structural stability of pipelines under operating conditions. Using ultrasound imaging is a non-destructive approach to assessing the state of internal surfaces. We present a web application for processing ultrasound signals and image reconstruction. However, it can be used in any non-destructive ultrasound inspection application. The software is developed mainly in Python and Typescript, using a different approach than conventional web applications. Instead of using a standard structure, with the front-end running in the browser and the back-end running the data processing on a remote server, our application runs entirely on the browser through Pyodide, a Python distribution for the browser and Node.js based on WebAssembly whilst the server side only hosts the web application files. The application is divided into modules for (i) graphical interface, (ii) reading inspection files, (iii) signal preprocessing, (iv) estimation of inspection parameters, (v) external surface detection (for inspection by immersion), and (vi) image reconstruction. The web application allows Python script execution and offers a userfriendly interface for running image reconstruction algorithms. This paper describes the development of critical features and indicates the chosen implementation of algorithms. The current state of development is presented, and the next steps toward the ultimate goal of corrosion mapping are defined.
X-ray Images Augmented with Simulated Virtual Flaws for Deep Learning Based Defect Detections
Authors: Miorelli Roberto , Touron Anthony , Escoda Julie , Bannouf Souad , Demaldent Edouard
Published: October 2024

This article analyzes the performance of object detection algorithms in detecting flaws in welds inspected by X-ray testing. We propose a learning framework that relies on both experimental acquisitions and simulations to build a training set of images with virtual flaws. This set is then used to fit object detection algorithms aiming at detecting flaws in welds. After training, we analyzed the machine learning performance against real flaws in welds using experimental X-ray testing images that were not included in the training process.
Peridynamics Based Modeling for Investigating the Effect of Topography and Topological Acoustic Sensing Performance in Monitoring Damage Growth
Authors: Zhang Guangdong , Deymier Pierre A. , Runge Keith , Kundu Tribikram
Published: October 2024

A newly developed nonlinear ultrasonic (NLU) technique called sideband band peak count-index (or SPC-I) measures the degree of nonlinearity associated with the inspected specimen – larger SPC-I values indicate higher nonlinearity. In various published papers, the SPC-I technique has shown its effectiveness and superiority in comparison to other techniques for nondestructive testing (NDT) and structural health monitoring (SHM) applications. In this work, the performance of SPC-I in non-homogeneous specimens having different topographies is investigated using peridynamics based periultrasound modeling. Three types of topographies – “X” topography, “Y” topography and “XY” topography are introduced by adding thin strips made up of a second material and thus converting the homogeneous plate into a heterogeneous structure. It is observed that “X” and “XY” topographies can help to hide the crack growth, thus making cracks undetectable to the nonlinear SPC-I based monitoring technique. In addition to the SPC-I technique, we investigate the applicability of the emerging method of topological acoustic sensing. This method monitors the changes in the geometric phase; a measure of the changes in linear or nonlinear wave’s spatial behavior during its propagation in plate structures having various topographies. The computed results show that the magnitudes of jumps in geometric phase change plots can be good indicators to distinguish cracks with different thicknesses although these cracks can remain hidden in some topographies during the single point inspection based on the nonlinear SPC-I based monitoring technique.
Simulation-Assisted Guided Waves Imaging for SHM : Tomography and Shape Derivative
Authors: Thomas Axel , Druet Tom , Recoquillay Arnaud , Chapuis Bastien
Published: October 2024

