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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

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.)