bluuebunny/crossref_metadata_2025 huggingface dataset:
The ethical pathway of individuals with stroke—A follow‐up study
Authors: Sunna Rannikko , Riitta Suhonen , Miko Pasanen , Helena Leino‐Kilpi
Published: October 2023

Aim

To analyse the ethical pathway as perceived by individuals with stroke (IwS) in the first three post‐stroke months. In the novel concept of ethical pathway, dignity, privacy, and autonomy are considered as dimensions of the ethical pathway while the pathway illustrates their potential change in the post‐stroke time. Furthermore, the focus of interest was on whether the perceived realisation of values is associated with the life situational factors of symptoms diminishing functioning, social environment, and self‐empowerment.

Methodological Design and Justification

A follow‐up study with a descriptive correlational design was used to capture the changes in the perceived realisation of values.

Ethical Issues and Approval

The study followed the ethical principles of research involving human participants. The study was approved by the ethics committee of the university and one of the university hospitals following national standards. Permission to conduct the study was obtained from the university hospitals.

Research Methods and Instrument

Data were collected from IwS after the onset of stroke and 3 months post‐stroke with the Ethical Pathway of Individuals with Stroke instrument and background questions and were analysed statistically.

Results

Thirty‐six participants completed the questionnaire at both measurement points. Wide variety in the ethical pathway was detected. IwS' perceived dignity decreased and autonomy increased. Privacy did not change significantly. Of the life situational factors, IwS perceived less symptoms diminishing functioning and stronger self‐empowerment while social environment was perceived as rather stable. Only one association was detected between the dimensions of the ethical pathway and life situational factors: autonomy had a low negative correlation with social environment of health care professionals.

Conclusions and Study Limitations

The results provide preliminary evidence of the dynamic nature of the ethical pathway. The ethical pathway was incompletely realised for most participants and requires special attention and improvement in health care. The sample size is small and the results are therefore not generalisable.
Extended maternity leave and children's long‐term development
Authors: Behaghel Luc , Pinto Maria Florencia
Published: October 2023

Countries around the world are increasingly expanding legal maternity leaves, with the dual objective of protecting mothers' jobs during their recovery after childbirth and enhancing child development. Using exhaustive census data, we find that a three‐year paid leave in France had zero average effects on children's long‐term schooling achievement, and no detectable impact heterogeneity. The lack of positive effects on children adds to the case against a policy that has strong adverse effects on mothers' careers.
Snapshot of a crisis: food security and dietary diversity levels among disrupted conventional and long‐term organic tea‐smallholders in Sri Lanka
Authors: Perera Bathige Nethmi S. , Moseley William G.
Published: October 2023

In Sri Lanka, conventional and organic smallholder producers grow seventy percent of the country's tea, bring in significant export earnings, and are differentially exposed to input supply shocks. While tea production may be advantageous for the nation's economy, it is less clear whether it is good for the food security of those smallholders involved. This study examines how economic status (income and wealth) and method of tea farming (organic or conventional) influences food security and dietary diversity outcomes in the midst of a fertiliser supply shock. We used data collected in the summer of 2021, a time when an inorganic fertiliser ban went into effect, from 47 organic and 67 conventional tea smallholders in five rural communities in southern and central Sri Lanka. Our findings show that long‐term organic farmers had higher dietary diversity measures than the conventional tea smallholders who were unevenly disrupted by the aforementioned fertiliser ban. The haphazard ban on conventional fertilizer adversely impacted dietary outcomes of conventional farmers. We also discuss how the transition to organic farming would have worked better with more time and planning.
Investigation of Rear Blisk Drum Dynamics Under Consideration of Multi-Stage Coupling
Authors: Gambitta Marco , Beirow Bernd , Klauke Thomas
Published: October 2023

The analysis of the structural dynamics of multistage cyclic structures as linked components is required to model the interstage coupling. In turbomachinery, this can result in a collaboration between different compressor or turbine stages. This paper investigates the coupling between two rear drum blade integrated disk stages of an axial compressor to support the mechanical design process. Considering the vibration modeshapes of a multistage system, different components may coparticipate in the dynamics. For this reason, criteria to identify the modes affected by the coupling and to quantify this coupling are defined. This allows to distinguish between modes with interstage coupling, requiring the multistage system for their description, and uncoupled modes, involving a single stage. In addition, it is of interest to research methods to reduce the impact of the coupling on the vibrating system without drastically altering the geometry of the components. The vibration analyses of a two-stage compressor generalized geometry, representative of a compressor rear drum blisk, are presented as a study case. The use of a reducing method allows to describe the behavior of the nominal multistage system with a computationally efficient technique, enabling a parametric analysis of the stages' coupling. The investigation considers the effect of a set of geometrical and mechanical parameters on the dynamics, identifying the driving parameters of the coupled vibration characteristics.
Improved Wear Profile Modeling of Planetary Roller Screw Mechanism With Thread Optimization
Authors: Miao Jiacheng , Du Xing , Li Chaoyang , Chen Bingkui
Published: October 2023

