bluuebunny/crossref_metadata_2025 huggingface dataset:
Biofilm Forming Capacity, Sanitizer Tolerance, and Genetic Characterization of Persistent and Non-PersistentListeria monocytogenesfrom Artisanal Cheese Processing Environments
Authors: Aboagye Eurydice , Forauer Emily , Gilmour Aislinn , Blackwell Hannah B. , Cushman Lara , Herren Calleigh , Denaro Sophia , Felten Lily , Ballard McKenzie , Etter Andrea
Published: January 2025

Listeria monocytogenesis known to colonize food production environments and cross-contaminate finished foods. We investigated 30L. monocytogenescollected from artisan cheese production facilities in Vermont from 2006-2008 for sanitizer tolerance, biofilm formation capacity, biofilm architecture, and tolerance to sanitizers of mature biofilms. Sixteen of these isolates represented a putatively persistent ribotype (DUP-1042B) found in one facility over two years. Isolates of the putatively persistent ribotype all aligned into ST191 and were 0-6 SNPs different, confirming they represented a persistent strain. We found no significant differences in sanitizer tolerance or crystal assay-based attachment capacity between persistent and non-persistent strains. However, using scanning electron microscopy, we found that isolates FML-10 and FML-19 formed substantially denser biofilms after 10 days on stainless steel. Ten-day old biofilms were highly resistant to sanitizers; neither quaternary ammonium nor sodium hypochlorite-based sanitizers achieved an EPA-recommended 6-log reduction. More EPS was found in low-nutrient biofilm conditions; thus, non-food contact surfaces in cheese environments may induce formation of biofilms with high sanitizer tolerance. Our results highlight the importance of regular environmental testing and strain typing for rapid detection ofL. monocytogenescolonization attempts while they can still be removed without major renovations or equipment replacement.

Highlights

Isolates from persistent ribotype DUP-1042B/ST191 were within 6 SNPs of each other

Two isolates from ST191 made dense biofilms in nutrient rich conditions

More EPS was produced in nutrient-poor conditions

Mature biofilms of all isolates were highly resistant to QAC and SH sanitizers

Importance

This study identifies strategies used by a set of persistently colonizingL. monocytogenesisolated from an artisanal cheese producer in Vermont, finding that some persistently colonizing isolates had high biofilm forming capacity, which may have contributed to their persistence.
A Novel Silver-Ruthenium-Based Antimicrobial Kills Gram-Negative Bacteria Through Oxidative Stress-Induced Macromolecular Damage
Authors: Tawiah Patrick Ofori , Gaessler Luca Finn , Anderson Greg M. , Oladokun Emmanuel Parkay , Dahl Jan-Ulrik
Published: January 2025

Amplified by the decline in antibiotic discovery, the rise of antibiotic resistance has become a significant global challenge in infectious disease control. ExtraintestinalEscherichia coli(ExPEC), known to be the most common instigators of urinary tract infections (UTIs), represent such global threat. Novel strategies for more efficient treatments are therefore desperately needed. These include silver nanoparticles, which have been used as antimicrobial surface-coatings on catheters to eliminate biofilm-forming uropathogens and reduce the risk of nosocomial infections. AGXX® is a promising silver coating that presumably kills bacteria through the generation of reactive oxygen species (ROS) but is more potent than silver. However, neither is AGXX®’s mode of action fully understood, nor have its effects on Gram-negative bacteria or bacterial response and defense mechanisms towards AGXX® been studied in detail. Here, we report that the bactericidal effects of AGXX® are primarily based on ROS formation, as supplementation of the media with a ROS scavenger completely abolished AGXX®-induced killing. We further show that AGXX® impairs the integrity of the bacterial cell envelope and causes substantial protein aggregation and DNA damage already at sublethal concentrations. ExPEC strains appear to be more resistant to the proteotoxic effects of AGXX® compared to non-pathogenicE. coli,indicating improved defense capabilities of the uropathogen. Global transcriptomic studies of AGXX®-stressed ExPEC revealed a strong oxidative stress response, perturbations in metal homeostasis, as well as the activation of heat shock and DNA damage responses. Finally, we present evidence that ExPEC counter AGXX® damage through the production of the chaperone polyphosphate.
An Entropy-Based Approach to Model Selection with Application to Single-Cell Time-Stamped Snapshot Data
Authors: Stewart William CL , Jayaprakash Ciriyam , Das Jayajit
Published: January 2025

Recent single-cell experiments that measure copy numbers of over 40 proteins in individual cells at different time points [time-stamped snapshot (TSS) data] exhibit cell-to-cell variability. Because the same cells cannot be tracked over time, TSS data provide key information about the time-evolution of protein abundances that could yield mechanisms that underlie signaling kinetics. We recently developed a generalized method of moments (GMM) based approach that estimates parameters of mechanistic models using TSS data. However, when multiple mechanistic models potentially explain the same TSS data, selecting the best model (i.e., model selection) is often challenging. Popular approaches like Kullback-Leibler divergence and Akaike’s Information Criterion are difficult to implement because the distribution that gave rise to the “noisy” data is only known numerically and approximately. To perform model selection in this situation, we introduce an entropy-based approach that incorporates our GMM based parameter estimation and commonly used estimators in kernel density estimation. Using simulated TSS data, we show that our approach can select the “ground truth” from a set of competing mechanistic models. Furthermore, we use a bootstrap procedure to compute model selection probabilities, which can be useful when measuring the relative support of a candidate model.
Emergence of a contrast-invariant representation of naturalistic texture in macaque visual cortex
Authors: Lee Gerick M. , Majaj Najib J. , Deliz C. L. Rodríguez , Kiorpes Lynne , Movshon J. Anthony
Published: January 2025

