bluuebunny/crossref_metadata_2025 huggingface dataset:
DYNamic Assessment of Multi‐Organ level dysfunction in patients recovering from COVID‐19: DYNAMO COVID‐19
Authors: Gupta Ayushman , Nicholas Rosemary , McGing Jordan J. , Nixon Aline V. , Mallinson Joanne E. , McKeever Tricia M. , Bradley Christopher R. , Piasecki Mathew , Cox Eleanor F. , Bonnington James , Lord Janet M. , Brightling Christopher E. , Evans Rachael A. , Hall Ian P. , Francis Susan T. , Greenhaff Paul L. , Bolton Charlotte E.
Published: June 2024

We evaluated the impacts of COVID‐19 on multi‐organ and metabolic function in patients following severe hospitalised infection compared to controls. Patients (n = 21) without previous diabetes, cardiovascular or cerebrovascular disease were recruited 5–7 months post‐discharge alongside controls (n = 10) with similar age, sex and body mass. Perceived fatigue was estimated (Fatigue Severity Scale) and the following were conducted: oral glucose tolerance (OGTT) alongside whole‐body fuel oxidation, validated magnetic resonance imaging and spectroscopy during resting and supine controlled exercise, dual‐energy X‐ray absorptiometry, short physical performance battery (SPPB), intra‐muscular electromyography, quadriceps strength and fatigability, and daily step‐count. There was a greater insulin response (incremental area under the curve, median (inter‐quartile range)) during the OGTT in patients [18,289 (12,497–27,448) mIU/min/L] versus controls [8655 (7948–11,040) mIU/min/L], P < 0.001. Blood glucose response and fasting and post‐prandial fuel oxidation rates were not different. This greater insulin resistance was not explained by differences in systemic inflammation or whole‐body/regional adiposity, but step‐count (P = 0.07) and SPPB scores (P = 0.004) were lower in patients. Liver volume was 28% greater in patients than controls, and fat fraction adjusted liver T1, a measure of inflammation, was raised in patients. Patients displayed greater perceived fatigue scores, though leg muscle volume, strength, force‐loss, motor unit properties and post‐exercise muscle phosphocreatine resynthesis were comparable. Further, cardiac and cerebral architecture and function (at rest and on exercise) were not different. In this cross‐sectional study, individuals without known previous morbidity who survived severe COVID‐19 exhibited greater insulin resistance, pointing to a need for physical function intervention in recovery.
Physics-Guided Bayesian Neural Networks and Their Application in ODE Problems
Authors: Xu Xinyue , Paneru Suman , Russcher Sez A. , Wang Julian
Published: June 2024

Deterministic Neural Networks (NNs) have been widely adopted to represent system behaviors in various engineering problems, which have been criticized for providing overconfident predictions. This challenge, i.e., overfitting, refers to a model that captures data patterns and random noise during the learning process, leading to an inferior predictive capability in the unobserved domains. As known to all, Bayesian inference offers an effective way for uncertainty quantification (UQ) to help enhance model predictions and offer informed decision-making. Integrating deterministic NN models with Bayesian inference provides a way to fast simulate and quantify both data and model uncertainty simultaneously. Thereby, Bayesian Neural Networks (BNNs), a combination of standard NNs with Bayesian philosophy, introduce probability to the network parameters, i.e., biases and weights. In BNNs, predictive uncertainty reflects how confident model predictions are regarding the corresponding credible intervals, which helps identify overfitting and interpreting abnormal predictions. Another advantage is that BNNs naturally implement regularization by integrating over the weights such that BNNs can reach good generalization when data availability is limited. BNNs rely heavily on observations as a purely data-driven approach. Besides, standard BNNs have relatively complex network structures, which makes it hard to provide detailed interpretability on model predictions. Researchers share concerns about their predictions that may violate real-world phenomena. The combination of physics knowledge with the optimization objective can improve the adherence of predictions with the known physical principles. Physics laws are usually embedded as constraint functions in the process of optimization. With the help of constrained optimization, model predictions keep consistent with the known physical principles.

The authors refine BNNs with physics-guided information, i.e., Physics-Guided BNNs (PG-BNNs), to reduce dependence on data, improve model interpretability, and offer reliable model predictions. PG-BNNs interpret the known physics knowledge as constraint functions to better guide optimization processes, especially for case studies with sparse and limited data sets. A case study of an ordinary differential equation (ODE) problem is carried out to compare the performance of PG-BNN and unconstrained BNN models and demonstrate the effectiveness of PG-BNN.
Uncertainty Quantification of Drill Collar Fatigue Performance Due to Manufacturing Tolerances
Authors: Ghosh Pritha , Du Michael H.
Published: June 2024

The bottomhole assembly (BHA), the lower part of the drillstring on an oil drilling rig, extends from the drillpipe to the drill bit. High dogleg severity (DLS) curvatures during directional drilling can create fatigue issues in the drillstring because of high alternating stresses and strains around the porthole in the collar. The manufacturing tolerances affect the collar-chassis and plug-porthole clearances, as well as the porthole dimensions and can cause significant variability or uncertainty in evaluating the drill tool fatigue life.