A systematic process of matrices-based wear profile modeling and a new optimization approach for planetary roller screw mechanism (PRSM) was proposed in this paper to improve the anti-wear performance with varied thread geometries. The wear evolution characteristics of thread surfaces for convex–concave contact and convex–straight contact were captured by incorporating updated axial clearances originated from accumulated thread wear, which provides a new perspective to predict the wear process of PRSM. The results show that the wear depth in convex–concave contact is 22% shallower than convex–straight contact with 105 numbers of cycles, which suggests thread wear can be limited with plausible geometrical parameters. Further analysis showed that as the surface roughness increases, the true equivalent pressure, the plastic strain, and the maximum wear depth become larger. In addition, the effect of the surface textures on the tribological properties of threads is also discussed to improve the applicability of the proposed methodology.
Frequency Domain Reflectometry Cable Inspection Simulation
Authors: Glass S.W. , Spencer M.P. , Sriraman A. , Son J. , Fifield L.S.
Published: October 2023

Simulation of cable system responses to frequency domain reflectometry (FDR) tests can be instrumental to understanding these tests and the influence of various cable anomalies on test signatures. Reflectometry simulations are based upon a finite element representation of the cable conductor and insulation to produce an S-parameter at each evaluated frequency. The aggregate collection of cable S-parameters can simulate influence on a test signal injected into the simulation network and can show reflections caused by cable anomaly impedance changes. Such a digital twin simulation was developed and examined for influence of both the test simulation parameters and relative influence of cable anomalies including thermal aging damage, water or moisture exposure on outside jacket, water or moisture ingress exposure to conductor through damaged cable, and other cable insulation anomalies.
A Deep Learning Framework for Efficient Global Sensitivity Analysis and Shap Values Calculations Applied to Eddy Current Testing Problems
Authors: Granados Gerardo E. , Miorelli Roberto , Gatti Filippo , Clouteau Didier
Published: October 2023

In the context of the nondestructive testing and evaluation research community, global sensitivity analysis (GSA) methods are widespread tools for quantifying the sensitivity of measurements concerning the variation of inputs over the whole design space. For parameter ranking purposes, GSA methods have been historically preferred by NDT&E scholars compared to feature importance (FI) techniques such as random forest-based, SHAP values, among others. For practical applications, GSA and FI can face limitations when the number of evaluations of the physical model is very high. The main issues that one needs to face with GSA and FI in practical problems are the low computing time efficiency of the numerical solver and/or the high cardinality (i.e., the number of inputs) of the problem considered. This paper targets two main goals. First, we propose to tackle the problem of an efficient GSA and FI procedure relying on a tailored deep neural network to be employed as a metamodel (or surrogate model) to replace the less efficient numerical model. Second, we compare GSA (i.e., Sobol’ indices and 𝛿-sensitivity measure) indices and FI (i.e., SHAP) method for parameter ranking purposes. In particular, we describe a generative deep neural network framework to be straightforwardly applied to GSA and FI studies. The numerical experiments in this communication correspond to an eddy current testing inspection problem where multiple arbitrarily oriented cracks lie in a conductive planar multilayered structure.
Battery Health Monitoring using Guided Wave Signal Features
Authors: Lao Dongjing , Shen Yanfeng , Ren Shaoteng , Lin Si , Zhang Fenglin
Published: October 2023

The high-speed development of the new energy industry and the renewable energy facilities have made battery energy storage critical for Electric Vehicles (EVs) and large-scale Energy Storage Systems (ESSs). However, the complexity of the internal chemical reactions and the uncertainty of the external service environment seriously affect the reliability of batteries. Therefore, Battery Management Systems (BMS) have become essential to monitor battery health and performance, detect potential issues at an early stage, improve safety, and reduce costs associated with battery maintenance and replacement. This paper proposes a Battery Health Monitoring (BHM) system based on guided wave signal features to monitor and predict State of Charge (SOC), State of Health (SOH), and Remaining Useful Life (RUL) of batteries. A data collection system is developed to realize the integration of wave generation and reception, with subsequent feature extraction of the recorded ultrasound signals and characterization in different forms, enabling the prediction of battery health status and early alert of rapid battery capacity deterioration. The proposed method is based on time-frequency analysis of ultrasonic responses and weighted averaging algorithms for signal feature extraction, which facilitates the acquisition of indicative trends corresponding to battery SOC, SOH, and RUL variations. Experimental results indicate that the system can achieve real-time monitoring of battery SOC cycles, obtain battery SOH trends and health warnings of severe battery aging, and accurately predict the decay rate of the standard battery capacity to achieve RUL estimation, thus demonstrating the excellent evaluating capability of the active sensing method in battery health monitoring.
Individual differences in speech-on-speech masking are correlated with cognitive and visual task performance
Authors: Byrne Andrew J. , Conroy Christopher , Kidd Gerald
Published: October 2023

