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Jake Littman,1 Chanika Phornphutkul,2 Celine Saade,3 Julia Katarincic,1 Roy Aaron1 1Department of Orthopedic Surgery, Warren Alpert Medical School of Brown University, Providence, RI, USA; 2Division of Human Genetics, Department of Pediatrics, Hasbro Children’s Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USA; 3Division of Ophthalmology, Lifespan Physician Group, Warren Alpert Medical School of Brown University, Providence, RI, USACorrespondence: Roy Aaron, Department of Orthopedic Surgery, Warren Alpert Medical School of Brown University, 2 Dudley Street. Suite 200, Providence, RI, 02905, USA, Tel +1 401-274-9660, Fax +1 401-270-1560, Email roy_aaron@brown.eduAbstract: Familial exudative vitreoretinopathy (FEVR) is a genetic disorder whose presentation can include osteoporosis, multiple fractures, and incomplete retinal angiogenesis leading to retinal detachment and blindness if left untreated. Discussed herein are the cases of two pediatric siblings who presented to the orthopedic service with multiple fractures and, through interdisciplinary management, were diagnosed with FEVR and treated appropriately before permanent visual impairment. The skeletal manifestations of FEVR, which have not been explored in depth in prior literature, are described. One sibling presented to orthopedic services for evaluation of a closed distal radius fracture sustained while playing sports. A comprehensive history revealed he had suffered at least four appendicular fractures in his lifetime, and dual-energy x-ray absorptiometry (DEXA) scan revealed his bone density to be in the first percentile for his age. Concurrent evaluation of his younger sibling revealed a similar history of multiple fractures and low bone density. Referral to genetic services and ensuing whole-exome sequencing revealed a likely pathogenic variant in both siblings’ LRP5 gene, the only known causative mutation for FEVR that leads to skeletal manifestations. While FEVR is well known in genetic and ophthalmologic settings, greater awareness of FEVR and other genetic disorders that predispose to fractures in pediatric populations is warranted in orthopedic settings. This will lead to reduced sequelae in pediatric patients with genetic disorders and improved interdisciplinary expertise. The story of these siblings illustrates that a high index of suspicion for genetic diseases is essential when treating children with osteoporosis and growth delays.Keywords: familial exudative vitreoretinopathy, FEVR, low-density lipoprotein receptor-related protein 5, LRP5, gracile bones, skeletal dysmorphogenesis

The presence of faults on feedback sensors can have serious effects on the performance of closed-loop systems. This note describes a method of using an auxiliary neural network controller to proviele the required closed-loop dynamic response even when sensorfaults are present. The effectiveness of the scheme is described in relation to a helicopter flight control system which operated with a variety of different types of sensor faults. [ABSTRACT FROM PUBLISHER]

Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are premalignant stages in the development of multiple myeloma (MM). Advances in detection, risk stratification, and therapeutic intervention have transformed our understanding of disease progression. Sensitive techniques like mass spectrometry have identified smaller monoclonal gammopathies, such as monoclonal gammopathy of indeterminate potential (MGIP), which may precede MGUS. Risk stratification models for MGUS and SMM, including the Mayo Clinic, PETHEMA, 2/20/20, IMWG, and PANGEA models, leverage tumor burden markers and cytogenetic abnormalities to predict prognosis. Genomic studies have revealed mutations, structural changes, and mutational signatures that predict progression. Immune microenvironmental alterations underscore the multifactorial nature of disease evolution, while epigenetics is emerging as a source of tumoral and microenvironmental changes. Therapies for high-risk SMM, including lenalidomide, daratumumab, and next-generation immunotherapies, demonstrate efficacy in delaying progression to MM but raise concerns regarding safety in asymptomatic patients. Future research must refine prognostic models, integrate genomic and immunophenotypic data, and establish consensus on optimal strategies for early intervention. This comprehensive review highlights the biological, clinical, and therapeutic advancements in MM and its precursors, emphasizing the importance of early risk assessment and targeted treatment to improve outcomes., (Copyright © 2025 Elsevier Masson SAS. All rights reserved.)