The 3D finite element analysis (FEA) method was used for stress and strain predictions of the drill tool under the effect of pressure and DLS. The rotating bending fatigue life of the drill collar was calculated using these prediction results and the life-strain model that was created through testing the collar material. The FEA models were verified with the developed analytical calculation models for stress predictions under the effect of pressure and DLS. The relevant manufacturing tolerance ranges for the collar, chassis, porthole, and port plug were considered. The uncertainty in the fatigue life of the tool was quantified for each of these variables at the expected operating bending moment to evaluate their contributing role in the fatigue performance of the tool.

For a drill tool with a nominal diameter size of 8.25 in, it was found that the collar could show up to 76% uncertainty in fatigue life when the chassis-collar clearances were increased from the minimum to the maximum within the manufacturing tolerance bands. Similarly, the collar showed up to 38% uncertainty in fatigue life when the plug-pothole clearances were changed from the minimum to the maximum. This uncertainty quantification study provides insight into the mechanics of structural fatigue from collar assembly components and their manufacturing tolerance conditions. This helps eliminate time-consuming design iterations and expensive fatigue testing.
Finite Element Model Validation of Cryogenic DOT-113 Tank Car Side Impact Tests
Authors: Eshraghi Shaun , Carolan Michael , Perlman Benjamin , González III Francisco
Published: June 2024

The U.S. Department of Transportation’s (USDOT’s) Federal Railroad Administration (FRA) has sponsored a series of four full-scale side impact tests on specification DOT-113 railroad tank cars. A DOT-113 is a specially designed tank car intended to transport cryogenic liquid commodities. For each side impact test, researchers at the USDOT’s Volpe National Transportation Systems Center (Volpe Center) created a pre-test finite element (FE) model to estimate the overall force-time response of the impactor, puncture/non-puncture outcomes of the impacted tank car, global motions of the tank car, internal pressures within the tank car, and the energy absorbed by the tank car during the impact. While researchers have previously compared FE model results to test measurements for tank car side impact tests, there are currently no formal guidelines on what measurable level of agreement is an acceptable demonstration of FE model validation. This paper presents FE model validation of DOT-113 and DOT-113 surrogate side impact tests using a publicly available software named Correlation and Analysis Plus (CORA) [1] which was originally developed for automotive crashworthiness using models of anthropomorphic test devices, i.e., crash test dummies.

The authors have previously presented FE model validation frameworks for impact simulations [2] and demonstrated FE model validation for non-cryogenic tank car side impacts [3] using CORA and another software called Roadside Verification and Validation Program (RSVVP) [4]. The authors have decided to use CORA in this paper because its validation metrics and rating procedures are included in an ISO technical specification for road vehicles (ISO/TS 18571:2014) [5]. Conversely, RSVVP is not incorporated in a US or international specification.

The results indicate that CORA can be directly applied to tank car side impact model results using the procedures in ISO/TS 18571:2014 when the model does not self-terminate due to puncture. The FE models achieved excellent and good CORA scores for cases without puncture of the tank car. However, early termination of the FE model due to puncture disrupted the automated post-processing of the model results for the two tests that produced a puncture outcome. Further consideration is necessary to develop guidelines that can produce useful validation scores for FE models that include a puncture outcome.
Modeling and Assessment for the Estimation of Heat Transfer Coefficients on Curved Downwards-Facing Heated Walls in Application to ERVC
Authors: Osman Sameer , Afgan Imran , Addad Yacine
Published: June 2024

External Reactor Vessel Cooling (ERVC) is a proposed technique for severe accident mitigation in nuclear power plants. ERVC is aimed at containing the molten corium inside the Reactor Pressure Vessel (RPV) by transporting heat through the coolant (water) which occupies the intentionally flooded reactor cavity and is in direct contact with the outer surface of the lower head. An experimental study along with a computational fluid dynamics (CFD) model are used in the present study to investigate the local convection heat transfer coefficient on curved heated upper walls during the early stages of this type of severe accidents. The CFD study is realized using the open-source code OpenFOAM, in which proper formulation of the physics in terms of mass, momentum, and energy conservation is implemented. Results from the CFD model are compared to the experimental data obtained from a flow-boiling test facility, commissioned, and operated at Khalifa University, in the single-phase regime. The experimental findings highlight that the flat plate correlations are inaccurate for the estimation of the heat transfer coefficient on RPV lower head, especially at high Reynolds number values. Furthermore, the fully resolved turbulence model k-omega SST is the most accurate in predicting the actual thermal boundary layer and turbulent mixing. Quantification of the uncertainty in the experimental measurements as well as the discretization error in the numerical results is provided. In addition, a sensitivity analysis is provided for the inlet turbulence conditions to highlight their importance for accurate solutions. This study provides a framework for the assessment and validation of CFD codes dealing with heat transfer in scenarios where the flow is affected by curved geometries and fluid properties’ variations. In addition, it paves the way for more accurate heat transfer correlations suitable for heat flux partitioning models that can accurately capture the boiling curve in ERVC systems.
Solution Verification Study for Finite Element Analysis of PLLA Stent Implantation
Authors: Osloub Ehsan , Teller Sean S.
Published: June 2024

Numerical simulation models are extensively used in the medical device industry to support device design and reduce costs associated with prototype testing. Regulatory agencies such as the US Food and Drug Administration (FDA) require device manufacturers to follow rigorous simulation verification procedures to assess credibility of numerical simulations used to support submissions. Verification techniques are categorized into code and solution verification, the latter employed to ensure that the numerical solution has converged to the exact solution to the mathematical model. These verification techniques are used even though the exact solution cannot be derived. In other words, solution verification is a method to quantify and minimize discretization error, one of the main sources of numerical error.