Individual differences in spatial tuning for masked target speech identification were determined using maskers that varied in type and proximity to the target source. The maskers were chosen to produce three strengths of informational masking (IM): high [same-gender, speech-on-speech (SOS) masking], intermediate (the same masker speech time-reversed), and low (speech-shaped, speech-envelope-modulated noise). Typical for this task, individual differences increased as IM increased, while overall performance decreased. To determine the extent to which auditory performance might generalize to another sensory modality, a comparison visual task was also implemented. Visual search time was measured for identifying a cued object among “clouds” of distractors that were varied symmetrically in proximity to the target. The visual maskers also were chosen to produce three strengths of an analog of IM based on feature similarities between the target and maskers. Significant correlations were found for overall auditory and visual task performance, and both of these measures were correlated with an index of general cognitive reasoning. Overall, the findings provide qualified support for the proposition that the ability of an individual to solve IM-dominated tasks depends on cognitive mechanisms that operate in common across sensory modalities.
Accuracy of Heart-Rate-Recovery Parameters Assessed From a Wrist-Worn Photoplethysmography Monitor (Polar Unite)
Authors: Bretonneau Quentin , Peruque-Gayou Etienne , Wolfs Etienne , Bosquet Laurent
Published: October 2023

Purpose: The accuracy of heart rate (HR) measured with a wrist-worn photoplethysmography (PPG) monitor is altered during rest–exercise and exercise–rest transitions, which questions the validity of postexercise HR-recovery (HRR) parameters estimated from this device. Methods: Thirty participants (50% female) randomly performed two 13-minute sequences (3′ rest, 5′ submaximal-intensity exercise, and 5′ passive recovery) on treadmill and bicycle ergometers. HR was measured concomitantly with a 10-lead electrocardiogram (ECG) and a wrist-worn PPG monitor (Polar Unite). HRR was assessed by calculating Δ60 (the difference between HR during exercise and HR 60 s after exercise cessation) and by fitting HRR data into a monoexponential model. Results: By focusing on Δ60 and τ (the time constant of the monoexponential curve), levels of association (r) of the Unite versus the 10-lead ECG were high to very high (.73 < r < .93), and coefficients of variation were >20% (in absolute value), except for Δ60 in the bicycle ergometer condition (11.7%). In 97% of cases, the decrease in HR after exercise appeared later with the Unite. By adjusting the time window used for the analysis according to this time lag, coefficients of variation of Δ60 decreased below 10% in the bicycle ergometer condition. Conclusions: If a wrist-worn PPG monitor is used to assess HRR, we recommend performing the submaximal-intensity exercise on a bicycle ergometer and focusing on Δ60. Furthermore, to obtain a more accurate Δ60, the time lag between the end of the exercise and the effective decrease in HR should also be considered before the calculation.
Effect of Core Muscle Training on Balance and Agility in Athletes: A Systematic Review
Authors: Shetty Saidan , Neelapala Y.V. Raghava , Srivastava Prateek
Published: October 2023

The objective of this review was to systematically summarize the existing literature on the effect of core muscle training on measures of balance and agility in athletes. A search was conducted to identify the eligible articles on core muscle training, balance, agility, and athletes in PubMed, Scopus, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, and Physiotherapy Evidence Database that were published from inception to April 15, 2022. The literature search retrieved 3,299 articles, of which 17 randomized controlled trials met the inclusion criteria of the review. Two reviewers independently performed study selection and assessed the quality of included studies using the Physiotherapy Evidence Database (PEDro) scale, and a third reviewer was consulted in case of disagreements. The quality of the studies was mixed. Core muscle training can be used to target balance and agility in athletes. Furthermore, core training of variable frequency, intensity, and type can be incorporated in athletic programs to improve balance and agility.
Hidden-information extraction from layered structures through terahertz imaging down to ultralow SNR
Authors: Cui Yuqing , Xu Yafei , Han Donghai , Wang Xingyu , Shen Zhonglei , Hou Yushan , Liang Junyan , Wang Xianqiao , Citrin David S. , Zhang Liuyang , Nandi Asoke K. , Yan Ruqiang , Chen Xuefeng
Published: October 2023

Noninvasive inspection of layered structures has remained a long-standing challenge for time-resolved imaging techniques, where both resolution and contrast are compromised by prominent signal attenuation, interlayer reflections, and dispersion. Our method based on terahertz (THz) time-domain spectroscopy overcomes these limitations by offering fine resolution and a broadband spectrum to efficiently extract hidden structural and content information from layered structures. We exploit local symmetrical characteristics of reflected THz pulses to determine the location of each layer, and apply a statistical process in the spatiotemporal domain to enhance the image contrast. Its superior performance is evidenced by the extraction of alphabetic characters in 26-layer subwavelength papers as well as layer reconstruction and debonding inspection in the conservation of Terra-Cotta Warriors. Our method enables accurate structure reconstruction and high-contrast imaging of layered structures at ultralow signal-to-noise ratio, which holds great potential for internal inspection of cultural artifacts, electronic components, coatings, and composites with dozens of submillimeter layers.
Live-cell imaging uncovers the relationship between histone acetylation, transcription initiation, and nucleosome mobility
Authors: Saxton Matthew N. , Morisaki Tatsuya , Krapf Diego , Kimura Hiroshi , Stasevich Timothy J.
Published: October 2023