Introduction To compare thoracic vasculature opacification between the direct-drive and the peristaltic drive contrast injection systems and the effect on quantitative and qualitative image quality during computed tomography. Method A retrospective chart review of 88 patients who underwent chest computed tomography (CT) following a direct-drive injector before 2016 (Group A) or a peristaltic injector after 2016 (Group B). Both protocols employed 80mL of iodinated contrast media volume. Quantitative measurements of the thoracic vascular opacification, contrast-to-noise ratio (CNR), effective radiation dose, and arterial venous contrast ratio (AVCR) for each vessel were computed and compared. The measured values of vascular opacification, CNR, and dose length product (DLP) were assessed utilizing paired t-test and Pearson's correlation. Receiver operating characteristic (ROC), visual grading characteristics (VGC), and Cohen's kappa methodology were measured. Results There was no significant difference in the mean opacification of the chest vasculature (p > 0.05). The CNR in Group B was significantly lower than in Group A (p < 0.05) except for the brachiocephalic artery, proximal descending aorta, and the right pulmonary artery. Arterial venous contrast ratio at all anatomic levels demonstrated no statistical significance between groups. There were no differences in ROC, VGC, or kappa values between groups. Conclusion When comparing two contrast media injection systems in chest CT, there was no qualitative difference in image quality or pathology detection. However, quantitatively, direct-drive injectors provided higher CNR. Direct-drive contrast injectors also provided a superior quantitative image quality of chest vasculature compared to peristaltic injectors., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. American University of Beirut Institutional Review Board issued approval BIO-2018-0023. Institutional Review Board approval was acquired before data collection. As part of the Institutional Review Board approval, informed consent was waived due to the retrospective nature of the study. . Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2025, Saade et al.)

Identifying parameters influencing SARS-CoV-2 antibody dynamics post infection or vaccination is crucial for refining vaccination strategies. In a longitudinal analysis of 1340 samples from 375 healthcare workers, we characterized peak serological response and IgG half-life. Peak antibody titers post 2 vaccine doses were ∼ 20 times higher than natural infection; conversely, infected individuals had extended antibody half-life. Clinical and demographical factors such as BMI, age and smoking shaped peak response without affecting anti-RBD IgG half-life. A third mRNA vaccine dose increased peak antibody titers and prolonged half-life compared to the second dose. These findings underscore the diverse kinetics of SARS-CoV-2 antibody responses, which is influenced by immunization type/number and clinical factors., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sophie Trouillet-Assant reports financial support was provided by Agence Nationale de Recherches sur le Sida et les Hépatites Virales. Sophie Trouillet-Assant reports a relationship with National Agency for Research on AIDS and Viral Hepatitis that includes: funding grants. Laurence Generenaz and Sylvie Pons are employees of bioMérieux SA, an in vitro diagnostic company. bioMérieux kindly provided all the serological kits. The other 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. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. If there are other authors, they 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The serine protease like (Spl) proteases of Staphylococcus aureus are a family of six proteases whose function and impact on virulence are poorly understood. Here we propose alpha-1-antitrypsin (AAT), an important immunomodulatory serine protease inhibitor as target of SplD, E and F. AAT is an acute phase protein, interacting with many proteases and crucial for prevention of excess tissue damage by neutrophil elastase during the innate immune response to infections., Methods: We used MALDI-TOF-MS to identify the cleavage site of Spl proteases within AAT's reactive center loop (RCL) and LC-MS/MS to quantify the resulting peptide cleavage product in in vitro digestions of AAT and heterologous expressed proteases or culture supernatants from different S. aureus strains. We further confirmed proteolytic cleavage and formation of a covalent complex with Western Blots, investigated AAT's inhibitory potential against Spls and examined the NETosis inhibitory activity of AAT-Spl-digestions., Results: SplD, E and F, but not A or B, cleave AAT in its RCL, resulting in the release of a peptide consisting of AAT's C-terminal 36 amino acids (C36). Synthetic C36, as well as AAT-SplD/E/F-digestions exhibit NETosis inhibition. Only SplE, but not D or F, was partly inhibited by AAT, forming a covalent complex., Conclusion: We unraveled a new virulence trait of S. aureus , where SplD/E/F cleave and inactivate AAT while the cleavage product C36 inhibits NETosis., Competing Interests: MK is an inventor of a patent application covering the utilized LC-MS/MS method as a tool for characterizing systemic inflammation applicant: Jena University Hospital; inventors: Arite Bigalke and MK; published as EP4224163A1. Jena University Hospital is owner of a patent related to methods determining the origin of an infection EP3239712: granted; inventors: MK, Diana Schmerler. A patent covering the initial identification of C42 was granted as well published as CN104204808B, JP6308946B2, US10712350B2, EP2592421B1, EP2780719B1; owner: Jena University Hospital; Inventors: MK, Diana Schmerler, Thomas Deufel, Frank Brunkhorst. The remaining author declares 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 Scherr, Darisipudi, Börner, Austermeier, Hoffmann, Eberhardt, Abdurrahman, Saade, von Eggeling, Kasper, Holtfreter, Bröker and Kiehntopf.)

