| 1. |
- Wiessner, M., et al.
(författare)
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Biallelic variants in HPDL cause pure and complicated hereditary spastic paraplegia
- 2021
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Ingår i: Brain : a journal of neurology. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 144:5, s. 1422-1434
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Tidskriftsartikel (refereegranskat)abstract
- Human 4-hydroxyphenylpyruvate dioxygenase-like (HPDL) is a putative iron-containing non-heme oxygenase of unknown specificity and biological significance. We report 25 families containing 34 individuals with neurological disease associated with biallelic HPDL variants. Phenotypes ranged from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spasticity and global developmental delays, sometimes complicated by episodes of neurological and respiratory decompensation. Variants included bona fide pathogenic truncating changes, although most were missense substitutions. Functionality of variants could not be determined directly as the enzymatic specificity of HPDL is unknown; however, when HPDL missense substitutions were introduced into 4-hydroxyphenylpyruvate dioxygenase (HPPD, an HPDL orthologue), they impaired the ability of HPPD to convert 4-hydroxyphenylpyruvate into homogentisate. Moreover, three additional sets of experiments provided evidence for a role of HPDL in the nervous system and further supported its link to neurological disease: (i) HPDL was expressed in the nervous system and expression increased during neural differentiation; (ii) knockdown of zebrafish hpdl led to abnormal motor behaviour, replicating aspects of the human disease; and (iii) HPDL localized to mitochondria, consistent with mitochondrial disease that is often associated with neurological manifestations. Our findings suggest that biallelic HPDL variants cause a syndrome varying from juvenile-onset pure hereditary spastic paraplegia to infantile-onset spastic tetraplegia associated with global developmental delays. © 2021 The Author(s).
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| 2. |
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| 3. |
- Nijs, Jo, et al.
(författare)
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Nociceptive, neuropathic, or nociplastic low back pain? : The low back pain phenotyping (BACPAP) consortium's international and multidisciplinary consensus recommendations
- 2024
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Ingår i: LANCET RHEUMATOLOGY. - : Elsevier. - 2665-9913. ; 6:3, s. e178-e188
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Tidskriftsartikel (refereegranskat)abstract
- The potential to classify low back pain as being characterised by dominant nociceptive, neuropathic, or nociplastic mechanisms is a clinically relevant issue. Preliminary evidence suggests that these low back pain phenotypes might respond differently to treatments; however, more research must be done before making specific recommendations. Accordingly, the low back pain phenotyping (BACPAP) consortium was established as a group of 36 clinicians and researchers from 13 countries (five continents) and 29 institutions, to apply a modified Nominal Group Technique methodology to develop international and multidisciplinary consensus recommendations to provide guidance for identifying the dominant pain phenotype in patients with low back pain, and potentially adapt pain management strategies. The BACPAP consortium's recommendations are also intended to provide direction for future clinical research by building on the established clinical criteria for neuropathic and nociplastic pain. The BACPAP consortium's consensus recommendations are a necessary early step in the process to determine if personalised pain medicine based on pain phenotypes is feasible for low back pain management. Therefore, these recommendations are not ready to be implemented in clinical practice until additional evidence is generated that is specific to these low back pain phenotypes.
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| 4. |
- Buffolo, M., et al.
(författare)
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Modeling of the Optical and Electrical Degradation of 845 nm VCSILs
- 2023
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Ingår i: 2023 Conference on Lasers and Electro-Optics, CLEO 2023.
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Konferensbidrag (refereegranskat)abstract
- Optical and electrical degradation of novel micro-transfer-printed VCSILs is investigated. Modeling of experimental data suggests that the main degradation mechanism is represented by the relocation of impurities, originating from the p-side, toward the active region.
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| 5. |
- Zenari, M., et al.
