bluuebunny/crossref_metadata_2025 huggingface dataset:
Tranexamic acid impact on platelet adhesion to the endothelium after shock conditions: A protective effect?
Authors: Karadjoff Alison , Liberati David M. , Diebel Lawrence N.
Published: February 2025

INTRODUCTION

Trauma and hemorrhagic shock lead to microcirculatory disturbances related to endothelial injury and endothelial glycocalyx (EG) degradation. Improved outcomes following trauma and hemorrhagic shock have been linked to protection of the EG layer, which is a topic of increasing investigation. Early tranexamic acid (TXA) administration following trauma and hemorrhagic shock improves outcomes in clinic studies. Recent translational studies have also shown that early TXA administration protects the EG following shock insults; the impact on blood-endothelial cell interactions is unknown. Platelet adherence to vascular endothelium may contribute to microcirculatory disturbances; the effects of TXA on this phenomenon are uncertain. Microfluidic devices have been used to study the behavior of endothelial cells and platelets under flow conditions. We hypothesize that the protective effect of TXA against EG degradation would prevent shock-induced platelet adhesion to the microvasculature. This was studied in a microfluidic cell culture model under a controlled microenvironment.

METHODS

Microfluidic endothelial cell cultures were exposed to flow conditions under control or hypoxia-epinephrine exposure. Tranexamic acid was added to the perfusate at various times in control and experimental groups. Endothelial glycocalyx thickness, degradation products, and platelet adhesion to the endothelium were measured.

RESULTS

Tranexamic acid protected the glycocalyx from degradation following hypoxia-reoxygenation-epinephrine exposure. Platelet adhesion to the endothelium was significantly reduced by TXA in a time sensitive manner.

CONCLUSION

Tranexamic acid may protect the microvasculature from perfusion abnormalities following shock conditions. This is likely due to inhibition of platelet adhesion and mitigating thromboinflammation at the endothelium in the microvasculature.
Feasibility, Outcomes, and Odds of Same-Day Surgery in Laparoscopic Elective Repair of Type IV Hiatal Hernia with Intrathoracic Stomach
Authors: Erabelli Nikhil , Bui Ethan , Shah Shalin , Hoffman Clarissa , Fritz Connor , Banki Farzaneh
Published: February 2025

Objective:

To assess the feasibility, outcomes, and odds of same-day surgery (SDS) in the laparoscopic elective primary repair of intrathoracic stomach (ITS). To assess the significance of percentage of intraoperative gastric incarceration in planning SDS.

Methods:

ITS was defined as 100% gastric herniation into the chest on preoperative imaging. The percentage of intraoperative gastric incarceration into the chest was assessed, and patients with partial gastric incarceration were compared to those with 100% incarceration. Planning for SDS started in 2019.

Results:

From 2012 to 2024, there were 1057 hiatal hernia repairs and 190/1057 (18%) primary laparoscopic ITS repairs, 8 procedures in whom percentage of intraoperative gastric incarceration was not documented were excluded, and 182 procedures were included, 127/182 (69.8%) were elective: 58/127 (45.7%) had intraoperative partial gastric incarceration and 69/127 (54.3%) had 100% incarceration. Since planning for SDS started, there were 56 elective repairs. SDS was planned in 36/56 (64.3%) and was performed in 33/36 (91.7%).

Comparing 33/56 (58.9%) procedures performed as SDS to 23/56 (41.1%) not performed as SDS showed comparable sex/age/BMI/ASA. The operative time, 117 min (IQR, 100-144) vs 129 min (IQR, 110-167), p=0.134, emergency department visits: 5/33 (15.2%) vs 3/23 (13.0%), p=1.00 and readmissions: 4/33 (12.1%) vs 1/23 (4.3%), p=0.64. The odds of SDS were comparable for sex, age, BMI, percentage of intraoperative gastric incarceration, and operative time.

Conclusion:

The percentage of gastric herniation on preoperative imaging does not correlate with the percentage of intraoperative gastric incarceration in about half of patients with ITS. SDS is feasible in the majority of laparoscopic elective ITS repairs and can be performed with good outcomes in patients with intraoperative partial or 100% gastric incarceration.
Semi-brittle flow of rocks: cracks, dislocations and strain hardening
Authors: Brantut Nicolas
Published: February 2025

Strain hardening is a key feature observed in many rocks deformed in the so-called ‘semi-brittle’ regime, where both crystal plastic and brittle deformation mechanisms operate. Dislocation storage has long been recognized as a major process leading to strain hardening. Here, it is suggested that tensile microcracks may be viewed as dislocation sinks, by offering internal free surfaces where dislocations can escape individual crystals within an aggregate. Strain hardening is modelled with a conventional approach, combining Taylor’s equation relating stress to dislocation density, and a dislocation density evolution law based on dislocation mean-free path and dynamic recovery. The initiation of microcracks is modelled as a function dislocation density, assuming dislocation pile-ups at grain boundaries. Microcrack growth is modelled using linear elastic fracture mechanics. The model captures important qualitative features observed in calcite marble deformation experiments: pressure-dependency of strength in the ductile regime and a reduction in hardening linked to an increase in crack growth with decreasing confining pressure. Grain size dependency of strength and hardening is also captured but requires significant toughening (or limitation to crack growth) at small grain sizes. The model can be improved significantly once detailed, systematic microstructural observations become available.
On the Gaussian beam tracing method for long-distance sound wave propagation in non-uniform mean flows
Authors: Bao Hongsen , Tan Qichen , Zhou Peng , Chen Wangqiao , Zhang Xin , Zhong Siyang
Published: February 2025