TSPO is a ubiquitous transmembrane protein used as a pharmacological marker in neuroimaging. The only known atomic structure of mammalian TSPOs comes from the solution NMR of mouse TSPO (mTSPO) bound to the PK11195 ligand and in a DPC surfactant environment. No structure is available in a biomimetic environment and without PK11195 which strongly stiffens the protein. We measured the effect of different amphiphilic environments on ligand-free mTSPO to study its structure/function and find optimal solubilization conditions. By replacing the SDS surfactant, where the recombinant protein is purified, with mixed lipid:surfactant (DMPC:DPC) micelles at different ratios (0:1, 1:2, and 2:1, w:w), the α-helix content and interactions and the intrinsic tryptophan (Trp) fluorescence of mTSPO are gradually increased. Small-angle X-ray scattering (SAXS) shows a more extended mTSPO/belt complex with the addition of lipids: D max ∼95 Å in DPC alone versus ∼142 Å in DMPC:DPC (1:2). SEC-MALLS shows that the molecular composition of the mTSPO belt is ∼98 molecules for DPC alone and ∼58 DMPC and ∼175 DPC for DMPC:DPC (1:2). Additionally, DMPC:DPC micelles stabilize mTSPO compared to DPC alone, where the protein has a greater propensity to aggregate. These structural changes are consistent with the increased affinity of mTSPO for the PK11195 ligand in presence of lipids (K d ∼70 μM in DPC alone versus ∼0.91 μM in DMPC:DPC, 1:2), as measured by microscale thermophoresis (MST). In conclusion, mixed lipid:surfactant micelles open new possibilities for the stabilization of membrane proteins and for their study in solution in a more biomimetic amphiphilic environment., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Context-dependent dispersal allows organisms to seek and settle in habitats improving their fitness. Despite the importance of species interactions in determining fitness, a quantitative synthesis of how they affect dispersal is lacking. We present a meta-analysis asking (i) whether the interaction experienced and/or perceived by a focal species (detrimental interaction with predators, competitors, parasites or beneficial interaction with resources, hosts, mutualists) affects its dispersal; and (ii) how the species' ecological and biological background affects the direction and strength of this interaction-dependent dispersal. After a systematic search focusing on actively dispersing species, we extracted 397 effect sizes from 118 empirical studies encompassing 221 species pairs; arthropods were best represented, followed by vertebrates, protists and others. Detrimental species interactions increased the focal species' dispersal (adjusted effect: 0.33 [0.06, 0.60]), while beneficial interactions decreased it (-0.55 [-0.92, -0.17]). The effect depended on the dispersal phase, with detrimental interactors having opposite impacts on emigration and transience. Interaction-dependent dispersal was negatively related to species' interaction strength, and depended on the global community composition, with cues of presence having stronger effects than the presence of the interactor and the ecological complexity of the community. Our work demonstrates the importance of interspecific interactions on dispersal plasticity, with consequences for metacommunity dynamics.This article is part of the theme issue 'Diversity-dependence of dispersal: interspecific interactions determine spatial dynamics'.

Dispersal is a well-recognized driver of ecological and evolutionary dynamics, and simultaneously an evolving trait. Dispersal evolution has traditionally been studied in single-species metapopulations so that it remains unclear how dispersal evolves in metacommunities and metafoodwebs, which are characterized by a multitude of species interactions. Since most natural systems are both species-rich and spatially structured, this knowledge gap should be bridged. Here, we discuss whether knowledge from dispersal evolutionary ecology established in single-species systems holds in metacommunities and metafoodwebs and we highlight generally valid and fundamental principles. Most biotic interactions form the backdrop to the ecological theatre for the evolutionary dispersal play because interactions mediate patterns of fitness expectations across space and time. While this allows for a simple transposition of certain known principles to a multispecies context, other drivers may require more complex transpositions, or might not be transferred. We discuss an important quantitative modulator of dispersal evolution-increased trait dimensionality of biodiverse meta-systems-and an additional driver: co-dispersal. We speculate that scale and selection pressure mismatches owing to co-dispersal, together with increased trait dimensionality, may lead to a slower and more 'diffuse' evolution in biodiverse meta-systems. Open questions and potential consequences in both ecological and evolutionary terms call for more investigation. This article is part of the theme issue 'Diversity-dependence of dispersal: interspecific interactions determine spatial dynamics'.

Objectives: In the post-SARS-CoV-2 pandemic era, "breakthrough infections" are still documented, due to variants of concerns (VoCs) emergence and waning humoral immunity. Despite widespread utilization, the definition of the anti-Spike (S) immunoglobulin-G (IgG) threshold to define protection has unveiled several limitations. Here, we explore the advantages of incorporating T-cell response assessment to enhance the definition of immune memory profile., Methods: SARS-CoV-2 interferon-gamma release assay test (IGRA) was performed on samples collected longitudinally from immunocompetent healthcare workers throughout their immunization by infection and/or vaccination, anti-receptor-binding domain IgG levels were assessed in parallel. The risk of symptomatic infection according to cellular/humoral immune capacities during Omicron BA.1 wave was then estimated., Results: Close to 40% of our samples were exclusively IGRA-positive, largely due to time elapsed since their last immunization. This suggests that individuals have sustained long-lasting cellular immunity, while they would have been classified as lacking protective immunity based solely on IgG threshold. Moreover, the Cox regression model highlighted that Omicron BA.1 circulation raises the risk of symptomatic infection while increased anti-receptor-binding domain IgG and IGRA levels tended to reduce it., Conclusion: The discrepancy between humoral and cellular responses highlights the significance of assessing the overall adaptive immune response. This integrated approach allows the identification of vulnerable subjects and can be of interest to guide antiviral prophylaxis at an individual level., (© 2024 The Authors. European Journal of Immunology published by Wiley‐VCH GmbH.)