The remaining thickness of a structure is critical information for many sensitive industries. To this end, Structural Health Monitoring (SHM) aims to establish regular monitoring of critical infrastructure. We are particularly interested here in tomographic methods using guided elastic waves. These methods can reconstruct the thickness of a structure from measurements of the guided wave propagation. Until now, the most studied guided waves tomographic method are based on an acoustic propagation model. Although it provides a quick and robust estimate of thickness, its resolution and applicability are limited due to simplified physics. To overcome this problem, we have adapted the so-called shape derivative to the elastodynamic case, which can be seen as a specific case of FullWaveformInversion where the shape of the structure is recovered. This iterative approach considers all the effects that occur during propagation, enabling the handling of complex structures. An optimized calculation is performed with the help of spectral finite element method. However, shape derivative method stay very time-consuming due to many iteration necessary for convergence. To address this issue, we have chosen to use the result of acoustic algorithm as an initial estimate. This strategy reduces computational times. This paper presents experimental case studies demonstrating the significance of initialization in the algorithm’s convergence process.
The impact of bowel preparation on MRI scans for confirming rectosigmoid endometriosis detected by transvaginal ultrasonography
Authors: Gürses Cemil , Yavuz Alpaslan , Kahvecioğlu Nevfel , Yalçın Mustafa , Ünal Gizem , Karadağ Burak , Çiyiltepe Hüseyin
Published: October 2024

Aims: The study aims to assess the impact of bowel preparation on MRI scans in diagnosing rectosigmoid endometriosis (RSE) and to examine the level of agreement among investigators, including radiologists and clinicians with varying levels of MRI experience.Material and methods: Fifty-eight patients underwent MRI scans, with 34 showing RSE and 24 without involvement, according to TVUS as the reference standard. The scans were conducted both with and without a bowel preparatory protocol (BPP).Results: The highest concordance was observed in the group 4, which included patients with RSE and BPP, with a Kappa value of 0.47-0.52. In contrast, for groups with MRI scans without the BPP, there was no consistency among the investigators (Kappa <0.20). The sensitivity, specificity, positive predictive value, and negative predictive value were 0.72, 0.47, 0.72, and 0.47 without BPP, and increased to 0.82, 0.74, 0.85, and 0.74, respectively, after BPP.Conclusions: The results reveal that the concordance between investigators in detecting RSE via MRI scan improves with the use of BPP. Additionally, the success rate of MRI and TVUS for detecting RSE can be comparable, but only if bowel preparatory techniques are utilized during MRI scans.
Interview With Rui (Blanca) Qi, Content Creator, Internet Celebrity, and Chinese Football Journalist in Europe
Authors: Yang Zesheng
Published: October 2024

Rui (Blanca) Qi earned her master’s degree in sports management from the Real Madrid Graduate School—Universidad Europea in 2022. Following her graduation, she began her career in sport media, serving as a special correspondent for several Chinese sport-media outlets covering La Liga. In 2021, she expanded her career into content creation, focusing on Spanish football as a blogger. Rui regularly produces and publishes videos on Weibo, a Chinese microblogging platform, and Bilibili, which is similar to YouTube. Through these platforms, she shares her football experiences and insights. You can follow her on Weibo, Bilibili, and Douyin under the username ???Blanca. Rui has been deeply passionate about Real Madrid for over a decade, and her content creation is primarily focused on the club. This dedication has made her a bridge between Real Madrid and Chinese fans. She has released over 230 videos on Bilibili and has nearly 500,000 followers on Chinese social media platforms, establishing her as one of the top football bloggers in China. As a signed journalist and content creator, Rui has reported on numerous international sporting events including the 2022 World Cup in Qatar, the 2024 European Championship, the Union of European Football Associations Champions League, La Liga, and the Bundesliga. In this interview, she shares her experiences as a distant fan of European clubs, her insights on the cross-cultural communication of European football, the stereotypes of women in sports, and the racial discrimination she has encountered in European stadiums.
Development of learning objectives to support undergraduate virology curriculum guidelines
Authors: Kushner David B. , Breitbart Mya , Debbink Kari M. , Ferran Maureen C. , Johnson Dylan M. , Newcomb Laura L. , O'Donnell Lauren A.
Published: October 2024

