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| 2. |
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| 3. |
- Willemse, E. A. J., et al.
(författare)
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Pre-analytical stability of novel cerebrospinal fluid biomarkers
- 2019
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Ingår i: Clinica Chimica Acta. - : Elsevier BV. - 0009-8981. ; 497, s. 204-211
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Tidskriftsartikel (refereegranskat)abstract
- Stability of the cerebrospinal fluid (CSF) composition under different pre-analytical conditions is relevant for the diagnostic potential of biomarkers. Our aim was to examine the pre-analytical stability of promising CSF biomarkers that are currently evaluated for their discriminative use in various neurological diseases. Pooled CSF was aliquoted and experimentally exposed to delayed storage: 0, 1, 2, 4, 24, 72, or 168 h at 4 °C or room temperature (RT), or 1–4 months at −20 °C; or up to 7 freeze/thaw (f/t) cycles, before final storage at −80 °C. Eleven CSF biomarkers were screened using immunoassays, liquid chromatography, or enzymatic methods. Levels of neurogranin (truncP75), chitinase-3-like protein (YKL-40), beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), acetylcholinesterase (AChE) enzymatic activity, theobromine, secreted protein acidic and rich in cysteine-like 1 (SPARCL-1) and homovanillic acid (HVA) levels were not affected by the applied storage conditions. 3-Methoxy-4-hydroxyphenylglycol (MHPG) levels linearly and strongly decreased after 4 h at RT (−10%) or 24 h at 4 °C (−27%), and with 6% after every f/t cycle. 5-Methyltetrahydrofolate (5-MTHF) (−29% after 1 week at RT) and 5-hydroxyindoleacetic acid levels (5-HIAA) (−16% after 1 week at RT) were reduced and 3,4-dihydroxyphenylacetic acid (DOPAC) levels (+22% after 1 week at RT) increased, but only after >24 h at RT. Ten out of eleven potential CSF novel biomarkers showed very limited change under common storage and f/t conditions, suggesting that these CSF biomarkers can be trustfully tested under the pre-analytical conditions present across different cohorts. © 2019 Elsevier B.V.
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| 4. |
- Crous, P. W, et al.
(författare)
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Fungal Planet description sheets: 1284-1382
- 2021
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Ingår i: Persoonia. - : Naturalis Biodiversity Center. - 0031-5850. ; 47, s. 178-374
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Tidskriftsartikel (refereegranskat)abstract
- Novel species of fungi described in this study include those from various countries as follows: Antartica, Cladosporium austrolitorale from coastal sea sand. Australia, Austroboletus yourkae on soil, Crepidotus innuopurpureus on dead wood, Curvularia stenotaphri from roots and leaves of Stenotaphrum secundatum and Thecaphora stajsicii from capsules of Oxalis radicosa. Belgium, Paraxerochrysium coryli (incl. Paraxerochrysium gen. nov.) from Corylus avellana. Brazil, Calvatia nordestina on soil, Didymella tabebuiicola from leaf spots on Tabebuia aurea, Fusarium subflagellisporum from hypertrophied floral and vegetative branches of Mangifera indica and Microdochium maculosum from living leaves of Digitaria insularis. Canada, Cuphophyllus bondii from a grassland. Croatia, Mollisia inferiseptata from a rotten Laurus nobilis trunk. Cyprus, Amanita exilis on calcareous soil. Czech Republic, Cytospora hippophaicola from wood of symptomatic Vaccinium corymbosum. Denmark, Lasiosphaeria deviata on pieces of wood and herbaceous debris. Dominican Republic, Calocybella goethei among grass on a lawn. France (Corsica), Inocybe corsica on wet ground. France (French Guiana), Trechispora patawaensis on decayed branch of unknown angiosperm tree and Trechispora subregularis on decayed log of unknown angiosperm tree. Germany, Paramicrothecium sambuci (incl. Paramicrothecium gen. nov.) on dead stems of Sambucus nigra. India, Aureobasidium microtermitis from the gut of a Microtermes sp. termite, Laccaria diospyricola on soil and Phylloporia tamilnadensis on branches of Catunaregam spinosa. Iran, Pythium serotinoosporum from soil under Prunus dulcis. Italy, Pluteus