Quantifying intestinal lipolysis with MRI and TD-NMR: Proof of concept using dairy cream digested in vitro.

Understanding lipid digestion is crucial for promoting human health. Traditional methods for studying lipolysis face challenges in sample representativeness and pre-treatment, and cannot measure real-time lipolysis in vivo. Thus, non-invasive techniques like magnetic resonance imaging (MRI) need to be developed.

Invasive procedures and surgery following etranacogene dezaparvovec gene therapy in people with hemophilia B.

Background: Little information regarding the management of invasive procedures in people with hemophilia B (HB) after undergoing gene therapy is available. Here, we report the management of invasive procedures in people with severe or moderately severe HB who had previously been treated with etranacogene dezaparvovec in the phase 2b and phase 3 Health Outcomes with Padua Gene; Evaluation in Hemophilia B clinical trials (NCT03489291 and NCT03569891).

Objectives: The objective of this study was to describe the use of exogenous FIX, endogenous FIX activity prior to invasive procedures, and peri- and postoperative bleeds in participants who underwent invasive procedures after receiving etranacogene dezaparvovec gene therapy.

Magnetic resonance imaging, water relation, gene expression and biochemical data for analysis of the effects of water stress on potato plant functioning and tuber development and quality.

The data presented in this paper include the original and processed MRI images acquired with a 1.5 T whole-body MRI scanner, describing the growth kinetics, spatialization and appearance of internal defaults of individual tubers of potato plants (Rosanna cultivar of ) grown in pots in a semi-controlled environment and exposed to two water regimes. The 2 conditions were a well-watered regime, in which soil moisture was maintained at 70 % of field capacity, and a variable water deficit regime, in which soil moisture was reduced to 20 % of field capacity several times during tuber growth, followed each time by a few-day period of rehydration to 70 % of field capacity.

Growth kinetics, spatialization and quality of potato tubers monitored in situ by MRI - long-term effects of water stress.

Understanding the potato tuber development and effects of drought at key stages of sensitivity on yield is crucial, particularly when considering the increasing incidence of drought due to climate change. So far, few studies addressed the time course of tuber growth in soil, mainly due to difficulties in accessing underground plant organs in a non-destructive manner. This study aims to understand the tuber growth and quality and the complex long-term effects of realistic water stress on potato tuber yield.

A 360-degree perspective on adeno-associated virus (AAV)-based gene therapy for haemophilia: Insights from the physician, the nurse and the patient.

Background: Adeno-associated virus (AAV)-based gene therapy for haemophilia has advanced substantially in the last 13 years; recently, three products have received approvals from regulatory authorities. Although the impact on quality of life seems promising, some limitations remain, such as the presence of pre-existing anti-AAV neutralising antibodies and the occurrence of hepatotoxicity. This review follows the CSL Behring-sponsored symposium at the 27th Congress of the European Hematology Association (EHA) 2022 that examined the haemophilia gene therapy process from a 360-degree multidisciplinary perspective.

Quantitative MRI imaging of parenchyma and venation networks in Brassica napus leaves: effects of development and dehydration.

Background: Characterisation of the structure and water status of leaf tissues is essential to the understanding of leaf hydraulic functioning under optimal and stressed conditions. Magnetic Resonance Imaging is unique in its capacity to access this information in a spatially resolved, non-invasive and non-destructive way. The purpose of this study was to develop an original approach based on transverse relaxation mapping by Magnetic Resonance Imaging for the detection of changes in water status and distribution at cell and tissue levels in Brassica napus leaves during blade development and dehydration.

Etranacogene dezaparvovec gene therapy for haemophilia B (HOPE-B): 24-month post-hoc efficacy and safety data from a single-arm, multicentre, phase 3 trial.

Background: Etranacogene dezaparvovec, the first gene therapy approved for haemophilia B treatment, was shown to be superior to treatment with continuous prophylactic factor IX in terms of bleeding protection 18 months after gene therapy in a phase 3 trial. We report post-hoc 24-month efficacy and safety data from this trial to evaluate the longer-term effects of etranacogene dezaparvovec in individuals with haemophilia B.