In this work, we simulate the crimping of a Poly L-lactic Acid (PLLA) stent in the implantation process using an advanced viscoplastic constitutive model to model the PLLA in a quasi-static implicit scheme with Dassault Systèmes Abaqus 2023 using a reference stent geometry from the literature. We monitor and extract the crimping force and peak maximum principal stress in the stent as the quantities of interest for solution verification. We use Richardson extrapolation to estimate the discretization error between the numerical model and the exact solution. Discretization errors for three systematically refined mesh configurations are quantified and we demonstrate that the solution is in the asymptotic range.
Credibility Assessment of Machine Learning-Based Surrogate Model Predictions on NACA 0012 Airfoil Flow
Authors: Kirsch Jared , Rider William , Fathi Nima
Published: June 2024

The use of surrogate models in computational mechanics is an area of high interest due to the potential for significant savings in computational cost. However, assessment and presentation of evidence for surrogate model credibility has yet to reach a standard form. The present study utilizes a deep neural network as a surrogate for a computational fluid dynamics simulation in order to predict the coefficients of lift and drag on a NACA 0012 airfoil for various Reynolds numbers and angles of attack. Using best practices, the credibility of the underlying simulation predictions and of the surrogate model predictions are analyzed. Conclusions are drawn which should better inform future uses of surrogate models in the context of their credibility.
A new species of Coprocarpais Hrúzová & Fenďa (Parasitiformes, Mesostigmata, Parasitidae) from China, with a key to world species of the genus
Authors: Yao Maoyuan , Chen Jian-xin , Wu You-fang , Yi Tian-ci , Jin Dao-chao
Published: June 2024

A new species, Coprocarpais maximus Yao & Jin sp. nov., is described based on deutonymph and female samples from Hainan provinces, China. An identification key to the known species of Coprocarpais is provided.
Tweaking synaptic plasticity: Deciphering the role of WWC1 in memory opens new therapeutic horizons
Authors: Papassotiropoulos Andreas , de Quervain Dominique J.-F.
Published: June 2024

WWC1 is a scaffolding protein in the evolutionarily conserved Hippo signaling network and is genetically linked to human memory and synaptic plasticity. In the archives of
Science Signaling
, Stepan
et al.
demonstrate the translational potential of modulating WWC1 through pharmacological inhibition of Hippo-pathway kinases to enhance cognition.
Palmitoylation promotes pores
Authors: Foley John F.
Published: June 2024

Palmitoylation of intact or cleaved gasdermin D causes plasma membrane pore formation.
Complete coding sequence of an Aedes flavivirus strain isolated from
Aedes albopictus
collected in Northern Italy
Authors: Korhonen Essi M. , Truong Nguyen Phuoc T. , Faolotto Giulia , Suvanto Maija T. , Nicosia Anna Maria , Crobu Maria Grazia , Grasso Ivan , Vapalahti Olli , Smura Teemu , Ravanini Paolo , Huhtamo Eili
Published: June 2024

Complete genome data for the globally distributed Aedes flavivirus (AEFV) is scarce. We analyzed a new Italian AEFV strain isolated from
Aedes albopictus
. The results demonstrated genetic diversity among Italian AEFVs. The high similarity between AEFV genomes across geographically distant regions suggests long distance spreading via invasive host mosquito species.
A panel of genotypically and phenotypically diverse clinical
Acinetobacter baumannii
strains for novel antibiotic development
Authors: Sun Chunli , Zhou Danyan , He Jintao , Liu Haiyang , Fu Ying , Zhou Zhihui , Leptihn Sebastian , Yu Yunsong , Hua Xiaoting , Xu Qingye
Published: June 2024

Acinetobacter baumannii
is one of the most important pathogens worldwide. The intrinsic and acquired resistance of
A. baumannii
, coupled with the slow pace of novel antimicrobial drug development, poses an unprecedented and enormous challenge to clinical anti-infective therapy of
A. baumannii
. Recent studies in the field of pathogenicity, antibiotic resistance, and biofilms of
A. baumannii
have focused on the model strains, including ATCC 17978, ATCC 19606, and AB5075. However, these model strains represent only a limited portion of the heterogeneity in
A. baumannii
. Furthermore, variants of these model strains have emerged that show significant diversity not only at the genotypic level but also reflected in differences at the phenotypic levels of capsule, virulence, pathogenicity, and antibiotic resistance. Research on
A. baumannii
, a key pathogen, would benefit from a standardized approach, which characterizes heterogeneous strains in order to facilitate rapid diagnosis, discovery of new therapeutic targets, and efficacy assessment. Our study provides and describes a standardized, genomically and phenotypically heterogeneous panel of 45 different
A. baumannii
strains for the research community. In addition, we performed comparative analyses of several phenotypes of this panel. We found that the sequence type 2 (ST2) group showed significantly higher rates of resistance, lower fitness cost for adaptation, and yet less biofilm formation. The Macrocolony type E (MTE, flat center and wavy edge phenotype reported in the literature) group showed a less clear correlation of resistance rates and growth rate, but was observed to produce more biofilms. Our study sheds light on the complex interplay of resistance fitness and biofilm formation within distinct strains, offering insights crucial for combating
A. baumannii
infection.