Sensory stimuli vary across a variety of dimensions, like contrast, orientation, or texture. The brain must rely on population representations to disentangle changes in one dimension from changes in another. To understand how the visual system might extract separable stimulus representations, we recorded multiunit neuronal responses to texture images varying along two dimensions: contrast, a property represented as early as the retina, and naturalistic statistical structure, a property that modulates neuronal responses in V2 and V4, but not in V1. We measured how sites in these 3 cortical areas responded to variation in both dimensions. Contrast modulated responses in all areas. In V2 and V4, the presence of naturalistic structure both modulated responses and increased contrast sensitivity. Tuning for naturalistic structure was strongest in V4; tuning in both dimensions was most heterogeneous in V4. We measured how well populations in each area could support the linear readout of both dimensions. Populations in V2 and V4 could support the linear readout of naturalistic structure, but only in V4 did we find evidence for a robust representation that was contrast-invariant.

Significance Statement

Single neurons in visual cortex respond selectively to multiple stimulus dimensions, so signals from single neurons cannot distinguish changes in one dimension from changes in another. We measured responses from simultaneously recorded neural populations in three hierarchically linked visual areas – V1, V2, and V4 – using texture stimuli that varied in two dimensions, contrast and naturalistic image structure. We used linear decoding methods to extract information about each dimension. In all three areas, contrast could be decoded independently of image structure. Only in V4, however, could image structure be decoded independently of contrast. The reason is that selectivity for texture and contrast in V4 was much more diverse than in V1 or V2. This heterogeneity allows V4 to faithfully represent naturalistic image structure independent of contrast.
Parenteral Vaccination with recombinant EtpA glycoprotein impairs enterotoxigenicE. colicolonization
Authors: Vickers Tim J , Buckley David , Khatoon Nazia , Sheikh Alaullah , Setu Bipul , Berndsen Zachary T. , Fleckenstein James M.
Published: January 2025

abstract

EnterotoxigenicE. coli(ETEC) cause hundreds of millions of cases of acute diarrheal illness in low-middle income regions, disproportionately in young children. To date there is no licensed, broadly protective vaccine to protect against these common but antigenically heterogeneous pathogens. One of the more highly conserved antigens of ETEC, EtpA, is an extracellular glycoprotein adhesin that preferentially binds to blood group A glycans on intestinal epithelia. EtpA contributes to increased severity of illness in blood group A individuals, elicits robust serologic and fecal antibody responses following infection, and has been associated with protection against subsequent infection. However, its utility as a protective antigen needs further examination. In the present studies we examined whether parenteral vaccination with recombinant EtpA (rEtpA) could afford protection against intestinal colonization in a murine model of ETEC infection. Here, we demonstrate that intramuscular vaccination with rEtpA when adjuvanted with double mutant LT (dmLT) primes IgG predominant mucosal antibody responses to ETEC challenge. Notably, however, both antibody levels and avidity, as well as protection were dependent on vaccination schedule. Likewise, by electron microscopy polyclonal epitope mapping (EMPEM) we observed a greater diversity of epitopes targeted by antibodies after a more protracted vaccination schedule. Next, we explored the utility of IM immunization with alum-adjuvanted rEtpA. This elicited strong serologic and fecal IgG responses. Although accompanied by negligible IgA mucosal responses, EtpA alum-adjuvanted IM vaccination nevertheless protected against ETEC intestinal colonization. Collectively, these data suggest that EtpA could expand the portfolio of antigens targeted in ETEC subunit vaccine development.
An mTOR Inhibitor Discovery System Using the Growth of Drug-Sensitized Yeast Strains
Authors: Breen Anna K. , Thomas Sarah , Beckett David , Agsalud Matthew , Gingras Graham , Williams Judd , Wasko Brian M.
Published: January 2025

Inhibition of the target of rapamycin (TOR/mTOR) protein kinase by the drug rapamycin extends lifespan and healthspan across diverse species. However, rapamycin has potential off-target and side effects that warrant the discovery of additional TOR inhibitors. TOR was initially discovered inSaccharomyces cerevisiae(yeast) which contains two TOR paralogs,TOR1andTOR2. Yeast lacking functional Tor1 are viable but are hypersensitive to growth inhibition by TORC1 inhibitors, which is a property of yeast that can be exploited to identify TOR inhibitors. Additionally, yeast lacking FK506-sensitive proline rotamase (FPR1) or containing ator1-1allele (a mutation in the Fpr1-rapamycin binding domain of Tor1) are robustly and selectively resistant to rapamycin and analogs that allosterically inhibit TOR activity via anFPR1-dependent mechanism.

To facilitate the identification of TOR inhibitors, we generated a panel of yeast strains with mutations in TOR pathway genes combined with the removal of 12 additional genes involved in drug efflux. This creates a drug sensitive strain background that can sensitively and effectively identify TOR inhibitors.

In a wildtype yeast strain background, 25 µM of Torin1 and 100 µM of GSK2126458 (omipalisib) are necessary to observeTOR1-dependent growth inhibition by these known TOR inhibitors. In contrast, 100 nM Torin1 and 500 nM GSK2126458 (omipalisib) are sufficient to identifyTOR1-dependent growth inhibition in the drug sensitized background. This represents a 200-fold and 250-fold increase in detection sensitivity for Torin1 and GSK2126458, respectively. Additionally, for the TOR inhibitor AZD8055, the drug sensitive system resolves that the compound results inTOR1-dependent growth sensitivity at 100 µM, whereas no growth inhibition is observed in a wildtype yeast strain background. Our platform also identifies the caffeine analog aminophylline as aTOR1-dependent growth inhibitor via selectivetor1growth sensitivity. We also tested nebivolol, isoliquiritigenin, canagliflozin, withaferin A, ganoderic acid A, and taurine, and found no evidence for TOR inhibition using our yeast growth-based model.