Abstract: Mycosis fungoides (MF) is the most prevalent primary cutaneous T-cell lymphoma, with an indolent or aggressive course and poor survival. The pathogenesis of MF remains unclear, and prognostic factors in the early stages are not well established. Here, we characterized the most recurrent genomic alterations using whole-exome sequencing of 67 samples from 48 patients from Lille University Hospital (France), including 18 sequential samples drawn across stages of the malignancy. Genomic data were analyzed on the Broad Institute's Terra bioinformatics platform. We found that gain7q, gain10p15.1 (IL2RA and IL15RA), del10p11.22 (ZEB1), or mutations in JUNB and TET2 are associated with high-risk disease stages. Furthermore, gain7q, gain10p15.1 (IL2RA and IL15RA), del10p11.22 (ZEB1), and del6q16.3 (TNFAIP3) are coupled with shorter survival. Del6q16.3 (TNFAIP3) was a risk factor for progression in patients at low risk. By analyzing the clonal heterogeneity and the clonal evolution of the cohort, we defined different phylogenetic pathways of the disease with acquisition of JUNB, gain10p15.1 (IL2RA and IL15RA), or del12p13.1 (CDKN1B) at progression. These results establish the genomics and clonality of MF and identify potential patients at risk of progression, independent of their clinical stage., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: The effect of gadolinium-based contrast agents (GBCA) on the spinal cord is not established, especially in patients with diabetes mellitus., Purpose: To investigate neuronal and myelin loss in the spinal cord when employing macrocyclic ionic Gadoterate Meglumine (Gd-DOTA) and non-ionic Gadobuterol (Gd-BT-DO3A) GBCA in rats with and without diabetes mellitus., Materials and Methods: This study was performed between November 2018 and February 2020. Sixty young Sprague Dawley white rats (n = 6/group) were given injections of two macrocyclic GBCA: 0.5 mmol/ml Gd-DOTA and 1 mmol/ml Gd-BT-DO3A, using volumes based of the recommended doses (0.1 ml and 0.2 ml) for 42 days in both healthy and diabetic rats. Control groups received saline injections. Morphological assessment of spinal cord tissues was performed on three spinal segments. Neuronal counts in the ventral horns and myelin sparing percentage in the white matter were determined and compared in each group employing one-way ANOVA and Dunnett test for each category followed by three-way factorial analysis., Results: Low neuronal count and myelin percentage-area were obtained in groups receiving 0.2 ml Gd-DOTA (p = .001;p = .002;p < .001 neurons; and p < .001;p = .007;p = .001 myelin %) and Gd-BT-DO3A (p = .01;p = .048;p = .006 neurons; p < .001;p = .01;p = .001 myelin %). Similarly, neuronal loss was seen in diabetics receiving low volume-injection (0.1 ml) of Gd-DOTA (p = .04;p = .03;p = .42), Gd-BT-DO3A (p = .002;p = .007;p = .01); or high volume-injection (0.2 ml) of Gd-DOTA (p = .001;p = .003;p = .01) or Gd-BT-DO3A (p < .001,p = .002;p = .002), with associated decrease in myelin sparing for each category with low dose Gd-DOTA (p < .001, p = .001; p. = 09),Gd-BT-DO3A (p = .003;p = .003;p = .007); or the higher dose counterparts of Gd-DOTA (p < .001; p < .00; p = .001) and Gd-BT-DO3A (p < .001, p < .001, p < .001). Damage was observed using the standard dose (equivalent of 0.1 mmol/kg for rats) of Gd-DOTA (0.2 ml) but not that of Gd-BT-DO3A (0.1 ml) in healthy rats., Conclusion: Multiple high-volume injections of gadoterate meglumine and gadobuterol are associated with neuronal and myelin injury in the spinal cord, more so in rats with diabetes mellitus., (Copyright © 2024. Published by Elsevier Inc.)