It has become increasingly important for microbiology educators to help students learn critical concepts of the discipline. This is particularly true in virology, where current challenges include increasing rates of vaccine hesitancy, misinformation about the COVID-19 pandemic, and controversy surrounding research on pathogens with pandemic potential. Having students learn virology can attract more people to the field and increase the number of people who can engage in meaningful discourse about issues relating to the discipline. However, the limited number of virologists who teach undergraduates, combined with the fact that many institutions lack stand-alone virology courses, results in virology often being taught as a limited number of lectures within an undergraduate microbiology course (if it is covered at all), which may or may not be taught by an individual trained as a virologist. To provide a framework to teach virology to undergraduate students, a team of virology educators, with support from the American Society for Virology (ASV), developed curriculum guidelines for use in a stand-alone undergraduate virology course or a virology section within another course (D. B. Kushner et al., J Virol 96:e01305-22, 2022,
https://doi.org/10.1128/jvi.01305-22
). These guidelines are available at the ASV website (
https://asv.org/curriculum-guidelines/
). To assist educators in implementing these guidelines, we created examples of measurable learning objectives. This perspective provides details about the virology curriculum guidelines and learning objectives and accompanies the perspective by Boury et al. in this issue of the
Journal of Microbiology & Biology Education
(25:e00126-24, 2024,
https://doi.org/10.1128/jmbe.00126-24
) about the recent revision of the microbiology curriculum guidelines overseen by the American Society for Microbiology.
Comprehensive phage display viral antibody profiling using VirScan: potential applications in chronic immune-mediated disease
Authors: Shrewsbury Jed Valentiner , Vitus Evangelin Shaloom , Koziol Adam Leslie , Nenarokova Anna , Jess Tine , Elmahdi Rahma
Published: October 2024

Phage immunoprecipitation sequencing (PhIP-Seq) is a high-throughput platform that uses programmable phage display for serology. VirScan, a specific PhIP-Seq library encoding viral peptides from all known human viruses, enables comprehensive quantification of past viral exposures. We review its use in immune-mediated diseases (IMDs), highlighting its utility in identifying viral exposures in the context of IMD development. Finally, we evaluate its potential for precision medicine by integrating it with other large-scale omics data sets.
Autographa californica multiple nucleopolyhedrovirus
ac106
is required for the nuclear egress of nucleocapsids and intranuclear microvesicle formation
Authors: Mo Mei , Chen Jiannan , Yang Yushan , Yu Yinyin , Wu Wenbi , Yang Kai , Yuan Meijin
Published: October 2024

Autographa californica multiple nucleopolyhedrovirus (AcMNPV)
orf106
(
ac106
) is highly conserved in baculoviruses. Previous studies have shown that
ac106
is required for the production of infectious budded virions (BVs). However, the functional role of
ac106
in virion morphogenesis remains unknown. In this report, an
ac106
knockout virus and an
ac106
repair virus were constructed. The effect of
ac106
deletion on virion morphogenesis was investigated, and the expression and subcellular localization of the Ac106 protein were characterized. Our data indicated that
ac106
is required for the nuclear egress of nucleocapsids and intranuclear microvesicle formation, as well as subsequent BV and occlusion-derived virion (ODV) production and the embedding of ODVs into polyhedra. Ac106 is a baculovirus late protein that is concentrated in discrete foci of virus-induced membrane structures in the intranuclear ring zone of virus-infected cells. Further studies on the relationship between Ac106 and four other proteins that are also required for intranuclear microvesicle formation, Ac75, Ac76, Ac93, and P48 (Ac103), revealed that Ac106 is associated with Ac75, Ac76, Ac93, P48, and itself. Ac106 is required for Ac75, Ac93, and P48 accumulation in foci of virus-induced intranuclear membrane structures and the intranuclear transport of Ac76. Analysis of the subcellular localization of ODV integral envelope proteins upon deletion of the genes required for intranuclear microvesicle formation indicated that intranuclear microvesicle formation may be essential for ODV integral envelope protein transport into the nucleus, supporting the hypothesis that intranuclear microvesicles originate from the nuclear membrane.