This paper presents an improved Gaussian beam tracing method to efficiently compute long-distance sound wave propagation in non-uniform mean flows. New dynamic ray tracing equations are derived from the convected wave equation in the vicinity of the ray path under the high-frequency asymptotic and paraxial conditions, based on which the solutions of acoustic potential and the corresponding Gaussian beams are developed. The sound pressure at the observer is accurately computed by an integral superposition of all vicinal beams, through a revised weighting function that considers the convection effect on each beam. The proposed method is valid at caustics and can capture the wave diffractions at different sound frequencies. Benchmark problems of the acoustic monopole radiation and the broadband pulse propagation in a free space uniform flow, sound wave interactions with a semi-infinite rigid plate in a moving medium, sound propagations in inhomogeneous stratified flows and in a large-scale vortex flow are studied to validate the proposed method. The results are compared with analytical solutions and high-fidelity numerical results using the finite element method or the fast field program. Good agreements are obtained, showing its potential for the effective assessment of the long-distance sound propagation in complex inhomogeneous flows.
Streptococcus mutans LiaSgene regulates its cross-kingdom interactions withCandida albicansto promote oral candidiasis
Authors: Cao Yanfan , Huang Shan , Du Jingyun , Wang Xiuqing , Gan Guowu , Chen Shuai , Huang Xiaojing
Published: February 2025

Candida albicansandStreptococcus mutansare commonly associated with oral candidiasis and dental caries, respectively.C. albicansis frequently detected in the dental plaque of early childhood caries. The synergistic interaction betweenC. albicansandS. mutansin dental caries suggests that fungi enhance the production of acidic metabolites and contributes to the development of caries. However, the cross-kingdom interaction ofS. mutansin oral candidiasis and the pathways regulating hyphal formation remain unclear. TheliaSgene ofS. mutans593 plays a crucial role in maintaining membrane homeostasis. In comparison to theS. mutans593 and liaS-complementary strains, the liaS-strain significantly diminished the proliferation, biofilm formation, extracellular polysaccharide production, andC. albicanshyphal transformation of co-cultured microorganisms. The deletion ofliaSgene in the dual-species downregulated the expression of yeast-hyphal transformation related geneshwp1, ece1, als1, andals3inC. albicans, while also impacted the expression ofphr1andphr2. Additionally, liaS-inhibited glycolysis and pyruvate kinase activity inS. mutans, leading to a decreased in water-soluble and water-insoluble glucans production in biofilm. The significant downregulation of glucosyltransferase transcription relates genes expression in liaS-resulted in inhibition of the cross-kingdom interaction in the dual-species. In the murine oropharyngeal candidiasis model, dual-species infection with liaS-results in a reduction of fungal and hyphal invasion compared to the combinations ofC. albicansandS. mutans593. In conclusion,S. mutans/liaSplay a crucial role in the development of oral candidiasis suggests that it could be a targeted strategy for managing this condition.

Importance

Candidiasisinvolves the transition ofC. albicansinto hyphae and the fungi invasion of the oropharyngeal mucosa. The transformation of hyphal is influenced by a variety of internal and external environmental factors. Our research findings suggest that the deletion of theliaSgene leads to a reduction ingtfsgene expression, impacting glycolysis efficiency and effectively decreasing EPS production in the dual-species biofilm. Also, downregulation of the expression levels of yeast-hyphal transformation related genes to inhibiting the virulence function ofC. albicans. Our study demonstrates thatS. mutans593/liaSpromotes epithelial invasion ofC. albicansin mouse oropharyngeal candidiasis, offering a potential therapeutic approach for addressing cross-kingdom infections.
A bioinformatic workflow to facilitate the study of less-understood proteins: the case of SH2D2A
Authors: Gilmour Brian C. , Chan Hanna , Singh Sachin , Nyman Tuula A. , Lossius Andreas , Borowicz Paweł , Phuyal Santosh , Spurkland Anne
Published: February 2025

Adaptor proteins are key regulators of immune signalling but are challenging to study due to redundant pathways that obscure clear functional “anchor” phenotypes. Making use of public single-cell RNA sequencing (scRNA-seq) datasets, we theorised that anchors could be identified by working in the reverse direction: starting from the transcriptomic level and working “bottom-up” to identify anchoring phenomena at the cell surface. We have produced a prototype workflow for this method using the case of the lymphocyte-enriched adaptor protein SH2D2A, whose function remains uncertain. Using our bottom-up analysis, we have identified a link between SH2D2A and T cell-T cell (T-T) synapses enriched for ITGB2. The functional implications of this link are currently being explored, but further application of this bioinformatic approach to less-understood proteins may prove useful in understanding the minutiae of immune cell signalling, with implications for immunotherapy.
Inactivated Zoonotic Influenza A(H5N8) Vaccine Induces Robust Antibody Responses Against Recent Highly Pathogenic Avian Influenza Clade 2.3.4.4b A(H5N1) Viruses
Authors: Liedes Oona , Ekström Nina , Haveri Anu , Solastie Anna , Vara Saimi , Rijnink Willemijn F. , Bestebroer Theo M. , Richard Mathilde , de Vries Rory D. , Lindh Erika , Ikonen Niina , Laaksonen Terhi , Holopainen Riikka , Kakkola Laura , Lappalainen Maija , Syrjänen Ritva K. , Julkunen Ilkka , Nohynek Hanna , Melin Merit
Published: February 2025