Histone acetylation and RNA polymerase II phosphorylation are associated with transcriptionally active chromatin, but their spatiotemporal relationship in live cells remains poorly understood. To address this problem, we combine Fab-based labeling of endogenous protein modifications with single-molecule tracking to quantify the dynamics of chromatin enriched with histone H3 lysine-27 acetylation (H3K27ac) and RNA polymerase II serine-5 phosphorylation (RNAP2-Ser5ph). Our analysis reveals that chromatin enriched with these two modifications is generally separate. In these separated sites, we show that the two modifications are inversely correlated with one another on the minutes time scale and that single nucleosomes within each region display distinct and opposing dynamics on the subsecond time scale. While nucleosomes diffuse ~15% faster in chromatin enriched with H3K27ac, they diffuse ~15% slower in chromatin enriched with RNAP2-Ser5ph. These results argue that high levels of H3K27ac and RNAP2-Ser5ph are not often present together at the same place and time, but rather each marks distinct transcriptionally poised or active sites, respectively.
Apollo-NADP
+
reveals in vivo adaptation of NADPH/NADP
+
metabolism in electrically activated pancreatic β cells
Authors: Bui Cindy V. , Boswell Curtis W. , Ciruna Brian , Rocheleau Jonathan V.
Published: October 2023

Several genetically encoded sensors have been developed to study live cell NADPH/NADP
+
dynamics, but their use has been predominantly in vitro. Here, we developed an in vivo assay using the Apollo-NADP
+
sensor and microfluidic devices to measure endogenous NADPH/NADP
+
dynamics in the pancreatic β cells of live zebrafish embryos. Flux through the pentose phosphate pathway, the main source of NADPH in many cell types, has been reported to be low in β cells. Thus, it is unclear how these cells compensate to meet NADPH demands. Using our assay, we show that pyruvate cycling is the main source of NADP
+
reduction in β cells, with contributions from folate cycling after acute electrical activation. INS1E β cells also showed a stress-induced increase in folate cycling and further suggested that this cycling requires both increased glycolytic intermediates and cytosolic NAD
+
. Overall, we show in vivo application of the Apollo-NADP
+
sensor and reveal that β cells are capable of adapting NADPH/NADP
+
redox during stress.
A key
O
-demethylase in the degradation of guaiacol by
Rhodococcus opacus
PD630
Authors: Xue Le , Zhao Yiquan , Li Ling , Rao Xinran , Chen Xinjie , Ma Fuying , Yu Hongbo , Xie Shangxian
Published: October 2023

Rhodococcus opacus
PD630 is a high oil-producing strain with the ability to convert lignin-derived aromatics to high values, but limited research has been done to elucidate its conversion pathway, especially the upper pathways. In this study, we focused on the upper pathways and demethylation mechanism of lignin-derived aromatics metabolism by
R. opacus
PD630. The results of the aromatic carbon resource utilization screening showed that
R. opacus
PD630 had a strong degradation capacity to the lignin-derived methoxy-containing aromatics, such as guaiacol, 3,4-veratric acid, anisic acid, isovanillic acid, and vanillic acid. The gene of

gcoA
R

, which encodes cytochrome P450, showed significant up-regulation when
R. opacus
PD630 grew on diverse aromatics. Deletion mutants of

gcoA
R

and its partner protein

gcoB
R

resulted in the strain losing the ability to grow on guaiacol, but no significant difference to the other aromatics. Only co-complementation alone of

gcoA
R

and

gcoB
R

restored the strain’s ability to utilize guaiacol, demonstrating that both genes were equally important in the utilization of guaiacol.
In vitro
assays further revealed that GcoA
R
could convert guaiacol and anisole to catechol and phenol, respectively, with the production of formaldehyde as a by-product. The study provided robust evidence to reveal the molecular mechanism of
R. opacus
PD630 on guaiacol metabolism and offered a promising study model for dissecting the demethylation process of lignin-derived aromatics in microbes.

IMPORTANCE

Aryl-
O
-demethylation is believed to be the key rate-limiting step in the catabolism of heterogeneous lignin-derived aromatics in both native and engineered microbes. However, the mechanisms of
O
-demethylation in lignin-derived aromatic catabolism remain unclear. Notably, guaiacol, the primary component unit of lignin, lacks
in situ
demonstration and illustration of the molecular mechanism of guaiacol
O
-demethylation in lignin-degrading bacteria. This is the first study to illustrate the mechanism of guaiacol metabolism by
R. opacus
PD630
in situ
as well as characterize the purified key
O
-demethylase
in vitro
. This study provided further insight into the lignin metabolic pathway of
R. opacus
PD630 and could guide the design of an efficient biocatalytic system for lignin valorization.
PhamClust: a phage genome clustering tool using proteomic equivalence
Authors: Gauthier Christian H. , Hatfull Graham F.
Published: October 2023

Bacteriophage comparative genomics is complex due to the mosaic nature of the genomes, and an underlying continuum of diversity confounds the identification of clear taxonomic boundaries. Nucleotide sequence comparison methods have been described for phage taxonomy, but they are computationally intensive and scale poorly as the number of sequenced phage genomes increases. Here, we describe PhamClust as a new bioinformatic approach for grouping phages according to their inter-genome relatedness. PhamClust calculates a proteomic equivalence quotient (PEQ) for each pair of phages based on amino acid sequence identity for those genes that are shared among phages. PEQ values span from 0% (no shared genes) to 100% (all genes shared at 100% identity), and using a large mycobacteriophage genome data set, we show that two-step clustering down to a PEQ of 25% constructs genome groupings (clusters) closely mirroring those constructed manually over time, with the differences attributable to historically arising incongruities rather than illogicalities in PhamClust. PEQ values can also faithfully divide clusters into subclusters, although the relationships are highly heterogeneous, with different PEQ values needed for the subdivision of different clusters. PhamClust can be used to assort any group of phages, including the RefSeq phage collection.