brunneovenosus on twigs of broadleaved trees on the ground. Japan, Heterophoma rehmanniae on leaves of Rehmannia glutinosa f. hueichingensis. Kazakhstan, Murispora kazachstanica from healthy roots of Triticum aestivum. Namibia, Caespitomonium euphorbiae (incl. Caespitomonium gen. nov.) from stems of an Euphorbia sp. Netherlands, Alfaria junci, Myrmecridium junci, Myrmecridium juncicola, Myrmecridium juncigenum, Ophioceras junci, Paradinemasporium junci (incl. Paradinemasporium gen. nov.), Phialoseptomonium junci, Sporidesmiella juncicola, Xenopyricularia junci and Zaanenomyces quadripartis (incl. Zaanenomyces gen. nov.), from dead culms of Juncus effusus, Cylindromonium everniae and Rhodoveronaea everniae from Evernia prunastri, Cyphellophora sambuci and Myrmecridium sambuci from Sambucus nigra, Kiflimonium junci, Sarocladium junci, Zaanenomyces moderatricis-academiae and Zaanenomyces versatilis from dead culms of Juncus inflexus, Microcera physciae from Physcia tenella, Myrmecridium dactylidis from dead culms of Dactylis glomerata, Neochalara spiraeae and Sporidesmium spiraeae from leaves of Spiraea japonica, Neofabraea salicina from Salix sp., Paradissoconium narthecii (incl. Paradissoconium gen. nov.) from dead leaves of Narthecium ossifragum, Polyscytalum vaccinii from Vaccinium myrtillus, Pseudosoloacrosporiella cryptomeriae (incl. Pseudosoloacrosporiella gen. nov.) from leaves of Cryptomeria japonica, Ramularia pararhabdospora from Plantago lanceolata, Sporidesmiella pini from needles of Pinus sylvestris and Xenoacrodontium juglandis (incl. Xenoacrodontium gen. nov. and Xenoacrodontiaceae fam. nov.) from Juglans regia. New Zealand, Cryptometrion metrosideri from twigs of Metrosideros sp., Coccomyces pycnophyllocladi from dead leaves of Phyllocladus alpinus, Hypoderma aliforme from fallen leaves Fuscopora solandri and Hypoderma subiculatum from dead leaves Phormium tenax. Norway, Neodevriesia kalakoutskii from permafrost and Variabilispora viridis from driftwood of Picea abies. Portugal, Entomortierella hereditatis from a biofilm covering a deteriorated limestone wall. Russia, Colpoma junipericola from needles of Juniperus sabina, Entoloma cinnamomeum on soil in grasslands, Entoloma verae on soil in grasslands, Hyphodermella pallidostraminea on a dry dead branch of Actinidia sp., Lepiota sayanensis on litter in a mixed forest, Papiliotrema horticola from Malus communis, Paramacroventuria ribis (incl. Paramacroventuria gen. nov.) from leaves of Ribes aureum and Paramyrothecium lathyri from leaves of Lathyrus tuberosus. South Africa, Harzia combreti from leaf litter of Combretum collinum ssp. sulvense, Penicillium xyleborini from Xyleborinus saxesenii, Phaeoisaria dalbergiae from bark of Dalbergia armata, Protocreopsis euphorbiae from leaf litter of Euphorbia ingens and Roigiella syzygii from twigs of Syzygium chordatum. Spain, Genea zamorana on sandy soil, Gymnopus nigrescens on Scleropodium touretii, Hesperomyces parexochomi on Parexochomus quadriplagiatus, Paraphoma variabilis from dung, Phaeococcomyces kinklidomatophilus from a blackened metal railing of an industrial warehouse and Tuber suaveolens in soil under Quercus faginea. Svalbard and Jan Mayen, Inocybe nivea associated with Salix polaris. Thailand, Biscogniauxia whalleyi on corticated wood. UK, Parasitella quercicola from Quercus robur. USA, Aspergillus arizonicus from indoor air in a hospital, Caeliomyces tampanus (incl. Caeliomyces gen. nov.) from office dust, Cippumomyces mortalis (incl. Cippumomyces gen. nov.) from a tombstone, Cylindrium desperesense from air in a store, Tetracoccosporium pseudoaerium from air sample in house, Toxicocladosporium glendoranum from air in a brick room, Toxicocladosporium losalamitosense from air in a classroom, Valsonectria portsmouthensis from air in men’s locker room and Varicosporellopsis americana from sludge in a water reservoir. Vietnam, Entoloma kovalenkoi on rotten wood, Fusarium chuoi inside seed of Musa itinerans, Micropsalliota albofelina on soil in tropical evergreen mixed forests and Phytophthora docyniae from soil and roots of Docynia indica. Morphological and culture characteristics are supported by DNA barcodes.
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| 5. |
- Dumurgier, J., et al.