In 2023, Finland faced an outbreak of highly pathogenic avian influenza caused by clade 2.3.4.4b A(H5N1) viruses, which spread from wild birds to fur farms. Vaccinations of individuals at-risk, such as fur and poultry farm workers, veterinarians, and laboratory workers, began in June 2024 using the MF59-adjuvanted inactivated (H5N8) vaccine manufactured by Seqirus (based on clade 2.3.4.4b A/Astrakhan/3212/2020). We investigated antibody responses following a two-dose vaccination regimen in 39 subjects. Vaccination induced comparable levels of functional antibodies both against the vaccine virus and two clade 2.3.4.4b viruses, either associated with outbreaks in fur animals in Finland or cattle in the United States. Upon two doses of the vaccine for previously unvaccinated people, the seroprotection rate against the vaccine virus was 83 % (95 % CI 70-97 %, titer ≥20) and 97 % (95 % CI 90-100 %, titer ≥40) using microneutralization or hemagglutinin inhibition assays, respectively. In a subset of previously H5-vaccinated individuals, the first dose already led to seroprotective titers, indicative of immunological recall. These data show that the vaccine is expected to confer cross-protection against currently circulating H5 clade 2.3.4.4b viruses.
State or personality trait: Determinants of boldness and shoal size preference in adult zebrafish
Authors: Singh Abhishek , Sharma Prabhat , Jain Mansha , Mahajan Pranati , Bajaj Jasmine , Gupta Vaidehi , Dingemanse Niels J. , Rajaraman Bittu Kaveri
Published: February 2025

Animals adjust their behavior in response to physiological states to optimize the trade-off between energy acquisition and survival. A key question in animal personality research is whether behavioral variation is driven by consistent physiological state differences or stable personality traits. This study evaluates boldness and shoal size discrimination in adult male zebrafish (Danio rerio) across three hunger states: same-day feeding (H0), 24-hour food deprivation (H1), and 48-hour food deprivation (H2). Behavioral assessments were conducted over two testing cycles, with each individual undergoing every test twice for each hunger state within each cycle. The assays comprised the Open Field Test (OFT), Emergence Test (ET), and Social Preference Test (SPT), with the SPT conducted under binary (4 vs. 2 fish) and ternary (4 vs. 2 vs. 1 fish) choice conditions. Hunger significantly reduced emergence latency, but did not affect exploratory behavior in the OFT. Hunger also enhanced preference for larger shoals above chance in the binary SPT during the second testing cycle, though this effect was absent in ternary choices. Testing cycle effects revealed habituation-driven increases in boldness in both the tests and a progressive shift toward larger shoal preferences in the binary SPT. Among all assays, only the OFT showed significant repeatability, making it a reliable measure of boldness. However, it did not show consistent individual differences in plasticity due to hunger. These results highlight the crucial role of labile physiological states, such as hunger and habituation, in driving behavioral variation and underscore the importance of designing studies that disentangle state-dependent behaviors from stable personality traits in animal personality research.
Neuromodulation of the endbulb of Held synapse in the cochlear nucleus
Authors: Groshkova Maria , Alvanos Theocharis , Qi Yumeng , Wang Fangfang , Wichmann Carolin , Hua Yunfeng , Moser Tobias
Published: February 2025

Synapses vary greatly in synaptic strength and plasticity, even within the same circuitry or set of pre- and postsynaptic neurons. Neuromodulation is a candidate mechanism to explain some of this variability. Neuromodulators such as monoamines can differentially regulate presynaptic function as well as neuronal excitability. Variability is found also for the large calyceal synapses of the auditory pathway that are endowed with high synaptic vesicle (SV) release probability (Pvr) and large postsynaptic currents enabling reliable and temporally precise transmission of auditory information. Here we investigated whether the calyceal endbulb of Held synapse formed by auditory nerve fibers onto bushy cells (BCs) in the anteroventral cochlear nucleus (AVCN) is modulated by norepinephrine (NE) and serotonin (5-HT).

Using electron microscopy (EM) of the cochlear nucleus we found evidence for putative monoaminergic varicosities in both ventral and dorsal divisions. Immunostaining for vesicular 5-HT and NE transporters revealed NE-containing and 5-HT-containing varicosities in the AVCN, juxtaposed to both endbulbs and BCs. Furthermore, we detected immunofluorescence for 5-HT1B, 5-HT4, 5-H7receptors (R) and α2C-adrenergic receptors (AR) in BCs. We used voltage-clamp recordings from mouse BCs in order to uncover potential presynaptic effects of neuromodulation, which revealed an increase in frequency of miniature excitatory postsynaptic currents (mEPSCs) upon application of NE but not 5-HT. Evoked synaptic transmission was unaffected by the application of either NE or 5-HT. Likewise, while studying the biophysical properties of the BCs, we did not observe effects of NE or 5-HT on low-voltage-activated K+(K+LVA) and hyperpolarization-activated mixed cation (HCN) channels during application. In summary, we report evidence for the presence of monoaminergic innervation in the cochlear nucleus and for subtle functional NE-neuromodulation at the endbulb of Held synapse.
Cold quark matter: Renormalization group improvement at next-to-next-to leading order
Authors: Fernandez Loïc , Kneur Jean-Loïc
Published: February 2025

We extend previous next-to-next-to leading order (NNLO) calculations of the quantum chromodynamics (QCD) pressure at zero temperature and nonzero baryonic densities using the renormalization group optimized perturbation theory (RGOPT), which entails an all-order RG-invariant resummation. First, we consider the approximation of three massless quark flavors, and then we add the running strange quark mass dependence. The resulting pressure displays a sizeably reduced sensitivity to variations of the arbitrary renormalization scale as compared to the state-of-the-art NNLO results. This confirms previous NLO investigations that the RGOPT resummation scheme provides improved convergence properties and reduced renormalization scale uncertainties, thus being a promising prescription to improve perturbative QCD at high and mid range baryonic densities.

