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Background and Objective: The rise in minimally invasive procedures has created a demand for efficient and reliable planning software to predict intra- and post-operative outcomes. Surrogate modelling has shown promise, but challenges remain, particularly in cardiovascular applications, due to the complexity of parametrising anatomical structures and the need for large training datasets. This study aims to apply statistical shape modelling and machine learning for predicting stent deployment in real time using patient-specific models. ► METHODS:: We built a statistical shape model starting from an open-source clinical dataset, which we then used to generate new synthetic cases. Finite element simulations of stent deployment were performed on these cases using an in-house software. A surrogate model was then trained to map the statistical features of the synthetic models to the corresponding stent configurations, evaluating sensitivity to dataset size. ► RESULTS:: Even with the smallest dataset (400 samples), the average prediction error in position among the tested cases never exceeded 8.6%, with a median one within the testing dataset of 1.6%. As the number of training samples increased (4900), we achieved a median position error lower than 0.1 mm (0.97%) and a maximum position error of 0.5 mm (4.8%). Notably, the largest errors occur in the radial direction of the stent, while the deployed length is accurately predicted in all the cases. ► CONCLUSIONS:: The consistent success in performance strongly suggests that surrogate modelling represents a clinically valuable tool for accurately computing stent deployment outcomes in real time, even within complex anatomical scenarios., 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 © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

The last decade has seen significant growth in the application of DNA-based methods for extended antigen typing, and the use of gene sequencing to consider variation in blood group genes to guide clinical care. The challenge for the field now lies in educating professionals, expanding accessibility and standardizing the use of genotyping for routine patient care. Here we discuss applications of genotyping when transfusion is not straightforward including when compatibility cannot be demonstrated by routine methods, when Rh type is unclear, when allo- and auto-antibodies are encountered in stem cell and organ transplantation, for prenatal testing to determine maternal and foetal risk for complications, and Group A subtyping for kidney and platelet donors. We summarize current commercial testing resources and new approaches to testing including high-density arrays and targeted next-generation sequencing (NGS)., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Background: Low-risk gestational trophoblastic neoplasia are currently receiving monochemotherapy as first-line therapy. In the case of a resistance, a second-line monochemotherapy or polychemotherapy is proposed. As an alternative to these toxic and historic chemotherapy agents, the efficacy of the anti-PD-L1 monoclonal antibody (avelumab) was assessed in the TROPHIMMUN phase II trial Cohort A. Avelumab yielded a 53% cure rate with an acceptable tolerance profile, including normal further pregnancy and delivery. Beyond the blockade of PD-1/PD-L1 interactions, avelumab effect could rely on the induction of antibody-dependent cell-mediated cytotoxicity mediated by FcγR3A-expressing natural killer cells., Objective: This translational study aimed at testing whether antibody-dependent cell-mediated cytotoxicity is involved in avelumab efficacy on gestational trophoblastic neoplasia and if FcγR3A affinity polymorphism could help predicting the response to avelumab in gestational trophoblastic neoplasia., Study Design: The expression of PD-L1 by the tumor and the phenotype of natural killer cells infiltrating gestational trophoblastic neoplasia were verified by performing transcriptomic and proteomic analyses. Then, JEG-3 choriocarcinoma cells were cocultured with human natural killer cells in the presence and absence of avelumab. The impact of FcγR3A functional polymorphism was assessed on the activation status of natural killer cells and the viability of JEG-3 choriocarcinoma cells. Finally, the data from TROPHIMMUN trial were re-analyzed to determine the impact of the FcγR3A polymorphism of patients on their response to avelumab., Results: We confirmed that FcγR3A+ natural killer cells infiltrated PD-L1-expressing gestational trophoblastic neoplasia. In vitro, avelumab-coated JEG-3 choriocarcinoma cells induced natural killer cell activation, which promoted the destruction of JEG-3 cells. Natural killer cell activation was abolished when the Fc portion of avelumab was removed, demonstrating the importance of Fcγ receptor in this process. Using this model of antibody-dependent cell-mediated cytotoxicity, we demonstrated that high-affinity FcγR3A polymorphism on natural killer cells was associated with better in vitro response to avelumab. In line with this result, patients from the TROPHIMMUN trial homozygous for the high-affinity FcγR3A polymorphism had better clinical response to avelumab., Conclusion: Our work demonstrates that antibody-dependent cell-mediated cytotoxicity contributes to the therapeutic effect of avelumab in gestational trophoblastic neoplasia and that the individual patient response is impacted by the FcγR3A polymorphism. The FcγR3A polymorphism could be