Background: Artificial intelligence (AI) applications are rapidly advancing in the field of medical imaging. This study is aimed at investigating the perception and knowledge of radiographers towards artificial intelligence., Methods: An online survey employing Google Forms consisting of 20 questions regarding the radiographers' perception of AI. The questionnaire was divided into two parts. The first part consisted of demographic information as well as whether the participants think AI should be part of medical training, their previous knowledge of the technologies used in AI, and whether they prefer to receive training on AI. The second part of the questionnaire consisted of two fields. The first one consisted of 16 questions regarding radiographers' perception of AI applications in radiology. Descriptive analysis and logistic regression analysis were used to evaluate the effect of gender on the items of the questionnaire., Results: Familiarity with AI was low, with only 52 out of 100 respondents (52%) reporting good familiarity with AI. Many participants considered AI useful in the medical field (74%). The findings of the study demonstrate that nearly most of the participants (98%) believed that AI should be integrated into university education, with 87% of the respondents preferring to receive training on AI, with some already having prior knowledge of AI used in technologies. The logistic regression analysis indicated a significant association between male gender and experience within the range of 23-27 years with the degree of familiarity with AI technology, exhibiting respective odds ratios of 1.89 (COR = 1.89) and 1.87 (COR = 1.87)., Conclusions: This study suggests that medical practices have a favorable attitude towards AI in the radiology field. Most participants surveyed believed that AI should be part of radiography education. AI training programs for undergraduate and postgraduate radiographers may be necessary to prepare them for AI tools in radiology development., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Mohammad A. Rawashdeh et al.)

Background: To reduce radiation dose and subsequent risks, several legislative documents in different countries describe the need for Diagnostic Reference Levels (DRLs). Spinal radiography is a common and high-dose examination. Therefore, the aim of this work was to establish the DRL for Computed Tomography (CT) examinations of the spine in healthcare institutions across Jordan., Methods: Data was retrieved from the picture archiving and communications system (PACS), which included the CT Dose Index (CTDI (vol) ) and Dose Length Product (DLP). The median radiation dose values of the dosimetric indices were calculated for each site. DRL values were defined as the 75th percentile distribution of the median CTDI (vol)  and DLP values., Results: Data was collected from 659 CT examinations (316 cervical spine and 343 lumbar-sacral spine). Of the participants, 68% were males, and the patients' mean weight was 69.7 kg (minimum = 60; maximum = 80, SD = 8.9). The 75th percentile for the DLP of cervical and LS-spine CT scans in Jordan were 565.2 and 967.7 mGy.cm, respectively., Conclusions: This research demonstrates a wide range of variability in CTDI (vol)  and DLP values for spinal CT examinations; these variations were associated with the acquisition protocol and highlight the need to optimize radiation dose in spinal CT examinations.

Background: Despite the escalated production rate, the Iodinated Contrast Media (ICM) shortage continues, and demand outweighs supply., Aim: The aim of this study is to investigate the knowledge and practice of ICM delivery in computed tomography (CT) among radiographers and radiologic technologists worldwide., Methods: An IRB-approved cross-sectional survey used Google Forms for data collection. It involved 94 CT radiographers from 27 countries and was divided into five sections. The first section gathered demographic information, followed by sections on experience, self-assessment of ICM reactions, and delivery technique. The third section explored ICM knowledge and its relation to CT parameters. The fourth and fifth sections focus on practices during pulmonary angiography CT and renal CT scans. Data analysis involved descriptive statistics, the Chi- Square test, and ANOVA., Results: Knowledge was assessed with seven questions, and a score of at least 3.5 was needed for categorization. The median score was two, indicating low knowledge. Specifically, 64.9% of the participants scored lower than the two scores. Years of experience are strongly correlated with the level of knowledge, with 51.6% of radiographers having more than 10 years of experience demonstrating adequate knowledge. 41.7% of respondents demonstrated adequate knowledge when their duty was focused on CT. Furthermore, wide practice variability exists in all CT pulmonary angiography protocols among radiographers with adequate and inadequate knowledge., Conclusion: Inexperienced individuals showed knowledge gaps, leading to varied practices and highlighting the need for educational programs. The study underscores establishing standardized Protocols and Practice Guidelines (PPGs) for contrast media administration in Radiology Departments. Additionally, it emphasizes the importance of regular training programs, and international knowledge sharing. The potential for self-selection bias in the online survey sample is highlighted., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

We aimed to evaluate the association between the humoral and cellular immune responses and symptomatic SARS-CoV-2 infection with Delta or Omicron BA.1 variants in fully vaccinated outpatients. Anti-receptor binding domain (RBD) IgG levels and interferon-gamma (IFN-γ) release were evaluated at PCR-diagnosis of SARS-CoV-2 in 636 samples from negative and positive patients during Delta and Omicron BA.1 periods. Median levels of anti-RBD IgG in positive patients were significantly lower than in negative patients for both variants (p < 0.05). The frequency of Omicron BA.1 infection in patients with anti-RBD IgG concentrations ≥1000 binding antibody units (BAU)/mL was 51.0% and decreased to 34.4% in patients with concentrations ≥3000 BAU/mL. For Delta infection, the frequency of infection was significantly lower when applying the same anti-RBD IgG thresholds (13.3% and 5.3% respectively, p < 0.05). In addition, individuals in the hybrid immunity group had a 4.5 times lower risk of Delta infection compared to the homologous vaccination group (aOR = 0.22, 95% CI: [0.05-0.64]. No significant decrease in the risk of Omicron BA.1 infection was observed in the hybrid group compared to the homologous group, but the risk decreased within the hybrid group as anti-RBD IgG titers increased (aOR = 0.08, 95% CI: [0.01-0.41], p = 0.008). IFN-γ release post-SARS-CoV-2 peptide stimulation was not different between samples from patients infected (either with Delta or Omicron BA.1 variant) or not (p > 0.05). Our results show that high circulating levels of anti-RBD IgG and hybrid immunity were independently associated with a lower risk of symptomatic SARS-CoV-2 infection in outpatients with differences according to the infecting variant (www.clinicaltrials.gov; ID NCT05060939)., (© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