(författare)
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A Pragmatic, Data-Driven Method to Determine Cutoffs for CSF Biomarkers of Alzheimer Disease Based on Validation Against PET Imaging
- 2022
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 99:7
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives To elaborate a new algorithm to establish a standardized method to define cutoffs for CSF biomarkers of Alzheimer disease (AD) by validating the algorithm against CSF classification derived from PET imaging. Methods Low and high levels of CSF phosphorylated tau were first identified to establish optimal cutoffs for CSF beta-amyloid (A beta) peptide biomarkers. These A beta cutoffs were then used to determine cutoffs for CSF tau and phosphorylated tau markers. We compared this algorithm to a reference method, based on tau and amyloid PET imaging status (ADNI study), and then applied the algorithm to 10 large clinical cohorts of patients. Results A total of 6,922 patients with CSF biomarker data were included (mean [SD] age: 70.6 [8.5] years, 51.0% women). In the ADNI study population (n = 497), the agreement between classification based on our algorithm and the one based on amyloid/tau PET imaging was high, with Cohen's kappa coefficient between 0.87 and 0.99. Applying the algorithm to 10 large cohorts of patients (n = 6,425), the proportion of persons with AD ranged from 25.9% to 43.5%. Discussion The proposed novel, pragmatic method to determine CSF biomarker cutoffs for AD does not require assessment of other biomarkers or assumptions concerning the clinical diagnosis of patients. Use of this standardized algorithm is likely to reduce heterogeneity in AD classification.
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| 6. |
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| 7. |
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| 8. |
- Ballantyne, Kaye N., et al.
(författare)
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Toward Male Individualization with Rapidly Mutating Y-Chromosomal Short Tandem Repeats
- 2014
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Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 35:8, s. 1021-1032
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Tidskriftsartikel (refereegranskat)abstract
- Relevant for various areas of human genetics, Y-chromosomal short tandem repeats (Y-STRs) are commonly used for testing close paternal relationships among individuals and populations, and for male lineage identification. However, even the widely used 17-loci Yfiler set cannot resolve individuals and populations completely. Here, 52 centers generated quality-controlled data of 13 rapidly mutating (RM) Y-STRs in 14,644 related and unrelated males from 111 worldwide populations. Strikingly, greater than99% of the 12,272 unrelated males were completely individualized. Haplotype diversity was extremely high (global: 0.9999985, regional: 0.99836-0.9999988). Haplotype sharing between populations was almost absent except for six (0.05%) of the 12,156 haplotypes. Haplotype sharing within populations was generally rare (0.8% nonunique haplotypes), significantly lower in urban (0.9%) than rural (2.1%) and highest in endogamous groups (14.3%). Analysis of molecular variance revealed 99.98% of variation within populations, 0.018% among populations within groups, and 0.002% among groups. Of the 2,372 newly and 156 previously typed male relative pairs, 29% were differentiated including 27% of the 2,378 father-son pairs. Relative to Yfiler, haplotype diversity was increased in 86% of the populations tested and overall male relative differentiation was raised by 23.5%. Our study demonstrates the value of RMY-STRs in identifying and separating unrelated and related males and provides a reference database.
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| 9. |
- Benkert, P., et al.
(författare)
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Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: a retrospective modelling and validation study
- 2022
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Ingår i: The Lancet Neurology. - 1474-4422 .- 1474-4465. ; 21:3, s. 246-257
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Tidskriftsartikel (refereegranskat)abstract
- Background: Serum neurofilament light chain (sNfL) is a biomarker of neuronal damage that is used not only to monitor disease activity and response to drugs and to prognosticate disease course in people with multiple sclerosis on the group level. The absence of representative reference values to correct for physiological age-dependent increases in sNfL has limited the diagnostic use of this biomarker at an individual level. We aimed to assess the applicability of sNfL for identification of people at risk for future disease activity by establishing a reference database to derive reference values corrected for age and body-mass index (BMI). Furthermore, we used the reference database to test the suitability of sNfL as an endpoint for group-level comparison of effectiveness across disease-modifying therapies. Methods: For derivation of a reference database of sNfL values, a control group was created, comprising participants with no evidence of CNS disease taking part in four cohort studies in Europe and North America. We modelled the distribution of sNfL concentrations in function of physiological age-related increase and BMI-dependent modulation, to derive percentile and Z score values from this reference database, via a generalised additive model for location, scale, and shape. We tested the reference database in participants with multiple sclerosis in the Swiss Multiple Sclerosis Cohort (SMSC). We compared the association of sNfL Z scores with clinical and MRI characteristics recorded longitudinally to ascertain their respective disease prognostic capacity. We validated these findings in an independent sample of individuals with multiple sclerosis who were followed up in the Swedish Multiple Sclerosis registry. Findings: We obtained 10 133 blood samples from 5390 people (median samples per patient 1 [IQR 1–2] in the control group). In the control group, sNfL concentrations rose exponentially with age and at a steeper increased rate after approximately 50 years of age. We obtained 7769 samples from 1313 people (median samples per person 6·0 [IQR 3·0–8·0]). In people with multiple sclerosis from the SMSC, sNfL percentiles and Z scores indicated a gradually increased risk for future acute (eg, relapse and lesion formation) and chronic (disability worsening) disease activity. A sNfL Z score above 1·5 was associated with an increased risk of future clinical or MRI disease activity in all people with multiple sclerosis (odds ratio 3·15, 95% CI 2·35–4·23; p<0·0001) and in people considered stable with no evidence of disease activity (2·66, 1·08–6·55; p=0·034). Increased Z scores outperformed absolute raw sNfL cutoff values for diagnostic accuracy. At the group level, the longitudinal course of sNfL Z score values in people with multiple sclerosis from the SMSC decreased to those seen in the control group with use of monoclonal antibodies (ie, alemtuzumab, natalizumab, ocrelizumab, and rituximab) and, to a lesser extent, oral therapies (ie, dimethyl fumarate, fingolimod, siponimod, and teriflunomide). However, longitudinal sNfL Z scores remained elevated with platform compounds (interferons and glatiramer acetate; p<0·0001 for the interaction term between treatment category and treatment duration). Results were fully supported in the validation cohort (n=4341) from the Swedish Multiple Sclerosis registry. Interpretation: The use of sNfL percentiles and Z scores allows for identification of individual people with multiple sclerosis at risk for a detrimental disease course and suboptimal therapy response beyond clinical and MRI measures, specifically in people with disease activity-free status. Additionally, sNfL might be used as an endpoint for comparing effectiveness across drug classes in pragmatic trials. Funding: Swiss National Science Foundation, Progressive Multiple Sclerosis Alliance, Biogen, Celgene, Novartis, Roche. © 2022 Elsevier Ltd
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| 10. |
- Mavrina, E., et al.
(författare)
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Multi-Omics Interdisciplinary Research Integration to Accelerate Dementia Biomarker Development (MIRIADE)
- 2022
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Proteomics studies have shown differential expression of numerous proteins in dementias but have rarely led to novel biomarker tests for clinical use. The Marie Curie MIRIADE project is designed to experimentally evaluate development strategies to accelerate the validation and ultimate implementation of novel biomarkers in clinical practice, using proteomics-based biomarker development for main dementias as experimental case studies. We address several knowledge gaps that have been identified in the field. First, there is the technology-translation gap of different technologies for the discovery (e.g., mass spectrometry) and the large-scale validation (e.g., immunoassays) of biomarkers. In addition, there is a limited understanding of conformational states of biomarker proteins in different matrices, which affect the selection of reagents for assay development. In this review, we aim to understand the decisions taken in the initial steps of biomarker development, which is done via an interim narrative update of the work of each ESR subproject. The results describe the decision process to shortlist biomarkers from a proteomics to develop immunoassays or mass spectrometry assays for Alzheimer's disease, Lewy body dementia, and frontotemporal dementia. In addition, we explain the approach to prepare the market implementation of novel biomarkers and assays. Moreover, we describe the development of computational protein state and interaction prediction models to support biomarker development, such as the prediction of epitopes. Lastly, we reflect upon activities involved in the biomarker development process to deduce a best-practice roadmap for biomarker development.
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| 11. |
- Andreasson, Ulf, 1968, et al.
(författare)
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Assessing the commutability of candidate reference materials for the harmonization of neurofilament light measurements in blood
- 2023
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Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter GmbH. - 1434-6621 .- 1437-4331. ; 61:7, s. 1245-1254
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Neurofilament light chain (NfL) concentration in blood is a biomarker of neuro-axonal injury in the nervous system and there now exist several assays with high enough sensitivity to measure NfL in serum and plasma. There is a need for harmonization with the goal of creating a certified reference material (CRM) for NfL and an early step in such an effort is to determine the best matrix for the CRM. This is done in a commutability study and here the results of the first one for NfL in blood is presented.Methods Forty paired individual serum and plasma samples were analyzed for NfL on four different analytical platforms. Neat and differently spiked serum and plasma were evaluated for their suitability as a CRM using the difference in bias approach.Results The correlation between the different platforms with regards to measured NfL concentrations were very high (Spearman's rho >= 0.96). Samples spiked with cerebrospinal fluid (CSF) showed higher commutability compared to samples spiked with recombinant human NfL protein and serum seems to be a better choice than plasma as the matrix for a CRM.Conclusions The results from this first commutability study on NfL in serum/plasma showed that it is feasible to create a CRM for NfL in blood and that spiking should be done using CSF rather than with recombinant human NfL protein.
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| 12. |
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| 13. |
- Chenouard, Nicolas, et al.