IMPORTANCE

Baculovirus occlusion-derived virions (ODVs) are known to acquire their envelopes from virus-induced intranuclear microvesicles within the nucleoplasm, and this strategy of intranuclear envelopment of nucleocapsids to form virions is unique among viruses. However, the mechanism of ODV morphogenesis, particularly intranuclear microvesicle formation, remains unclear. In this study, we identified
ac106
as the fifth gene, in addition to
ac75
,
ac76
,
ac93
, and
p48
(
ac103
), which are required for intranuclear microvesicle formation. Further studies on the relationship between
ac106
and the other four genes, as well as the effect of
ac106
or
ac75
deletion on the localization of ODV integral envelope proteins, indicated that intranuclear microvesicle formation may be essential for the transport of ODV integral envelope proteins into the nucleus, which strongly supports the hypothesis that intranuclear microvesicles originate from the nuclear membrane. These findings greatly enhance our understanding of the molecular mechanism of baculovirus ODV morphogenesis.
Strain-specific differences in reovirus infection of murine macrophages segregate with polymorphisms in viral outer-capsid protein σ3
Authors: Fiske Kay L. , Brigleb Pamela H. , Sanchez Luzmariel Medina , Hinterleitner Reinhard , Taylor Gwen M. , Dermody Terence S.
Published: October 2024

Mammalian orthoreovirus (reovirus) strains type 1 Lang (T1L) and type 3 Dearing-RV (T3D-RV) infect the intestine in mice but differ in the induction of inflammatory responses. T1L infection is associated with the blockade of oral immunological tolerance to newly introduced dietary antigens, whereas T3D-RV is not. T1L infection leads to an increase in infiltrating phagocytes, including macrophages, in gut-associated lymphoid tissues that are not observed in T3D-RV infection. However, the function of macrophages in reovirus intestinal infection is unknown. Using cells sorted from infected intestinal tissue and primary cultures of bone-marrow-derived macrophages (BMDMs), we discovered that T1L infects macrophages more efficiently than T3D-RV. Analysis of T1L × T3D-RV reassortant viruses revealed that the viral S4 gene segment, which encodes outer-capsid protein σ3, is responsible for strain-specific differences in infection of BMDMs. Differences in the binding of T1L and T3D-RV to BMDMs also segregated with the σ3-encoding S4 gene. Paired immunoglobulin-like receptor B (PirB), which serves as a receptor for reovirus, is expressed on macrophages and engages σ3. We found that PirB-specific antibody blocks T1L binding to BMDMs and that T1L binding to PirB
−/−
BMDMs is significantly diminished. Collectively, our data suggest that reovirus T1L infection of macrophages is dependent on engagement of PirB by viral outer-capsid protein σ3. These findings raise the possibility that macrophages function in the innate immune response to reovirus infection that blocks immunological tolerance to new food antigens.

IMPORTANCE

Mammalian orthoreovirus (reovirus) infects humans throughout their lifespan and has been linked to celiac disease (CeD). CeD is caused by a loss of oral immunological tolerance (LOT) to dietary gluten and leads to intestinal inflammation following gluten ingestion, which worsens with prolonged exposure and can cause malnutrition. There are limited treatment options for CeD. While there are genetic risk factors associated with the illness, triggers for disease onset are not completely understood. Enteric viruses, including reovirus, have been linked to CeD induction. We found that a reovirus strain associated with oral immunological tolerance blockade infects macrophages by virtue of its capacity to bind macrophage receptor PirB. These data contribute to an understanding of the innate immune response elicited by reovirus, which may shed light on how viruses trigger LOT and inform the development of CeD vaccines and therapeutic agents.
Combining culture optimization and synthetic biology to improve production and detection of secondary metabolites in
Myxococcus xanthus
: application to myxoprincomide
Authors: Sourice Mathieu , Simmler Charlotte , Maresca Marc , Py Béatrice , Aubert Corinne
Published: October 2024

