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Agrobacterium biovar 1 is a soilborne plant pathogen with the ability to colonize the irrigation system of greenhouses, causing hairy root disease (HRD). Currently, management focuses on using hydrogen peroxide to disinfect the nutrient solution, but due to the emergence of resistant strains, its efficacy and sustainability are questioned. Using a relevant collection of pathogenic Agrobacterium biovar 1 strains, OLIVR1 to 6, six phages specific to this pathogen and belonging to three different genera were isolated from Agrobacterium biovar 1-infected greenhouses. All phages were named OLIVR, referring to their location of isolation, Onze-Lieve-Vrouwe-Waver, and were characterized by whole-genome analysis, confirming their strictly lytic lifestyle. They remained stable under greenhouse-relevant conditions. To assess the efficacy of the phages, their ability to disinfect greenhouse nutrient solution inoculated with agrobacteria was tested. Each of the phages infected their host, but their ability to decrease the bacterial concentration differed. For instance, OLIVR1 reduced the bacterial concentration with 4 log units without phage resistance emerging. While OLIVR4 and OLIVR5 were also infectious in nutrient solution, they did not always decrease the bacterial load below the limit of detection, and phage resistance emerged. Finally, the mutations causing phage resistance by receptor modification were identified. For OLIVR4-resistant Agrobacterium isolates, but not for OLIVR5-resistant isolates, motility decreased. Together, these data show the potential of some of these phages as disinfectant of nutrient solution, and they might be a valuable tool to tackle HRD. IMPORTANCE: Hairy root disease, caused by rhizogenic Agrobacterium biovar 1 is a rapidly emerging bacterial disease worldwide. It affects tomatoes, cucumbers, eggplant, and bell pepper, causing high yield losses in hydroponic greenhouses. Recent findings suggest that the current management practices, mainly focusing on UV-C and hydrogen peroxide to disinfect contaminated water, have a questionable efficacy. Hence, we investigate the potential of phages as a biological means of preventing this disease. Using a diverse collection of Agrobacterium biovar 1, we isolated three different phage species that together infect 75% of the collection. Since these phages are strictly lytic, while remaining both stable and infectious under greenhouse-relevant conditions, they might be suitable candidates for biological control. [ABSTRACT FROM AUTHOR]

Individuals with autism spectrum condition (ASC) are suggested to experience difficulties with categorization and generalization. However, empirical studies have mainly focused on one process at a time, and neglected underlying neural mechanisms. Here, we investigated categorization and generalization at a behavioral and neural level in 38 autistic and 38 neurotypical (NT) adults. By presenting shapes sampled from an artificial multidimensional stimulus space, we investigated (1) behavioral and neural underpinnings of category learning and (2) behavioral generalization of trained categorization to both an extended version of the stimulus space and a novel stimulus space. Our previous findings showed that individuals with autism were slower in category learning. In this study, we demonstrate that this slower learning in autism was not related to differences in applied categorization strategy. In contrast, electroencephalography recordings during training did reveal a reduced amplitude of the N1 component in the right occipital temporal cortex after stimulus presentation in autistic participants, which suggests atypical categorical proficiency. In addition, we observed delayed and higher activation in the frontal regions after receiving (negative) feedback in the autistic group, potentially suggesting more explicit feedback processing or a higher salience of prediction errors in autism. Finally, autistic and NT individuals were able to generalize their learned categorization after training. However, when generalizing to a novel set of shapes, autistic individuals were significantly less accurate. Reduced generalization significantly correlated with increased intolerance to uncertainty scores. This multi-level approach reveals behavioral and neural differences in learning and generalization that could be related to clinical symptoms in autism., (© 2024 International Society for Autism Research and Wiley Periodicals LLC.)

