| 1. |
- Bou-Jaoudeh, Melissa, et al.
(author)
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The IgG-degrading enzyme, Imlifidase, restores the therapeutic activity of FVIII in inhibitor-positive hemophilia A mice
- 2023
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In: Haematologica. - : Ferrata Storti Foundation (Haematologica). - 0390-6078 .- 1592-8721. ; 108:5, s. 1322-1334
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Journal article (peer-reviewed)abstract
- Neutralizing anti-factor VIII (FVIII) antibodies, known as FVIII inhibitors, represent a major drawback of replacement therapy in persons with congenital hemophilia A (PwHA), rendering further infusions of FVIII ineffective. FVIII inhibitors can also appear in non-hemophilic individuals causing acquired hemophilia A (AHA). The use of non-FVIII bypassing agents in cases of bleeds or surgery in inhibitor-positive patients is complicated by the lack of reliable biological monitoring and increased thrombotic risk. Imlifidase (IdeS) is an endopeptidase that degrades human immunoglobulin G (IgG); it was recently approved for hyperimmune patients undergoing renal transplants. Here we investigated the ability of IdeS to eliminate FVIII inhibitors in vitro and in a model of inhibitor-positive HA mice. IdeS cleaved anti-FVIII plasma IgG from PwHA and AHA patients, and hydrolyzed recombinant human anti-FVIII IgG independently from their subclass or specificity for the A2, A3, C1 or C2 domains of FVIII. In HA mice passively immunized with recombinant human anti-FVIII IgG, IdeS restored the hemostatic efficacy of FVIII, as evidenced by the correction of the bleeding tendency. Our results provide the proof of concept for the transient removal of FVIII inhibitors by IdeS, thereby opening a therapeutic window for efficient FVIII replacement therapy in inhibitor-positive patients.
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| 2. |
- Franco-Vidal, Valerie, et al.
(author)
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The Oticon Medical Neuro Zti cochlear implant and the Neuro 2 sound processor: multicentric evaluation of outcomes in adults and children
- 2020
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In: International Journal of Audiology. - : TAYLOR & FRANCIS LTD. - 1499-2027 .- 1708-8186. ; 59:2, s. 153-160
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Journal article (peer-reviewed)abstract
- Objective: This study evaluated the outcomes of the Oticon Medical Neuro Zti cochlear implant and the Neuro 2 sound processor. Design: Neuro One users were upgraded to Neuro 2. Monosyllabic word identification was evaluated in adults with Neuro One after >= 5 months, with Neuro 2 at upgrade, and with Neuro 2 after 3 months. Self-reported listening ability, satisfaction, and usability were measured in adults and children. Study sample: Participants were 44 adults and 26 children. Results: Speech identification scores in quiet and noise were 58% and 45% with Neuro One and 67% and 55% with Neuro 2 after 3 months, respectively. Hearing impairment duration and number of active electrodes significantly predicted speech identification in noise with Neuro 2. Significantly higher questionnaire ratings were obtained for Neuro 2 than Neuro One regarding listening ability in complex listening situations, comfort and music, as well as nine aspects of satisfaction and usability. Conclusion: This study demonstrates the clinical superiority of the Neuro 2 sound processor over Neuro One in terms of speech identification in quiet and in noise and reported patient benefit and satisfaction. Given the study design, sources of improvement may include factors unrelated to the sound processor itself.
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| 3. |
- Lévesque, Valérie, et al.
(author)
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Implantable Cardioverter-Defibrillators and Patient-Reported Outcomes in Adults with Congenital Heart Disease : an International Study
- 2020
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In: Heart Rhythm. - : Elsevier BV. - 1547-5271 .- 1556-3871. ; 17:5, s. 768-776
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Journal article (peer-reviewed)abstract
- BACKGROUND: Implantable cardioverter-defibrillators (ICDs) are increasingly used to prevent sudden deaths in the growing population of adults with congenital heart disease (CHD). Yet, little is known about their impact on patient-reported outcomes (PROs).OBJECTIVE: We assessed and compared PROs in adults with CHD with and without ICDs.METHODS: A propensity-based matching weight analysis was conducted to evaluate PROs in an international cross-sectional study of adults with CHD from 15 countries across 5 continents.RESULTS: A total of 3,188 patients were included: 107 with ICDs and 3,081 weight-matched controls without ICDs. ICD recipients averaged 40.1±12.4 years of age, with >95% having moderate or complex CHD. Defibrillators were implanted for primary and secondary prevention in 38.3% and 61.7%, respectively. Perceived health status, psychological distress, sense of coherence, and health behaviours did not differ significantly in patients with and without ICDs. However, ICD recipients had a more threatening view of their illness (relative % difference 8.56, P=0.011). Those with secondary compared to primary prevention indications had a significantly lower quality of life score (linear analogue scale 72.0±23.1 versus 79.2±13.0, P=0.047). Marked geographic variations were observed. Overall sense of well-being, assessed by a summary score that combines various PROs, was significantly lower in ICD recipients (versus controls) from Switzerland, Argentina, Taiwan, and USA.CONCLUSIONS: In an international cohort of adults with CHD, ICDs were associated with a more threatening illness perception, with a lower quality of life in those with secondary compared to primary prevention indications. However, marked geographic variability in PROs was observed.
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| 4. |
- Roslin, Tomas, et al.
(author)
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A molecular-based identification resource for the arthropods of Finland
- 2022
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In: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 22:2, s. 803-822
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Journal article (peer-reviewed)abstract
- To associate specimens identified by molecular characters to other biological knowledge, we need reference sequences annotated by Linnaean taxonomy. In this study, we (1) report the creation of a comprehensive reference library of DNA barcodes for the arthropods of an entire country (Finland), (2) publish this library, and (3) deliver a new identification tool for insects and spiders, as based on this resource. The reference library contains mtDNA COI barcodes for 11,275 (43%) of 26,437 arthropod species known from Finland, including 10,811 (45%) of 23,956 insect species. To quantify the improvement in identification accuracy enabled by the current reference library, we ran 1000 Finnish insect and spider species through the Barcode of Life Data system (BOLD) identification engine. Of these, 91% were correctly assigned to a unique species when compared to the new reference library alone, 85% were correctly identified when compared to BOLD with the new material included, and 75% with the new material excluded. To capitalize on this resource, we used the new reference material to train a probabilistic taxonomic assignment tool, FinPROTAX, scoring high success. For the full-length barcode region, the accuracy of taxonomic assignments at the level of classes, orders, families, subfamilies, tribes, genera, and species reached 99.9%, 99.9%, 99.8%, 99.7%, 99.4%, 96.8%, and 88.5%, respectively. The FinBOL arthropod reference library and FinPROTAX are available through the Finnish Biodiversity Information Facility (www.laji.fi) at https://laji.fi/en/theme/protax. Overall, the FinBOL investment represents a massive capacity-transfer from the taxonomic community of Finland to all sectors of society.
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