Publications by authors named "Crepin T"

Unlabelled: Intestinal microsporidiosis caused by is an opportunistic infection that especially affects solid organ transplant (SOT) recipients. Management revolves around tapering the immunosuppressive regimen and/or using a specific anti-microsporidia treatment, but only fumagillin has demonstrated efficacy for treatment of this infection. Since fumagillin has been commercially discontinued, nitazoxanide is increasingly being used in this indication.

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Influenza A viruses are responsible for human seasonal epidemics and severe animal pandemics with a risk of zoonotic transmission to humans. The viral segmented RNA genome is encapsidated by nucleoproteins (NP) and attached to the heterotrimeric polymerase, forming the viral ribonucleoproteins (vRNPs). Flexible helical vRNPs are central for viral transcription and replication.

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Background: The PEXIVAS (Plasma exchange and glucocorticoids in severe antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis) trial showed that a reduced-dose glucocorticoid regimen (redGC) was non-inferior to a standard-dose regimen (standGC) with respect to death or end-stage kidney disease (ESKD) in patients with ANCA-associated vasculitis (AAV). However, the primary endpoint did not include disease progression or relapse, cyclophosphamide was the main induction therapy and rituximab (RTX)-treated patients tended to have a higher risk of death or ESKD with redGC. We aimed to evaluate the real-world use of redGC.

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Article Synopsis
  • Campylobacteriosis is the leading bacterial cause of diarrhea in kidney transplant recipients (KTRs), but risk factors for this infection remain unclear.
  • A 10-year study in France identified 326 KTRs with campylobacteriosis, revealing an incidence rate of 2.3 cases per 1,000 patient-years, primarily occurring around 2.4 years after transplantation.
  • The main risk factors for developing campylobacteriosis include the use of corticosteroids, acute rejection episodes, low lymphocyte counts, and low estimated glomerular filtration rate (eGFR); treatment should prioritize azithromycin due to high resistance to fluoroquinolones.
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  • Apheresis is a medical procedure used to quickly remove harmful antibodies in diseases like anti-GBM and severe ANCA-associated vasculitis, and the CINEVAS study compared two methods: immunoadsorption (IA) and plasma exchange (PEx).
  • The study analyzed results from 38 patients and found that both IA and PEx effectively reduced autoantibody levels similarly, with 98% reduction for IA and 96% for PEx after seven sessions.
  • While IA showed a greater reduction in total IgG and better preservation of IgA and IgM, the volume of plasma used and session lengths differed between the techniques, but overall, their effectiveness in removing antibodies was comparable.
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Influenza viruses transcribe and replicate their genome in the nucleus of the infected cells, two functions that are supported by the viral RNA-dependent RNA-polymerase (FluPol). FluPol displays structural flexibility related to distinct functional states, from an inactive form to conformations competent for replication and transcription. FluPol machinery is constituted by a structurally-invariant core comprising the PB1 subunit stabilized with PA and PB2 domains, whereas the PA endonuclease and PB2 C-domains can pack in different configurations around the core.

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  • Immune checkpoint inhibitors (ICIs) can significantly improve cancer treatment outcomes but are linked to serious side effects, including kidney issues like acute tubulointerstitial nephritis and glomerulonephritis.
  • A reported case of severe IgA nephropathy (IgAN) developed within 5 months of starting ICIs, highlighting the need for awareness and monitoring of kidney health in patients receiving these treatments.
  • While IgAN is less common than acute tubulointerstitial nephritis, it may often go undetected; thus, doctors should routinely check for symptoms like hematuria before administering ICIs.
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  • - Influenza A viruses have a segmented genome of eight RNA segments and use a nucleoprotein (NP) and polymerase for replication, but the effect of NP on the structure of viral RNA (vRNA) is not fully understood.
  • - This study used SHAPE chemical probing to analyze the structure of two specific vRNAs (NS and M) in different conditions: without NP, with NP, and after NP removal, revealing that NP induces limited structural changes but has a significant remodeling effect on both local and long-range interactions in the NS vRNA.
  • - Results indicate that NP not only binds to single-stranded RNA but also interacts with complex structures like bulges and loops, showing a preference for regions low in G and rich
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Introduction: Rituximab is a first-line treatment for membranous nephropathy. Nephrotic syndrome limits rituximab exposure due to urinary drug loss. Rituximab underdosing (serum level <2 μg/ml at month-3) is a risk factor for treatment failure.

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Influenza virus genome encapsidation is essential for the formation of a helical viral ribonucleoprotein (vRNP) complex composed of nucleoproteins (NP), the trimeric polymerase, and the viral genome. Although low-resolution vRNP structures are available, it remains unclear how the viral RNA is encapsidated and how NPs assemble into the helical filament specific of influenza vRNPs. In this study, we established a biological tool, the RNP-like particles assembled from recombinant influenza A virus NP and synthetic RNA, and we present the first subnanometric cryo-electron microscopy structure of the helical NP-RNA complex (8.