Published by the American Physical Society
2025
Fiber optics in curved space-times
Authors: Mieling Thomas B. , Hudelist Mario
Published: February 2025

Single-mode fibers are used in fiber-optic gyroscopes to measure the Sagnac effect and are planned to be used in forthcoming experiments on the gravitationally induced phase shift in single photons. However, current theoretical models of such experiments are limited to ray-optics approximations or, if based on wave optics, to a restricted class of fiber alignments. To overcome these shortcomings, this paper develops a comprehensive perturbative scheme to solve for electromagnetic modes, i.e., monochromatic solutions to Maxwell's equations, of arbitrarily bent step-index fibers in general stationary space-times. This leads to transport equations for the electromagnetic phase and polarization that include the gravitational redshift, the Sagnac effect, a generalization of Rytov's law to curved space, a gravitational Faraday effect in the form of shift-induced gyrotropy, as well as inverse spin Hall effects caused by fiber bending, gravitational acceleration, and space-time curvature.

Published by the American Physical Society
2025
Disequilibrium in plant distributions: Challenges and approaches for species distribution models
Authors: Sandel Brody , Merow Cory , Serra‐Diaz Josep M. , Svenning Jens‐Christian
Published: February 2025

Environmental conditions are dynamic, and plants respond to those dynamics on multiple time scales. Disequilibrium occurs when a response occurs more slowly than the driving environmental changes. We review evidence regarding disequilibrium in plant distributions, including their responses to paleoclimate changes, recent climate change and new species introductions. There is strong evidence that plant species distributions are often in some disequilibrium with their environmental conditions.

This disequilibrium poses a challenge when projecting future species distributions using species distribution models (SDMs). Classically, SDMs assume that the set of species occurrences is an unbiased sample of the suitable environmental conditions. However, a species in disequilibrium with the environment may have higher‐than‐expected occurrence probabilities (e.g. due to extinction debts) or lower‐than‐expected occurrence probabilities (e.g. due to dispersal limitation) in different areas. If unaccounted for, this will lead to biased estimates of the environmental suitability.

We review methods for avoiding such biases in SDMs, ranging from simple thinning of the occurrence dataset to complex dynamic and process‐based models. Such models require large data inputs, natural history knowledge and technical expertise, so implementing them can be challenging. Despite this, we advocate for their increased use, since process‐based models provide the best potential to account for biases in model training data and to then represent the dynamics of species occupancy as ranges shift.

Synthesis. Occurrence records for a species are often in disequilibrium with climate. SDMs trained on such data will produce biased estimates of a species' niche unless this disequilibrium is addressed in the modelling. A range of tools, spanning a wide gradient of complexity and realism, can resolve this bias.
On the Morphology of Toponyms: What Greek Inflectional Paradigms Can Teach us?
Authors: Marinis Michail I.
Published: February 2025

The research is a contribution to the investigation of the grammatical status of toponyms from the point of view of inflectional paradigmatic morphology. By examining data from Standard Modern Greek, as well as select data from its historical development, the analysis reveals that the inflectional morphology of toponyms shows significant differences not only from that of homonymous common nouns but also from certain categories of proper names, such as anthroponyms. Specifically, I conclude that (1) toponyms must have a tantum inflectional paradigm (either pluralia or singularia), and (2) they may present anti‐defective phenomena in their paradigm when they are compared with common nouns and other proper names. In the broader framework of Canonical Morphology, I introduce the term anti‐defectiveness to describe the second idiosyncratic property of toponyms: their capacity to circumvent the restrictions that lead to defective paradigms in other nouns of the same class.
The Adoption of Certification Policy for Gazelle Enterprises in China: A Bottom‐Up Approach
Authors: Wang Lei , Song Hui
Published: February 2025

As a measure to cultivate innovative firms, a certification has been introduced and spread rapidly in many Chinese cities. We use data of Chinese prefecture‐level cities from 2008 to 2019 and investigate the causes of the adoption of the policy. Events such as term expirations (TEs) and cadres exchanges (CEs) are considered as potential internal causes, whereas pressure from peers and seniors is considered as potential external cause. A panel data model is used to analyze the causes of adoption. We find that, first, both TE and CE significantly promote adoption. Second, peer pressures significantly promote adoption but pressures from seniors do not. Third, TE significantly promotes adoption in northern China and CE significantly promotes adoption in southern China.
The gendered politics of the ‘local turn’ in peacebuilding: Acholi traditional justice and gender in post‐conflict Uganda
Authors: Fosu Richard , Gordon Eleanor
Published: February 2025