AbstractEven when environments deteriorate gradually, ecosystems may shift abruptly from one state to another. Such catastrophic shifts are difficult to predict and sometimes to reverse (so-called hysteresis). While well studied in simplified contexts, we lack a general understanding of how catastrophic shifts spread in realistically spatially structured landscapes. For different types of landscape structures, including typical terrestrial modular and riverine dendritic networks, we here investigate landscape-scale stability in metapopulations whose patches can locally exhibit catastrophic shifts. We find that such metapopulations usually exhibit large-scale catastrophic shifts and hysteresis and that the properties of these shifts depend strongly on the metapopulation spatial structure and on the population dispersal rate: an intermediate dispersal rate, a low average degree, or a riverine spatial structure can largely reduce hysteresis size. Our study suggests that large-scale restoration is easier with spatially clustered restoration efforts and in populations characterized by an intermediate dispersal rate.

This study reports the 6-month humoral immune response in vaccinated patients concomitantly infected with Delta and Omicron BA.1 variants of SARS-CoV-2. Interestingly, the simultaneous exposure to the Delta and BA.1 S proteins does not confer an additional immune advantage compared to exposure to the BA.1 S protein alone., (© 2023. The Author(s).)

This work focused on the comprehensive study of two provincial transit abattoirs in Tucumán, Argentina, with no Hazard Analysis Critical Control Point (HACCP) plan. Visits (n=20) were conducted between 2016 and 2018 during the operational and post-operational processes. Risk was estimated and the bacteriological analysis of carcass and environmental samples was performed. Risk estimation showed the predominance of high risk in both abattoirs. The main deviations from the HACCP plan were: deficient building conditions, deficient workflow, lack of sectorization of changing rooms and bathrooms, lack of implementation of Standardized Sanitary Operational Procedures, and no food safety training of workers. The counts of indicator microorganisms from both abattoirs were not significant. Salmonella spp. was isolated from 7.5% carcass and 7.3% environmental samples. The Salmonella serovars identified were Cerro, Corvallis, Havana and Agona. Shiga toxin (stx) genes were detected in 24.4% carcass and 30.9% environmental samples. The isolates were characterized as Escherichia coli O8:H7/stx 1 , O116:H49/stx 2 and O136:H40/stx 2 . Based on these results, it would be possible to implement an improvement plan in Tucumán abattoirs together with the local health authorities. Still, the need to work jointly with the sanitary authority in search of a unique sanitary standard for Argentina remains unaddressed., (Copyright © 2022 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.)

The diversity of vaccination modalities and infection history are both variables that have an impact on the immune memory of individuals vaccinated against SARS-CoV-2. To gain more accurate knowledge of how these parameters imprint on immune memory, we conducted a long-term follow-up of SARS-CoV-2 spike protein-specific immune memory in unvaccinated and vaccinated COVID-19 convalescent individuals as well as in infection-naïve vaccinated individuals. Here, we report that individuals from the convalescent vaccinated (hybrid immunity) group have the highest concentrations of spike protein-specific antibodies at 6 months after vaccination. As compared with infection-naïve vaccinated individuals, they also display increased frequencies of an atypical mucosa-targeted memory B cell subset. These individuals also exhibited enhanced T H 1 polarization of their SARS-CoV-2 spike protein-specific follicular T helper cell pool. Together, our data suggest that prior SARS-CoV-2 infection increases the titers of SARS-CoV-2 spike protein-specific antibody responses elicited by subsequent vaccination and induces modifications in the composition of the spike protein-specific memory B cell pool that are compatible with enhanced functional protection at mucosal sites.