(författare)
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Analysis of defect-related optical degradation of VCSILs for photonic integrated circuits
- 2023
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 12439
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Konferensbidrag (refereegranskat)abstract
- Laser diodes are of paramount importance for on-chip telecommunications applications, and a wide range of sensing devices that require near-infrared sources. In this work, the devices under test are vertical-cavity silicon-integrated lasers (VCSILs) designed for operation at 845 nm in photonic integrated circuits (PICs). We focus on the analysis of the degradation of the optical performance during aging. To investigate the reliability of the devices, we carried out several stress tests at constant current, ranging from 3.5 mA to 4.5 mA representing a highly accelerated stress condition. We observed two different degradation modes. In the first part of the experiments, the samples exhibited a worsening of the threshold current, but the sub-threshold emission was unaffected by degradation. We associated this behavior to the diffusion of impurities that, from the p-contact, were crossing the upper mirror implying a worsening of the DBR optical absorption. In the second stage of the stress test, the devices showed a higher degradation rate of the threshold current, whose variation was found to be linearly correlated to the worsening of the sub-threshold emission. We related this second degradation mode to the migration of the same impurities degrading the top DBR that, when reaching the active region of the laser, induced an increase in the non-radiative recombination rate. In addition to that, we related the two degradation modes to the change in series resistance, which was ascribed to the resistivity increment of the top DBR first and of oxide aperture afterwards.
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| 6. |
- Zenari, M., et al.
(författare)
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Understanding the optical degradation of 845nm micro-transfer-printed VCSILs for photonic integrated circuits
- 2023
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Ingår i: IEEE Journal of Quantum Electronics. - 0018-9197 .- 1558-1713. ; 59:4
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Tidskriftsartikel (refereegranskat)abstract
- For the first time we investigate the optical degradation of vertical-cavity silicon-integrated lasers (VCSILs) designed for operation at 845 nm in photonic integrated circuits (PICs). The study is based on the combined electro-optical characterization of VCSIL, submitted to constant-current stress tests at different current levels. The original results obtained within the manuscript indicate that degradation is related to the diffusion of impurities. Remarkably, depending on the region through which these impurities are migrating, the diffusion process affects device characteristics in different ways. During Phase 1 (Ph1), compensating impurities originating from the metal-semiconductor contact cross the top DBR, thus degrading mirror reflectivity, which is rarely observed in the literature, and leading to an increase in the threshold current of the device. As the impurities start reaching the active region we observe the onset of Phase 2 (Ph2), during which both threshold current and sub-threshold slope worsen, due to the increase of the Shockley-Read-Hall recombination rate. This phase is also characterized by a measurable increase in series resistance, which is ascribed to a change in the resistance of the oxide aperture. The identification of the root cause of physical degradation represents a fundamental step for future lifetime improvement of these novel optical sources, which are set to replace conventional solid-state sources in the 0.85 μm communication window.
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| 7. |
- Zenari, M., et al.
(författare)
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Addressing the electrical degradation of 845 nm micro-transfer printed VCSILs through TCAD simulations
- 2023
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Ingår i: Proceedings of the International Conference on Numerical Simulation of Optoelectronic Devices, NUSOD. - 2158-3234. ; 2023-September, s. 91-92
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Konferensbidrag (refereegranskat)abstract
- In this work we present the electrical modeling of novel 845 nm vertical-cavity silicon-integrated lasers (VCSILs) for silicon photonics (SiPh). We tested the reliability of the devices by submitting them to high current stress, corresponding to ≈ 20xIth, to observe the degradation as a function of time. During the stress experiment, we monitored the electrical characteristics at regular intervals and we observed two separate degradation phenomena: the series resistance increment and the lowering of the turn-on voltage. Thanks to a Poisson-drift diffusion simulator we simulated the I-V characteristics and the band diagrams to interpret the degradation phenomena. The results of the simulations confirmed that the electrical degradation can be caused by the diffusion of compensation impurities originating from the p-contact layers. The same mechanism was also responsible of the optical degradation of the devices.
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| 8. |
- Bilterys, T., et al.