(författare)
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Objective comparison of particle tracking methods
- 2014
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Ingår i: Nature Methods. - : Springer Science and Business Media LLC. - 1548-7091 .- 1548-7105. ; 11:3, s. 281-U247
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Tidskriftsartikel (refereegranskat)abstract
- Particle tracking is of key importance for quantitative analysis of intracellular dynamic processes from time-lapse microscopy image data. Because manually detecting and following large numbers of individual particles is not feasible, automated computational methods have been developed for these tasks by many groups. Aiming to perform an objective comparison of methods, we gathered the community and organized an open competition in which participating teams applied their own methods independently to a commonly defined data set including diverse scenarios. Performance was assessed using commonly defined measures. Although no single method performed best across all scenarios, the results revealed clear differences between the various approaches, leading to notable practical conclusions for users and developers.
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| 14. |
- Cornford, Philip, et al.
(författare)
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EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer-2024 Update. Part I: Screening, Diagnosis, and Local Treatment with Curative Intent.
- 2024
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Ingår i: European urology. - 1873-7560.
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Tidskriftsartikel (refereegranskat)abstract
- The European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Urological Pathology (ISUP)-International Society of Geriatric Oncology (SIOG) guidelines provide recommendations for the management of clinically localised prostate cancer (PCa). This paper aims to present a summary of the 2024 version of the EAU-EANM-ESTRO-ESUR-ISUP-SIOG guidelines on the screening, diagnosis, and treatment of clinically localised PCa.The panel performed a literature review of all new data published in English, covering the time frame between May 2020 and 2023. The guidelines were updated, and a strength rating for each recommendation was added based on a systematic review of the evidence.A risk-adapted strategy for identifying men who may develop PCa is advised, generally commencing at 50yr of age and based on individualised life expectancy. The use of multiparametric magnetic resonance imaging in order to avoid unnecessary biopsies is recommended. When a biopsy is considered, a combination of targeted and regional biopsies should be performed. Prostate-specific membrane antigen positron emission tomography imaging is the most sensitive technique for identifying metastatic spread. Active surveillance is the appropriate management for men with low-risk PCa, as well as for selected favourable intermediate-risk patients with International Society of Urological Pathology grade group 2 lesions. Local therapies are addressed, as well as the management of persistent prostate-specific antigen after surgery. A recommendation to consider hypofractionation in intermediate-risk patients is provided. Patients with cN1 PCa should be offered a local treatment combined with long-term intensified hormonal treatment.The evidence in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. These PCa guidelines reflect the multidisciplinary nature of PCa management.This article is the summary of the guidelines for "curable" prostate cancer. Prostate cancer is "found" through a multistep risk-based screening process. The objective is to find as many men as possible with a curable cancer. Prostate cancer is curable if it resides in the prostate; it is then classified into low-, intermediary-, and high-risk localised and locally advanced prostate cancer. These risk classes are the basis of the treatments. Low-risk prostate cancer is treated with "active surveillance", a treatment with excellent prognosis. For low-intermediary-risk active surveillance should also be discussed as an option. In other cases, active treatments, surgery, or radiation treatment should be discussed along with the potential side effects to allow shared decision-making.
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| 15. |
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| 16. |
- Gandaglia, Giorgio, et al.
(författare)
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Clinical Characterization of Patients Diagnosed with Prostate Cancer and Undergoing Conservative Management : A PIONEER Analysis Based on Big Data
- 2024
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Ingår i: European Urology. - 0302-2838. ; 85:5, s. 457-465
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Tidskriftsartikel (refereegranskat)abstract
- Background: Conservative management is an option for prostate cancer (PCa) patients either with the objective of delaying or even avoiding curative therapy, or to wait until palliative treatment is needed. PIONEER, funded by the European Commission Innovative Medicines Initiative, aims at improving PCa care across Europe through the application of big data analytics. Objective: To describe the clinical characteristics and long-term outcomes of PCa patients on conservative management by using an international large network of real-world data. Design, setting, and participants: From an initial cohort of >100 000 000 adult individuals included in eight databases evaluated during a virtual study-a-thon hosted by PIONEER, we identified newly diagnosed PCa cases (n = 527 311). Among those, we selected patients who did not receive curative or palliative treatment within 6 mo from diagnosis (n = 123 146). Outcome measurements and statistical analysis: Patient and disease characteristics were reported. The number of patients who experienced the main study outcomes was quantified for each stratum and the overall cohort. Kaplan-Meier analyses were used to estimate the distribution of time to event data. Results and limitations: The most common comorbidities were hypertension (35–73%), obesity (9.2–54%), and type 2 diabetes (11–28%). The rate of PCa-related symptomatic progression ranged between 2.6% and 6.2%. Hospitalization (12–25%) and emergency department visits (10–14%) were common events during the 1st year of follow-up. The probability of being free from both palliative and curative treatments decreased during follow-up. Limitations include a lack of information on patients and disease characteristics and on treatment intent. Conclusions: Our results allow us to better understand the current landscape of patients with PCa managed with conservative treatment. PIONEER offers a unique opportunity to characterize the baseline features and outcomes of PCa patients managed conservatively using real-world data. Patient summary: Up to 25% of men with prostate cancer (PCa) managed conservatively experienced hospitalization and emergency department visits within the 1st year after diagnosis; 6% experienced PCa-related symptoms. The probability of receiving therapies for PCa decreased according to time elapsed after the diagnosis.