used as a biomarker to identify patients diagnosed with monochemoresistant gestational trophoblastic neoplasia who are most likely to respond to avelumab., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Rituximab (RTX), an anti CD20 monoclonal antibody, is now a gold standard treatment for several auto-immune and chronic inflammatory diseases. Receiving RTX exposes patients to more severe infections as vaccinations become virtually inefficient in terms of B cell responses. During the COVID-19 crisis, RTX-exposed patients exhibited more severe forms of the disease, and in some cases, the introduction of RTX was delayed or avoided to protect patients as much as possible against SARS-CoV-2 infections. We retrospectively collected cellular and humoral responses from thirteen patients with dermatological and rheumatological autoimmune diseases who had been vaccinated after receiving RTX. Memory T cells subsets from patients that exposed to RTX showed few differences when compared to a cohort of healthy donors. The IFN ᵧ ELISpot assay using SARS-CoV-Prot_S1 showed that eight patients exhibited a positive response that was neither correlated to the time between RTX infusion and the sampling nor to the time between RTX and the vaccination. Conversely, analysis of the SARS-CoV-2 serology showed a clearly lower binding antibody units per mL in case of recent RTX infusion. The safe threshold forconsistently positive serology was to vaccinate at least 300 days after RTX infusion (p = 0.02). Our data illustrate the difficulty in obtaining a satisfactory response to vaccination after RTX treatment within almost a year after the latest infusion, and emphasize the need to better evaluate the risk of relapses in auto-immune diseases before administering RTX in order to maintain RTX only in patients whose medical situation requires it., Competing Interests: The authors have no conflict of interest to declare, please see statement in the manuscript., (© 2024 The Authors. Published by Elsevier Ltd.)

Few data exist on the role of genetic factors involving the HLA system on response to Covid-19 vaccines. Moving from suggestions of a previous study investigating the association of some HLA alleles with humoral response to BNT162b2, we here compared the HLA allele frequencies among weak (n = 111) and strong (n = 123) responders, defined as those healthcare workers with the lowest and the highest anti-Spike antibody levels after vaccination. Individuals with clinical history of Covid-19 or positive anti-nucleocapside antibodies were excluded. We found the common HLA-A*03:01 allele as an independent predictor of strong humoral response (OR = 12.46, 95% CI: 4.41-35.21, p < 0.0001), together with younger age of vaccines (p = 0.004). Correlation between antibody levels and protection from breakthrough infection has been observed, with a 2-year cumulative incidence of 42% and 63% among strong and weak responders, respectively (p = 0.03). Due to the high frequency of HLA-A*03:01 and the need for seasonal vaccinations against SARS-CoV-2 mutants, our findings provide useful information about the inter-individual differences observed in humoral response after Covid-19 vaccine and might support further studies on the next seasonal vaccines., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: De novo donor-specific antibody (dnDSA) is a strong biomarker associated with the development of antibody-mediated rejection (AMR) and graft loss after kidney transplantation. This procedure is expensive; however, systematic annual screening was recommended by some national organ transplant agencies or societies even though its clinical utility was not clearly established., Methods: To address this question, we retrospectively assessed the incidence of dnDSA according to the test justification (clinically indicated or systematic) in a cohort of low-immunological risk patients, defined by being nonhuman leukocyte antigen (non-HLA)-sensitized and having no previous kidney transplants., Results: A total of 1072 patients, for whom 4611 anti-HLA tests were performed, were included in the study. During the follow-up period of 8 (interquartile range, IQR: 5-11) years, 77 recipients developed dnDSA (prevalence of 7.2%). Thirty-five of these dnDSAs (45.5%) were detected during the first year posttransplantation. In 95% of patients with dnDSA, an immunizing event was identified in their medical records. dnDSA was detected in 46 of 4267 systematic screening tests (1.08%) performed. Active and chronic AMR were frequently observed in biopsies performed after systematic DSA testing (17.9% and 15.4%, respectively)., Conclusion: Our results suggest that the detection by systematic screening of dnDSA in low-immunological risk kidney transplant patients without sensitizing events is a rare event, especially after 1 year. Moreover, in real life, systematic annual screening for dnDSA, seems having a limited impact to detect AMR at an earlier stage compared to patients in whom dnDSA was detected after a clinically indicated test., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Background: Aspirin and platelet P2Y 12 inhibitors, such as ticagrelor, suboptimally inhibit microvascular thrombosis during ST-elevation myocardial infarction. Glycoprotein (GP) IIb/IIIa inhibitors may further inhibit this but cause excessive bleeding., Objectives: We investigated whether combination of glenzocimab, a GPVI inhibitor, with aspirin and ticagrelor provides additional antithrombotic effects, as GPVI has a critical role in