Background: Xanthomonas vasicola pv. musacearum is responsible for the widespread Banana Xanthomonas Wilt in banana cultivation regions across the globe. Biocontrol measures for disease management remain limited amidst increasing antimicrobial resistance and unsustainable conventional agricultural practices. The purpose of this study is to explore a viable alternative or adjunct strategy through the use of bacteriophages for disease management., Results: Kintu was isolated from sewage and displayed clear and circular plaques measuring 3 mm. Based on transmission electron microscopy, Kintu displays siphovirus characteristics, including an icosahedral head and a non-contractile tail. Kintu infects 78% (22 out of 28) Ugandan Xvm strains, has an optimal multiplicity of infection of 1, a 10 min adsorption and latent period, a 35 min burst period, and a burst size of 15 particles per bacterium. Phage titers remain stable for two and half months (75 days) in SM buffer at -20 o C and - 40 o C but decrease significantly (p ≤ 0.0001) at 4 o C. Kintu is active at pH 3 and 11, maintains viability at temperatures between 25 o C and 120 o C and tolerates UV irradiation for up to 2 min and 20 s. Kintu inhibits Xvm growth at MOI ratios of 0.1, 1 and 10. The genome is a double stranded DNA molecule that consists of 48,985 base pairs and a G + C content of 51.71%. Antibiotic resistance genes or genes associated with a lysogenic life cycle are absent. There is limited sequence similarity of Kintu with other phages, making it a novel phage belonging to an unclassified genus of the class Caudoviricetes., Conclusion: Kintu is a novel bacteriophage that infects and lyses Xanthomonas vasicola pv. musacearum, the causative agent for Banana Xanthomonas Wilt. Its stability across diverse temperatures and pH conditions highlights its potential as a biocontrol agent for managing the disease., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Antimicrobial resistance (AMR) presents a significant threat to global healthcare. Proteus mirabilis causes catheter-associated urinary tract infections (CAUTIs) and exhibits increased antibiotic resistance. Traditional diagnostics still rely on culture-based approaches, which remain time-consuming. Here, we study the use of machine learning (ML) to classify bacterial resistance profiles using straightforward microscopic imaging of P. mirabilis for resistance classification integrated with radiomics feature analysis and ML models. From 150 P. mirabilis strains isolated from catheters of patients diagnosed with a CAUTI, 30 % displayed multidrug resistance using the standardized disk diffusion method, and 60 % showed strong biofilm activity in microtiter plate assays. As a more rapid alternative, we introduce wavelet-based and regular microscopy imaging with feature extraction/selection, following image preprocessing steps (image denoising, normalization, and mask creation). These features enable training and testing different ML models with 5-fold cross-validation for P. mirabilis resistance classification. From these models, the Random Forest (RF) algorithm exhibited the highest performance with ACC = 0.95, specificity = 0.97, sensitivity = 0.88, and AUC = 0.98 among the other ML algorithms considered in this study for P. mirabilis resistance classification. This successful application of wavelet-based feature Radiomics analysis with RF model represents a crucial step towards a precise, rapid, and cost-effective method to distinguish antibiotic resistant P. mirabilis strains., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to declare, and all the listed authors have actively contributed to the research and preparation of this manuscript. We have included the names and affiliations of all authors in the manuscript file., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Bacterial black spot, caused by Acidovorax valerianellae , is responsible for significant yield losses in lamb's lettuce ( Valerianella locusta ) in many producing countries, especially Europe. Currently, no resistant varieties of V. locusta are available that effectively control the disease under field conditions. Bacteriophage-based biocontrol has been suggested as a sustainable and natural alternative strategy to combat bacterial pathogens. In this study, novel phages infecting A. valerianellae and Acidovorax cattleyae , Alfacinha1, Alfacinha3, Acica, and Aval, were isolated and characterized. Based on comparative genomics, these phages represent three new phage genera. Aval and Acica phages revealed genomic features characteristic of temperate lifestyle, encoding toxins likely associated with lysogenic conversion, which contrasts with Alfacinha1 and Alfacinha3. The latter was selected for application as a biocontrol agent during seed steeping. This phage reaches an 87% reduction in the A. valerianellae concentration on artificially infested seeds. Importantly, this reduction results in an increased germination rate from 58.9% to 93.3%. Moreover, the infected seedlings had a dramatic reduction in vigor index after 22 days of growth, whereas the phage-treated ones had a vigor index similar to the negative control, reinforcing the ability of bacteriophages to effectively reduce disease progression. We further evaluated the impact of lipopolysaccharides in phage suspensions on the development of seedlings. Here, we demonstrated that the presence of lipopolysaccharides do have an impact on seedling development, significantly reducing the number of roots developed. This study shows how genomic analyses and tailored bioassays represent an essential route to ensure safe phage application and demonstrates the potential of a phage-based biocontrol strategy against A. valerianellae .IMPORTANCEBacteria continue to globally cause serious damage to a variety of crops. One example is a bacterial black spot of lamb's lettuce caused by Acidovorax valerianellae . It has spread across Europe, resulting in economic losses of at least 10% in tonnage annually. Faced with the inefficiency of conventional control methods, an alternative and sustainable strategy based on the use of bacteriophages was pursued in this study. We present for the first time the isolation and characterization of A. valerianellae -specific phages. Moreover, we assessed their biocontrol potential in seed decontamination since the disease primarily spreads from seeds to seedlings. Interestingly, seed treatment with one of our phages reaches an 87% reduction in bacterial concentration. More importantly, this reduction results in an increased germination rate from 58.9% to 93.3%. Finally, our study demonstrated for the first time the need for removing endotoxins from phage suspensions as they impact plant development when used as a biocontrol agent.