Purpose: To report a pediatric case of optic neuritis with subsequent development of central retinal vein occlusion (CRVO). Methods: A case and its findings were analyzed. Results: A 16-year-old boy presented with painful vision loss in the left eye, an afferent pupillary defect, and optic disc edema. Magnetic resonance imaging showed optic nerve enhancement and contrast-enhancing cerebral white-matter lesions, consistent with optic neuritis and demyelinating disease. He received intravenous methylprednisolone followed by a prednisone taper. At the 3-week follow-up, the visual acuity (VA) in the left eye had worsened and fundoscopic examination showed a new CRVO. A hypercoagulable workup showed antiphospholipid syndrome, which was treated with warfarin. He received intravitreal antivascular endothelial growth factor treatment with subsequent improvement in VA and resolution of the macular edema. Conclusions: This case describes an unusual mechanism for CRVO via a combination of optic disc edema from optic neuritis and hypercoagulability from antiphospholipid syndrome. It is important to recognize this complication of optic disc edema and the necessary workup for a pediatric CRVO., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Increased radiation doses from computed tomography (CT) examinations is well known with proven risks of inducing cancers for effective dose >100 mSv (according to some studies >50 mSvs)., Purpose: To establish the diagnostic reference level (DRL) for low-dose renal CT examinations in the evaluation of renal stones., Material and Methods: Patient demographics, CT parameters, and dosimetric indices (CTDI vol and dose length product [DLP]) were collected from 12 tertiary hospitals that routinely perform renal CT in the detection and evaluation of renal stones over a period of 12 weeks. Data obtained from 1418 average-sized patients in each category were recorded. The median values of dosimetric indices for each site were calculated. The DRL values were defined as the 75th percentile of the distribution of the median values of CTDI vol and DLP., Results: There were no significant differences between patient demographics. Mean kVp and mAs for protocols were 121.67 ± 11.56 and 226.91 ± 78.44, respectively. The CTDI vol values were in the range of 2-36.2 mGy, while the DLP values were in the range of 43-1942 mGy.cm. The DRL for the CTDI vol was 16.15 mGy and for the DLP 851.77 mGy.cm. The local median values of CDTI vol and DLP are higher than DRL in two hospitals., Conclusion: Comparison of local median values of CDTI vol and DLP with DRL suggests the needs of an optimization strategy in some hospitals.

The translocator protein (TSPO) is a ubiquitous transmembrane protein of great pharmacological interest thanks to its high affinity to many drug ligands. The only high-resolution 3D-structure known for mammalian TSPO was obtained by NMR for the mouse mTSPO in DPC detergent only in presence of the high-affinity PK 11195 ligand. An atomic structure of free-ligand mTSPO is still missing to better understand the interaction of ligands with mTSPO and their effects on the protein conformation. Here, we decipher the solution structures of the recombinant mTSPO without ligand both in (i) SDS, the detergent used to extract and purify the protein from E. coli inclusion bodies, and (ii) DPC, the detergent used to solve the PK 11195-binding mTSPO NMR structure. We report partially refolded and less flexible mTSPO helices in DPC compared to SDS. Besides, DPC stabilizes the tertiary structure of mTSPO, as shown by a higher intrinsic Trp fluorescence and changes in indole environment. We evaluate by SEC-MALLS that ∼135 SDS and ∼100 DPC molecules are bound to mTSPO. SEC-small-angle X-ray (SAXS) and neutron (SANS) scattering confirm a larger mTSPO-detergent complex in SDS than in DPC. Using the contrast-matching technique in SEC-SANS, we demonstrate that mTSPO conformation is more compact and less flexible in DPC than in SDS. Combining ab initio modeling with SANS, we confirm that mTSPO conformation is less elongated in DPC than in SDS. However, the free-ligand mTSPO envelope in DPC is not as compact as the PK 11195-binding protein NMR structure, the ligand stiffening the protein., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2022 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Omicron variant is circulating in the presence of a globally acquired immunity unlike the ancestral SARS-CoV-2 isolate. Herein, we investigated the normalized viral load dynamics and viral culture status in 44 fully vaccinated healthcare workers (HCWs) infected with the Omicron BA.1 variant. Viral load dynamics of 38 unvaccinated HCWs infected with the 20A variant during the first pandemic wave was also studied. We then explored the impact of Omicron infection on pre-existing immunity assessing anti-RBD IgG levels, neutralizing antibody titres against 19A, Delta and Omicron isolates, as well as IFN-γ release following cell stimulation with SARS-CoV-2 peptides. We reported that two weeks after diagnosis a greater proportion of HCWs infected with 20A (78.9%, 15/19) than with Omicron BA.1 (44.7%, 17/38; p = 0.02) were still positive by RT-qPCR. We found that Omicron breakthrough infections led to an overall enhancement of vaccine-induced humoral and cellular immunity as soon as a median [interquartile range] of 8 [7-9] days post symptom onset. Among samples with similar high viral loads, non-culturable samples exhibited higher neutralizing antibody titres and anti-RBD IgG levels than culturable samples. Additionally, Omicron infection led to an enhancement of antibodies neutralization capacity against other SARS-CoV-2 isolates. Taken together, the results suggest that Omicron BA.1 vaccine breakthrough infection is associated with a faster viral clearance than that of the ancestral SARS-CoV-2, in addition this new variant leads to a rapid enhancement of the humoral response against multiple SARS-CoV-2 variants, and of the cellular response.