atherothrombosis but minimal involvement in hemostasis., Methods: We investigated the effects of glenzocimab (monoclonal antibody Fab fragment) using blood from healthy donors and patients with acute coronary syndrome treated with aspirin and ticagrelor. Platelets were stimulated with multiple agonists, including atherosclerotic plaque, from patients undergoing carotid endarterectomy., Results: Aspirin and ticagrelor partially inhibited atherosclerotic plaque-induced platelet aggregation by 48% compared with control (34 ± 3 vs 65 ± 4 U; P < .001). Plaque-induced platelet aggregation, adhesion, secretion, and activation were critically dependent on GPVI activation. Glenzocimab alone reduced plaque-induced aggregation by 75% compared with control (16 ± 4 vs 65 ± 4 U; P < .001) and by >95% when combined with aspirin and ticagrelor (3 ± 1 vs 65 ± 4 U; P < .001). Glenzocimab reduced platelet aggregation, adhesion, and thrombin generation when added to blood of aspirin- and ticagrelor-treated patients with acute coronary syndrome. Glenzocimab shared several antithrombotic effects with the GPIIb/IIIa inhibitor eptifibatide with less effect on general hemostasis assessed by rotational thromboelastometry. In a murine intravital model of ST-elevation myocardial infarction, genetic depletion of GPVI reduced microvascular thrombosis., Conclusion: Addition of glenzocimab to aspirin and ticagrelor enhances platelet inhibition via multiple mechanisms of atherothrombosis. Compared with a GPIIb/IIIa inhibitor, glenzocimab shares multiple antithrombotic effects, with less inhibition of mechanisms involved in general hemostasis., Competing Interests: Declaration of competing interests P.L.R.N. reports institutional research grants from Novartis, Rigel Pharmaceuticals, Principia Biopharma, Acticor Biotech, and honoraria from Bayer, Grifols, and Takeda. P.K. receives research support for basic, translational, and clinical research projects from the European Union, British Heart Foundation, Leducq Foundation, Medical Research Council (UK), German Centre for Cardiovascular Research, and several drug and device companies active in atrial fibrillation, and has received honoraria from several such companies in the past, but not in the last 3 years. P.K. is listed as an inventor on 2 patents held by the University of Birmingham (Atrial Fibrillation Therapy WO 2015140571 and Markers for Atrial Fibrillation WO 2016012783). M.J.-P. is the founder of Acticor Biotech and scientific adviser of the company. S.P.W. reports institutional research grants from Acticor Biotech, Novartis, Rigel Pharmaceuticals, and Principia Biopharma. M.R.T. declares institutional research grants from Acticor Biotech, Novartis, Rigel Pharmaceuticals, and Principia Biopharma. M.R.T. declares consultancy fees from Cytosorbents. F.O.A., M.H.H., D.P.K., J.P., P.B., O.H., P.H., A.S., N.K., A.T., and P.H.M. have no competing interests to disclose., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the efficacy of covid-19 convalescent plasma to treat patients admitted to hospital for moderate covid-19 disease with or without underlying immunodeficiency (CORIPLASM trial)., Design: Open label, randomised clinical trial., Setting: CORIMUNO-19 cohort (publicly supported platform of open label, randomised controlled trials of immune modulatory drugs in patients admitted to hospital with moderate or severe covid-19 disease) based on 19 university and general hospitals across France, from 16 April 2020 to 21 April 2021., Participants: 120 adults (n=60 in the covid-19 convalescent plasma group, n=60 in the usual care group) admitted to hospital with a positive SARS-CoV2 test result, duration of symptoms <9 days, and World Health Organization score of 4 or 5. 49 patients (n=22, n=27) had underlying immunosuppression., Interventions: Open label randomisation to usual care or four units (200-220 mL/unit, 2 units/day over two consecutive days) of covid-19 convalescent plasma with a seroneutralisation titre >40., Main Outcome Measures: Primary outcomes were proportion of patients with a WHO Clinical Progression Scale score of ≥6 on the 10 point scale on day 4 (higher values indicate a worse outcome), and survival without assisted ventilation or additional immunomodulatory treatment by day 14. Secondary outcomes were changes in WHO Clinical Progression Scale scores, overall survival, time to discharge, and time to end of dependence on oxygen supply. Predefined subgroups analyses included immunosuppression status, duration of symptoms before randomisation, and use of steroids., Results: 120 patients were recruited and assigned to covid-19 convalescent plasma (n=60) or usual care (n=60), including 22 (covid-19 convalescent plasma) and 27 (usual care) patients who were immunocompromised. 