(författare)
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Relationship, differences, and agreement between objective and subjective sleep measures in chronic spinal pain patients with comorbid insomnia: a cross-sectional study
- 2023
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Ingår i: Pain. - 0304-3959. ; 164:9, s. 2016-2028
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Tidskriftsartikel (refereegranskat)abstract
- Sleep disturbances are one of the most frequent reported problems in people with nonspecific chronic spinal pain (nCSP) and presents an additional treatment challenge. Interventions targeting sleep problems are mainly based on subjective sleep complaints and do not take objective sleep into consideration. The aim of this cross-sectional study was to evaluate the relationship and conformity between self-reported and objectively measured sleep parameters (ie, questionnaire vs polysomnography and actigraphy). The baseline data of 123 people with nCSP and comorbid insomnia who are participating in a randomized controlled trial were analyzed. Pearson correlations were used to investigate the relationship between objective and subjective sleep parameters. Differences between objective and subjective sleep parameters were analyzed using t tests. Bland-Altman analyses were performed to quantify and visualize agreement between the different measurement methods. Except for the significant moderate correlation between perceived time in bed (TIB) and actigraphic TIB (r = 0.667, P < 0.001), all other associations between subjective and objective measures were rather weak (r < 0.400). Participants underestimated their total sleep time (TST) (mean difference [MD] = -52.37 [-67.94, -36.81], P < 0.001) and overestimated sleep onset latency (SOL) (MD = 13.76 [8.33, 19.20], P < 0.001) in general. The results of this study suggest a discrepancy (differences and lack of agreement) between subjective and objective sleep parameters in people with nCSP and comorbid insomnia. No or weak associations were found between self-reported sleep and objectively measured sleep. Findings suggest that people with nCSP and comorbid insomnia tend to underestimate TST and overestimate SOL. Future studies are necessary to confirm our results.
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| 9. |
- De Baets, L., et al.
(författare)
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The interplay between symptoms of insomnia and pain in people with osteoarthritis: A narrative review of the current evidence
- 2023
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Ingår i: Sleep Medicine Reviews. - 1087-0792. ; 70
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Forskningsöversikt (refereegranskat)abstract
- Osteoarthritis (OA) is a leading cause of disability worldwide and clinical pain is the major symptom of OA. This clinical OA-related pain is firmly associated with symptoms of insomnia, which are reported in up to 81% of people with OA. Since understanding the association between both symptoms is critical for their appropriate management, this narrative review synthesizes the existing evidence in people with OA on i) the mechanisms underlying the association between insomnia symptoms and clinical OA-related pain, and ii) the effectiveness of conservative non-pharmacological treatments on insomnia symptoms and clinical OA-related pain. The evidence available identifies depressive symptoms, pain catastrophizing and pain self-efficacy as mechanisms partially explaining the cross-sectional association between insomnia symptoms and pain in people with OA. Furthermore, in comparison to treatments without a specific insomnia intervention, the ones including an insomnia intervention appear more effective for improving insomnia symptoms, but not for reducing clinical OA-related pain. However, at a withinperson level, treatment-related positive effects on insomnia symptoms are associated with a longterm pain reduction. Future longitudinal prospective studies offering fundamental insights into neurobiological and psychosocial mechanisms explaining the association between insomnia symptoms and clinical OA-related pain will enable the development of effective treatments targeting both symptoms.
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| 10. |
- Donkervoort, S., et al.
(författare)
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Pathogenic Variants in the Myosin Chaperone UNC-45B Cause Progressive Myopathy with Eccentric Cores
- 2020
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 107:6, s. 1078-1095
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Tidskriftsartikel (refereegranskat)abstract
- The myosin-directed chaperone UNC-45B is essential for sarcomeric organization and muscle function from Caenorhabditis elegans to humans. The pathological impact of UNC-45B in muscle disease remained elusive. We report ten individuals with bi-allelic variants in UNC45B who exhibit childhood-onset progressive muscle weakness. We identified a common UNC45B variant that acts as a complex hypomorph splice variant. Purified UNC-45B mutants showed changes in folding and solubility. In situ localization studies further demonstrated reduced expression of mutant UNC-45B in muscle combined with abnormal localization away from the A-band towards the Z-disk of the sarcomere. The physiological relevance of these observations was investigated in C. elegans by transgenic expression of conserved UNC-45 missense variants, which showed impaired myosin binding for one and defective muscle function for three. Together, our results demonstrate that UNC-45B impairment manifests as a chaperonopathy with progressive muscle pathology, which discovers the previously unknown conserved role of UNC-45B in myofibrillar organization.
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