Our results demonstrate that this system is highly effective at identifying compounds that inhibit the TOR pathway. It offers a rapid, cost-efficient, and sensitive tool for drug discovery, with the potential to expedite the identification of new TOR inhibitors that could serve as geroprotective and/or anti-cancer agents.
Structural basis of lipopolysaccharide translocon assembly mediated by the small lipoprotein LptM
Authors: Miyazaki Ryoji , Kimoto Mai , Kohga Hidetaka , Tsukazaki Tomoya
Published: January 2025

Gram-negative bacteria possess an outer membrane (OM) that acts as a barrier against toxic compounds. Lipopolysaccharide (LPS) in the outer leaflet of the OM is crucial for barrier function. After its synthesis in the cytoplasm and translocation to the periplasm, LPS is transported to the OM by the LPS transport system. The LPS translocon, composed of an OM protein LptD and a lipoprotein LptE, mediates LPS assembly into the OM. Recently, the small lipoprotein LptM (YifL) was identified as a novel LptD/E-interactor that facilitates LptD maturation. However, its mechanism remains unclear. Here, we investigated the detailed interaction between LptM and LptD. We found that LptM interacts with the folded LptD intermediate at the late stage of its maturation. Mutational analyses demonstrated that the N-terminal conserved region (C20GLKGPLYF28) of LptM is essential for its function. Cryo-EM structural analysis of theE. coliLptD/E/M complex, combined with biochemical analyses, revealed the molecular basis of the LptM–LptD interaction and its functional importance. Thus, we propose that LptM functions as a “barrel-rivet,” stabilizing LptD for its proper assembly.
Identification and Characterization of Novel Outer Membrane Proteins ofBrachyspira pilosicoli
Authors: Panda Amisha , Kapoor Jahnvi , Hareramadas B. , Naqvi Ilmas , Chhabra Ravindresh , Kumar Sanjiv , Bandyopadhyay Anannya
Published: January 2025

Brachyspira pilosicoliis a pathogenic, Gram-negative, spirochete bacterium that causes intestinal spirochetosis (IS) in birds, pigs, and humans and is distributed worldwide. This anaerobic intestinal bacterium colonizes the large intestine, potentially leading to colitis, diarrhoea, and decreased growth rate. Outer membrane proteins of Gram-negative bacteria play crucial roles in adhesion and host-pathogen interaction, helping the bacteria to evade the host immune system, and enhancing their virulence. However,B. pilosicoliouter membrane proteins are yet to be identified and characterized. Here, we report the computational discovery of 42 outer membrane β-barrel (OMBB) proteins inB. pilosicoliproteome predicted using a consensus-based computational framework. β-barrel architectures of the predicted proteins were confirmed by generating AlphaFold 3-based structural models. Structure-based functional annotation predicted putative functions for the identified OMBB proteins, including BamA homolog involved in folding and membrane insertion of OMPs, LptD homolog involved in transport of lipopolysaccharides into the OM, efflux pumps, transporters, enzymes, diffusion channels, and porins. Sequence variations across nine strains ofB. pilosicoliwere identified and mapped onto structural models, revealing that many of the variations were present on the surface exposed loop regions of the β-barrel structures. Ourin-silicoanalysis has identified 42 OMBB proteins, including homologs of BamA, LptD, TolC, TonB-dependent receptors, CsgG. Seven of these were identified as hypothetical proteins. Computational characterization of the predicted OMBB proteins offer insights into their potential roles in physiology, virulence, and disease pathogenesis, highlighting their potential for applications in diagnostics, vaccine development, or therapeutic interventions.
T Lymphocyte-Specific Deletion of SHP1 and SHP2 Promotes Activation-Induced Cell Death of CD4+ T Cells and Impairs Antitumor Response
Authors: Foster Connor J.R. , Du Jasper , Pundel Oscar , Geer Mitchell J. , Ripert Ryan C. , Liu Jia , Heim Taylor A. , Araki Kiyomi Y. , Lund Amanda W. , Wang Jun , Neel Benjamin G.
Published: January 2025

SHP1 (PTPN6) and SHP2 (PTPN11) are closely related protein-tyrosine phosphatases (PTPs), which are autoinhibited until their SH2 domains bind paired tyrosine-phosphorylated immunoreceptor tyrosine-based inhibitory/switch motifs (ITIMs/ITSMs). These PTPs bind overlapping sets of ITIM/ITSM-bearing proteins, suggesting that they might have some redundant functions. By studying T cell-specific single and double knockout mice, we found that SHP1 and SHP2 redundantly restrain naïve T cell differentiation to effector and central memory phenotypes, with SHP1 playing the dominant role. Surprisingly, loss of SHP2 alone in T cells enhanced the antitumor effects of anti-PD-1 antibodies, whereas there was no effect of SHP1 deletion. Also unexpectedly, the absence of both PTPs resulted in poorer tumor control and failure to respond to PD-1 blockade, associated with reduced frequency and activation of T cells and dendritic cells. Mechanistic studies revealed that CD4+, but not CD8+ T cells lacking SHP1 and SHP2 show increased activation-induced cell death upon anti-CD3/CD28 stimulation. Adoptive transfer of antigen-specific CD4+ T cells restored normal levels of tumor control in mice lacking both PTPs. Together, our results demonstrate that SHP1 or SHP2 is required to prevent activation-induced cell death of CD4+ T cells and is critical for tumor immunity, raising the possibility that inhibition of SHP2 might augment the therapeutic efficacy of PD-1-based immune therapy.