Background: Infections following shoulder surgery, particularly periprosthetic joint infection (PJI), are challenging to treat. Cutibacterium acnes is the causative pathogen in 39% to 76% of these cases. This study explores the efficacy of bacteriophage therapy as an alternative to conventional antibiotics for treating such infections., Methods: Nine phages with lytic activity were isolated from the skin of humans using C. acnes ATCC 6919 as the indicator host. These phages were tested individually or in combination to assess host range and antibiofilm activity against clinical strains of C. acnes associated with PJIs. The phage cocktail was optimized for broad-spectrum activity and tested in vitro against biofilms formed on titanium discs to mimic the prosthetic environment., Results: The isolated phages displayed lytic activity against a range of C. acnes clinical isolates. The phage cocktail significantly reduced the bacterial load of C. acnes strains 183, 184, and GG2A, as compared with untreated controls ( p < 0.05). Individual phages, particularly CaJIE7 and CaJIE3, also demonstrated significant reductions in bacterial load with respect to specific strains. Moreover, phages notably disrupted the biofilm structure and reduced biofilm biomass, confirming the potential of phage therapy in targeting biofilm-associated infections., Conclusions: Our preclinical findings support the potential of phage therapy as a viable adjunct to traditional antibiotics for treating C. acnes infections in orthopedic device-related infections. The ability of phages to disrupt biofilms may be particularly beneficial for managing infections associated with prosthetic implants.

Spread of multidrug-resistant Pseudomonas aeruginosa strains threatens to render currently available antibiotics obsolete, with limited prospects for the development of new antibiotics. Lytic bacteriophages, the viruses of bacteria, represent a path to combat this threat. In vitro-directed evolution is traditionally applied to expand the bacteriophage host range or increase bacterial suppression in planktonic cultures. However, while up to 80% of human microbial infections are biofilm-associated, research towards targeted improvement of bacteriophages' ability to combat biofilms remains scarce. This study aims at an in vitro biofilm evolution assay to improve multiple bacteriophage parameters in parallel and the optimisation of bacteriophage cocktail design by exploiting a bacterial bacteriophage resistance trade-off. The evolved bacteriophages show an expanded host spectrum, improved antimicrobial efficacy and enhanced antibiofilm performance, as assessed by isothermal microcalorimetry and quantitative polymerase chain reaction, respectively. Our two-phage cocktail reveals further improved antimicrobial efficacy without incurring dual-bacteriophage-resistance in treated bacteria. We anticipate this assay will allow a better understanding of phenotypic-genomic relationships in bacteriophages and enable the training of bacteriophages against other desired pathogens. This, in turn, will strengthen bacteriophage therapy as a treatment adjunct to improve clinical outcomes of multidrug-resistant bacterial infections., (© 2024. The Author(s).)

Given the increasing threat of antimicrobial resistance, scientists are urgently seeking adjunct antimicrobial strategies, such as phage therapy (PT). However, despite promising results for the treatment of musculoskeletal infections in our center, crucial knowledge gaps remain. Therefore, a prospective observational study (PHAGEFORCE) and a multidisciplinary approach was set up to achieve and optimize standardized treatment guidelines. At our center, PT is strictly controlled and monitored by a multidisciplinary taskforce. Each phage treatment follows the same pathway to ensure standardization and data quality. Within the PHAGEFORCE framework, we established a testing platform to gain insight in the safety and efficacy of PT, biodistribution, phage kinetics and the molecular interaction between phages and bacteria. The draining fluid is collected to determine the phage titer and bacterial load. In addition, all bacterial isolates are fully characterized by genome sequencing to monitor the emergence of phage resistance. We hereby present a standardized bench-to-bedside protocol to gain more insight in the kinetics and dynamics of PT for musculoskeletal infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Bessems, Chen, Uyttebroek, Devolder, Lood, Verwimp, De Munter, Debaveye, Depypere, Spriet, Van Gerven, Dupont, Wagemans, van Noort, Lavigne, Metsemakers and Onsea.)