IMPORTANCE

Acinetobacter baumannii
is globally notorious, and in an effort to combat the spread of such pathogens, several emerging candidate therapies have already surfaced. However, the strains used to test these therapies vary across studies (the sources and numbers of test strains are varied and often very large, with little heterogeneity). The variation complicates the studies. Furthermore, the limited standardized resources of
A. baumannii
strains have greatly restricted the research on the physiology, pathogenicity, and antibiotic resistance. Therefore, it is crucial for the research community to acquire a standardized and heterogeneous panel of
A. baumannii
. Our study meticulously selected 45 diverse
A. baumannii
strains from a total of 2,197 clinical isolates collected from 64 different hospitals across 27 provinces in China, providing a scientific reference for the research community. This assistance will significantly facilitate scientific exchange in academic research.
Biodegradation of phenol-contaminated soil and plant growth promotion by
Myroides xuanwuensis
H13
Authors: Wang Zhonghua , Zhang Huihong , Zhang Dengxiao , Wang Yi , Han Yanlai , Xue Xia , Jiang Ying
Published: June 2024

Physicochemical methods for remediating phenol-contaminated soils are costly and inefficient, making biodegradation an environmentally friendly alternative approach. This study aims to screen for potential phenol-degrading bacteria and to verify the removal capacities of a selected strain in a bioaugmentation experiment at the greenhouse level using
Brassica chinensis
L. (Chinese cabbage) as the model plant and phenol-contaminated soil. In parallel, pot experiments were conducted using a collaborative approach based on this model system. We found that
Myroides xuanwuensis
strain H13 showed a high degradation capability, with a 97.67% efficiency in degrading 100 mg/L phenol. Under shaking flask conditions, H13 facilitated the solubilization of tricalcium phosphate and potassium feldspar powder. Pot experiments suggested a phenol removal percentage of 89.22% and enhanced availability of soil phosphorus and potassium for plants with H13 inoculation. In this case, the abundance of soil microbes and the activity of soil enzymes significantly increased as well. Furthermore, both photosynthesis and the antioxidant system in Chinese cabbage were enhanced following H13 inoculation, resulting in its increased yield and quality. Partial least squares path modeling revealed that H13 can primarily affect plant root growth, with a secondary impact on photosynthesis. These findings highlight the potential of biodegradation from phenol-degrading bacteria as a promising strategy for efficient phenol removal from soil while promoting plant growth and health.

IMPORTANCE

This study is significant for environmental remediation and agriculture by its exploration of a more environmentally friendly and cost-effective bio-strategy in treating phenol-contaminated soil. These findings have essential implications for environmental remediation efforts and sustainable agriculture. By utilizing the biodegradation capabilities of
Myroides xuanwuensis
strain H13, it is possible to remove phenol contaminants from the soil efficiently, reducing their negative effects. Furthermore, the enhanced growth and health of the Chinese cabbage plants indicate the potential of this approach to promote sustainable crop production.
Risk factors for vancomycin treatment failure in heterogeneous vancomycin-intermediate
Staphylococcus aureus
bacteremia
Authors: Yun Ji Hyun , Chang Euijin , Bae Seongman , Jung Jiwon , Kim Min Jae , Chong Yong Pil , Kim Sung-Han , Choi Sang-Ho , Lee Sang-Oh , Kim Yang Soo
Published: June 2024

The incidence of heterogeneous vancomycin-intermediate
Staphylococcus aureus
(hVISA) infection is increasing and is associated with vancomycin treatment failures. However, studies investigating the risk factors for treatment failure in hVISA infection are limited. Patients with hVISA bacteremia treated with vancomycin over 7 days between August 2008 and June 2020 were enrolled in this study. Clinical and microbiological characteristics were compared between vancomycin treatment failure and success groups to identify the risk factors for vancomycin treatment failure. Among the 180 patients with hVISA bacteremia, 102 patients treated with vancomycin over 7 days were included. Vancomycin treatment failed in 80 (78%) patients. Patients in the vancomycin treatment failure group were older (
P
< 0.001) and more frequently had solid cancer (
P
= 0.04) than those in the vancomycin treatment success group. Solid organ transplantation (SOT) was more frequent (
P
< 0.001) in the vancomycin treatment success group. The Charlson comorbidity index (
P
= 0.01) and Acute Physiology and Chronic Health Evaluation II scores (
P
< 0.001) were higher in the vancomycin treatment failure group. In multivariate analysis, independent risk factors for vancomycin treatment failure were old age and severity of bacteremia. SOT and vancomycin minimal inhibitory concentration (MIC) ≤ 1.0 mg/L using the broth microdilution (BMD) method were associated with successful vancomycin treatment. Old age and infection severity were independent risk factors for vancomycin treatment failure. Vancomycin MIC using the BMD method is an important risk factor for vancomycin treatment failure, and its use should be considered in hVISA bacteremia.