SIGNIFICANCE STATEMENT

SHP1 and SHP2 are related protein tyrosine phosphatases that associate with several of the same ITIM/ITSM-containing receptors or T cell receptor (TCR) signaling molecules. The individual roles of SHP1 and SHP2 in T cells have been reported previously, but potentially redundant functions are less well understood. Here we uncover an essential function in CD4+ T cells that is manifest only in the absence of both enzymes and is critical for the control of tumors.
Altered brain-ventricle coupling modes over Alzheimer’s disease progression detected with fMRI
Authors: Campo Fulvia Francesca , Brattico Elvira , Magalhães Vicente , Nigro Salvatore , Tafuri Benedetta ,   the Alzheimer’s Disease Neuroimaging Initiative, Logroscino Giancarlo , Cabral Joana
Published: January 2025

The origins of resting-state functional MRI (rsfMRI) signal fluctuations remain debated. Recent evidence shows coupling between global cortical rsfMRI signals and cerebrospinal fluid inflow in the fourth ventricle, increasing during sleep and decreasing with Alzheimer’s disease (AD) progression, potentially reflecting brain clearance mechanisms. However, the existence of more complex brain-ventricle coupling modes and their relationship to cognitive decline remains unexplored.

Analyzing 599 minimally-preprocessed rsfMRI scans from 163 elderly participants across the AD spectrum, we identified distinct brain-ventricle coupling modes that differentiate across groups and correlate with cognitive scores. Beyond the known anti-phase coupling between global brain signals and ventricles —more frequent in cognitively normal controls— we discovered additional modes where specific brain areas temporarily align with ventricle signals. At the cortical level, these modes form canonical resting-state networks, such as the Default Mode Network, which occurs less in AD or the Frontoparietal Network, which correlates positively with memory scores.

The direct link between ventricle and brain signals challenges the common practice of removing CSF components from rsfMRI analyses and questions the origin of cortical signal fluctuations forming functional networks, which may reflect region-specific fluid inflow patterns. These findings provide new insights into the relationship between brain clearance mechanisms and network dysfunction in neurodegenerative diseases.
How do auditors price financial secrecy culture? An international study
Authors: Sun Xuan Sean , Houqe Muhammad Nurul , Bhuiyan Md. Borhan Uddin , Zaman Mahbub
Published: January 2025

Purpose

This research examines the influence of financial secrecy culture on audit fees. Additionally, we investigate the potential moderating effect of adopting International Financial Reporting Standards (IFRS) on the relationship between financial secrecy culture and audit fees.

Design/methodology/approach

We use an international dataset comprising 249,217 firm-year observations from 30 countries/regions listed between 1996 and 2022. Our analysis includes regression analysis, the Heckman self-selection bias test, change analysis and various robustness tests.

Findings

Our results reveal a significant positive association between audit fees and firms listed in secretive jurisdictions, suggesting that auditors charge higher fees to accommodate additional audit effort or risk premiums. Furthermore, our empirical findings indicate that implementing IFRS in countries/regions with higher levels of secrecy introduces complexities or ambiguities in audit procedures, leading to increased audit fees. These results hold up under rigorous endogeneity tests and remain consistent across alternative measures and tests.

Research limitations/implications

Our findings establish a direct link between financial secrecy and audit fees, demonstrating higher costs for firms with greater secrecy. Additionally, they show that implementing IFRS in secretive jurisdictions intensifies audit complexities, resulting in higher fees. These findings emphasize the critical importance of transparency, regulatory compliance and risk management in financial reporting, with implications for investor confidence and regulatory strategies.

Originality/value

This study contributes to the literature by exploring the previously unexamined relationship between financial secrecy culture and audit fees while also assessing the moderating effect of IFRS adoption. By utilizing a comprehensive international dataset spanning multiple jurisdictions and years, our research provides valuable insights into cross-border variations in audit practices and their broader implications.
Am I making a difference? A scoping review of the consultant’s individual characteristics fostering organizational consulting effectiveness
Authors: Lallier Beaudoin Marie-Claude , Samson Irène , Dionne Émilie , Kusion Pierre-Yves
Published: January 2025

Purpose

The field of organizational consulting is often criticized for the lack of data supporting the practice and limited understanding of individual characteristics required for consultants to make a positive impact on organizations. The aims of this study were (1) to identify existing evidence on consultants’ knowledge, skills, abilities and other personal attributes (KSAO) related to organizational consulting effectiveness and (2) to lay the foundation of an empirically derived competency framework for effective consulting.

Design/methodology/approach

A scoping review of scientific peer-reviewed papers published between 1973 and 2023 and exploring attributes of the consultant related to consulting effectiveness was carried out among three academic databases and one consulting-specific journal. Content analysis was conducted in NVivo using an inductive/deductive approach.

Findings

In total, 32 single individual characteristics were extracted from 13 empirical papers and organized into 3 broad categories: (1) knowledge, (2) skills and abilities, and (3) other personal attributes. Results showed that skills and abilities have received the most attention from scholars, emphasizing the importance for consulting training programs to focus on the development of process-related and relational skills. Knowledge and personal attributes, including personality traits, were marked by a paucity of research.