Methods: The phase 3 HOPE-B trial enrolled males aged 18 years or older with inherited haemophilia B, classified as severe (plasma factor IX activity level <1%) or moderately severe (plasma factor IX activity level ≥1% and ≤2%), with a severe bleeding phenotype and who were on stable continuous factor IX prophylaxis.

In vivo intranasal delivery of coagulation factor IX: a proof-of-concept study.

Background: Hemophilia B (HB) is a bleeding disorder characterized by coagulation factor (F) IX (FIX) deficiency. The current standard-of-care for severe HB is prophylaxis with long-term repetitive intravenous (i.v.

Quantitative magnetic resonance imaging of in vitro gastrointestinal digestion of a bread and cheese meal.

The monitoring of food degradation during gastrointestinal digestion is essential in understanding food structure impacts on the bioaccessibility and bioavailability of nutrients. Magnetic Resonance Imaging (MRI) has the unique ability to access information on changes in multi-scale structural features of foods in a spatially resolved and non-destructive way. Our objective was to exploit various opportunities offered by MRI for monitoring starch, lipid and protein hydrolysis, as well as food particle breakdown during the semi-dynamic in vitro gastrointestinal digestion of complex foods combined in a meal.

Characterization of Potato Tuber Tissues Using Spatialized MRI T2 Relaxometry.

Magnetic Resonance Imaging is a powerful non-destructive tool in the study of plant tissues. For potato tubers, it greatly assists the study of tissue defects and tissue evolution during storage. This paper describes the MRI analysis of potato tubers with internal defects in their flesh tissue at eight sampling dates from 14 to 33 weeks after harvest.

Stable and durable factor IX levels in patients with hemophilia B over 3 years after etranacogene dezaparvovec gene therapy.

Etranacogene dezaparvovec (AMT-061) is a recombinant adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX (FIX) transgene with a liver-specific promoter. Here, we report 3-year outcomes from a phase 2b, open-label, single-dose, single-arm, multicenter trial conducted among adults with severe or moderately severe hemophilia B (FIX ≤2%). All participants (n = 3) received a single intravenous dose (2 × 1013 gene copies per kg) and will be followed up for 5 years.

Characterization of the Water Shortage Effects on Potato Tuber Tissues during Growth Using MRI Relaxometry and Biochemical Parameters.

The potato is one of the most cultivated crops worldwide, providing an important source of food. The quality of potato tubers relates to their size and dry matter composition and to the absence of physiological defects. It depends on the spatial and temporal coordination of growth and metabolic processes in the major tuber tissues: the cortex, flesh and pith.

Recombinant porcine factor VIII corrects thrombin generation in vitro in plasma from patients with congenital hemophilia A and inhibitors.

Background: Neutralizing factor VIII (FVIII) antibodies are a major complication in hemophilia A. Antihemophilic factor VIII (recombinant), porcine sequence (rpFVIII; susoctocog alfa; Baxalta US Inc., a Takeda company) has low cross-reactivity to anti-human FVIII antibodies and can provide functional FVIII activity in the presence of FVIII inhibitors.

Report of surgeries, their outcome and the thrombin generation assay in patients with Factor XI deficiency: A retrospective single-centre study.

Background: In patients with FXI deficiency, the risk of surgery-related bleeding is poorly correlated with plasma FXI activity (FXI:C); the latter can therefore not be used as a reliable predictor of bleeding in surgeries.

Objectives: The aim of this retrospective study was to determine whether thrombin generation assay (TGA) could be used to evaluate the risk of surgery-related bleeding in FXI-deficient patients. TGA parameters were compared to FXI:C values, haemostatic treatments and surgical outcomes.

Immune tolerance induction in the era of emicizumab - still the first choice for patients with haemophilia A and inhibitors?

Introduction: The development of inhibitory antibodies is a severe complication of clotting factor replacement therapy in patients with severe haemophilia A (HA). Current World Federation of Hemophilia (WFH) guidelines for haemophilia care indicate that eradication of inhibitors is best achieved through immune tolerance induction (ITI) therapy.