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| 17. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 18. |
- Leard, Lorriana E., et al.
(författare)
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Consensus document for the selection of lung transplant candidates: An update from the International Society for Heart and Lung Transplantation
- 2021
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Ingår i: Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1053-2498 .- 1557-3117. ; 40, s. 1349-1379
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Tidskriftsartikel (refereegranskat)abstract
- Tens of thousands of patients with advanced lung diseases may be eligible to be considered as potential candidates for lung transplant around the world each year. The timing of referral, evaluation, determination of candidacy, and listing of candidates continues to pose challenges and even ethical dilemmas. To address these challenges, the International Society for Heart and Lung Transplantation appointed an international group of members to review the literature, to consider recent advances in the management of advanced lung diseases, and to update prior consensus documents on the selection of lung transplant candidates. The purpose of this updated consensus document is to assist providers throughout the world who are caring for patients with pulmonary disease to identify potential candidates for lung transplant, to optimize the timing of the referral of these patients to lung transplant centers, and to provide transplant centers with a framework for evaluating and selecting candidates. In addition to addressing general considerations and providing disease specific recommendations for referral and listing, this updated consensus document includes an ethical framework, a recognition of the variability in acceptance of risk between transplant centers, and establishes a system to account for how a combination of risk factors may be taken into consideration in candidate selection for lung transplantation.
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| 19. |
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| 20. |
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| 21. |
- Marra, Giancarlo, et al.
(författare)
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Impact of Epithelial Histological Types, Subtypes, and Growth Patterns on Oncological Outcomes for Patients with Nonmetastatic Prostate Cancer Treated with Curative Intent: A Systematic Review.
- 2023
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Ingår i: European urology. - 0302-2838 .- 1873-7560. ; 84:1, s. 65-85
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Tidskriftsartikel (refereegranskat)abstract
- The optimal management for men with prostate cancer (PCa) with unconventional histology (UH) is unknown. The outcome for these cancers might be worse than for conventional PCa and so different approaches may be needed.To compare oncological outcomes for conventional and UH PCa in men with localized disease treated with curative intent.A systematic review adhering to the Referred Reporting Items for Systematic Reviews and Meta-Analyses was prospectively registered on PROSPERO (CRD42022296013) was performed in July 2021.We screened 3651 manuscripts and identified 46 eligible studies (reporting on 1871814 men with conventional PCa and 6929 men with 10 different PCa UHs). Extraprostatic extension and lymph node metastases, but not positive margin rates, were more common with UH PCa than with conventional tumors. PCa cases with cribriform pattern, intraductal carcinoma, or ductal adenocarcinoma had higher rates of biochemical recurrence and metastases after radical prostatectomy than for conventional PCa cases. Lower cancer-specific survival rates were observed for mixed cribriform/intraductal and cribriform PCa. By contrast, pathological findings and oncological outcomes for mucinous and prostatic intraepithelial neoplasia (PIN)-like PCa were similar to those for conventional PCa. Limitations of this review include low-quality studies, a risk of reporting bias, and a scarcity of studies that included radiotherapy.Intraductal, cribriform, and ductal UHs may have worse oncological outcomes than for conventional and mucinous or PIN-like PCa. Alternative treatment approaches need to be evaluated in men with these cancers.We reviewed the literature to explore whether prostate cancers with unconventional growth patterns behave differently to conventional prostate cancers. We found that some unconventional growth patterns have worse outcomes, so we need to investigate if they need different treatments. Urologists should be aware of these growth patterns and their clinical impact.
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| 22. |
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| 23. |
- Roos, Floris J.M., et al.