13 (22%) patients who received convalescent plasma had a WHO Clinical Progression Scale score of ≥6 at day 4 versus eight (13%) patients who received usual care (adjusted odds ratio 1.88, 95% credible interval 0.71 to 5.24). By day 14, 19 (31.6%) patients in the convalescent plasma group and 20 (33.3%) patients in the usual care group needed ventilation, additional immunomodulatory treatment, or had died. For cumulative incidence of death, three (5%) patients in the convalescent plasma group and eight (13%) in the usual care group died by day 14 (adjusted hazard ratio 0.40, 95% confidence interval 0.10 to 1.53), and seven (12%) patients in the convalescent plasma group and 12 (20%) in the usual care group by day 28 (adjusted hazard ratio 0.51, 0.20 to 1.32). In a subgroup analysis performed in patients who were immunocompromised, transfusion of covid-19 convalescent plasma was associated with mortality (hazard ratio 0.39, 95% confidence interval 0.14 to 1.10)., Conclusions: In this study, covid-19 convalescent plasma did not improve early outcomes in patients with moderate covid-19 disease. The efficacy of convalescent plasma in patients who are immunocompromised should be investigated further., Trial Registration: ClinicalTrials.gov NCT04345991., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from Programme Hospitalier de recherche Clinique (DGOS-French Ministry of Health), Fondation pour la Recherche Médicale, Sorbonne Université AAP 2020, and Emergency Support Instrument (ESI), Direction Générale de la Santé, European Commission for the submitted work; PT, PM, and AF are employees of Etablissement Français du Sang (EFS), the French public transfusion service, which collects, manufactures, tests and issues all blood components in France; KL is contributing to the development of monoclonal and polyclonal anti-SARS-CoV Antibodies (Spikimm, Xenothera, Fabentech); no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: COVID-19 convalescent plasma (CCP) is a possible treatment option for COVID-19. A comprehensive number of clinical trials on CCP efficacy have already been conducted. However, many aspects of CCP treatment still require investigations: in particular (1) Optimisation of the CCP product, (2) Identification of the patient population in need and most likely to benefit from this treatment approach, (3) Timing of administration and (4) CCP efficacy across viral variants in vivo. We aimed to test whether high-titre CCP, administered early, is efficacious in preventing hospitalisation or death in high-risk patients., Methods and Analysis: COVIC-19 is a multicentre, randomised, open-label, adaptive superiority phase III trial comparing CCP with very high neutralising antibody titre administered within 7 days of symptom onset plus standard of care versus standard of care alone. We will enrol patients in two cohorts of vulnerable patients [(1) elderly 70+ years, or younger with comorbidities; (2) immunocompromised patients]. Up to 1020 participants will be enrolled in each cohort (at least 340 with a sample size re-estimation after reaching 102 patients). The primary endpoint is the proportion of participants with (1) Hospitalisation due to progressive COVID-19, or (2) Who died by day 28 after randomisation. Principal analysis will follow the intention-to-treat principle., Ethics and Dissemination: Ethical approval has been granted by the University of Ulm ethics committee (#41/22) (lead ethics committee for Germany), Comité de protection des personnes Sud-Est I (CPP Sud-Est I) (#2022-A01307-36) (ethics committee for France), and ErasmusMC ethics committee (#MEC-2022-0365) (ethics committee for the Netherlands). Signed informed consent will be obtained from all included patients. The findings will be published in peer-reviewed journals and presented at relevant stakeholder conferences and meetings., Trial Registration: Clinical Trials.gov (NCT05271929), EudraCT (2021-006621-22)., Competing Interests: Competing interests: PT is an employee of Établissement Français du Sang, the blood establishment responsible for blood collection, qualification and supply in France. HS, SH, SK, TA and ES are employees of the German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen (or its affiliates), the establishment responsible for blood collection, qualification and supply in Baden-Württemberg and Hesse, Germany. CEV, is an employee of Sanquin, the establishment responsible for blood collection, qualification and supply in the Netherlands. The authors declare no other competing interests., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The basal cell adhesion molecule (BCAM) carries the antigens of the Lutheran (LU, ISBT005) system. We report a novel Lutheran antigen and propose an updated, full-length 3D model of BCAM., Study Design and Methods: Red blood cell testing, antibody identification, and BCAM genomic DNA sequencing were done by standard methods. Multi-template homology modeling of BCAM used structural templates selected for coverage, highest sequence identity, and protein domain family. All variants causing the loss or gain of a Lutheran antigen were analyzed for residue accessibility and intraprotein interactions., Results: An antibody to a high-prevalence antigen in the plasma of a pregnant woman was determined to be directed at a novel Lutheran antigen. Sequencing of BCAM found three homozygous changes: c.212G > A (p.Arg71His) and two silent, c.711C > T and c.714C > T. The model was built from the first two immunoglobulin crystallized domains of BCAM (D1, D2), three other templates (for D3, D4 and D5 with a higher sequence identity with the target than those used for the model proposed by Burton and Brady in 2008, and for the transmembrane region) and RaptorX (for the intracellular domain). All residues associated with a Lutheran antigen were found to be exposed in wild-type or variant proteins, except p.447 associated with loss of Lu13 expression., Conclusion: The c.212G > A change results in the loss of LUGA (LU24) antigen. Whole genome sequencing continues to reveal polymorphisms with uncertain immunogenicity. This model and demonstration that nearly all residues associated with the expression of a Lutheran antigen are exposed will help evaluate the significance of new polymorphisms., (© 2023 AABB.)