Originality/value

The findings laid the foundation of a first data-based competency model for consulting effectiveness, useful for both researchers and practitioners. The current review identified gaps in the literature and highlighted opportunities for consolidating research in the field of organizational consulting.
CuMg2GaS4: a novel photocatalyst with promising properties
Authors: Hocine Hayat , Khelfaoui Friha , Al-Douri Y. , Boudia Keltouma , Fontaine-Vive Fabien , Sadouki Ouafaa , Slamani Amel , Amara Kadda , Belabbas Mawloud , Belkharroubi Fadila , Ameri M.
Published: January 2025

Purpose

The mechanical properties, including elastic constants and moduli, indicate the material’s stiffness and stability. Our calculations reveal that CuMg2GaS4 is a direct bandgap semiconductor, 2.18 eV. A detailed analysis of the electronic structure provides an insight into the bonding characteristics and charge distribution within the material.

Design/methodology/approach

This work presents a comprehensive investigation of the structural, electronic, optical, mechanical properties of the CuMg2GaS4 compound using density functional theory (DFT) calculations. Unlike its counterpart CuMg2InS4, which exhibits a tetragonal WS structure, CuMg2GaS4 is found to be an energetically stable in the monoclinic phase.

Findings

The calculated effective masses of electrons (0.38 m0) and holes (1.28 m0) suggest promising charge carrier mobility within the compound. Furthermore, based on the evaluation of electronic structure and optical absorption properties of CuMg2GaS4 in relation with the redox potentials of water, this demonstrates its potential as a promising candidate for efficient photocatalytic water splitting under visible light irradiation. These findings contribute to the understanding of the structural and functional properties of CuMg2GaS4 and pave the way for its potential applications in optoelectronic and energy conversion devices.

Originality/value

The prime novelty is to employ ab initio self-consistent Full-Potential Linearized augmented plane wave + local orbital method (FP-LAPW + lo) and investigate the properties of CuMg2GaS4 of structural, mechanical, thermodynamic stabilities, linear optical response.
Navigating new threats: Prey naïveté in native mammals
Authors: McKee Rebecca K. , Hart Kristen M. , Zeitoune Spencer , McCleery Robert A.
Published: January 2025

Invasive predators pose a substantial threat to global biodiversity. Native prey species frequently exhibit naïveté to the cues of invasive predators, and this phenomenon may contribute to the disproportionate impact of invasive predators on prey populations. However, not all species exhibit naïveté, which has led to the generation of many hypotheses to explain patterns in prey responses. These hypotheses primarily fall into two categories: system‐centric hypotheses related to biogeographic isolation (BIH) and species‐centric hypotheses, like the archetype similarity hypothesis (ASH).

We tested the predictions of these hypotheses by assessing the response of the common raccoon (Procyon lotor) and hispid cotton rat (Sigmodon hispidus), two native mammal species with divergent snake predation histories, to the cues of the invasive Burmese python (Python bivittatus) in the Florida Everglades (USA). Using giving‐up densities (GUDs), we assessed the responses of both cotton rats and raccoons to life‐size replicas of Burmese pythons and two North American predators—eastern diamondback rattlesnakes (Crotalus adamanteus) and coyotes (Canis latrans).

Although cotton rats increased their GUD in the presence of all three predators relative to the novel‐object control, raccoons only increased their GUD in coyote treatments.

These results align with the predictions of the ASH but not the BIH, and mirror observed patterns of population declines in invaded areas of the Florida Everglades.

More broadly, our findings suggest that naïveté may contribute to the vulnerability of some species to invasive predators even in large continental systems.
Evaluation of the effect of therapeutic plasma exchange on serum cytokine levels in pediatric intensive care unit
Authors: Cakmak Selen Ceren , Tugrul Hazal Ceren , Akgun Unlu Dilan , Albayrak Rasit Alkan , Atay Gurkan , Erdogan Seher , Sozeri Betul
Published: January 2025

Introduction

Therapeutic plasma exchange (TPE) is crucial for saving lives when used appropriately. This study aimed to assess TPE's impact on tumor necrosis factor‐like weak inducer of apoptosis (TWEAK) protein and IL‐6 levels in critically ill pediatric patients.

Methods

Conducted between May 2022 and December 2022, the study observed pediatric intensive care unit (PICU) patients undergoing TPE, recording demographics, lab results, TWEAK, and IL‐6 levels pre‐ and post‐procedure.

Results

Of 41 patients, 53.7% were male, 51.2% had underlying conditions, and 39% showed sepsis symptoms. IL‐6 levels significantly rose post‐TPE (p: 0.006), while TWEAK protein levels dropped (p: 0.030). Positive correlations were found between interleukin‐6 (IL‐6) pre‐TPE and ventilation duration, ferritin levels (p <0.05), and TWEAK pre‐TPE and organ failure indicators, D‐Dimer levels (p <0.05). Prognosis showed no significant difference in IL‐6/TWEAK levels (p >0.05).

Conclusion

Serum IL‐6 and TWEAK can indicate disease severity and inflammation level, but may not predict prognosis accurately.