(författare)
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Human branching cholangiocyte organoids recapitulate functional bile duct formation
- 2022
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Ingår i: Cell Stem Cell. - : Elsevier BV. - 1934-5909. ; 29:5, s. 13-794
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Tidskriftsartikel (refereegranskat)abstract
- Human cholangiocyte organoids show great promise for regenerative therapies and in vitro modeling of bile duct development and diseases. However, the cystic organoids lack the branching morphology of intrahepatic bile ducts (IHBDs). Here, we report establishing human branching cholangiocyte organoid (BRCO) cultures. BRCOs self-organize into complex tubular structures resembling the IHBD architecture. Single-cell transcriptomics and functional analysis showed high similarity to primary cholangiocytes, and importantly, the branching growth mimics aspects of tubular development and is dependent on JAG1/NOTCH2 signaling. When applied to cholangiocarcinoma tumor organoids, the morphology changes to an in vitro morphology like primary tumors. Moreover, these branching cholangiocarcinoma organoids (BRCCAOs) better match the transcriptomic profile of primary tumors and showed increased chemoresistance to gemcitabine and cisplatin. In conclusion, BRCOs recapitulate a complex process of branching morphogenesis in vitro. This provides an improved model to study tubular formation, bile duct functionality, and associated biliary diseases.
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| 24. |
- Teunissen, Charlotte E, et al.
(författare)
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Methods to Discover and Validate Biofluid-Based Biomarkers in Neurodegenerative Dementias.
- 2023
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Ingår i: Molecular & cellular proteomics : MCP. - : Elsevier BV. - 1535-9484 .- 1535-9476. ; 22:10
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Tidskriftsartikel (refereegranskat)abstract
- Neurodegenerative dementias are progressive diseases that cause neuronal network breakdown in different brain regions often because of accumulation of misfolded proteins in the brain extracellular matrix, such as amyloids or inside neurons or other cell types of the brain. Several diagnostic protein biomarkers in body fluids are being used and implemented, such as for Alzheimer's disease. However, there is still a lack of biomarkers for co-pathologies and other causes of dementia. Such biofluid-based biomarkers enable precision medicine approaches for diagnosis and treatment, allow to learn more about underlying disease processes, and facilitate the development of patient inclusion and evaluation tools in clinical trials. When designing studies to discover novel biofluid-based biomarkers, choice of technology is an important starting point. But there are so many technologies to choose among. To address this, we here review the technologies that are currently available in research settings and, in some cases, in clinical laboratory practice. This presents a form of lexicon on each technology addressing its use in research and clinics, its strengths and limitations, and a future perspective.
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| 25. |
- van Tienderen, Gilles S, et al.
(författare)
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Extracellular matrix drives tumor organoids toward desmoplastic matrix deposition and mesenchymal transition
- 2023
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1878-7568 .- 1742-7061. ; 158, s. 115-131
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Tidskriftsartikel (refereegranskat)abstract
- Patient-derived tumor organoids have been established as promising tools for in vitro modelling of multiple tumors, including cholangiocarcinoma (CCA). However, organoids are commonly cultured in basement membrane extract (BME) which does not recapitulate the intricacies of the extracellular matrix (ECM). We combined CCA organoids (CCAOs) with native tumor and liver scaffolds, obtained by decellularization, to effectuate a model to study the interaction between epithelial tumor cells and their surrounding ECM. Decellularization resulted in removal of cells while preserving ECM structure and retaining important characteristics of the tissue origin, including stiffness and presence of desmoplasia. The transcriptome of CCAOs in a tumor scaffold much more resembled that of patient-paired CCA tissue in vivo compared to CCAOs cultured in BME or liver scaffolds. This was accompanied by an increase in chemoresistance to clinically-relevant chemotherapeutics. CCAOs in decellularized scaffolds revealed environment-dependent proliferation dynamics, driven by the occurrence of epithelial-mesenchymal transition. Furthermore, CCAOs initiated an environment-specific desmoplastic reaction by increasing production of multiple collagen types. In conclusion, convergence of organoid-based models with native ECM scaffolds will lead to better understanding of the in vivo tumor environment. STATEMENT OF SIGNIFICANCE: The extracellular matrix (ECM) influences various facets of tumor behavior. Understanding the exact role of the ECM in controlling tumor cell fate is pertinent to understand tumor progression and develop novel therapeutics. This is particularly the case for cholangiocarcinoma (CCA), whereby the ECM displays a distinct tumor environment, characterized by desmoplasia. However, current models to study the interaction between epithelial tumor cells and the environment are lacking. We have developed a fully patient-derived model encompassing CCA organoids (CCAOs) and human decellularized tumor and tumor-free liver ECM. The tumor ECM induced recapitulation of various aspects of CCA, including migration dynamics, transcriptome and proteome profiles, and chemoresistance. Lastly, we uncover that epithelial tumor cells contribute to matrix deposition, and that this phenomenon is dependent on the level of desmoplasia already present.