Pictorial awareness is addressed through experimental phenomenology involving over 90 naïve participants. Since one can't look at the "same" picture twice the study uses one-shot trials. The participant's fascination for the duration of a session is held through the artistic principle of theme and variation. Six variations focus on the theme of pictorial geometry, both two-dimensional and three-dimensional. Major findings are: Idiosyncratic deviations from veridical are huge as compared to common textbook "effects." Observers wield arbitrary heuristics for tasks that are "formally related." The assumption of a common formal framework is apparently unsound. The notion of "inverse optics" is misleading. A fair fraction of the population appears to lack monocular stereopsis as intuitive awareness. It suggests an as-yet unrecognized, but perhaps common variety of aphantasia., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Key Points: Treatment of cystic fibrosis-related chronic rhinosinusitis should target sinonasal biofilms. NaHCO 3 salts with/without xylitol have limited antibiofilm properties, whereas rhDNAse has not. Phage effectivity varies and depends on the phage and the combination with antibiotics., (© 2024 The Author(s). International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Fracture-related infections (FRIs), particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA), are challenging to treat. This study designed and evaluated a hydrogel loaded with a cocktail of bacteriophages and vancomycin (1.2 mg/mL). The co-delivery hydrogel showed 99.72% reduction in MRSA biofilm in vitro. The hydrogel released 54% of phages and 82% of vancomycin within 72 h and maintained activity for eight days, in vivo the co-delivery hydrogel with systemic antibiotic significantly reduced bacterial load by 0.99 log10 CFU compared to controls, with active phages detected in tissues at euthanasia (2 × 10 3 PFU/mL). No phage resistance was detected in the phage treatment groups, and serum neutralization resulted in only a 20% reduction in phage count. In this work, we show that a phage-antibiotic co-delivery system via CMC hydrogel is a promising adjunct to systemic antibiotic therapy for MRSA-induced FRI, highlighting its potential for localized, sustained delivery and improved treatment outcomes., (© 2024. The Author(s).)

Staphylococcus aureus ´ biofilm-forming ability and rapid resistance development pose a significant challenge to successful treatment, particularly in postoperative complications, emphasizing the need for enhanced therapeutic strategies. Bacteriophage (phage) therapy has reemerged as a promising and safe option to combat multidrug-resistant bacteria. However, questions regarding the efficacy of phages against biofilms and the development of phage resistance require further evaluation. Expanding on the adaptable and evolutionary characteristics of phages, we introduce an evolutionary approach to enhance the activity of S. aureus phages against biofilms. Unlike other in vitro directed evolution methods performed in planktonic cultures, we employed pre-stablished biofilms to do a serial-passage assay to evolve phages monitored by real-time isothermal microcalorimetry (IMC). The evolved phages demonstrated an expanded host range, with the CUB&#95;MRSA-COL&#95;R9 phage infecting 83% of strains in the collection ( n  = 72), surpassing the ISP phage, which represented the widest host range (44%) among the ancestral phages. In terms of antimicrobial efficacy, IMC data revealed superior suppression of bacterial growth by the evolved phages compared to the ancestral CUB-M and/or ISP phages against the respective bacterial strain. The phage cocktail exhibited higher efficacy, achieving over 90% suppression relative to the growth control even after 72 h of monitoring. Biofilm cell-counts, determined by RT-qPCR, confirmed the enhanced antibiofilm performance of evolved phages with no biofilm regrowth up to 48 h in treated MRSA15 and MRSA-COL strains. Overall, our results underscore the potential of biofilm-adapted phage cocktails to improve clinical outcomes in biofilm-associated infections, minimizing the emergence of resistance and lowering the risk of infection relapse. However, further investigation is necessary to evaluate the translatability of our results from in vitro to in vivo models, especially in the context of combination therapy with the current standard of care treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Ponce Benavente, Wagemans, Hinkel, Aguerri Lajusticia, Lavigne, Trampuz and Gonzalez Moreno.)

Nowadays finding the new antimicrobials is necessary due to the emerging of multidrug resistant strains. The present study aimed to isolate and characterize bacteriophages against S. aureus. Strains Huma and Simurgh were the two podovirus morphology phages which isolated and then characterized. Huma and Simurgh had a genome size of 16,853 and 17,245 bp, respectively and both were Rosenblumvirus with G + C content of 29%. No lysogeny-related genes, nor virulence genes were identified in their genomes. They were lytic only against two out of four S. aureus strains. They also were able to inhibit S. aureus for 8 h in-vitro. Both showed a rapid adsorption. Huma and Simurgh had the latent period of 80 and 60 m and the burst sizes of 45 and 40 PFU/ml and also, they showed very low cell toxicity of 1.23%-1.79% on HT-29 cells, respectively. Thus, they can be considered potential candidates for biocontrol applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Infections due to antimicrobial-resistant bacteria have become a major threat to global health. Some patients may carry resistant bacteria in their gut microbiota. Specific risk factors may trigger the conversion of these carriages into infections in hospitalized patients. Preventively eradicating these carriages has been postulated as a promising preventive intervention. However, previous attempts at such eradication using oral antibiotics or probiotics have led to discouraging results. Phage therapy, the therapeutic use of bacteriophage viruses, might represent a worthy alternative in this context. Taking inspiration from this clinical challenge, we built Gut-On-A-Chip (GOAC) models, which are tridimensional cell culture models mimicking a simplified gut section. These were used to better understand bacterial dynamics under phage pressure using two relevant species: Pseudomonas aeruginosa and Escherichia coli . Model mucus secretion was documented by ELISA assays. Bacterial dynamics assays were performed in GOAC triplicates monitored for 72 h under numerous conditions, such as pre-, per-, or post-bacterial timing of phage introduction, punctual versus continuous phage administration, and phage expression of mucus-binding properties. The potential genomic basis of bacterial phage resistance acquired in the model was investigated by variant sequencing. The bacterial "escape growth" rates under phage pressure were compared to static in vitro conditions. Our results suggest that there is specific bacterial prosperity in this model compared to other in vitro conditions. In E. coli assays, the introduction of a phage harboring unique mucus-binding properties could not shift this balance of power, contradicting previous findings in an in vivo mouse model and highlighting the key differences between these models. Genomic modifications were correlated with bacterial phage resistance acquisition in some but not all instances, suggesting that alternate ways are needed to evade phage predation, which warrants further investigation.