Microbial secondary metabolites play crucial ecological roles in governing species interactions and contributing to their defense strategies. Their unique structures and potent bioactivities have been key in discovering antibiotics and anticancer drugs. Genome sequencing has undoubtedly revealed that myxobacteria constitute a huge reservoir of secondary metabolites as the well-known producers, actinomycetes. However, because most secondary metabolites are not produced in the laboratory context, the natural products from myxobacteria characterized to date represent only the tip of the iceberg. By combining the engineering of a dedicated
Myxococcus xanthus
DZ2 chassis strain with a two-step growth medium protocol, we provide a new approach called two-step Protocol for Resource Integration and Maximization–Biomolecules Overproduction and Optimal Screening Therapeutics (2PRIM-BOOST) for the production of non-ribosomal peptides synthetases (NRPS)/polyketides synthases (PKS) secondary metabolites from myxobacteria. We further show that the 2PRIM-BOOST strategy will facilitate the screening of secondary metabolites for biological activities of medical interest. As proof of concept, using a constitutive strong promoter, the myxoprincomide from
M. xanthus
DZ2 has been efficiently produced and its biosynthesis has been enhanced using the 2PRIM-BOOST approach, allowing the identification of new features of myxoprincomide. This strategy should allow the chances to produce and discover new NRPS, PKS, and mixed NRPS/PKS hybrid natural metabolites that are currently considered as cryptic and are the most represented in myxobacteria.

IMPORTANCE

Microbial secondary metabolites are important in species interactions and are also a prolific source of drugs. Myxobacteria are ubiquitous soil-dwelling bacteria constituting a huge reservoir of secondary metabolites. However, because most of these molecules are not produced in the laboratory context, one can estimate that only one-tenth have been characterized to date. Here, we developed a new strategy called two-step Protocol for Resource Integration and Maximization–Biomolecules Overproduction and Optimal Screening Therapeutics (2PRIM-BOOST) that combines the engineering of a dedicated
Myxococcus xanthus
chassis strain together with growth medium optimization. By combining these strategies with the insertion of a constitutive promoter upstream the biosynthetic gene cluster (BGC), the production of myxoprincomide, a characterized low-produced secondary metabolite, was successfully and significantly increased. The 2PRIM-BOOST enriches the toolbox used to produce previously cryptic metabolites, unveil their ecological role, and provide new molecules of medical interest.
Vasospasm in traumatic brain injury
Authors: Carqueja Inês Miranda , Silva Adriana América , Albuquerque Luís , Monteiro Elisabete
Published: October 2024

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality in young individuals. Management of TBI is complex and aims to prevent secondary injury and optimise conditions for neurological recovery. Vasospasm is a possible complication of TBI, and its significance is unknown. Its incidence is underestimated and there are currently no preventive or therapeutic approaches with proven efficacy. The occurrence of vasospasm contributes to secondary brain injury and worsens prognosis. The diagnosis of vasospasm in TBI is challenging due to the difficulty in perceiving neurological deterioration in these patients. We present a case of a young patient admitted to the neurocritical care unit following TBI. He presented a partial neurological recovery, followed by clinical deterioration and persistent coma. The diagnosis of extensive ischaemic lesions due to severe vasospasm was established. Suspicion of vasospasm and timely screening, particularly in high-risk patients, may improve survival and outcomes in TBI.
Long Covid: a global health issue – a prospective, cohort study set in four continents
Authors: Pazukhina Ekaterina , Garcia-Gallo Esteban , Reyes Luis Felipe , Kildal Anders Benjamin , Jassat Waasila , Dryden Murray , Holter Jan Cato , Chatterjee Allegra , Gomez Kyle , Søraas Arne , Puntoni Matteo , Latronico Nicola , Bozza Fernando A , Edelstein Michael , Gonçalves Bronner P , Kartsonaki Christiana , Kruglova Oksana , Gaião Sérgio , Chow Yock Ping , Doshi Yash , Duque Vallejo Sara Isabel , Ibáñez-Prada Elsa D , Fuentes Yuli V , Hastie Claire , O'Hara Margaret E , Balan Valeria , Menkir Tigist , Merson Laura , Kelly Sadie , Citarella Barbara Wanjiru , Semple Malcolm G , Scott Janet T , Munblit Daniel , Sigfrid Louise ,   ISARIC Global Covid-19 follow up working group
Published: October 2024

Introduction

A proportion of people develop Long Covid after acute COVID-19, but with most studies concentrated in high-income countries (HICs), the global burden is largely unknown. Our study aims to characterise long-term COVID-19 sequelae in populations globally and compare the prevalence of reported symptoms in HICs and low-income and middle-income countries (LMICs).