Typically, advancing localised approaches to peacebuilding has evaded critical reflection on the power dynamics and harms that can arise. This paper considers the gender dynamics and gendered harms that can manifest themselves when adopting an uncritical approach to localisation in peacebuilding. To do so, it examines the use of mato oput (drinking the bitter root) in post‐conflict northern Uganda, as an example of a localised approach to post‐conflict transitional justice, to investigate these dynamics and harms. It draws from interviews and focus‐group discussions that were conducted in northern Uganda between 2020 and 2022 and engages with critical international relations scholarship on the ‘local turn’ in peacebuilding and the gendered nature of conflict and peace. The paper argues that in patriarchal societies, advancing localisation may entail a return to the traditional or customary order that reaffirms and reifies oppressive gender power relations and helps to consolidate gender inequalities, including unequal access to both security and justice.
Meditation Linked to Enhanced MRI Signal Intensity in the Pineal Gland and Reduced Predicted Brain Age
Authors: Plini Emanuele R. G. , Melnychuk Michael C. , Dockree Paul M.
Published: February 2025

Growing evidence demonstrates that meditation practice supports cognitive functions, including attention and interoceptive processing, and is associated with structural changes across cortical networks, including prefrontal regions and the insula. However, the extent of subcortical morphometric changes linked to meditation practice is less appreciated. A noteworthy candidate is the pineal gland, a key producer of melatonin, which regulates circadian rhythms that augment sleep‐wake patterns and may also provide neuroprotective benefits to offset cognitive decline. Increased melatonin levels, as well as increased fMRI BOLD signal in the pineal gland, have been observed in meditators versus controls. However, it is not known if long‐term meditators exhibit structural changes in the pineal gland linked to the lifetime duration of practice. In the current study, we performed voxel‐based morphometry (VBM) analysis to investigate: (1) whether long‐term meditators (LTMs) (n = 14) exhibited greater pineal gland MRI‐derived signal intensity compared to a control group (n = 969), (2) a potential association between the estimated lifetime hours of meditation (ELHOM) and pineal gland signal intensity, and (3) whether LTMs show greater grey matter (GM) maintenance (BrainPAD) that is associated with pineal gland signal intensity. The results revealed greater pineal gland signal intensity and lower BrainPAD scores (younger brain age) in LTMs compared to controls. Exploratory analysis revealed a positive association between ELHOM and greater signal intensity in the pineal gland but not with GM maintenance as measured by BrainPAD score. However, greater pineal signal intensity and lower BrainPAD scores were correlated in LTMs. The potential mechanisms by which meditation influences pineal gland function, hormonal metabolism, and GM maintenance are discussed – in particular, melatonin's roles in sleep, immune response, inflammation modulation, and stem cell and neural regeneration.
Localization accuracy of phantom sound sources on the horizontal plane by bilateral hearing aid users in aided free-field and non–free-field conditions
Authors: Fernandez Janani , Hyvärinen Petteri , Kressner Abigail Anne
Published: February 2025

This study investigates the use of amplitude panning in a localization accuracy test and the influence of a non-ideal environment on its feasibility as a clinical tool. The horizontal localization accuracy of 16 normal-hearing participants and ten bilateral hearing aid users was assessed for real and amplitude panned sound sources produced over loudspeakers. Localization accuracy was measured with speech-shaped noise in both an anechoic chamber (free-field) and an acoustically treated listening room (non–free-field). The root mean square error between the response angle and the target angle was calculated for each participant. Thus, the root mean square error for the two sound source types for each test environment could be calculated and compared, and also contrasted against existing literature. Statistical analysis of the control group results revealed an effect of the target angle, method used (real vs amplitude panning) and environment (free-field vs non–free-field). An interaction between target angle and environment was also found. For the hearing aid user group, however, only an effect of target angle was found, which may lend support to simpler setups with fewer loudspeakers in non–free-field environments. However, the effect of the room varied between individuals within this group, thereby warranting further exploration.
A fast measure of spatial separation for release from masking and its relation to intelligibility
Authors: Peng Z. Ellen , Sweeney Victoria
Published: February 2025

This study validates a fast measure for spatial release from masking—minimum angular separation (MAS), the smallest spatial separation between a target and two-talker maskers to improve speech intelligibility by 20%. Three psychophysical methods to estimate MAS were compared, including the constant stimuli, adaptive staircase, and progressive tracking, which revealed no significant difference in the estimated threshold on the group level with bootstrapping. Results suggest that the MAS measurement can be expedited using the progressive tracking method without compromising robustness in the threshold estimation. The non-linear relationship between target-masker spatial separation, signal-to-noise ratio, and accuracy is explored.
Autoinducer-2 signaling promotes intestinal colonization of
Aeromonas veronii
and induces cell apoptosis in loach (
Misgurnus anguillicaudatus
)
Authors: Li Yi , Han Shuo , Niu Wenfang , Gao Chao , Wang Yuqi , Qin Mengyuan , Han Jingjing , Xia Xiaohua , Wang Hailei
Published: February 2025

Quorum sensing systems, particularly autoinducer-2 (AI-2) signaling, have significant effects on bacterial colonization and virulence. However, how they affect intestinal colonization by pathogens and subsequent host immune responses remains unclear. Here, we investigated the influence of AI-2 signaling on the intestinal colonization ability of
Aeromonas veronii
Z12 and the host’s immune response. We found that AI-2 signaling promoted the colonization of
A. veronii
to the intestine of loach (
Misgurnus anguillicaudatus
) and caused severe intestinal damage, while D-ribose, an AI-2 signaling inhibitor, effectively inhibited the colonization of
A. veronii
. Transcriptomic sequencing elucidated the molecular mechanism of this damage, revealing upregulation of p53 pathway genes associated with apoptosis. Furthermore, intestinal microbiota dysbiosis induced by
A. veronii
colonization was associated with host cell apoptosis, leading to nitrite accumulation, which increased intracellular reactive oxygen species (ROS) levels, which activated the p53 pathway, and induction of cell apoptosis. These findings provide insights into the interaction among bacterial quorum sensing, intestinal microbiota, and the host immune response, which highlight potential therapeutic targets for mitigating bacterial-induced intestinal damage.