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Introduction: Kidney transplant recipients (KTRs) have an increased risk of cardiovascular (CV) events (CVEs) compared with the general population. The impact of insulin resistance on CV risk after transplantation is not well defined.

Methods: We tested whether triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, may predict posttransplant CVEs in a cohort of 715 consecutive KTRs all included 1 year after transplant.

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For 30 years, photopheresis is used to treat graft versus host disease and heart or lung allograft rejection. In this review, we discuss the place of photopheresis in kidney transplantation both in prevention or treatment of rejection. Mechanisms of action in kidney transplantation are mainly based on results observed in graft versus host disease and in heart or lung transplantation.

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  • The study aimed to assess how switching from ceftriaxone to cefotaxime affects the rates of third-generation cephalosporin-resistant Enterobacterales (3GC-RE).
  • Conducted over 24 months, the trial compared a control phase (where both antibiotics were used) to an intervention phase (where only cefotaxime was prescribed).
  • Results showed a decrease in 3GC-RE incidence during the intervention phase, suggesting that cefotaxime may be more effective in reducing these resistant infections, although further research is necessary to validate these findings.
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Adaptation of avian influenza RNA polymerase (FluPol) to human cells requires mutations on the 627-NLS domains of the PB2 subunit. The E627K adaptive mutation compensates a 33-amino-acid deletion in the acidic intrinsically disordered domain of the host transcription regulator ANP32A, a deletion that restricts FluPol activity in mammalian cells. The function of ANP32A in the replication transcription complex and in particular its role in host restriction remains poorly understood.

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In recent years, cryo-electron microscopy (cryo-EM) has emerged as an important standalone technique within structural biology [...

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Background: Interstitial inflammation and peritubular capillaritis are observed in many diseases on native and transplant kidney biopsies. A precise and automated evaluation of these histological criteria could help stratify patients' kidney prognoses and facilitate therapeutic management.

Methods: We used a convolutional neural network to evaluate those criteria on kidney biopsies.

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Rationale & Objective: C3 glomerulopathy (C3GN) and atypical hemolytic uremic syndrome (aHUS) are 2 distinct rare kidney diseases caused by dysregulation of the alternative complement pathway. Patients with C3GN and concurrent kidney lesions of thrombotic microangiopathy (TMA) have been rarely reported. We characterized the clinical features and underlying immunological abnormalities in these patients.

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  • The study focuses on using a neural network to enhance the MEST-C classification method for diagnosing immunoglobulin A nephropathy (IgAN), which currently has variability in results between different pathologists.
  • A dataset of biopsies was divided into training, testing, and application groups to train the neural network and evaluate its accuracy compared to human assessments.
  • Results showed that the neural network could correctly classify over 73% of biopsy pixels and had substantial agreement with pathologists for most scores, highlighting its potential for reliable, automated analysis in clinical settings.
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Introduction: Adverse events (AEs) of immune checkpoint inhibitors (ICIs) are frequent and mainly due to an overactivity of the immune system leading to excessive inflammatory responses (immune-related AE) that can affect any organ of the body. Beside the most frequent AEs, there are rare AEs whose diagnosis and treatment can be challenging. We report here a singular case of capillary leak syndrome (CLS) associated with chylothorax occurring in a patient who has been treated with adjuvant nivolumab (anti-PD1) for resected AJCC stage IIB primary melanoma.

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Determining the structural organisation of viral replication complexes and unravelling the impact of infection on cellular homeostasis represent important challenges in virology. This may prove particularly useful when confronted with viruses that pose a significant threat to human health, that appear unique within their family, or for which knowledge is scarce. Among , bornaviruses (family ) stand out due to their compact genomes and their nuclear localisation for replication.

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Cryptococcosis is the third most common cause of invasive fungal infection in solid organ transplant recipients and cryptococcal meningitis (CM) its main clinical presentation. CM outcomes, as well as its clinical features and radiological characteristics, have not yet been considered on a large scale in the context of kidney transplantation (KT). We performed a nationwide retrospective study of adult patients diagnosed with cryptococcosis after KT between 2002 and 2020 across 30 clinical centers in France.

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Influenza virus infection causes considerable morbidity and mortality, but current therapies have limited efficacy. We hypothesized that investigating the metabolic signaling during infection may help to design innovative antiviral approaches. Using bronchoalveolar lavages of infected mice, we here demonstrate that influenza virus induces a major reprogramming of lung metabolism.

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The development of safe and effective vaccines in a record time after the emergence of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a remarkable achievement, partly based on the experience gained from multiple viral outbreaks in the past decades. However, the Coronavirus Disease 2019 (COVID-19) crisis also revealed weaknesses in the global pandemic response and large gaps that remain in our knowledge of the biology of coronaviruses (CoVs) and influenza viruses, the 2 major respiratory viruses with pandemic potential. Here, we review current knowns and unknowns of influenza viruses and CoVs, and we highlight common research challenges they pose in 3 areas: the mechanisms of viral emergence and adaptation to humans, the physiological and molecular determinants of disease severity, and the development of control strategies.

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