IMPORTANCE

Bacteriophage genomes are pervasively mosaic, presenting challenges to describing phage relatedness. Here, we describe PhamClust, a bioinformatic approach for phage genome comparisons that uses a new metric of proteomic equivalence quotient for comparative genomics. PhamClust reliably assorts genomes into groups or clusters of related phages and can subdivide clusters into subclusters. PhamClust is computationally efficient and can readily process thousands of phage genomes. It is also a useful analytic tool for exploring the different types of inter-genome relatedness characteristic of phages in different clusters.
The tip protein PAAR is required for the function of the type VI secretion system
Authors: Beauvois Solène G. , Flaugnatti Nicolas , Ilbert Marianne , Boyer Marie , Gavello-Fernandez Esther , Fronzes Rémi , Jurėnas Dukas , Journet Laure
Published: October 2023

Bacteria are constantly competing to colonize crowded ecological niches, such as the human gut. The type VI secretion system (T6SS) is a critical bacterial weapon in this warfare. It resembles a crossbow with a poisoned arrow allowing bacteria to inject toxic effectors directly into target cells. This machinery is formed by an envelope-spanning complex which recruits the baseplate, an assembly platform allowing the polymerization of a contractile structure. The tail consists of a tube surrounded by a sheath and topped by the needle complex composed of the VgrG and PAAR proteins. In the enteric pathogen enteroaggregative
Escherichia coli
(EAEC), the Tle1 phospholipase toxin ensures the antibacterial activity of the T6SS-1. For its transport, Tle1 interacts directly with the trimeric spike protein VgrG. However, the importance and the function of the tip protein PAAR in the T6SS remain unclear. Here, we characterized the PAAR protein of EAEC using biochemical, fluorescence microscopy, and antibacterial competition approaches. Using pull-down assays and cryo-electron microscopy analysis of the (VgrG)
3
-(Tle1)
3
-PAAR complex, we show that PAAR tops and closes the β-prism structure of the VgrG spike. The PAAR protein structure is further tightened by the zinc atom coordinated via conserved residues essential for its function. We provide evidence that PAAR is necessary for T6SS-1-mediated killing due to its requirement for proper T6SS baseplate assembly and further sheath polymerization. Our results suggest that the PAAR protein is an essential component of T6SS.

IMPORTANCE

The type VI secretion system (T6SS) is a bacterial contractile injection system involved in bacterial competition by the delivery of antibacterial toxins. The T6SS consists of an envelope-spanning complex that recruits the baseplate, allowing the polymerization of a contractile tail structure. The tail is a tube wrapped by a sheath and topped by the tip of the system, the VgrG spike/PAAR complex. Effectors loaded onto the puncturing tip or into the tube are propelled in the target cells upon sheath contraction. The PAAR protein tips and sharpens the VgrG spike. However, the importance and the function of this protein remain unclear. Here, we provide evidence for association of PAAR at the tip of the VgrG spike. We also found that the PAAR protein is a T6SS critical component required for baseplate and sheath assembly.
An oral commensal attenuates
Pseudomonas aeruginosa
-induced airway inflammation and modulates nitrite flux in respiratory epithelium
Authors: Baty Joshua J. , Stoner Sara N. , McDaniel Melissa S. , Huffines Joshua T. , Edmonds Sara E. , Evans Nicholas J. , Novak Lea , Scoffield Jessica A.
Published: October 2023

Polymicrobial airway infections in persons with cystic fibrosis (pwCF) can positively or negatively impact the course of disease. A major CF pathogen,
Pseudomonas aeruginosa,
often establishes a chronic infection leading to lung deterioration. Interestingly, the presence of certain oral commensal streptococci is correlated with improved outcomes for pwCF. We previously reported that hydrogen peroxide production by these commensals combined with nitrite generates reactive nitrogen intermediates (RNI), which inhibit
P. aeruginosa in vitro
. In this study, we utilized a rat co-infection lung model to assess whether oral commensal-generated RNI can restrict the pathogenesis of a CF isolate of
P. aeruginosa
. We report that the oral commensal
Streptococcus parasanguinis
and nitrite reduce
P. aeruginosa
-induced host inflammation in wild-type rats. To better recapitulate CF-specific airway conditions, we used a bronchial epithelial cell culture model to gain a better understanding of how
S. parasanguinis
and nitrite may influence
P. aeruginosa
burden during a CF infection. Hence, we co-infected wild-type and cystic fibrosis transconductance regulator (CFTR) channel-deficient bronchial epithelial cells with
P. aeruginosa
and
S. parasanguinis
with or without nitrite. Strikingly,
S. parasanguinis
reduced the bacterial burden of
P. aeruginosa
without nitrite, promoted epithelial cell viability, and stimulated nitrite production in the wild-type and CFTR-deficient epithelial cells, where nitrite induction was more apparent in the CFTR mutant cells. Taken together, our study demonstrates that the commensal
S. parasanguinis
may provide protection against
P. aeruginosa
-induced inflammation and cell death, as well as modulate nitrite flux in airway epithelial cells.