IMPORTANCE

In this study, we assessed the clinical and microbiological characteristics of heterogeneous vancomycin-intermediated
Staphylococcus aureus
(hVISA) bacteremia and identified risk factors for vancomycin treatment failure. We found that advanced age and severity of infection were independent risk factors for vancomycin treatment failure. On the other hand, solid organ transplantation and a low vancomycin minimal inhibitory concentration were associated with successful vancomycin treatment. This study highlights the importance of vancomycin minimal inhibitory concentration in hVISA bacteremia.
Emergence of a novel GIII Getah virus variant in pigs in Guangdong, China, 2023
Authors: Chu Pin-Pin , Guo Hongyuan , Zhou Xia , Chen Sheng-Nan , Sun Xinran , Tian Sicheng , Zou Yu-Gen , Li Chun-Ling , Zhang Rong , Zhai Shao-Lun
Published: June 2024

From May to July of 2023, one pig farm in Heyuan city, Guangdong Province of China, suffered severe piglet death and sow reproductive disorders. The common pig viruses and bacteria tested negative. To uncover the possible cause of the disease, a metagenomic analysis was performed in the pooled small intestine samples from three 8-day-old diseased piglets. The results showed that Getah virus (GETV), an RNA virus, might be the potential pathogen that affects pig health. Subsequently, GETV nucleotide was detected in all of the 15 samples collected from three diseased piglets using quantitative reverse transcription PCR, suggesting GETV as the main pathogen of the disease. A GETV strain, designated as GDHYLC23, was successfully isolated using the swine testicle cell line. Sequence analysis showed that the epidemic strain had a unique 32-nucleotide repeat insertion in the 3′ noncoding region. Phylogenetic analysis showed that GDHYLC23 belonged to the pandemic group III. The identification of GETV with new variations implies the continuous evolution of the virus, which poses potential threats to the swine industry.

IMPORTANCE

Pig farms are faced with emerging and re-emerging viruses that may cause substantial economic loss. The identification of potentially pathogenic viruses helps to prevent and control the spread of diseases. In this study, by using metagenomic analysis, we found that a neglected virus, GETV with a unique insertion in the genome, was the main pathogen in one pig farm that suffered severe piglet death and sow reproductive disorders. Although the potential impact of such an insertion on viral pathogenicity is unknown, the surveillance of the continuing evolution of GETV in pig farms cannot be ignored.
The
dmsEFABGH
operon encodes an essential and modular electron transfer pathway for extracellular iodate reduction by
Shewanella oneidensis
MR-1
Authors: Hou Lingyu , Zheng Beiling , Jiang Zhou , Hu Yidan , Shi Liang , Dong Yiran , Jiang Yongguang
Published: June 2024

Extracellular iodate reduction by
Shewanella
spp. contributes to iodide generation in the biogeochemical cycling of iodine. However, there is a disagreement on whether
Shewanella
spp. use different extracellular electron transfer pathways with dependence on electron donors in iodate reduction. In this study, a series of gene deletion mutants of
Shewanella oneidensis
MR-1 were created to investigate the roles of
dmsEFABGH
,
mtrCAB,
and
so4357–so4362
operons in iodate reduction. The iodate-reducing activity of the mutants was tested with lactate, formate, and H
2
as the sole electron donors, respectively. In the absence of single-
dms
gene, iodate reduction efficiency of the mutants was only 12.9%–84.0% with lactate at 24 hours, 22.1%–85.9% with formate at 20 hours, and 19.6%–57.7% with H
2
at 42 hours in comparison to complete reduction by the wild type. Progressive inhibition of iodate reduction was observed when the
dms
homolog from the
so4357–so4362
operon was deleted in the single-
dms
gene mutants. This result revealed complementation of
dmsEFABGH
by
so4357–so4362
at the single-gene level, indicating modularity of the extracellular electron transfer pathway encoded by
dmsEFABGH
operon. Under the conditions of all electron donors, significant inhibition of iodate reduction and accumulation of H
2
O
2
were detected for Δ
mtrCAB
. Collectively, these results demonstrated that the
dmsEFABGH
operon encodes an essential and modular iodate-reducing pathway without electron donor dependence in
S. oneidensis
MR-1. The
mtrCAB
operon was involved in H
2
O
2
elimination with all electron donors. The findings in this study improved the understanding of molecular mechanisms underlying extracellular iodate reduction.

IMPORTANCE

Iodine is an essential trace element for human and animals. Recent studies revealed the contribution of microbial extracellular reduction of iodate in biogeochemical cycling of iodine. Multiple reduced substances can be utilized by microorganisms as energy source for iodate reduction. However, varied electron transfer pathways were proposed for iodate reduction with different electron donors in the model strain
Shewanella oneidensis
MR-1. Here, through a series of gene deletion and iodate reduction experiments, we discovered that the
dmsEFABGH
operon was essential for iodate reduction with at least three electron donors, including lactate, formate, and H
2
. The
so4357–so4362
operon was first demonstrated to be capable of complementing the function of
dmsEFABGH
at single-gene level.
Pangenome-wide association study reveals the selective absence of CRISPR genes (Rv2816c-19c) in drug-resistant
Mycobacterium tuberculosis
Authors: Bhalla Nikhil , Nanda Ranjan Kumar
Published: June 2024