Competing Interests: The authors declare no funding or conflicts of interest.

The choice between Basiliximab (BSX) or Anti-Thymocyte Globulin (ATG) as induction therapy in non-immunized kidney transplant recipients remains uncertain. Whilst ATG may allow steroid withdrawal and a decrease in tacrolimus, it also increases infectious complications. We investigated outcomes in non-immunized patients receiving a very low dosage of ATG versus BSX as induction. Study outcomes were patient/graft survival, cumulative probabilities of biopsy proven acute rejection (BPAR), infectious episode including CMV and post-transplant diabetes (PTD). Cox, logistic or linear statistical models were used depending on the studied outcome and models were weighted on propensity scores. 100 patients received ATG (mean total dose of 2.0 mg/kg) and 83 received BSX. Maintenance therapy was comparable. Patient and graft survival did not differ between groups, nor did infectious complications. There was a trend for a higher occurrence of a first BPAR in the BSX group (HR at 1.92; 95%CI: [0.77; 4.78]; p = 0.15) with a significantly higher BPAR episodes (17% vs 7.3%, p = 0.01). PTD occurrence was significantly higher in the BSX group (HR at 2.44; 95%CI: [1.09; 5.46]; p = 0.03). Induction with a very low dose of ATG in non-immunized recipients was safe and associated with a lower rate of BPAR and PTD without increasing infectious complications., 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 © 2023 Masset, Kerleau, Blancho, Hourmant, Walencik, Ville, Kervella, Cantarovich, Houzet, Giral, Garandeau, Dantal and the Nantes DIVAT Consortium.)

With the rising popularity of endovascular aortic repair (EVAR) for aortic aneurysms and dissections, there is a crucial need for investigating the delayed appearance of post-EVAR complications such as stent-graft kinking, fracture and migration respectively. These complications have been noted to be influenced by the radial stiffness and bending flexibility attributes of stent-grafts. Auxetic designs with negative Poisson's ratio offer interesting advantages such as enhanced fracture toughness, superior indentation resistance and adaptive stiffness in response to intricate morphology for stenting applications over conventional stent designs. The objective of this study is to propose different auxetic stent candidates and to compare their mechanical performance with two conventional stent candidates for endovascular applications using numerical simulation through crimp/crushing tests for their radial stiffness and three-point bending/kinking tests for their flexibility, respectively. The results demonstrate that the novel hybrid auxetic designs (CRE and CSTAR) possess the best trade-off between radial stiffness and bending flexibility characteristics among all candidates for stent-graft applications., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Stephane Avril is a cofounder of Predisurge SAS, France., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Scianna (Sc) antigens, seven high and two of low prevalence, are expressed on erythrocyte membrane-associated protein (ERMAP). We investigated SC (ERMAP) in individuals who made antibodies to high prevalence Scianna antigens, and propose a 3D model for ERMAP to precisely localize the residues associated with the known antigens., Methods: Serological testing and DNA sequencing was performed by standard methods. A 3D structural model was built using a multi-template homology approach. Protein structures representing missense variants associated with the loss or gain of an antigen were generated. Residue accessibility and intraprotein interactions were compared with the wild-type protein., Results: Two new SC alleles, one with c.349C > T (p.Arg117Cys) in a woman from South India with anti-Sc3 in her plasma, and a c.217&#95;219delinsTGT (p.Arg73Cys) in an African-American woman with an antibody to a new high prevalence antigen, termed SCAC, were identified. Six structural templates were used to model ERMAP. 3D analysis showed that residues key for Scianna antigen expression were all exposed at the surface of the extracellular domain. The p.Arg117Cys change was predicted to abolish interactions between residues 93 and 117, with no compensating interactions., Conclusion: We confirm the extracellular location of Scianna residues responsible for antigen expression which predicts direct accessibility to antibodies. Loss of intraprotein interactions appear to be responsible for a Sc null and production of anti-Sc3 with p.117Cys, SC*01 N.03, and for loss of a high prevalence antigen with p.73Cys, termed SCAC for Sc Arg to Cys. Comparative modeling aids our understanding of new alleles and Scianna antigen expression., (© 2022 AABB.)

Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-α2 alone (five patients) or with IFN-ω (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-α2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-ω. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients <70 yr of age (5.7 vs. 1.1%, P = 2.2 × 10-5), but not >70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-α2 and IFN-ω (OR = 11.7, P = 1.3 × 10-5), especially those <70 yr old (OR = 139.9, P = 3.1 × 10-10). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for ∼5% of cases of life-threatening influenza pneumonia in patients <70 yr old., (© 2022 Zhang et al.)

Background: Cromer antigens are carried on decay accelerating factor (DAF, CD55), for which the crystal structure is available. We investigated two samples with an unidentified antibody to a high prevalence antigen and evaluate the location and characteristics of amino acids associated with antigens on the CD55 by 3D modelling., Materials and Methods: Antigen typing and antibody identification were by standard methods. CD55 was sequenced, and Cromer variants were generated using the protein's crystal structure (1OK3, chain A). Antigen-associated residues and intraprotein interactions were investigated in 3D (Naccess, Protein Interactions Calculator)., Results: The antibody in the sample from a woman of Kashmiri descent was identified as anti-IFC (anti-CROM7). Her RBCs were negative for high-prevalence Cromer antigens including IFC. CD55 sequencing revealed a silent c.147G>A (p.Leu49=) and c.148G>T (p.Glu50Ter) changes, designated CROM*01N.05. The antibody in the sample from a woman of Greek ancestry was only compatible with IFC- RBCs but her RBCs were positive for known high-prevalence Cromer antigens. CD55 sequencing found she was homozygous for c.173A>G (p.Asp58Gly). The high prevalence antigen was named CRAG (ISBT CROM18 or 021018) and the allele designated CROM*01.-18. By 3D analysis, all known antigen-associated residues, including the new CRAG antigen, were exposed at the protein surface. Interactions between antigen-associated residues within the same CD55 domains were identified., Discussion: Identification of antibodies to high prevalence Cromer antigens can be challenging. The surface exposure of antigen-associated residues likely accounts for their immunogenicity. 3D analysis of CD55 provides insight into previous serologic observations regarding the influence of some Cromer antigens on the expression of others.

The most common method to study the mechanical behavior of soft tissue is to test animal specimens, which should be prepared as soon as possible after the death to avoid biological deterioration effects such as rigor mortis. Freezing and cryo-preservation could allow extending the time between procurement and implantation. From a mechanical perspective, tissue preservation could influence mechanical testing results. Therefore, this study focuses on the influence of cryo-preserved samples on their mechanical behavior, especially at the rupture. In order to analyze this aspect, two tests were performed on the porcine abdominal wall. A tensile test to study the elastic behavior of samples and the tensile strength until rupture. A peeling test to more finely investigate the cohesion between muscle fibers. No statistical difference could be observed following tensile test. However, peeling tests between cryo-preserved and control samples showed a clear statistical difference with a p-value of 0.0097 for G p . Indeed, energy release rate was higher for the Cryo-preserve group than the Control group with G p  = 0.36 ± 0.07 N/mm vs 0.26 ± 0.10 N/mm. This difference suggests that the characterization of rupture energies for muscular tissue should be done without having frozen the samples, even with a cryopreservative agent. These results could also indicate that even if the rupture mode is the same between mechanical tests, a different rupture direction could imply different mechanical preservations for soft tissues. This study could help to understand the difficult mechanical preservation of soft tissues, especially on the rupture behavior. Future studies on skeletal muscles will be necessary to compare our results, especially in peeling., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Skin irritation is a common phenomenon that becomes a real concern when caused by the use of medical devices. Because the materials used for the design of these devices are usually carefully selected for chemical compatibility with the skin, it is reasonable to assume that the irritations result from the mechanical interaction between the devices and the skin. The aim of this work was to develop a new device to study both the shear strains in the layers of the skin, using Digital Image Correlation (DIC), and the friction behaviour of ex vivo skin interacting with objects. Pig skin samples with various surface preparations were tested in friction experiments involving different contacting materials encountered in the conception of medical devices. The measure of the static and dynamic coefficients of friction as well as the length of adhesion has highlighted the great influence of skin surface conditioning on friction properties. Strain maps obtained through DIC provided insights into the impact of friction and adhesion effects on shear strain distribution in the skin as a function of depth beneath its surface., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Natural killer (NK) cells are involved in innate defense against viral infection and cancer. NK cells can be divided into subsets based on the ability of different receptors to bind to major histocompatibility (MHC) class 1 molecules, resulting in differential responses upon activation in a process called "licensing" or "arming." NK cells expressing receptors that bind self-MHC are considered licensed due to an augmented effector lytic function capability compared with unlicensed subsets. However, we demonstrated that unlicensed NK subsets instead positively regulate the adaptive T-cell response during viral infections that are related to localization and cytokine production. In this study, the differential effects of the two types of NK subsets were contingent on the environment in viral infection and hematopoietic stem cell transplantation (HSCT) models. Infection of mice with high-dose (HD) murine cytomegalovirus (MCMC) led to a loss of licensing-associated differences, as compared with mice with low-dose (LD) infection: the unlicensed NK subset no longer localized in lymph nodes (LNs), but instead remained at the site of infection. Similarly, the patterns observed during HD infection paralleled the phenotypes of both human and mouse NK cells in an HSCT setting where NK cells exhibit an activated phenotype. However, in contrast to the effects of subset depletion in T-cell replete models, the licensed NK cell subsets still dominated antiviral responses after HSCT. Overall, our results highlight the intricate tuning of NK cells and how it affects overall immune responses with regard to licensing patterns and their dependency on the level of stimulation and activation status., (© 2021 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.)