Clinical Trial Registration

Our study has clinical study registration number B.10.1.TKH.4.34.H.GP.0.01/154 of the University of Health Sciences Ümraniye Training and Research Hospital.
Morphological Features of the Pecten Oculi in the Common Kestrel (Falco tinnunculus)
Authors: Kilinç Bahadır , Toprak Burhan , Yüksel Süleyman , Kandir Emine Hesna , Koçak Gökhan
Published: January 2025

This study aimed to investigate the macroscopic, light microscopic (LM) and scanning electron microscopic (SEM) characteristics of the pecten oculi in common kestrels (Falco tinnunculus). A total of six eyeballs from three common kestrels were used as the study material. The examination revealed that the bulbus oculi was spherical in shape and its diameter exceeded the axial‐global length. In the equatorial section of the eyeball, the pecten oculi were observed to be situated on the retina layer where the optic nerve enters the eyeball, showing a posterior‐to‐anterior distribution. The pecten oculi appeared dark brown, with a convoluted structure, comprising approximately 15–17 vascular folds. Scanning electron microscopic examination revealed dense capillary vascular folds on the surface of the pecten oculi. Within these capillary vessels, a few hyalocytes were noted, and melanocytes were found at the edges of the folds. Light microscopic examination detected numerous large, medium and small diameter vessels within the folds of the pecten oculi, especially at the periphery of the folds and the apical parts of the pecten oculi. The findings of this study were compared with the morphological characteristics of the pecten oculi in other bird species, revealing both similarities and differences.
The Adelaide Score: prospective implementation of an artificial intelligence system to improve hospital and cost efficiency
Authors: Kovoor Joshua G. , Stretton Brandon , Gupta Aashray K. , Beath Alexander , Jacob Mathew O. , Kefalianos John M. , Carmichael Gavin J. , Zaka Ammar , O'Callaghan Gerry , Satheakeerthy Shrirajh , Booth Andrew , Delloso Thomson , Hugh Thomas J. , Chan Weng Onn , Maddern Guy J. , Balan‐Vnuk Eva , Cusack Michael , Gilbert Toby , Maddison John , Bacchi Stephen ,   the Adelaide Score Advisory Group
Published: January 2025

Background

The Adelaide Score is an artificial intelligence system that integrates objective vital signs and laboratory tests to predict likelihood of hospital discharge.

Methods

A prospective implementation trial was conducted at the Lyell McEwin Hospital in South Australia. The Adelaide Score was added to existing human, artificial intelligence, and other technological infrastructure for the first 28 days of April 2024 (intervention), and outcomes were compared using parametric, non‐parametric and health economic analyses, to those in the first 28 days of April 2023 (control). Artificial intelligence evaluated inpatients admitted under 18 surgical and medical teams, and patients of high likelihood of discharge were provided, on working shifts between Thursday to Sunday, to the Supportive Weekend Interprofessional Flow Team (SWIFT) comprising a senior nurse and pharmacist.

Results

Two thousand nine hundred and sixty‐eight admissions were included across intervention and control periods. Relative to the control group, use of the Adelaide Score in the intervention group resulted in significantly shorter median length of stay (3.1 versus 2.9 days, P = 0.028) and significantly lower seven‐day readmission rate (7.1 versus 5.0%, p = 0.02). The 0.2 bed‐day reduction in median length of stay produced a cost saving of $735 708.60 across the 28‐day period, or $9 564 211.80 across a 52‐week year. There was no significant difference between intervention and control groups in median length of stay for patients discharged on weekends, in‐hospital mortality, or discharge to non‐home destinations.

Conclusions

The prospective implementation of the Adelaide Score was associated with improved hospital and cost efficiency, alongside lower readmissions, for patients across surgical and medical services.
Spatial frequency of environments and myopia: A systematic review on associated evidence and underlying mechanisms
Authors: Li Dan‐Lin , Lanca Carla , Zhang Xiu‐Juan , Grzybowski Andrzej , He Xian‐Gui , Pan Chen‐Wei
Published: January 2025

Purpose

Previous animal studies have found a relationship between spatial frequency and myopia. New research in humans suggest that reduced high spatial content of the visual environment may be a contributing factor for myopia development. This study aims to review the literature and elucidate the potential biological mechanisms linking spatial frequency and myopia.

Methods

A systematic search was conducted across PubMed and Web of Science databases. The studies published from their inception to August 2024 that have explored the connection between spatial frequency and myopia. Only full‐text articles in English were included. PRISMA was used for data validity.

Results

A total of 13 articles were included in this review, comprising seven animal model studies, four population‐based studies, one pictorial analysis and one study on research design. Epidemiological evidence is comparatively limited and has only begun to emerge in recent years. Mid‐ to high spatial frequencies were found to play an important role in the emmetropization process of the eye. Low spatial frequencies can increase the risk of myopia incidence. Furthermore, the potential mechanisms of how spatial frequency affects myopia are summarized as visual information processing characteristics, eye accommodation function and eye movements, contrast sensitivity and relevant molecules involved in the pathway.

Conclusion

The evidence suggests that indoor spatial frequency may be related to the development of myopia. Further studies are warranted to understand if the incorporation of changes in indoor environments is helpful in the prevention and control of myopia.
Limited benefits of organic management and fungicide reduction to ground beetles in vineyards
Authors: Gieser Julia T. , Kolb Sebastian , Reiff Jo Marie , Riess Kai , Hunke Maura , Entling Martin H. , Schirmel Jens
Published: January 2025