The presence of intermittently dispersed insertion sequences and transposases in the
Mycobacterium tuberculosis
(Mtb) genome makes intra-genome recombination events inevitable. Understanding their effect on the gene repertoires (GR), which may contribute to the development of drug-resistant Mtb, is critical. In this study, publicly available WGS data of clinical Mtb isolates (endemic region
n
= 2,601; non-endemic region
n
= 1,130) were
de novo
assembled, filtered, scaffolded into assemblies, and functionally annotated. Out of 2,601 Mtb WGS data sets from endemic regions, 2,184 (drug resistant/sensitive: 1,386/798) qualified as high quality. We identified 3,784 core genes, 123 softcore genes, 224 shell genes, and 762 cloud genes in the pangenome of Mtb clinical isolates from endemic regions. Sets of 33 and 39 genes showed positive and negative associations (
P
< 0.01) with drug resistance status, respectively. Gene ontology clustering showed compromised immunity to phages and impaired DNA repair in drug-resistant Mtb clinical isolates compared to the sensitive ones. Multidrug efflux pump repressor genes (Rv3830c and Rv3855c) and CRISPR genes (Rv2816c-19c) were absent in the drug-resistant Mtb. A separate WGS data analysis of drug-resistant Mtb clinical isolates from the Netherlands (
n
= 1130) also showed the absence of CRISPR genes (Rv2816c-17c). This study highlights the role of CRISPR genes in drug resistance development in Mtb clinical isolates and helps in understanding its evolutionary trajectory and as useful targets for diagnostics development.

IMPORTANCE

The results from the present Pan-GWAS study comparing gene sets in drug-resistant and drug-sensitive Mtb clinical isolates revealed intricate presence-absence patterns of genes encoding DNA-binding proteins having gene regulatory as well as DNA modification and DNA repair roles. Apart from the genes with known functions, some uncharacterized and hypothetical genes that seem to have a potential role in drug resistance development in Mtb were identified. We have been able to extrapolate many findings of the present study with the existing literature on the molecular aspects of drug-resistant Mtb, further strengthening the relevance of the results presented in this study.
TusA influences Fe-S cluster assembly and iron homeostasis in
E. coli
by reducing the translation efficiency of Fur
Authors: Olivieri Paolo , Zupok Arkadiuz , Yildiz Tugba , Oltmanns Jonathan , Lehmann Angelika , Sokolowska Ewelina , Skirycz Aleksandra , Schünemann Volker , Leimkühler Silke
Published: June 2024

All sulfur transfer pathways have generally a
l
-cysteine desulfurase as an initial sulfur-mobilizing enzyme in common, which serves as a sulfur donor for the biosynthesis of numerous sulfur-containing biomolecules in the cell. In
Escherichia coli
, the housekeeping
l
-cysteine desulfurase IscS has several interaction partners, which bind at different sites of the protein. So far, the interaction sites of IscU, Fdx, CyaY, and IscX involved in iron-sulfur (Fe-S) cluster assembly have been mapped, in addition to TusA, which is required for molybdenum cofactor biosynthesis and mnm
5
s
2
U34 tRNA modifications, and ThiI, which is involved in thiamine biosynthesis and s
4
U8 tRNA modifications. Previous studies predicted that the sulfur acceptor proteins bind to IscS one at a time.
E. coli
TusA has, however, been suggested to be involved in Fe-S cluster assembly, as fewer Fe-S clusters were detected in a

∆

tusA
mutant. The basis for this reduction in Fe-S cluster content is unknown. In this work, we investigated the role of TusA in iron-sulfur cluster assembly and iron homeostasis. We show that the absence of TusA reduces the translation of
fur
, thereby leading to pleiotropic cellular effects, which we dissect in detail in this study.

IMPORTANCE

Iron-sulfur clusters are evolutionarily ancient prosthetic groups. The ferric uptake regulator plays a major role in controlling the expression of iron homeostasis genes in bacteria. We show that a
∆tusA
mutant is impaired in the assembly of Fe-S clusters and accumulates iron. TusA, therefore, reduces
fur
mRNA translation leading to pleiotropic cellular effects.
Unraveling the role of toxin-antitoxin systems in
Burkholderia pseudomallei
: exploring bacterial pathogenesis and interactions within the HigBA families
Authors: Chapartegui-González Itziar , Stockton Jacob L. , Bowser Sarah , Badten Alexander J. , Torres Alfredo G.
Published: June 2024

Burkholderia pseudomallei
(
Bpm
) is a Gram-negative intracellular pathogen that causes melioidosis in humans, a neglected, underreported, and lethal disease that can reach a fatal outcome in over 50% of the cases. It can produce both acute and chronic infections, the latter being particularly challenging to eliminate because of the intracellular life cycle of the bacteria and its ability to generate a “persister” dormant state. The molecular mechanism that allows the switch between growing and persister phenotypes is not well understood but it is hypothesized to be due at least in part to the participation of toxin-antitoxin (TA) systems. We have previously studied the link between one of those systems (defined as HigBA) with specific expression patterns associated with levofloxacin antibiotic exposure. Through
in silico
methods, we predicted the presence of another three pairs of genes encoding for additional putative HigBA systems. Therefore, our main goal was to establish which mechanisms are conserved as well as which pathways are specific among different
Bpm
TA systems from the same family. We hypothesize that the high prevalence, and sometimes even redundancy of these systems in the
Bpm
chromosomes indicates that they can interact with each other and not function as only individual systems, as it was traditionally thought, and might be playing an undefined role in
Bpm
lifecycle. Here, we show that both the toxin and the antitoxin of the different systems contribute to bacterial survival and that toxins from the same family can have a cumulative effect under environmental stressful conditions.