Meigs syndrome is a rare disorder characterized by a triad of benign ovarian tumor, ascites, and pleural effusion. Despite its benign nature, its presentation can be similar to metastatic malignancy, making preoperative diagnosis often challenging. The differential diagnosis includes serious and even life-threatening conditions. Meigs syndrome is most common in postmenopausal women and is extremely rare in children. It is often undiagnosed until an invasive surgery is performed. The fact that surgery includes a unilateral salpingo-oophorectomy in females of reproductive age raises concerns for future fertility and other risks associated with this intervention. Familiarity of radiologists and pediatric surgeons with clinical and imaging findings is beneficial to improve preoperative planning, thereby minimizing invasive surgery and preserving ovarian tissue., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Hatoum et al.)

Background: Collecting information on sustainability of immune responses after infection or vaccination is crucial to inform medical decision-making and vaccination strategies. Data on how long-lasting antibodies against SARS-COV-2 could provide a humoral and protective immunity and prevent reinfection with SARS-CoV-2 or its variants is particularly valuable. This study presents a novel method to quantitatively measure and monitor the diversity of SARS-CoV-2 specific antibody profiles over time., Methods: Serum samples from two groups were used in this study: Samples from 20 naturally infected subjects (followed for up to 1 year) and samples from 83 subjects vaccinated with one or two doses of the Pfizer BioNtech vaccine (BNT162b2/BNT162b2) (followed for up to 6 months). The Multi-SARS-CoV-2 assay, a multiparameter serology test developed for the serological confirmation of past-infections, was used to determine the reactivity of six different SARS-CoV-2 antigens. For each subject sample, 3 dilutions (1/50, 1/400 and 1/3200) were defined as an optimal set over the six antigens and their respective linear ranges. This allowed accurate quantification of the corresponding six antibodies. Nonlinear mixed-effects modelling was applied to convert intensity readings from 3 determined dilutions to a single quantification value for each antibody., Results: Median half-life for the 20 naturally infected vs 74 vaccinated subjects (two doses) was 120 vs 50 days for RBD, 127 vs 53 days for S1 and 187 vs 86 days for S2 antibodies respectively., Conclusion: The newly proposed method, based on a series of a limited number of dilutions, can convert a conventional qualitative assay into a quantitative assay. This conversion helps define the sustainability of specific immune responses against each relevant viral antigen and can help in defining the protection characteristics after an infection or a vaccination., Competing Interests: Ursula Saade, Elodie Granjon and Maan Zrein are employed by InfYnity Biomarkers. All other co-authors declare no competing interests.

Purpose: To investigate the use of weight-based protocols during full- and half-body fluorodeoxyglucose F 18 (FDG) positron emission tomography-computed tomography (PET-CT) and their effect on image quality, radiation dose, and lifetime attributable risks., Methods: A total of 1817 patients were referred for FDG PET-CT studies. Each scanning group (4 total: full-body groups A and C and half-body groups B and D) was randomly allotted into conventional or weight-based CT. Groups A and B followed a conventional protocol of 120 kVp, 120 mA, 0.5 second rotation time, and pitch 0.8 mm/rotation for all body weights. Groups C and D were scanned using 1 of 4 weight-based CT protocols. All 4 weight-based protocols used 140 kVp, 0.75 seconds rotation time, and pitch 0.8 mm/rotation. Milliamperage varied by body weight as follows: protocol I (≤ 60kg [132.3 lb]), 35 mA; protocol II (61-80 kg [134.5-176.4 lb]), 50 mA; protocol III (81-100 kg [178.6-220.5 lb]), 65 mA; and protocol IV (> 100kg [222.7 lb]), 100 mA. All protocols (weight based and conventional) employed tube current modulation. CT quantitative image quality measurements were evaluated for each protocol, and lifetime attributable risks were calculated for each age group and sex., Results: Patient demographics demonstrated no significant differences between groups. Mean effective dose was significantly lower for group C (full body, weight based) compared with A (full body, conventional) ( P < .001), as were lifetime attributable risks ( P < .001). Mean effective dose and lifetime attributable risks also were significantly lower ( P < .001) for group D (half body, weight based) compared with B (half body, conventional). Contrast-to-noise ratios showed no difference between groups ( P = .12), supporting a preference for the weigh-based protocols used for groups C and D. For half-body, weight-based protocols (group D), the lifetime attributable risks decreased for men by 91.9% and for women by 38.9%. For full-body, weight-based protocols (group C), the lifetime attributable risks decreased by 72.5% and 66.3% for men and women, respectively., Discussion: Radiologists and radiologic technologists face the challenge of balancing the potential risks of radiation-induced cancer against providing diagnostic-quality images and uncompromised disease detection. Weight-based protocols address this challenge without compromising image quality or pathology detection., Conclusion: Significant reductions in radiation dose and lifetime attributable risks can be achieved using CT weight-based protocols during half- and whole-body FDG PET-CT without compromising CT image quality., (© 2022 American Society of Radiologic Technologists.)