The use of fungicides in agriculture can reduce animal biodiversity. Such non‐target effects could be mitigated through fungus‐resistant cultivars that reduce the need for fungicide applications. Hence, we conducted a study in 32 commercial vineyards in southwest Germany. We investigated the effect of fungicide spraying intensities (susceptible vs resistant cultivars) and management (conventional vs organic) on ground beetles as a widely used indicator group in agroecological studies. In addition, we examined the effects of local habitat conditions (e.g., microclimate, vegetation) and landscape characteristics. Fungicide applications were reduced by half in conventional, and almost by two‐thirds in organic vineyards with fungus‐resistant cultivars, compared to susceptible grape varieties in the same management regime. While there was no evidence that fungus‐resistant cultivars positively affect the diversity of ground beetles, organic management doubled the number of individuals of conservation‐relevant species per vineyard. Additionally, the proportion of semi‐natural habitats in the surrounding landscape, and the vegetation height significantly affected the species composition across vineyards. We conclude that local habitat conditions and landscape characteristics influence ground beetles more than the fungicide spraying intensity. Additional measures such as organic management, moderate ground vegetation management, and landscape diversification are needed for the conservation of ground beetles in viticulture.
A novel BLK heterozygous mutation (p.Met121lle) in maturity‐onset diabetes mellitus: A case report and literature review
Authors: Xu Fenjuan , Chen Xiaoting , Hu Tingting , Sun Ruqiong , Zhu Fangying , Wu Xiaohong
Published: January 2025

Maturity onset diabetes of the young (MODY) is a highly heterogeneous monogenic disease that occurs due to β‐cell dysfunction. It is divided into different types depending on the gene mutated, and a total of 16 genes have been found to be associated with MODY. However, due to the current lack of understanding of monogenic diabetes, 90% of MODY is currently misdiagnosed and ignored in clinical practice. In this paper, we report the clinical data of a patient diagnosed with diabetes. Genetic testing revealed a novel BLK heterozygous mutation (c.363G>A) in the patient and in his father and son. He had no islet‐specific autoantibodies and showed a reduced meal‐induced response of insulin. Precise diagnosis of MODY individuals is important to the treatment.
The structure of FCGBP is formed as a disulfide‐mediated homodimer between its C‐terminal domains
Authors: Ehrencrona Erik , Gallego Pablo , Trillo‐Muyo Sergio , Garcia‐Bonete Maria‐Jose , Recktenwald Christian V. , Hansson Gunnar C. , Johansson Malin E. V.
Published: January 2025

Mucus in the colon is crucial for intestinal homeostasis by forming a barrier that separates microbes from the epithelium. This is achieved by the structural arrangement of the major mucus proteins, such as MUC2 and FCGBP, both of which are comprised of several von Willebrand D domains (vWD) and assemblies. Numerous disulfide bonds stabilise these domains, and intermolecular bonds generate multimers of MUC2. The oligomeric nature of FCGBP is not known. Human hFCGBP contains 13 vWD domains whereas mouse mFCGBP consists of only 7. We found unpaired cysteines in the vWD1 (human and mouse) and vWD5 (mouse)/vWD11 (human) assemblies which were not involved in disulfide bonds. However, the most C‐terminal vWD domains, vWD7 (mouse)/vWD13 (human), formed disulfide‐linked dimers. The intermolecular bond between C5284 and C5403 of human hFCGBP was observed by using mass spectrometry to generate the dimer. Cryo‐EM structure analysis of recombinant mouse mFCGBP revealed a compact dimer with two symmetric intermolecular disulfide bonds between C2462 and C2581, corresponding to the dimerising cysteines in the human hFCGBP. This compact conformation involves interactions between the vWD assemblies, but although the domains involved at the interface are the same, the nature of the interactions differ. Mouse mFCGBP was also found to exist in a semi‐extended conformation. These different interactions offer insights into the dynamic nature of the FCGBP homodimer.
Championing fundamental discovery research: quality over quantity
Authors: Gronenborn Angela M.
Published: January 2025

Rapidly emerging technologies, such as generative AI tools, have already had a reverberating impact on science and society. The notion that such tools could be entrusted with ‘mapping’ the trajectory of scientific discovery toward immediate measurable applications, however, is problematic. I instead argue that curiosity‐driven fundamental research should remain the base upon which to build progress.
HLA‐E: Immune Receptor Functional Mechanisms Revealed by Structural Studies
Authors: Gillespie Geraldine M. , Quastel Max N. , McMichael Andrew J.
Published: January 2025

HLA‐E is a nonclassical, nonpolymorphic, class Ib HLA molecule. Its primary function is to present a conserved nonamer peptide, termed VL9, derived from the signal sequence of classical MHC molecules to the NKG2x‐CD94 receptors on NK cells and a subset of T lymphocytes. These receptors regulate the function of NK cells, and the importance of this role, which is conserved across mammalian species, probably accounts for the lack of genetic polymorphism. A second minor function is to present other, weaker binding, pathogen‐derived peptides to T lymphocytes. Most of these peptides bind suboptimally to HLA‐E, but this binding appears to be enabled by the relative stability of peptide‐free, but receptive, HLA‐E‐β2m complexes. This, in turn, may favor nonclassical antigen processing that may be associated with bacteria infected cells. This review explores how the structure of HLA‐E, bound to different peptides and then to NKG2‐CD94 or T‐cell receptors, relates to HLA‐E cell biology and immunology. A detailed understanding of this molecule could open up opportunities for development of universal T‐cell and NK‐cell‐based immunotherapies.
MAP Kinase Signaling at the Crossroads of Inflammasome Activation
Authors: Vervaeke Alex , Lamkanfi Mohamed
Published: January 2025