IMPORTANCE

The intestinal colonization of pathogens regulated by autoinducer-2 (AI-2) signaling and its induced host response have not been fully characterized. Here, we revealed the effect of AI-2 on intestinal colonization of
Aeromonas veronii
and its induced cell apoptosis in loach. Our study demonstrated that the deficiency of AI-2 significantly reduced
A. veronii
colonization in the loach intestine and mitigated the tissue damage. Additionally,
A. veronii
colonization induced significant upregulation of p53 pathway genes and proteins, indicating a key role of AI-2 signaling in host responses. Understanding these mechanisms not only helps to elucidate the pathogenicity of
A. veronii
but also may provide broader insights into the pathogenic mechanisms of other pathogens, thus revealing general principles of pathogen–host interactions across different models. Furthermore, we found that
A. veronii
colonization led to intestinal microbiota dysbiosis, notably an increase in the abundance of
Hypomicrobium
sp., which was associated with nitrite accumulation, elevating reactive oxygen species levels, activating the p53 pathway, and inducing cell apoptosis. These findings provide important insights into the complex mechanisms of AI-2 signaling in bacterial–host interactions. Additionally, the regulatory role of AI-2 signaling may have potential clinical applications as an intervention strategy, offering new directions for developing treatments against intestinal infections.
Deciphering reductive dehalogenase specificity through targeted mutagenesis of chloroalkane reductases
Authors: Picott Katherine J. , Bowers Connor M. , Edwards Elizabeth A.
Published: February 2025

Reductive dehalogenases (RDases) are essential in the anaerobic degradation of various organohalide contaminants. This family of enzymes has broad sequence diversity, but high structural conservation. There have been few studies assessing how RDase amino acid sequences affect their substrate selectivity. Here, we focus on two chloroalkane RDases, CfrA and DcrA, which have 95% protein sequence identity but have diverged to have opposite substrate preferences. CfrA dechlorinates chloroform (CF) and 1,1,1-trichloroethane (TCA) but not 1,1-dichloroethane (DCA), while DcrA will dechlorinate 1,1-DCA but not CF or 1,1,1-TCA. We mutated several residues in the active site of CfrA to investigate a change in substrate preference and to identify which wild-type residues contribute the most to substrate specialization. We determined that no individual residue solely dictates substrate discrimination, but both Y80W and F125W mutations were needed to force CfrA to prefer 1,1-DCA as a substrate. When using 1,1,2-TCA as a substrate, CfrA predominately performs hydrogenolysis to 1,2-DCA, yet the introduction of the double mutant changed this preference to dihaloelimination (forming vinyl chloride). We use predictive protein models and substrate docking to predict what interactions are made between the enzyme and substrate to aid in selection. The residues of significance identified in this study are consistent with those identified from chloroethene RDases, suggesting residue locations with a particularly high impact on activity.

IMPORTANCE

Reductive dehalogenases (RDases) play an integral role in the removal of chlorinated solvents from the environment. These enzymes have specificity toward different chlorinated compounds, and it is known that natural variants of highly similar RDases can have distinct activities. How specific differences in protein sequence influence activity is largely unknown. In this study, we demonstrate that mutating a few residues within the active site of CfrA—a chloroform and trichloroethane-specific dehalogenase—changes its substrate preference to dichloroethane. We determine that only two mutations are needed to disrupt the native activity, underscoring the nuances in substrate-structure relationships in RDases. Though we are still far from predicting function from the sequence, this knowledge can give some insight into engineering RDases for new target contaminants.
Colonization or coinfection? A case report of
Mycobacterium avium
complex detected in a patient with pulmonary tuberculosis
Authors: Bui Tina I. , Rowe Jackson , Eberly Allison R.
Published: February 2025

Background

Nontuberculous mycobacteria (NTM) infections have been increasingly reported in the literature; however, isolation of both NTM and
Mycobacterium tuberculosis
complex (MTBC) in respiratory samples may indicate transient NTM colonization rather than true coinfection. Distinguishing between NTM colonization and true infection is necessary for guiding appropriate antimicrobial treatment regimen.

Case Summary

Here, we describe a case of a 41-year-old immunocompetent female with pulmonary tuberculosis in which
Mycobacterium avium
and
Mycobacterium intracellulare
, both members of the
M. avium
complex (MAC), were independently identified with MTBC in two of three sputum cultures using Bruker Biotyper matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). After completing MTBC-targeted therapy, the patient fully returned to her baseline physical activity, and all subsequent cultures were negative for MTBC and MAC.