Methods

A prospective, observational study in 17 countries in Africa, Asia, Europe and South America, including adults with confirmed COVID-19 assessed at 2 to <6 and 6 to <12 months post-hospital discharge. A standardised case report form developed by International Severe Acute Respiratory and emerging Infection Consortium’s Global COVID-19 Follow-up working group evaluated the frequency of fever, persistent symptoms, breathlessness (MRC dyspnoea scale), fatigue and impact on daily activities.

Results

Of 11 860 participants (median age: 52 (IQR: 41–62) years; 52.1% females), 56.5% were from HICs and 43.5% were from LMICs. The proportion identified with Long Covid was significantly higher in HICs vs LMICs at both assessment time points (69.0% vs 45.3%, p<0.001; 69.7% vs 42.4%, p<0.001). Participants in HICs were more likely to report not feeling fully recovered (54.3% vs 18.0%, p<0.001; 56.8% vs 40.1%, p<0.001), fatigue (42.9% vs 27.9%, p<0.001; 41.6% vs 27.9%, p<0.001), new/persistent fever (19.6% vs 2.1%, p<0.001; 20.3% vs 2.0%, p<0.001) and have a higher prevalence of anxiety/depression and impact on usual activities compared with participants in LMICs at 2 to <6 and 6 to <12 months post-COVID-19 hospital discharge, respectively.

Conclusion

Our data show that Long Covid affects populations globally, manifesting similar symptomatology and impact on functioning in both HIC and LMICs. The prevalence was higher in HICs versus LMICs. Although we identified a lower prevalence, the impact of Long Covid may be greater in LMICs if there is a lack of support systems available in HICs. Further research into the aetiology of Long Covid and the burden in LMICs is critical to implement effective, accessible treatment and support strategies to improve COVID-19 outcomes for all.
Defining blood deserts and access to blood products for 660 million people: a geospatial analysis of eight states in Northern India
Authors: Kundu Shreenik , Munoz Valencia Alejandro , Virk Sargun Kaur , Kumar Nikathan , Gadgil Anita , Mammen Joy John , Roy Nobhojit , Raykar Nakul
Published: October 2024

Introduction

Blood transfusion is crucial, but low-income and middle-income countries like India face a severe shortage of banked blood. This study focuses on the Empowered Action Group (EAG) states in India, where healthcare is limited, and health outcomes are poor. Our objective was to assess the blood banking infrastructure and access to blood products in these states.

Methods

We used e-Rakht Khosh, an online platform for blood availability data. We collected data on blood bank locations and stocks from 18 January to 9 February 2022 and used ArcGIS to determine the population residing within 30–60–90 min of a blood bank. Availability ratios were calculated by dividing available blood products by population in these catchment areas. Descriptive analysis characterised availability, and statistical tests evaluated differences across states and over the 4-week period.

Results

806 of 824 blood banks reported data on blood stocks. Our analysis showed that 25.72% of the EAG states’ population live within 30 min of a blood bank, while 61.45% and 92.46% live within 60 and 90 min, respectively.