IMPORTANCE

Respiratory infections are a leading cause of morbidity and mortality in people with cystic fibrosis (CF). These infections are polymicrobial in nature with overt pathogens and other colonizing microbes present. Microbiome data have indicated that the presence of oral commensal bacteria in the lungs is correlated with improved outcomes. We hypothesize that one oral commensal,
Streptococcus parasanguinis,
inhibits CF pathogens and modulates the host immune response. One major CF pathogen is
Pseudomonas aeruginosa
, a Gram-negative, opportunistic bacterium with intrinsic drug resistance and an arsenal of virulence factors. We have previously shown that
S. parasanguinis
inhibits
P. aeruginosa in vitro
in a nitrite-dependent manner through the production of reactive nitrogen intermediates. In this study, we demonstrate that while this mechanism is evident in a cell culture model of the CF airway, an alternative mechanism by which
S. parasanguinis
may improve outcomes for people with CF is through immunomodulation.
The RND efflux system ParXY affects siderophore secretion in
Pseudomonas putida
KT2440
Authors: Stein Nicola Victoria , Eder Michelle , Burr Fabienne , Stoss Sarah , Holzner Lorenz , Kunz Hans-Henning , Jung Heinrich
Published: October 2023

Tripartite efflux systems transport antimicrobial agents, toxic metabolites, and siderophores from Gram-negative cells into the environment. For example, the main siderophore pyoverdine of the soil bacterium
Pseudomonas putida
KT2440 is secreted into the environment via the PvdRT-OpmQ and MdtABC-OpmB systems. Here, we looked for efflux systems that might be involved in the secretion of pyoverdine in addition to the latter two systems. Screening of different efflux systems revealed that
parX
(encoding the periplasmic adapter protein of the ParXY system) is of particular importance for bacterial growth under iron limitation. Further analysis showed that the deletion of
parX
impairs the production and secretion of pyoverdine, causing the observed growth effect. The effects were dependent on the presence of other tripartite efflux systems and the conditions of iron limitation. The results suggest that ParXY not only plays a role in antibiotic resistance, as shown previously, but also influences the secretion of siderophores in a network of overlapping activities of different tripartite efflux systems.

IMPORTANCE

Gram-negative bacteria from the
Pseudomonas
group are survivors in various environmental niches. For example, the bacteria secrete siderophores to capture ferric ions under deficiency conditions. Tripartite efflux systems are involved in the secretion of siderophores, which are also important for antibiotic resistance. For one of these efflux systems, the resistance-nodulation-cell division transporter ParXY from the model organism
Pseudomonas putida
KT2440, we show that it influences the secretion of the siderophore pyoverdine in addition to its already known involvement in antibiotic resistance. Phenotypically, its role in pyoverdine secretion is only apparent when other pyoverdine secretion systems are inactive. The results confirm that the different tripartite efflux systems have overlapping substrate specificities and can at least partially functionally substitute for each other, especially in important physiological activities such as supplying the cell with iron ions. This fact must be taken into account when developing specific inhibitors for tripartite efflux systems.
RNAseq analysis of
Cellvibrio japonicus
during starch utilization differentiates between genes encoding carbohydrate active enzymes controlled by substrate detection or growth rate
Authors: Garcia Cecelia A. , Gardner Jeffrey G.
Published: October 2023

Bacterial utilization of starch is increasingly of interest as the importance and contributions of animal gut microbiomes become more defined. Consequently, identifying and characterizing the bacterial enzymes responsible for the degradation, transport, and metabolism of starch will enable developments in pharmaceutical, biotechnological, and culinary industries searching for novel prebiotics, carrier molecules, and low glycemic index sweeteners. The current challenge is that bacteria proficient at starch utilization often have hundreds of carbohydrate active enzymes, and it is unclear which are essential for starch utilization using only homology-based bioinformatics or computational methods. Complementary experimental data are also needed, especially to understand the regulation of bacterial starch utilization. We have completed an RNAseq analysis of the Gram-negative bacterium
Cellvibrio japonicus
and found that it has sophisticated regulation that includes substrate sensing and growth rate components for genes that encode starch-degrading enzymes. Among the 22 genes predicted to encode starch-active enzymes,
C. japonicus
has 10 alpha-amylases, 4 alpha-glucosidases, 2 pullulnases, and 2 cyclomaltodextrin glucanotransferases, 15 of which were up-regulated during exponential growth on starch and 8 up-regulated in stationary phase. Growth analyses with an enzyme secretion deficient mutant of
C. japonicus
suggested that secreted amylases are essential for this bacterium to degrade starch. Our approach of coupling a physiological growth assay with transcriptomic data provides a platform to identify targets for further genetic or biochemical analysis that can be broadly applied to other starch-utilizing bacteria.