Inflammasomes are crucial mediators of both antimicrobial host defense and inflammatory pathology, requiring stringent regulation at multiple levels. This review explores the pivotal role of mitogen‐activated protein kinase (MAPK) signaling in modulating inflammasome activation through various regulatory mechanisms. We detail recent advances in understanding MAPK‐mediated regulation of NLRP3 inflammasome priming, licensing and activation, with emphasis on MAPK‐induced activator protein‐1 (AP‐1) signaling in NLRP3 priming, ERK1 and JNK in NLRP3 licensing, and TAK1 in connecting death receptor signaling to NLRP3 inflammasome activation. Furthermore, we discuss novel insights into MAPK signaling in human NLRP1 inflammasome activation, focusing on the MAP3K member ZAKα as a key kinase linking ribosomal stress to inflammasome activation. Lastly, we review recent work elucidating how Bacillus anthracis lethal toxin (LeTx) manipulates host MAPK signaling to induce macrophage apoptosis as an immune evasion strategy, and the counteraction of this effect through genotype‐specific Nlrp1b inflammasome activation in certain rodent strains.
Barriers and Enablers in the Implementation of Physical Activity Improvement for Pregnant Women With Gestational Diabetes Mellitus: A Mixed‐Methods Study
Authors: Wang Yan , Zhu Wei , Pu Yan , Wang Yuyang , Luo Biru
Published: January 2025

Aim

To identify the barriers and enablers in the implementation of evidence‐based physical activity (PA) programmes for the improvement of health outcomes among pregnant women with gestational diabetes mellitus (GDM), and to develop strategies for implementing this evidence in clinical practice.

Methods

A convergent mixed‐methods study was conducted, integrating a descriptive qualitative research design with a cross‐sectional survey. In‐depth interview was used to collect the views and cognitions about physical activity from medical staff, leaders and pregnant women. The qualitative data was analysed using directed content analysis, guided by the Ottaw Model of Research Use (OMRU). A self‐designed questionnaire, which was based on the current best evidence for physical activity during pregnancy, was administered to gather data regarding nurse’ knowledge of physical activity (PA safety, managing blood glucose with PA, etc.), their management practice (timing of assessments, provision of information, etc.), as well as the knowledge levels of physical activity among pregnant women with GDM (principles of exercise, PA precautions, etc.).

Results

A total of 12 medical staff members and 14 pregnant women were interviewed. Ten nurses and 102 pregnant women with GDM completed the questionnaire. We generated 12 subthemes organised within three themes of the OMRU from the data, including insufficient professional autonomy, positive attitudes towards evidence implementation, shortage of nursing staff, implementation climate, etc. The average knowledge score of physical activity among nurses and pregnant women was 5 (SD 2.36) points and 5.2 (SD 1.70) points, respectively. Ten strategies for overcoming barriers and amplifying enablers for the implementation of the physical activity improvement programme for pregnant women with GDM, under the guidance of the OMRU were constructed.

Conclusion

An accumulation of evidence, adopters and practice environment factors across the OMRU domains explains why physical activity improvement initiatives for pregnant women with GDM are hard to implement.

Impacts

This study helps to recognise barriers and facilitators to physical activity improvement particularly at the evidence, potential adopter and practical environment level.

Patient

Healthcare workers (doctors, nurses, etc.) and pregnant women with GDM in a university hospital located in Sichuan Province.
Color Change and Cytotoxic Effects of a Bleaching Gel With 22% Carbamide Peroxide Catalyzed by Manganese Oxide
Authors: de Oliveira Ribeiro Rafael Antonio , Peruchi Victória , Sônego Leonardo Novaes Gaeta , Soares Igor Paulino Mendes , Soares Diana Gabriela , Hebling Josimeri , de Souza Costa Carlos Alberto
Published: January 2025

Objectives

To evaluate the color change and trans‐amelodentinal cytotoxicity of a 22% carbamide peroxide (CP) bleaching gel containing different concentration of manganese oxide (MnO2).

Material and Methods

Enamel/dentin discs adapted to artificial pulp chambers were distributed according to treatments: CN—No treatment; CP22%–22%CP; CP22 + 2MnO2–22%CP + 2 mg/mLMnO2; CP22% + 6MnO2–22%CP + 6 mg/mLMnO2; CP22% + 10MnO2–22%CP + 10 mg/mLMnO2 applied for 2 h for 15 days. Color change—CC (ΔE00 and ΔWID) (n = 8) was determined at 5, 10, and 15‐day periods (ANOVA/Sidak). Trans‐amelodentinal cytotoxicity (TC) was assessed after applying the extracts to cultured MDPC‐23 cells, which were analyzed concerning their viability (Vi) (n = 8) and oxidative stress (OxS) (n = 8). The amount of hydroxyl radical (OH•) (n = 4) generated by H2O2 degradation (ANOVA/Sidak), and trans‐amelodentinal diffusion of H2O2 (n = 8) (ANOVA/Tukey) were also evaluated.

Results

CP22 + 10MnO2 presented higher CC than CP22 for both evaluated equations in all analysis periods (p ≤ 0.04). Among bleached groups, CP22 + 10MnO2 presented the highest OH• generation (p ≤ 0.02) and the lowest trans‐amelodentinal diffusion of H2O2 (p ≤ 0.0004). Therefore, MDPC‐23 cells in CP22 + 10MnO2 exhibited the lowest OxS (p < 0.0001) and consequently the highest Vi (p ≤ 0.0146).

Conclusion

Besides increasing the bleaching efficacy, the strategy of adding 10 mg/mL of MnO2 to a 22%CP bleaching gel also reduces significantly the trans‐amelodentinal diffusion of H2O2, diminishing the cytotoxicity caused by at‐home bleaching therapy.

Clinical Significance

The addition of MnO2 to a 22% carbamide peroxide bleaching gel improves the color change and reduces the cytotoxicity effects of the product, making at‐home bleaching faster and biologically safer.