IMPORTANCE

Toxin-antitoxin (TA) systems play a significant role in bacterial persistence, a phenomenon where bacterial cells enter a dormant or slow-growing state to survive adverse conditions such as nutrient deprivation, antibiotic exposure, or host immune responses. By studying TA systems in
Burkholderia pseudomallei
, we can gain insights into how this pathogen survives and persists in the host environment, contributing to its virulence and ability to cause melioidosis chronic infections.
Vibrio cholerae
O1 experiences mild bottlenecks through the gastrointestinal tract in some but not all cholera patients
Authors: Lypaczewski Patrick , Chac Denise , Dunmire Chelsea N. , Tandoc Kristine M. , Chowdhury Fahima , Khan Ashraful I. , Bhuiyan Taufiqur R. , Harris Jason B. , LaRocque Regina C. , Calderwood Stephen B. , Ryan Edward T. , Qadri Firdausi , Shapiro B. Jesse , Weil Ana A.
Published: June 2024

Vibrio cholerae
O1 causes the diarrheal disease cholera, and the small intestine is the site of active infection. During cholera, cholera toxin is secreted from
V. cholerae
and induces a massive fluid influx into the small intestine, which causes vomiting and diarrhea. Typically,
V. cholerae
genomes are sequenced from bacteria passed in stool, but rarely from vomit, a fluid that may more closely represents the site of active infection. We hypothesized that
V. cholerae
O1 population bottlenecks along the gastrointestinal tract would result in reduced genetic variation in stool compared to vomit. To test this, we sequenced
V. cholerae
genomes from 10 cholera patients with paired vomit and stool samples. Genetic diversity was low in both vomit and stool, consistent with a single infecting population rather than coinfection with divergent
V. cholerae
O1 lineages. The amount of single-nucleotide variation decreased from vomit to stool in four patients, increased in two, and remained unchanged in four. The variation in gene presence/absence decreased between vomit and stool in eight patients and increased in two. Pangenome analysis of assembled short-read sequencing demonstrated that the toxin-coregulated pilus operon more frequently contained deletions in genomes from vomit compared to stool. However, these deletions were not detected by PCR or long-read sequencing, indicating that interpreting gene presence or absence patterns from short-read data alone may be incomplete. Overall, we found that
V. cholerae
O1 isolated from stool is genetically similar to
V. cholerae
recovered from the upper intestinal tract.

IMPORTANCE

Vibrio cholerae
O1, the bacterium that causes cholera, is ingested in contaminated food or water and then colonizes the upper small intestine and is excreted in stool. Shed
V. cholerae
genomes from stool are usually studied, but
V. cholerae
isolated from vomit may be more representative of where
V. cholerae
colonizes in the upper intestinal epithelium.
V. cholerae
may experience bottlenecks, or large reductions in bacterial population sizes and genetic diversity, as it passes through the gut. Passage through the gut may select for distinct
V. cholerae
mutants that are adapted for survival and gut colonization. We did not find strong evidence for such adaptive mutations, and instead observed that passage through the gut results in modest reductions in
V. cholerae
genetic diversity, and only in some patients. These results fill a gap in our understanding of the
V. cholerae
life cycle, transmission, and evolution.
Lactobacilli decrease the susceptibility of
Salmonella
Typhimurium to azithromycin
Authors: Blais Lya , Couture Laurence , Laforest-Lapointe Isabelle , Côté Jean-Philippe
Published: June 2024

Bacteria are involved in numerous interactions during infection and among host-associated microbial populations.
Salmonella enterica
serovar Typhimurium is a foodborne pathogen of great importance as well as a model organism to study interactions within a microbial community. In this study, we found that
S
. Typhimurium becomes tolerant to azithromycin when co-cultured with lactobacilli strains. Similarly, acidified media, from cell-free supernatant of lactobacilli cultures for instance, also induced the tolerance of
S
. Typhimurium to azithromycin. The addition of membrane disruptors restored the normal sensitivity to azithromycin in acidified media, but not when lactobacilli were present. These results suggested that the acidification of the media led to modification in envelope homeostasis, but that a different mechanism promoted the tolerance to azithromycin in the presence of lactobacilli strains. To further understand how lactobacilli strains modify the sensitivity of
S
. Typhimurium to azithromycin, a high-throughput assay was performed using the single-gene deletion collection of the
S
. Typhimurium (1) in co-culture with
Lacticaseibacillus rhamnosus
and (2) in sterile acidic conditions (pH 5.5 media only). As expected, both screens identified genes involved in envelope homeostasis and membrane permeability. Our results also suggest that changes in the metabolism of
S
. Typhimurium induce the tolerance observed in the presence of
L. rhamnosus
. Our results thus highlight two different mechanisms by which lactobacilli induce the tolerance of
S
. Typhimurium to azithromycin.

IMPORTANCE

This study provides valuable insights into the intricate interactions between bacteria during infections and within host-associated microbial communities. Specifically, it sheds light on the significant role of lactobacilli in inducing antibiotic tolerance in
Salmonella enterica
serovar Typhimurium, a critical foodborne pathogen and model organism for microbial community studies. The findings not only uncover the mechanisms underlying this antibiotic tolerance but also reveal two distinct pathways through which strains of lactobacilli might influence
Salmonella
’s response to antibiotics. Understanding these mechanisms has the potential to enhance our knowledge of bacterial infections and may have implications for the development of strategies to combat antibiotic resistance in pathogens, such as
Salmonella
. Furthermore, our results underscore the necessity to explore beyond the direct antimicrobial effects of antibiotics, emphasizing the broader microbial community context.
The current state of gender-based diversity within the field of Canadian professional structural timber engineering
Authors: Philion Ethan , Jeanneret Chloe , Gales John , Chorlton Bronwyn
Published: June 2024