IMPORTANCE

Understanding the bacterial metabolism of starch is important as this polysaccharide is a ubiquitous ingredient in foods, supplements, and medicines, all of which influence gut microbiome composition and health. Our RNAseq and growth data set provides a valuable resource to those who want to better understand the regulation of starch utilization in Gram-negative bacteria. These data are also useful as they provide an example of how to approach studying a starch-utilizing bacterium that has many putative amylases by coupling transcriptomic data with growth assays to overcome the potential challenges of functional redundancy. The RNAseq data can also be used as a part of larger meta-analyses to compare how
C. japonicus
regulates carbohydrate active enzymes, or how this bacterium compares to gut microbiome constituents in terms of starch utilization potential.
A conserved metabolic signature associated with response to fast-acting anti-malarial agents
Authors: Simwela Nelson V. , Guiguemde W. Armand , Straimer Judith , Regnault Clement , Stokes Barbara H. , Tavernelli Luis E. , Yokokawa Fumiaki , Taft Benjamin , Diagana Thierry T. , Barrett Michael P. , Waters Andrew P.
Published: October 2023

Characterizing the mode of action of anti-malarial compounds that emerge from high-throughput phenotypic screens is central to understanding how parasite resistance to these drugs can emerge. Here, we have employed untargeted metabolomics to inform on the mechanism of action of anti-malarial leads with different speed of kill profiles being developed by the Novartis Institute of Tropical Diseases (NITD). Time-resolved global changes in malaria parasite metabolite profiles upon drug treatment were quantified using liquid chromatography-based mass spectrometry and compared to untreated controls. Using this approach, we confirmed previously reported metabolomics profiles of the fast-killing (2.5 h) drug dihydroartemisinin (DHA) and the slower killing atovaquone. A slow-acting anti-malarial lead from NITD of imidazolopiperazine (IZP) class, GNF179, elicited little or no discernable metabolic change in malaria parasites in the same 2.5-h window of drug exposure. In contrast, fast-killing drugs, DHA and the spiroindolone (NITD246), elicited similar metabolomic profiles both in terms of kinetics and content. DHA and NITD246 induced peptide losses consistent with disruption of hemoglobin catabolism and also interfered with the pyrimidine biosynthesis pathway. Two members of the recently described class of anti-malarial agents of the 5-aryl-2-amino-imidazothiadiazole class also exhibited a fast-acting profile that featured peptide losses indicative of disrupted hemoglobin catabolism. Our screen demonstrates that structurally unrelated, fast-acting anti-malarial compounds generate similar biochemical signatures in
Plasmodium
pointing to a common mechanism associated with rapid parasite death. These profiles may be used to identify and possibly predict the mode of action of other fast-acting drug candidates.

IMPORTANCE

In malaria drug discovery, understanding the mode of action of lead compounds is important as it helps in predicting the potential emergence of drug resistance in the field when these drugs are eventually deployed. In this study, we have employed metabolomics technologies to characterize the potential targets of anti-malarial drug candidates in the developmental pipeline at NITD. We show that NITD fast-acting leads belonging to spiroindolone and imidazothiadiazole class induce a common biochemical theme in drug-exposed malaria parasites which is similar to another fast-acting, clinically available drug, DHA. These biochemical features which are absent in a slower acting NITD lead (GNF17) point to hemoglobin digestion and inhibition of the pyrimidine pathway as potential action points for these drugs. These biochemical themes can be used to identify and inform on the mode of action of fast drug candidates of similar profiles in future drug discovery programs.
Pneumatic Transport System REGATA-2 for Automation of Activation Analysis at the IREN Facility, FLNP JINR
Authors: Lobachev V. V. , Dmitriev A. Yu. , Borzakov S. B. , Smirnov A. A. , Zhironkin I. S. , Golubkov E. A. , Shvetsov V. N.
Published: October 2023

The IREN facility at the Frank Laboratory of Neutron Physics (FLNP) of the Joint Institute for Nuclear Research (JINR) is used for experiments to determine elemental composition of various samples by neutron activation analysis (NAA). A pneumatic transport system (PTS) REGATA-2 was implemented to automate the delivery of containers with samples to the irradiation position and back. The article describes the characteristics of the PTS, its adaptation for operation at the IREN facility, and also plans for subsequent modernization and future prospects. After the assembling of the system, the optimal parameters were chosen for irradiating the typical samples, and a calibration was created for a high-purity germanium detector, which let to consider the volume nature of the samples. Samples of archaeological ceramics from Kazakhstan were studied using the PTS. The features of the IREN facility let to use not only a neutron, but also a gamma-producing target. The first experiments on the qualitative determination of elements by gamma-activation analysis (GAA) were carried out, and the prospects for using the facility for these purposes were confirmed. The creation of the PTS let to automate the process of irradiation samples and increase the efficiency of research in NAA and GAA, especially for short-lived isotopes. It also reduces the negative impact of radiation on the human body.
A critical analysis of COVAX alliance and corresponding global health governance and policy issues: a scoping review
Authors: Pushkaran Anjali , Chattu Vijay Kumar , Narayanan Prakash
Published: October 2023

Introduction

The COVAX alliance is a novel approach to international partnership in global health intended to achieve the worthy goal of ‘COVID-19 vaccine equity’. This study aimed to identify the implementation challenges and framework gaps of COVAX and to explore the interconnected global health policy and governance gaps in ensuring equity, accessibility and affordability of vaccines.