Background: Categorization and its influence on perceptual discrimination are essential processes to organize information efficiently. Individuals with Autism Spectrum Condition (ASC) are suggested to display enhanced discrimination on the one hand, but also to experience difficulties with generalization and ignoring irrelevant differences on the other, which underlie categorization. Studies on categorization and discrimination in ASC have mainly focused on one process at a time, however, and typically only used either behavioral or neural measures in isolation. Here, we aim to investigate the interrelationships between these perceptual processes using novel stimuli sampled from a well-controlled artificial stimulus space. In addition, we complement standard behavioral psychophysical tasks with frequency-tagging EEG (FT-EEG) to obtain a direct, non-task related neural index of discrimination and categorization., Methods: The study was completed by 38 adults with ASC and 38 matched neurotypical (NT) individuals. First, we assessed baseline discrimination sensitivity by administering FT-EEG measures and a complementary behavioral task. Second, participants were trained to categorize the stimuli into two groups. Finally, participants again completed the neural and behavioral discrimination sensitivity measures., Results: Before training, NT participants immediately revealed a categorical tuning of discrimination, unlike ASC participants who showed largely similar discrimination sensitivity across the stimuli. During training, both autistic and non-autistic participants were able to categorize the stimuli into two groups. However, in the initial training phase, ASC participants were less accurate and showed more variability, as compared to their non-autistic peers. After training, ASC participants showed significantly enhanced neural and behavioral discrimination sensitivity across the category boundary. Behavioral indices of a reduced categorical processing and perception were related to the presence of more severe autistic traits. Bayesian analyses confirmed overall results., Limitations: Data-collection occurred during the COVID-19 pandemic., Conclusions: Our behavioral and neural findings indicate that adults with and without ASC are able to categorize highly similar stimuli. However, while categorical tuning of discrimination sensitivity was spontaneously present in the NT group, it only emerged in the autistic group after explicit categorization training. Additionally, during training, adults with autism were slower at category learning. Finally, this multi-level approach sheds light on the mechanisms underlying sensory and information processing issues in ASC., (© 2024. The Author(s).)

Viewers use contextual information to visually explore complex scenes. Object recognition is facilitated by exploiting object-scene relations (which objects are expected in a given scene) and object-object relations (which objects are expected because of the occurrence of other objects). Semantically inconsistent objects deviate from these expectations, so they tend to capture viewers' attention (the semantic-inconsistency effect ). Some objects fit the identity of a scene more or less than others, yet semantic inconsistencies have hitherto been operationalized as binary (consistent vs. inconsistent). In an eye-tracking experiment ( N = 21 adults), we study the semantic-inconsistency effect in a continuous manner by using the linguistic-semantic similarity of an object to the scene category and to other objects in the scene. We found that both highly consistent and highly inconsistent objects are viewed more than other objects (U-shaped relationship), revealing that the (in)consistency effect is more than a simple binary classification.