The public French Cord Blood Banks Network was established in 1999 with the objective of standardizing the practices governing umbilical cord blood (UCB) banking in France. The Network adopted a strategy to optimize its inventory and improve the quality of its banked units based on a quality improvement process using outcome data regularly provided by Eurocord. This study aimed to describe the results, over 10 years, of UCBT facilitated by a national network that used the same criteria of UCB collection and banking and to assess how modifications of banking criteria and unit selection might influence transplant outcomes. Nine hundred and ninety-nine units (593 single-unit and 203 double-unit grafts) were released by the Network to transplant 796 patients with malignant (83%) and non-malignant (17%) diseases. Median cell dose exceeded 3.5 × 10 7 TNC/kg in 86%. There was a trend to select units more recently collected and with higher cell dose. Neutrophil engraftment was 88.2% (85.7-90.7) and 79.3% (72.6-86.5) respectively for malignant and non-malignant diseases with a trend to faster recovery with higher cell doses. The respective 3-year transplant-related mortality were 31.1% (27.5-35.1) and 34.3% (27.0-43.5). OS was 49% ± 4 in malignant and 62% ± 4 in non-malignant disorders. In multivariate analysis, cell dose was the only unit-related factor associated with outcomes. Our results reflect the benefit on clinical outcomes of the strategy adopted by the Network to bank units with higher cell counts., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Many RhD variants associated with anti-D formation (partial D) in carriers exposed to the conventional D antigen carry mutations affecting extracellular loop residues. Surprisingly, some carry mutations affecting transmembrane or intracellular domains, positions not thought likely to have a major impact on D epitopes., Study Design and Methods: A wild-type Rh trimer (RhD 1 RhAG 2 ) was modeled by comparative modeling with the human RhCG structure. Taking trimer conformation, residue accessibility, and position relative to the lipid bilayer into account, we redefine the domains of the RhD protein. We generated models for RhD variants carrying one or two amino acid substitutions associated with anti-D formation in published articles (25 variants) or abstracts (12 variants) and for RHD*weak D type 38. We determined the extracellular substitutions and compared the interactions of the variants with those of the standard RhD., Results: The findings of the three-dimensional (3D) analysis were correlated with anti-D formation for 76% of RhD variants: 15 substitutions associated with anti-D formation concerned extracellular residues, and structural differences in intraprotein interactions relative to standard RhD were observed in the others. We discuss the mechanisms by which D epitopes may be modified in variants in which the extracellular residues are identical to those of standard RhD and provide arguments for the benignity of p.T379M (RHD*DAU0) and p.G278D (RHD*weak D type 38) in transfusion medicine., Conclusion: The study of RhD intraprotein interactions and the precise redefinition of residue accessibility provide insight into the mechanisms through which RhD point mutations may lead to anti-D formation in carriers., (© 2021 AABB.)