There is currently minimal data that may be used for retention and recruitment strategies for timber professional engineering in Canada. A comprehensive survey performed in 2022 to address this lack of data are discussed. The survey was generated and analyzed by York University (Canada) and distributed through the Canadian Wood Council’s membership directory. This survey explored participants’ motivations for working on timber-based structural projects and the existing state of EDI training within the workspace. Findings from the context of analysis illustrated that retention in the work force appears not to be affected by gender, with participants overwhelmingly indicating their plan is to continue to work in the timber structural engineering sector. Gender specific findings suggest that most men who practice timber structural design have had more recorded work experience, whereas women were more likely to obtain a PhD when pursuing graduate school.
The movement of Efimov states in 2n halo nucleus: probing the roles of mass asymmetry and short range of interaction
Authors: Mazumdar Indranil
Published: June 2024

This brief communication presents the results of our work to study the movement of Efimov states in two-neutron halo nuclei. We discuss the emergence and evolution of Efimov states into resonances beyond the two-body (n–core) breakup threshold and also the movement of the Efimov state in a two-neutron halo nucleus to the region of the so-called Thomas collapse. We especially probe the roles of mass asymmetry of the three-body system (n–n–core) and the short range of the n–core interaction in the movement of the Efimov states. The analysis has been carried out within the framework of a three-body model, assuming two-body, non-local, separable potentials for the binary sub-systems, namely, the n–n and n–core systems. The primary motivation has been to scan the parameter space of the range parameter and determine the value(s) for which the system can support the Efimov states. The analysis shows that the value of the range parameter β = 5.2α (α being the energy parameter given in terms of the deuteron binding energy) produces the realistic three-body binding energy for 20C and also generates the excited Efimov states. However, as the value of β is increased corresponding to decrease in the range of the two-body (n–core) interaction the ground and excited state binding energies increase drastically. In other words, as the range of the two-body interaction tends to zero the system enters the Thomas collapse region away from the Efimov region.
Stamping Platinum Electrodes – Design, Fabrication, and Characterization
Authors: Jedlińska Katarzyna , Eidenschink Johannes , Matysik Frank-Michael , Baś Bogusław
Published: June 2024

This communication introduces a quick and easy method to modify a typical disk electrode’s surface geometry. The method involves masking fragments of the flat surface of the working electrode, by applying a specific thin layer of chemically stable insulating material, leaving unvarnished, electrochemically active surface. Desired shapes are achieved by using a properly laser-engraved stainless-steel plate and a stamper to transfer the profiled varnish from the steel plate to the surface of the electrode. Three shapes - microdisk, microband, and ring electrodes - were applied to a platinum disk electrode, validated through optical and scanning electrochemical microscopies, and cyclic voltammetry.
Sharp Lower Bound of Cacti Graph with respect to Zagreb Eccentricity Indices
Authors: Alamer Ahmed , Hakami Khalil Hadi , Rahimi Mohammad Rahim , Ahmad Yasir
Published: June 2024

The first Zagreb eccentricity index E1(℧) is the sum of square of eccentricities of the vertices, and the second Zagreb eccentricity index E2(℧) is the sum of product squares of the eccentricities of the vertices. A linked graph G is called a cactus if any two of its cycles share only one vertex. In other words, there are no two independent cycles that share an edge. Cactus graphs are also known as “block graphs” or “sensitized graphs.” They are closely related to chordal graphs and can be used to represent various types of networks, including communication networks and road networks. In this contribution, E1(℧) and E2(℧) values of cacti with k pendant vertices and k cycles, respectively, are considered. We determine the minimum E1, E2 indices for n order cacti with k pendant vertices and k cycles.
Impact of Focal Muscle Vibration on Flaccid Upper Limb Motor Paralysis following Acute Brain Disease: A Case Study
Authors: Saito Hirotaka , Kobayashi Haruka , Oba Kodai , Hamaya Yosuke
Published: June 2024

Focal muscle vibration (FMV) is increasingly being recognized as a rehabilitative therapy for enhancing motor function in central nervous system (CNS) diseases, particularly in patients with fine motor control deficits stemming from CNS damage. Brain lesions from these diseases disrupt the motor networks, necessitating novel rehabilitation strategies. By applying vibrations to muscles, FMV stimulates sensory fibers to induce cortical activity and kinesthetic illusions. While initial studies have highlighted FMV’s role in reducing spasticity, recent evidence points to its potential in treating motor paralysis. However, prior research has been limited by the lack of acute‐phase studies and a focus on patients with minimal muscle contraction capability. This report aimed to explore FMV’s efficacy on upper limb motor function in patients with flaccid motor paralysis immediately after acute CNS diseases. We report the case of a septuagenarian male with a brain abscess in the right parietal lobe, leading to flaccid motor paralysis. Rehabilitation included 28 sessions of occupational and physical therapy that incorporated FMV. Significant improvements were observed in upper extremity function, with moderate to very large effect sizes, while lower limb function showed lesser improvement without adverse effects. This case suggests the utility of FMV in enhancing upper‐limb motor function after acute CNS injuries, potentially serving as a supplementary therapy for spontaneous recovery. This report contributes to emerging evidence on FMV’s benefits in acute flaccid motor paralysis, expanding the documented therapeutic scope.