In real-world vision, people prioritise the most informative scene regions via eye-movements. According to the cognitive guidance theory of visual attention, viewers allocate visual attention to those parts of the scene that are expected to be the most informative. The expected information of a scene region is coded in the semantic distribution of that scene. Meaning maps have been proposed to capture the spatial distribution of local scene semantics in order to test cognitive guidance theories of attention. Notwithstanding the success of meaning maps, the reason for their success has been contested. This has led to at least two possible explanations for the success of meaning maps in predicting visual attention. On the one hand, meaning maps might measure scene semantics. On the other hand, meaning maps might measure scene features, overlapping with, but distinct from, scene semantics. This study aims to disentangle these two sources of information by considering both conceptual information and non-semantic scene entropy simultaneously. We found that both semantic and non-semantic information is captured by meaning maps, but scene entropy accounted for more unique variance in the success of meaning maps than conceptual information. Additionally, some explained variance was unaccounted for by either source of information. Thus, although meaning maps may index some aspect of semantic information, their success seems to be better explained by non-semantic information. We conclude that meaning maps may not yet be a good tool to test cognitive guidance theories of attention in general, since they capture non-semantic aspects of local semantic density and only a small portion of conceptual information. Rather, we suggest that researchers should better define the exact aspect of cognitive guidance theories they wish to test and then use the tool that best captures that desired semantic information. As it stands, the semantic information contained in meaning maps seems too ambiguous to draw strong conclusions about how and when semantic information guides visual attention., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In contrast to the many reports of successful real-world cases of personalized bacteriophage therapy (BT), randomized controlled trials of non-personalized bacteriophage products have not produced the expected results. Here we present the outcomes of a retrospective observational analysis of the first 100 consecutive cases of personalized BT of difficult-to-treat infections facilitated by a Belgian consortium in 35 hospitals, 29 cities and 12 countries during the period from 1 January 2008 to 30 April 2022. We assessed how often personalized BT produced a positive clinical outcome (general efficacy) and performed a regression analysis to identify functional relationships. The most common indications were lower respiratory tract, skin and soft tissue, and bone infections, and involved combinations of 26 bacteriophages and 6 defined bacteriophage cocktails, individually selected and sometimes pre-adapted to target the causative bacterial pathogens. Clinical improvement and eradication of the targeted bacteria were reported for 77.2% and 61.3% of infections, respectively. In our dataset of 100 cases, eradication was 70% less probable when no concomitant antibiotics were used (odds ratio = 0.3; 95% confidence interval = 0.127-0.749). In vivo selection of bacteriophage resistance and in vitro bacteriophage-antibiotic synergy were documented in 43.8% (7/16 patients) and 90% (9/10) of evaluated patients, respectively. We observed a combination of antibiotic re-sensitization and reduced virulence in bacteriophage-resistant bacterial isolates that emerged during BT. Bacteriophage immune neutralization was observed in 38.5% (5/13) of screened patients. Fifteen adverse events were reported, including seven non-serious adverse drug reactions suspected to be linked to BT. While our analysis is limited by the uncontrolled nature of these data, it indicates that BT can be effective in combination with antibiotics and can inform the design of future controlled clinical trials. BT100 study, ClinicalTrials.gov registration: NCT05498363 ., (© 2024. The Author(s).)

The allure of aesthetic appeal in images captivates our senses, yet the underlying intricacies of aesthetic preferences remain elusive. In this study, we pioneer a novel perspective by utilizing several different machine learning (ML) models that focus on aesthetic attributes known to influence preferences. Our models process these attributes as inputs to predict the aesthetic scores of images. Moreover, to delve deeper and obtain interpretable explanations regarding the factors driving aesthetic preferences, we utilize the popular Explainable AI (XAI) technique known as SHapley Additive exPlanations (SHAP). Our methodology compares the performance of various ML models, including Random Forest, XGBoost, Support Vector Regression, and Multilayer Perceptron, in accurately predicting aesthetic scores, and consistently observing results in conjunction with SHAP. We conduct experiments on three image aesthetic benchmarks, namely Aesthetics with Attributes Database (AADB), Explainable Visual Aesthetics (EVA), and Personalized image Aesthetics database with Rich Attributes (PARA), providing insights into the roles of attributes and their interactions. Finally, our study presents ML models for aesthetics research, alongside the introduction of XAI. Our aim is to shed light on the complex nature of aesthetic preferences in images through ML and to provide a deeper understanding of the attributes that influence aesthetic judgements., (© 2024 The Authors. British Journal of Psychology published by John Wiley & Sons Ltd on behalf of The British Psychological Society.)

The mechanisms underlying atypical sensory processing in autism remain to be elucidated, but research points toward a role of the glutamatergic/GABAergic balance. To investigate the potential relationships between visual sensitivity and its molecular correlates in autism, we combined data from electroencephalography (EEG) and magnetic resonance spectroscopy (MRS) studies. Twenty autistic adults and sixteen neurotypical adults (NT) participated in both an EEG study assessing visual sensitivity (Sapey-Triomphe et al., Autism Research, 2023) and in an MRS study measuring Glx and GABA+ concentrations in the occipital cortex (Sapey-Triomphe et al., Molecular Autism, 2021). These studies revealed no group differences in neural detection thresholds or in Glx/GABA levels in the occipital cortex. Neural detection thresholds for contrast and spatial frequency (SF) were determined using fast periodic visual stimulations and neural frequency tagging. In the present study, Glx/GABA+ concentrations in the occipital cortex and neural detection thresholds did not differ between groups. Interestingly, lower Glx/GABA+ ratios were associated with lower contrast detection thresholds and higher SF detection thresholds. These correlations were also significant within the neurotypical and autistic groups. This report suggests that the Glx/GABA balance regulates visual detection thresholds across individuals. In both autistic and NTs, lower Glx/GABA ratios in the occipital cortex allow for better detection of visual inputs at the neural level. This study sheds light on the neurochemical underpinnings of visual sensitivity in autism and warrants further investigation., (© 2024 International Society for Autism Research and Wiley Periodicals LLC.)