Aim: The European Collaborative Haemophilia Network conducted a survey to determine whether ITI is still used in the routine management of patients with HA, and whether the availability of emicizumab prophylaxis has influenced treatment decisions.

A global non-invasive methodology for the phenotyping of potato under water deficit conditions using imaging, physiological and molecular tools.

Background: Drought is a major consequence of global heating that has negative impacts on agriculture. Potato is a drought-sensitive crop; tuber growth and dry matter content may both be impacted. Moreover, water deficit can induce physiological disorders such as glassy tubers and internal rust spots.

FcRn as a Transporter for Nasal Delivery of Biologics: A Systematic Review.

FcRn plays a major role in regulating immune homeostasis, but it is also able to transport biologics across cellular barriers. The question of whether FcRn could be an efficient transporter of biologics across the nasal epithelial barrier is of particular interest, as it would allow a less invasive strategy for the administration of biologics in comparison to subcutaneous, intramuscular or intravenous administrations, which are often used in clinical practice. A focused systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Spatial and temporal evolution of quantitative magnetic resonance imaging parameters of peach and apple fruit - relationship with biophysical and metabolic traits.

Fruits are complex organs that are spatially regulated during development. Limited phenotyping capacity at cell and tissue levels is one of the main obstacles to our understanding of the coordinated regulation of the processes involved in fruit growth and quality. In this study, the spatial evolution of biophysical and metabolic traits of peach and apple fruit was investigated during fruit development.

Novel manifestations of immune dysregulation and granule defects in gray platelet syndrome.

Gray platelet syndrome (GPS) is a rare recessive disorder caused by biallelic variants in NBEAL2 and characterized by bleeding symptoms, the absence of platelet α-granules, splenomegaly, and bone marrow (BM) fibrosis. Due to the rarity of GPS, it has been difficult to fully understand the pathogenic processes that lead to these clinical sequelae. To discern the spectrum of pathologic features, we performed a detailed clinical genotypic and phenotypic study of 47 patients with GPS and identified 32 new etiologic variants in NBEAL2.

[Discrepancies in FVII:C levels depending on the thromboplastin: about a case].

Factor VII deficiency is the most common of the rare coagulation deficiencies. A hemorrhagic syndrome may occur in patients with FVII deficiency below 20%, although no correlation exist between the plasma FVII activity level (FVII:C) and the bleeding risk. Therefore, the management of surgery in patients with FVII deficiency remains challenging.

Clinical Evidence and Safety Profile of Emicizumab for the Management of Children with Hemophilia A.

Emicizumab is a bispecific, humanized, monoclonal antibody mimicking the factor (F) VIII cofactor activity in mediating the generation of FXa by FIXa in patients with hemophilia A (HA). This subcutaneous non-factor agent has been recently extensively approved for the prophylaxis of patients of HA patients with and without FVIII-inhibitors of all ages, although few data are currently available in children. In Phase 3 clinical trials and case series, emicizumab prophylaxis significantly reduced bleeding rates compared to previous treatment in HA adolescents and children with or without FVIII-inhibitors and was generally well tolerated.

Recombinant Adeno-Associated Viral Vectors Expressing Human Coagulation FIX-E456H Variant in Hemophilia B Mice.

Gene therapy using recombinant adeno-associated virus (AAV) has induced sustained long-term coagulation human factor IX (hFIX) levels in hemophilia B (HB) patients. However, asymptomatic transient liver toxicity was observed at high vector doses, highlighting the need to improve the potency of these vectors. We report the generation of an AAV transgene cassette containing the hyperfunctional hFIX-E456H variant showing improved binding to platelets, with a comparison to wild-type hFIX (hFIX-WT) and hFIX-R384L variant (Padua) transgenes, containing truncated-intron 1 (I1).

A Prolonged Treatment Response in Acquired Von Willebrand Syndrome.

Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder. We report herein a case of AVWS due to a monoclonal gammopathy of undetermined significance, in which a transient but prolonged response to a treatment by intravenous immunoglobulin (IVIG) was observed. The diagnosis was fortuitously made in a preoperative setting for neurosurgery, after biological exploration of an isolated prolonged activated partial thromboplastin time.