Conclusion

Blood availability rates were low in the EAG states, with only 0.6 units per 1000 people. Additionally, only 61% of the population had access to blood-equipped facilities within an hour. These rates fell below the standards of the Lancet Commission on Global Surgery (15 units per 1000 population) and the WHO (10 donations per 1000 population). The study highlights the challenges in meeting demand for blood in emergencies due to inadequate blood banking infrastructure.
A cost-effectiveness analysis of sentinel lymph node biopsy compared with lymphadenectomy in intermediate- and high-risk endometrial carcinoma
Authors: Bjerre Trent Pernille , Eriksson Ane Gerda , Staff Anne Cathrine , Juul-Hansen Knut Erling , Burger Emily Annika , Wangen Knut Reidar
Published: October 2024

Background

Sentinel lymph node biopsy (SLN) is increasingly used for surgical staging of endometrial carcinoma.

Objective

To estimate the effect and cost-effectiveness of the implementation of an SLN algorithm for surgical staging in patients with intermediate- and high-risk endometrial carcinoma compared with lymphadenectomy.

Methods

We performed a model-based, cost-effectiveness analysis using primary data from a tertiary referral hospital that included 829 patients with endometrial carcinoma undergoing surgical staging. We quantified the health and economic outcomes from two time periods, before and after implementation of the SLN algorithm by robotic surgery. Costs were measured directly from the hospital’s financial department, while long-term health outcomes were estimated using self-reported lymphedema and health-related quality-of-life among survivors. Sensitivity analyses were conducted to evaluate uncertainty.

Results

We projected that the SLN implementation period, predominately reflecting use of robotic SLN, simultaneously improved health outcomes (0.08 incremental quality-adjusted life-years) and lowered costs (US$1051) compared with the prior period involving robotic or open lymphadenectomy. SLN remained more beneficial and less costly across key sensitivity analyses—namely, varying the cost of the robotic platform, surgical equipment, number of yearly robotic procedures, percentage of robotic procedures versus percentage of laparotomies, length of stay, and lymphedema development. After 1000 simulations of the model, SLN implementation provided greater health benefits for lower costs (ie, cost saving) in 89% of simulations.

Conclusion

Implementation of an SLN algorithm in the staging of intermediate- and high-risk endometrial carcinoma improved health outcomes for lower costs compared with lymphadenectomy. Cost-effectiveness could further improve by continuing to increase the proportion of robotic procedures.
Lynch syndrome diagnostic testing pathways in endometrial cancers: a nationwide English registry-based study
Authors: Loong Lucy , Huntley Catherine , Pethick Joanna , McRonald Fiona , Santaniello Francesco , Shand Brian , Tulloch Oliver , Goel Shilpi , Lüchtenborg Margreet , Allen Sophie , Torr Bethany , Snape Katie , George Angela , Lalloo Fiona , Norbury Gail , Eccles Diana M , Tischkowitz Marc , Antoniou Antonis C , Pharoah Paul , Shaw Adam , Morris Eva , Burn John , Monahan Kevin , Hardy Steven , Turnbull Clare
Published: October 2024

Background

For female patients with Lynch syndrome (LS), endometrial cancer (EC) is often their first cancer diagnosis. A testing pathway of somatic tumour testing triage followed by germline mismatch repair (MMR) gene testing is an effective way of identifying the estimated 3% of EC caused by LS.

Methods

A retrospective national population-based observational study was conducted using comprehensive national data collections of functional, somatic and germline MMR tests available via the English National Cancer Registration Dataset. For all EC diagnosed in 2019, the proportion tested, median time to test, yield of abnormal results and factors influencing testing pathway initiation were examined.

Results

There was an immunohistochemistry (IHC) or microsatellite instability (MSI) test recorded for 17.8% (1408/7928) of patients diagnosed with EC in 2019. Proportions tested varied by Cancer Alliance and age. There was anMLH1promoter hypermethylation test recorded for 43.1% (149/346) of patients with MLH1 protein IHC loss or MSI. Of patients with EC eligible from tumour-testing, 25% (26/104) had a germline MMR test recorded. Median time from cancer diagnosis to germline MMR test was 315 days (IQR 222–486).