Introduction: This study estimated the costs and incremental cost per case detected of screening strategies for high-grade cervical intraepithelial neoplasia (CIN2+) in women living with HIV (WLHIV) attending HIV clinics in Burkina Faso., Methods: The direct healthcare provider costs of screening tests (visual inspection with acetic acid (VIA), VIA combined visual inspection with Lugol's iodine (VIA/VILI), cytology and a rapid HPV DNA test (careHPV)) and confirmatory tests (colposcopy, directed biopsy and systematic four-quadrant (4Q) biopsy) were collected alongside the HPV in Africa Research Partnership (HARP) study. A model was developed for a hypothetical cohort of 1000 WLHIV using data on CIN2+ prevalence and the sensitivity of the screening tests. Costs are reported in USD (2019)., Results: The study enrolled 554 WLHIV with median age 36 years (inter-quartile range, 31-41) and CIN2+ prevalence of 5.8%. The average cost per screening test ranged from US$3.2 for VIA to US$24.8 for cytology. Compared to VIA alone, the incremental cost per CIN2+ case detected was US$48 for VIA/VILI and US$814 for careHPV. Despite higher costs, careHPV was more sensitive for CIN2+ cases detected compared to VIA/VILI (97% and 56%, respectively). The cost of colposcopy was US$6.6 per person while directed biopsy was US$33.0 and 4Q biopsy was US$48.0., Conclusion: Depending on the willingness to pay for the detection of a case of cervical cancer, decision makers in Burkina Faso can consider a variety of cervical cancer screening strategies for WLHIV. While careHPV is more costly, it has the potential to be cost-effective depending on the willingness to pay threshold. Future research should explore the lifetime costs and benefits of cervical cancer screening to enable comparisons with interventions for other diseases., Competing Interests: The authors have declared that no competing interests exist. The careHPV and Digene HC-II kits used in this project were obtained through the QIAGEN Corporation donation program to the London School of Hygiene & Tropical Medicine. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Perinatal treatment with lopinavir boosted by ritonavir (LPV/r) is associated with steroidogenic abnormalities. Long-term effects in infants have not been studied., Methods: Adrenal-hormone profiles were compared at weeks 6 and 26 between human immunodeficiency virus (HIV)-1-exposed but uninfected infants randomly assigned at 7 days of life to prophylaxis with LPV/r or lamivudine (3TC) to prevent transmission during breastfeeding. LPV/r in vitro effect on steroidogenesis was assessed in H295R cells., Results: At week 6, 159 frozen plasma samples from Burkina Faso and South Africa were assessed (LPV/r group: n = 92; 3TC group: n = 67) and at week 26, 95 samples from Burkina Faso (LPV/r group: n = 47; 3TC group: n = 48). At week 6, LPV/r-treated infants had a higher median dehydroepiandrosterone (DHEA) level than infants from the 3TC arm: 3.91 versus 1.48 ng/mL (P < .001). Higher DHEA levels (>5 ng/mL) at week 6 were associated with higher 17-OH-pregnenolone (7.78 vs 3.71 ng/mL, P = .0004) and lower testosterone (0.05 vs 1.34 ng/mL, P = .009) levels in LPV/r-exposed children. There was a significant correlation between the DHEA and LPV/r AUC levels (ρ = 0.40, P = .019) and Ctrough (ρ = 0.40, P = .017). At week 26, DHEA levels remained higher in the LPV/r arm: 0.45 versus 0.13 ng/mL (P = .002). Lopinavir, but not ritonavir, inhibited CYP17A1 and CYP21A2 activity in H295R cells., Conclusions: Lopinavir was associated with dose-dependent adrenal dysfunction in infants. The impact of long-term exposure and potential clinical consequences require evaluation., Clinical Trials Registration: NCT00640263., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

The most common, severe cases of fetal and neonatal alloimmune thrombocytopenia among whites are caused by antibodies against human platelet antigen 1a (HPA-1a). The aims of this systematic review and meta-analysis are to determine the association between maternal HLA-DRB3*01:01 and: (1) HPA-1a-alloimmunization and (2) neonatal outcome in children born of HPA-1a-immunized women. A systematic literature search identified 4 prospective and 8 retrospective studies. Data were combined across studies to estimate pooled odds ratios (ORs) and the associated 95% confidence intervals (CIs). The population represented by the prospective studies was more than 150 000. In the prospective studies, there were 64 severely thrombocytopenic newborns (platelet count <50 × 109/L) of whom 3 had intracranial hemorrhage. The mothers of all 64 children were HLA-DRB3*01:01+. The number of severely thrombocytopenic children born of HPA-1a-alloimmunized women in the retrospective studies was 214; 205 of whom were born of HLA-DRB3*01:01+ women. For HLA-DRB3*01:01- women, the OR (95% CI) for alloimmunization was 0.05 (0.00-0.60), and for severe neonatal thrombocytopenia 0.08 (0.02-0.37). This meta-analysis demonstrates that the risk of alloimmunization and of having a child with severe thrombocytopenia are both very low for HPA-1a- women who are HLA-DRB3*01:01-., (© 2020 by The American Society of Hematology.)