Conclusion

This case study underscores the challenges in the adjudication of colonization from coinfection in mixed mycobacterial specimens. Although there are microbiological guidelines for diagnosing independent NTM infections and MTBC infections, there is an unmet need for guidance on diagnosing and treating NTM in patients with pulmonary tuberculosis.
Persistent delay in maturation of the developing gut microbiota in infants with cystic fibrosis
Authors: Verster Adrian J. , Salerno Paige , Valls Rebecca , Barrack Kaitlyn , Price Courtney E. , McClure Emily A. , Madan Juliette C. , O’Toole George A. , Sanville Julie L. , Ross Benjamin D.
Published: February 2025

The healthy human infant gut microbiome undergoes stereotypical changes in taxonomic composition between birth and maturation to an adult-like stable state. During this time, extensive communication between microbiota and the host immune system contributes to health status later in life. Although there are many reported associations between microbiota compositional alterations and disease in adults, less is known about how microbiome development is altered in pediatric diseases. One pediatric disease linked to altered gut microbiota composition is cystic fibrosis (CF), a multi-organ genetic disease involving impaired chloride secretion across epithelia and heightened inflammation both in the gut and at other body sites. Here, we use shotgun metagenomics to profile the strain-level composition and developmental dynamics of the infant fecal microbiota from several CF and non-CF longitudinal cohorts spanning from birth to greater than 36 months of life. We identify a set of keystone species that define microbiota development in early life in non-CF infants but are missing or decreased in relative abundance in infants with CF, resulting in a delayed pattern of microbiota maturation, persistent entrenchment in a transitional developmental phase, and subsequent failure to attain an adult-like stable microbiota. Delayed maturation is strongly associated with cumulative antibiotic treatments, and we also detect the increased relative abundance of oral-derived bacteria and higher levels of fungi in infants with CF, features that are associated with decreased gut bacterial density. These findings suggest the potential for future directed therapies targeted at overcoming developmental delays in microbiota maturation for infants with CF.

IMPORTANCE

The human gastrointestinal tract harbors a diversity of microbes that colonize upon birth and collectively contribute to host health throughout life. Infants with the disease cystic fibrosis (CF) harbor altered gut microbiota compared to non-CF counterparts, with lower levels of beneficial bacteria. How this altered population is established in infants with CF and how it develops over the first years of life is not well understood. By leveraging multiple large non-CF infant fecal metagenomic data sets and samples from a CF cohort collected prior to highly effective modulator therapy, we define microbiome maturation in infants up to 3 years of age. Our findings identify conserved age-diagnostic species in the non-CF infant microbiome that are diminished in abundance in CF counterparts that instead exhibit an enrichment of oral-derived bacteria and fungi associated with antibiotic exposure. Together, our study builds toward microbiota-targeted therapy to restore healthy microbiota dynamics in infants with CF.
Abundance of clinically relevant antimicrobial resistance genes in the golden jackal (
Canis aureus
) gut
Authors: Lapid Roi , Motro Yair , Craddock Hillary , Salah Ikram , King Roni , Winner Katherine , Kahila Bar-Gal Gila , Moran-Gilad Jacob
Published: February 2025

The spread of antimicrobial resistance (AMR) is a critical One Health issue. Wildlife could act as reservoirs or vehicles of AMR bacteria (ARBs) and AMR genes (ARGs) but are relatively understudied. We sought to investigate clinically relevant ARGs in golden jackals (
Canis aureus
) thriving near human settlements in Israel. Fecal samples were collected from 111 jackals across four regions over a 10-month period. Various animal and spatio-temporal metadata were collected. Samples were analyzed by quantitative PCR (qPCR) for beta-lactamases (
bla
TEM,
bla
CTX-M15, and
bla
SHV),
qnrS
and
int1
. A subset of samples was subject to shotgun metagenomic sequencing followed by resistome and microbiome analyses. qPCR detected a high prevalence of ARGs, including beta-lactamases (
bla
TEM-1, 96.4%;
bla
CTX-M-15, 51.4%,
bla
SHV, 15.3%), fluoroquinolone resistance (
qnrS
, 87.4%), and class 1 integrons (
Int1
, 94.6%). The
bla
TEM-1 gene was found to be more prevalent in adult jackals compared to younger ones. Metagenomic analysis of a subset of samples revealed a diverse gut microbiome harboring a rich resistome with tetracycline resistance genes being the most prevalent. Metagenome-assembled genome analysis further identified several ARGs associated with clinically relevant bacteria. These findings highlight the potential role of golden jackals as reservoirs for AMR and emphasize the need for ongoing surveillance to better understand AMR transmission dynamics at the wildlife–human interface.

IMPORTANCE

The research highlights the potential role of the golden jackals as reservoirs for antimicrobial resistance (AMR). The high prevalence of clinically relevant AMR genes in these jackals emphasizes the need for ongoing surveillance and monitoring to better understand AMR transmission dynamics at the wildlife–human interface.
Paraneoplastic scleroderma: a patient with a history of breast cancer presenting with sclerodactyly and Raynaud’s phenomenon
Authors: Phillips Emma Catherine , Clark Meagan J , Schirtzinger Matthew
Published: February 2025