Conclusion

This analysis highlights the regional variation in recorded testing, patient attrition, delays and missed opportunities to diagnose LS, providing an informative baseline for measuring the impact of the national guidance from the National Institute for Health and Care Excellence on universal reflex LS testing in EC, implemented in 2020.
Management of a fractured microcatheter during middle meningeal artery embolization
Authors: Webb Matthew , Luo Anqi , Al Saiegh Fadi , Birnbaum Lee , Gragnaniello Cristian , Mascitelli Justin R
Published: October 2024

Middle meningeal artery embolization (MMAE) is an effective adjunctive treatment for chronic subdural hematomas and carries a low risk of significant complications.1 Here we describe the management of a retained and fractured microcatheter following liquid embolic MMAE. A patient with chronic recurrent subdural hematomas underwent bilateral MMAE with Onyx liquid embolic material (Medtronic). The Headway Duo (Microvention) microcatheter was placed in a small distal frontal branch of the middle meningeal artery to aid in reflux into the posterior middle meningeal artery branches. Following successful MMAE, the microcatheter became trapped within the Onyx cast and, on attempted removal, the microcatheter fractured, resulting in a retained fragment extending from the middle meningeal artery cast to the guide catheter in the common carotid artery.

To retrieve the fractured microcatheter, a stent retriever was deployed and resheathed multiple times until the retained microcatheter became visibly entangled with the stent retriever. Next, the stent retriever was pulled back into the guide catheter and continuous aspiration was performed through the guide catheter, and the fragmented microcatheter was successfully removed in entirety. Final angiography demonstrated no further catheter fragments, vessel damage, extravasation, flow limitation, or thromboembolic complications.

Methods to avoid the complication include using a detachable tip microcatheter, dual lumen balloon microcatheter, allowing less reflux, embolizing from a larger caliber branch, and a slower microcatheter pull. Additional methods for managing the complication include using a snare, leaving the retained microcatheter and putting the patient on aspirin, and carotid stenting to tack the fractured portion down (video 1).

Video 1

 Management of a fractured microcatheter during middle meningeal artery embolization

This case demonstrates the successful use of a stent retriever and aspiration to retrieve a retained and fractured microcatheter following liquid embolic MMAE.
Nitrosamine and nicotine exposure after switching from filtered to unfiltered cigarette smoking: a cross-over clinical trial
Authors: Appolon Giovanni , Oren Eyal , Pulvers Kim , Romero Devan , Hoh Eunha , Dodder Nathan G , Wong Jade , Nynas Katelyn , Tracey LaRee , Lemus Hector , Novotny Thomas E
Published: October 2024

Background

The cellulose acetate filter is a plastic attachment on nearly all commercial cigarettes sold worldwide. It is the main component of discarded cigarette butts, and the most prevalent waste item collected during urban and beach cleanups. This waste leaches toxic chemicals, including nicotine, metals and tobacco-specific nitrosamines and contributes to environmental microplastic pollution. There is growing international interest in reducing plastic waste from single-use, non-essential products such as cellulose acetate cigarette filters. Public health and environmental advocates recommend a ban on the sale of filtered cigarettes to reduce environmental pollution caused by discarded cigarette butts and to discourage cigarette smoking.

Research question

What potential health and behavioural implications might arise among people who smoke if filtered cigarettes are removed from the market.

Methods

We conducted a cross-over, randomised clinical trial of 29 people who smoke to evaluate changes in biomarkers for nicotine and tobacco-specific nitrosamine exposure when switching between filtered and unfiltered cigarette smoking.

Results

Although unfiltered smoking showed a higher trend in the geometric means of 4-[(methylnitrosamino])−1-[3-pyridyl]−1-butanol (NNAL) compared with filtered cigarettes, regression models for urinary cotinine and NNAL showed no significant differences when switching between filtered and unfiltered cigarettes.

Conclusion

This proof-of-principle study suggests there is no increased risk to people who smoke when switching to unfiltered cigarette smoking. Although larger studies might provide more evidence regarding unfiltered cigarette smoking, banning the sale of filtered cigarettes may be an important policy intervention to both reduce hazardous tobacco waste and discourage smoking.