It has previously been shown that grouping by proximity is well described by a linear function relating the perceived orientation of a dot lattice to the ratio of the distances between the dots in the different orientations. Similarly, luminance influences how observers perceptually group stimuli. Using the dot lattice paradigm, it has been shown that proximity and luminance similarity interact additively, which means that their effects can be summed to predict an observers' percept. In this study, we revisit the additive interplay between proximity and luminance similarity and we ask whether this pattern might be the result of inappropriately averaging different types of observers or the imbalance between the strength of proximity grouping and luminance similarity grouping. To address these questions, we first ran a replication of the original study reporting the additive interplay between proximity and luminance similarity. Our results showed a convincing replication at the aggregate and individual level. However, at the individual level, all observers showed grouping by proximity whereas some observers did not show grouping by luminance similarity. In response, we ran a second experiment with enlarged luminance differences to reinforce the strength of grouping by luminance similarity and balance the strength of the two grouping cues. Interestingly, in this second experiment, additivity was not observed but instead a significant interaction was obtained. This disparity suggests that the additivity or interaction between two grouping cues in a visual stimulus is not a general rule of perceptual grouping but a consequence of relative grouping strength., (© 2023. The Psychonomic Society, Inc.)

The specificity of phages and their ability to evolve and overcome bacterial resistance make them potentially useful as adjuncts in the treatment of antibiotic-resistant bacterial infections. The goal of this study was to mimic a natural grouping of phages of interest and to evaluate the nature of their proliferation dynamics with bacteria. We have, for the first time, transferred naturally occurring phage groups directly from their sources of isolation to in vitro and identified 13 P. aeruginosa and 11 K. pneumoniae phages of 18 different genera, whose host range was grouped as 1.2-17%, 28-48% and 60-87%, using a large collection of P. aeruginosa (n = 102) and K. pneumoniae (n = 155) strains carrying different virulence factors and phage binding receptors. We introduced the interpretation model curve for phage liquid culturing, which allows easy and quick analysis of bacterial and phage co-proliferation and growth of phage-resistant mutants (PRM) based on qualitative and partially quantitative evaluations. We assayed phage lytic activities both individually and in 14 different cocktails on planktonic bacterial cultures, including three resistotypes of P. aeruginosa (PAO1, PA14 and PA7) and seven K. pneumoniae strains of different capsular serotypes. Based on the results, the natural phage cocktails designed and tested in this study largely performed well and inhibited PRM growth either synergistically or in proto-cooperation. This study contributes to the knowledge of phage behavior in cocktails and the formulation of therapeutic phage preparations. The paper also provides a detailed description of the methods of working with phages.

Categorization is an essential cognitive and perceptual process, which happens spontaneously. However, earlier research often neglected the spontaneous nature of this process by mainly adopting explicit tasks in behavioral or neuroimaging paradigms. Here, we use frequency-tagging (FT) during electroencephalography (EEG) in 22 healthy human participants (both male and female) as a direct approach to pinpoint spontaneous visual categorical processing. Starting from schematic natural visual stimuli, we created morph sequences comprising 11 equal steps. Mirroring a behavioral categorical perception discrimination paradigm, we administered a FT-EEG oddball paradigm, assessing neural sensitivity for equally sized differences within and between stimulus categories. Likewise, mirroring a behavioral category classification paradigm, we administered a sweep FT-EEG oddball paradigm, sweeping from one end of the morph sequence to the other, thereby allowing us to objectively pinpoint the neural category boundary. We found that FT-EEG can implicitly measure categorical processing and discrimination. More specifically, we could derive an objective neural index of the required level to differentiate between the two categories, and this neural index showed the typical marker of categorical perception (i.e., stronger discrimination across as compared with within categories). The neural findings of the implicit paradigms were also validated using an explicit behavioral task. These results provide evidence that FT-EEG can be used as an objective tool to measure discrimination and categorization and that the human brain inherently and spontaneously (without any conscious or decisional processes) uses higher-level meaningful categorization information to interpret ambiguous (morph) shapes., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