A woman in her 70s with a past history of breast cancer in remission presented with several months of dyspnoea, skin tightness and Raynaud’s phenomenon. Physical examination was significant for hypertension, hypoxaemia, sclerodactyly, diffuse crackles on auscultation and mild respiratory distress. Work-up revealed elevated serum creatinine, elevated right ventricular systolic pressure on echocardiography and nuclear bone scan findings of osseous metastatic disease. Captopril was initiated with concern for scleroderma renal crisis. The scleroderma panel was positive for RNA polymerase 11 and 155. Vertebral biopsy was diagnostic of recurrent breast cancer. Through multidisciplinary discussion, rituximab was initiated, and malignancy treatment was deferred; however, the patient developed several complications and ultimately elected to pursue inpatient hospice. In the setting of recurrent breast cancer, this case is suggestive of paraneoplastic scleroderma. The presence of underlying malignancy is an important consideration in new cases of scleroderma, and multidisciplinary management is key to determining treatment preference.
Paediatric gluten ataxia: a rare neurological presentation of gluten sensitivity in a toddler
Authors: Rasool Ahsan , Power Claire Marie
Published: February 2025

A toddler presented with a 6 week history of progressively worsening ataxia, weight loss and loose stool. There was no developmental regression, history of fever or foreign travel. Extensive investigation, including cerebrospinal fluid studies and neuroimaging, were inconclusive. In coeliac screen, the endomysial antibodies were positive with above tenfold elevation of IgA TTG from normal limit, making the diagnosis of coeliac disease (CD). The association of CD with neurological symptoms in our case led to the clinical impression of gluten ataxia. She was started on gluten free diet and had complete symptom resolution in over 4 weeks’ time since the start of gluten-free diet. Although common in adults, it has not been reported in toddlers, expanding the differential diagnosis of ataxia.
Clinical and surgical insights into parameatal urethral cyst
Authors: Laxman Krishnamurthy Ganesh , Agarwal Ankit , Gunashekar Vijay , Chawla Arun
Published: February 2025

Parameatal urethral cysts are rare, benign congenital abnormalities of the urethra, usually presenting in early childhood. Although often asymptomatic, they may sometimes result in urinary flow disturbances, difficulties during sexual intercourse or cosmetic concerns. Here, we present two cases of parameatal urethral cysts in males, diagnosed relatively later in life: one in a young adult in his early 20s and the other in a mid-adolescent. The young adult sought treatment for urine splaying and challenges with sexual intercourse, whereas the adolescent was primarily concerned about the cosmetic appearance of the cyst. Both cases were treated with surgical excision, considering the optimal approach according to the literature. Histopathological examination revealed that the cyst walls were lined with stratified squamous epithelium in both instances. Follow-up showed excellent cosmetic results, with no recurrence or voiding difficulties.
Transoesophageal echocardiography in diagnosing pulmonary arteriovenous malformation
Authors: Shoji Tatsuro , Izumo Masaki , Tanabe Yasuhiro , Akashi Yoshihiro
Published: February 2025

Pulmonary arteriovenous malformation (PAVM) is a rare cause of embolic stroke of undetermined source (ESUS) and can be challenging to diagnose promptly. In this case, a woman in her 40s with ESUS was diagnosed with PAVM after a transoesophageal echocardiography (TOE) microbubble test revealed bubbles flowing from the right superior pulmonary vein. Endovascular treatment was performed, and follow-up transthoracic echocardiography showed no right-to-left shunt, confirming successful shunt closure. This case is significant as it is the first reported instance where both treatment and postoperative evaluation of PAVM were conducted using echocardiography. The early detection of the shunt through the microbubble test, within three cardiac cycles, was crucial and differs from typical delayed shunt detection. This suggests that focused imaging during TOE can enhance diagnostic accuracy for PAVM.
Trends in depression and anxiety prevalence by cancer status among US adults: analyses of the 2019-2022 National Health Interview Survey
Authors: Kim Ian , Lee Michelle , Begay Cynthia M , Lee Jonathan , Unger Jennifer
Published: February 2025

Objective

To examine trends in the prevalence of depression and anxiety during the COVID-19 pandemic among US adult cancer patients and survivors (CPS) in comparison to those of non-CPS (NCPS).

Methods and analysis

National Health Interview Survey 2019–2022 data were analysed using spline logistic regression.

Results

A total of 115 664 participants completed the survey (mean age (SD), 52.8 (18.4) years; 54.3% female; 12.6% CPS). The age-adjusted prevalence of depression significantly increased from 26.53% in 2019 to 29.78% in 2022 among CPS, while that of anxiety increased from 24.02% in 2019 to 28.08% in 2022. Throughout the pandemic, there were consistently significant annual increases in the prevalence of both depression and anxiety with CPS experiencing significantly faster rates of increase compared with NCPS (average annual absolute increase 0.72% in NCPS vs 1.08% in CPS, p<0.01 for depression; 0.98% in NCPS vs 1.35% in CPS, p<0.01 for anxiety). Difficulty in social activity engagement emerged as the primary risk factor for both depression (adjusted OR (aOR), 7.38 (95% CI, 7.04 to 7.73), p<0.01) and anxiety disorders (aOR, 7.58 (95% CI, 7.23 to 7.95), p<0.01). Significant interactions were found between difficulty in social engagement and cancer status on the diagnoses of depression (aOR, 0.72 (95% CI, 0.63 to 0.83), p<0.01) and anxiety (aOR, 0.62 (95% CI, 0.55 to 0.70), p<0.01).

Conclusions

The notably higher prevalence and more rapid increase in rates of depression and anxiety disorders among CPS compared with NCPS underscore the disproportionate impact of the COVID-19 pandemic on CPS and the necessity of prioritising mental health support and interventions for this population.