Methods

A scoping review was conducted to identify the implementation challenges and framework gaps of COVAX and related global health policy and governance gaps. A search was carried out in PubMed, Scopus, Springer Link and Embase databases. Manually searched the grey literature, such as official reports and articles. EndNote V.20 was used to manage the evidence screening, and data extraction was carried out in Microsoft Excel.

Results

Searches of four electronic databases and official UN, GAVI and WHO websites identified 4686 pieces of evidence. The 937 duplicates were removed, and the remaining 3749 articles were screened for the title and abstract. Most articles were eliminated as they do not address global COVAX or COVID-19 vaccine equity. The remaining 53 pieces of evidence were reviewed for full text, and ultimately 40 articles found eligible were included in the scoping review.

Conclusions

The implementation challenges of COVAX were attributed mainly to the phenomenon of vaccine nationalism by rich countries. The future global health policy and governance structure must be re-examined to address the inadequacies of such novel super public-and-private partnership models.
Plant-based diet and COVID-19 severity: results from a cross-sectional study
Authors: Soltanieh Samira , Salavatizadeh Marieh , Ghazanfari Tooba , Jahromi Soodeh Razeghi , Yari Zahra , Mansournia Mohammad Ali , Nazemipour Maryam , Kheradmand Jalil Arab , Ardestani Sussan K , Karimi Sara , Hekmatdoost Azita
Published: October 2023

Although previous findings have shown the beneficial role of healthy eating pattern on the human immune system, the association between plant-based diet and COVID-19 severity has not yet been elucidated. This study aimed to determine the possible role of plant-based diet index (PDI) in COVID-19 severity. This cross-sectional, multicentral study was conducted on 141 patients with confirmed COVID-19. Dietary intakes of the patients were evaluated using a validated food frequency questionnaire. Then, PDI was compared between patients who needed to be hospitalised (considered severe cases), and those who got treatment at home (considered non-severe cases). After adjustment for confounders including age, sex, energy intake and body mass index, lower odds of hospitalisation were found for participants having a greater score of overall PDI (OR per 10 units increase: 0.42; 95% CI 0.22 to 0.80) and healthy PDI (OR per 10 unit increase: 0.45; 95% CI 0.26 to 0.78). In conclusion, our data presented that there is a relation between PDI and lower risk of hospitalisation in COVID-19 patients, possibly through boosting the immune function.
Prediction of refractive error and its progression: a machine learning-based algorithm
Authors: Barraza-Bernal Maria J , Ohlendorf Arne , Sanz Diez Pablo , Feng Xiancai , Yang Li-Hua , Lu Mei-Xia , Wahl Siegfried , Kratzer Timo
Published: October 2023

Objective

Myopia is the refractive error that shows the highest prevalence for younger ages in Southeast Asia and its projection over the next decades indicates that this situation will worsen. Nowadays, several management solutions are being applied to help fight its onset and development, nonetheless, the applications of these techniques depend on a clear and reliable assessment of risk to develop myopia.

Methods and analysis

In this study, population-based data of Chinese children were used to develop a machine learning-based algorithm that enables the risk assessment of myopia’s onset and development. Cross-sectional data of 12 780 kids together with longitudinal data of 226 kids containing age, gender, biometry and refractive parameters were used for the development of the models.

Results

A combination of support vector regression and Gaussian process regression resulted in the best performing algorithm. The Pearson correlation coefficient between prediction and measured data was 0.77, whereas the bias was −0.05 D and the limits of agreement was 0.85 D (95% CI: −0.91 to 0.80D).

Discussion

The developed algorithm uses accessible inputs to provide an estimate of refractive development and may serve as guide for the eye care professional to help determine the individual best strategy for management of myopia.
Increasing staff time for patient facing care on an inpatient geriatric unit through modification of multidisciplinary board rounds: a quality improvement project
Authors: Britton Hannah
Published: October 2023

Background

NHS staff recruitment and retention have failed to keep pace with service demands and workforce burn-out is of significant concern. This quality improvement project (QIP) aimed to increase staff time for patient facing care through reducing duplication of hospital board rounds within a 36-bedded NHS inpatient geriatric ward.

Intervention

Thirty-minute board rounds were reduced from twice daily (Monday–Friday) at 08:30 hours and midday to once daily at midday with the aim of freeing up staff time for patient care. A multidisciplinary team (MDT) safety briefing at 08:30 hours lasting 5–10 min was implemented to enable review of shift pressures and identification of patients who are unwell, newly admitted or due for discharge. Safety briefing format was amended to further support staff prioritisation.

Methods

This QIP was underpinned by the model for improvement, using Plan-Do-Study-Act cycles. Data were collected through a staff questionnaire alongside calculation of staff time spent at board rounds and safety huddles. Staff verbal feedback and questionnaire results were also used to improve and modify process’. Patient discharge data were collated via trust metrics as a balancing measure.

Results

Through board round modification, 25 hours of MDT time was saved each week, with all responding staff reporting increased time for patient facing care following QIP implementation. >85% of questionnaire respondents agreed that board round changes resulted in improvement. Balancing measures collected as part of the project also revealed an increase in weekly ward discharges from an average of 15.75–17.5 confirming no negative impact on patient flow following board round amendments.

Conclusion

While significant staffing shortages continue, local innovations focused on staff time may have the potential to support effective use of limited resources.