A novel temperate phage, named Hesat, was isolated by the incubation of a dairy strain of Staphylococcus aureus belonging to spa-type t127 with either bovine or ovine milk. Hesat represents a new species of temperate phage within the Phietavirus genus of the Azeredovirinae subfamily. Its genome has a length of 43,129 bp and a GC content of 35.11% and contains 75 predicted ORFs, some of which linked to virulence. This includes (i) a pathogenicity island (SaPln2), homologous to the type II toxin-antitoxin system PemK/MazF family toxin; (ii) a DUF3113 protein (gp30) that is putatively involved in the derepression of the global repressor Stl; and (iii) a cluster coding for a PVL. Genomic analysis of the host strain indicates Hesat is a resident prophage. Interestingly, its induction was obtained by exposing the bacterium to milk, while the conventional mitomycin C-based approach failed. The host range of phage Hesat appears to be broad, as it was able to lyse 24 out of 30 tested S. aureus isolates. Furthermore, when tested at high titer (10 8 PFU/ml), Hesat phage was also able to lyse a Staphylococcus muscae isolate, a coagulase-negative staphylococcal strain. KEY POINTS: • A new phage species was isolated from a Staphylococcus aureus bovine strain. • Pathogenicity island and PVL genes are encoded within phage genome. • The phage is active against most of S. aureus strains from both animal and human origins., (© 2024. The Author(s).)

In multistable dot lattices, the orientation we perceive is attracted toward the orientation we perceived in the immediately preceding stimulus and repelled from the orientation for which most evidence was present previously (Van Geert, Moors, Haaf, & Wagemans, 2022). Theoretically-inspired models have been proposed to explain the co-occurrence of attractive and repulsive context effects in multistable dot lattice tasks, but these models artificially induced an influence of the previous trial on the current one without detailing the process underlying such an influence (Gepshtein & Kubovy, 2005; Schwiedrzik et al., 2014). We conducted a simulation study to test whether the observed attractive and repulsive context effects could be explained with an efficient Bayesian observer model (Wei & Stocker, 2015). This model assumes variable encoding precision of orientations in line with their frequency of occurrence (i.e., efficient encoding) and takes the dissimilarity between stimulus space and sensory space into account. An efficient Bayesian observer model including both a stimulus and a perceptual level was needed to explain the co-occurrence of both attractive and repulsive temporal context effects. Furthermore, this model could reproduce the empirically observed strong positive correlation between individuals' attractive and repulsive effects (Van Geert et al., 2022), by assuming a positive correlation between temporal integration constants at the stimulus and the perceptual level. To conclude, the study brings evidence that efficient encoding and likelihood repulsion on the stimulus level can explain the repulsive context effect, whereas perceptual prior attraction can explain the attractive temporal context effect when perceiving multistable dot lattices.

How do we perceptually and cognitively organize incoming stimulation? A century ago, Gestalt psychologists posited the law of Prägnanz: psychological organization will always be as 'good' as possible given the prevailing conditions. To make the Prägnanz law a useful statement, it needs to be specified further (a) what a 'good' psychological organization entails, (b) how the Prägnanz tendency can be realized, and (c) which conditions need to be taken into account. Although the Gestalt school did provide answers to these questions, modern-day mentions of Prägnanz or good Gestalt often lack these clarifications. The concept of Prägnanz has been (mis)understood in many different ways, and by looking back on the rich history of the concept, we will attempt to present a more fine-grained view and promote a renewed understanding of the central role of Prägnanz in visual perception and beyond. We review Gestalt psychology's answers to the questions listed above, and also discuss the four main uses of the Prägnanz concept in more detail: (a) a Prägnanz tendency in each organizational process, (b) Prägnanz as a property of a Gestalt, (c) Prägnanz steps as internal reference points, and (d) Prägnanz in relation to aesthetic appreciation. As a key takeaway, Prägnanz is a multifaceted Gestalt psychological concept indicating the "goodness" of an experienced organization. Both the removal of unnecessary details and the emphasis on characteristic features of the overall organization compared to a reference organization can contribute to the emergence of a 'better' Gestalt. The stimulus constellation is not the only factor in determining the goodness of an organization, also the stimulus' interaction with an individual in a specific spatial and temporal context plays a role. Taking the ideas on Prägnanz as a generative framework and keeping the original Gestalt psychological context in mind, future research on perceptual organization can improve our understanding of the principles underlying psychological organization by further specifying how different organizational principles interact in concrete situations. Public significance statement: This paper reviews what a 'good' psychological organization entails, and how the incoming stimulation is clarified in human perception to achieve the best possible psychological organization. The review debunks common misconceptions on the meaning of "goodness" and synthesizes the most important perspectives and developments on "goodness" from its conception until now., (© 2023. The Author(s).)