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| 26. |
- Waury, Katharina, et al.
(författare)
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Bioinformatics tools and data resources for assay development of fluid protein biomarkers.
- 2022
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Ingår i: Biomarker research. - : Springer Science and Business Media LLC. - 2050-7771. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Fluid protein biomarkers are important tools in clinical research and health care to support diagnosis and to monitor patients. Especially within the field of dementia, novel biomarkers could address the current challenges of providing an early diagnosis and of selecting trial participants. While the great potential of fluid biomarkers is recognized, their implementation in routine clinical use has been slow. One major obstacle is the often unsuccessful translation of biomarker candidates from explorative high-throughput techniques to sensitive antibody-based immunoassays. In this review, we propose the incorporation of bioinformatics into the workflow of novel immunoassay development to overcome this bottleneck and thus facilitate the development of novel biomarkers towards clinical laboratory practice. Due to the rapid progress within the field of bioinformatics many freely available and easy-to-use tools and data resources exist which can aid the researcher at various stages. Current prediction methods and databases can support the selection of suitable biomarker candidates, as well as the choice of appropriate commercial affinity reagents. Additionally, we examine methods that can determine or predict the epitope - an antibody's binding region on its antigen - and can help to make an informed choice on the immunogenic peptide used for novel antibody production. Selected use cases for biomarker candidates help illustrate the application and interpretation of the introduced tools.
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| 27. |
- Willemse, Eline A J, et al.
(författare)
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Neurogranin as Cerebrospinal Fluid Biomarker for Alzheimer Disease: An Assay Comparison Study.
- 2018
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Ingår i: Clinical chemistry. - : Oxford University Press (OUP). - 1530-8561 .- 0009-9147. ; 64:6, s. 927-937
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Tidskriftsartikel (refereegranskat)abstract
- Neurogranin in cerebrospinal fluid (CSF) correlates with cognitive decline and is a potential novel biomarker for Alzheimer disease (AD) dementia. We investigated the analytical and diagnostic performance of 3 commonly used neurogranin assays in the same cohort of patients to improve the interpretability of CSF neurogranin test results.The neurogranin Singulex assay from Washington University, St. Louis, MO (WashU); ELISA from ADx Neurosciences; and ELISA from Gothenburg University, Mölndal, Sweden (UGot), were compared using silver staining and Western blot after gel electrophoresis. Clinical performance of the 3 assays was compared in samples from individuals diagnosed with subjective cognitive decline (n = 22), and in patients with AD (n = 22), frontotemporal dementia (n = 22), dementia with Lewy bodies (n = 22), or vascular dementia (n = 20), adjusted for sex and age.The assays detected different epitopes of neurogranin: the WashU assay the N-terminal part of neurogranin (S10-D23) and a C-terminal part (G49-G60), the ADx assay C-terminal neurogranin truncated at P75, and the UGot assay the C-terminal neurogranin with intact ending (D78). Spearman ρ was 0.95 between ADx and WashU, 0.87 between UGot and WashU, and 0.81 between UGot and ADx. ANCOVA (analysis of covariance) showed group differences for ranked neurogranin concentrations in each assay (allP< 0.05), with specific increases in AD.Although the 3 assays target different epitopes on neurogranin and have different calibrators, the high correlations and the similar group differences suggest that the different forms of neurogranin in CSF carry similar diagnostic information, at least in the context of neurodegenerative diseases.
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| 28. |
- Wilson, D., et al.
(författare)
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Development and multi-center validation of a fully automated digital immunoassay for neurofilament light chain: toward a clinical blood test for neuronal injury
- 2024
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Ingår i: Clinical Chemistry and Laboratory Medicine. - 1434-6621 .- 1437-4331. ; 62:2, s. 322-331
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Neurofilament light chain (NfL) has emerged as a promising biomarker for detecting and monitoring axonal injury. Until recently, NfL could only be reliably measured in cerebrospinal fluid, but digital single molecule array (Simoa) technology has enabled its precise measurement in blood samples where it is typically 50-100 times less abundant. We report development and multi-center validation of a novel fully automated digital immunoassay for NfL in serum for informing axonal injury status.Methods A 45-min immunoassay for serum NfL was developed for use on an automated digital analyzer based on Simoa technology. The analytical performance (sensitivity, precision, reproducibility, linearity, sample type) was characterized and then cross validated across 17 laboratories in 10 countries. Analytical performance for clinical NfL measurement was examined in individual patients with relapsing remitting multiple sclerosis (RRMS) after 3 months of disease modifying treatment (DMT) with fingolimod.Results The assay exhibited a lower limit of detection (LLoD) of 0.05 ng/L, a lower limit of quantification (LLoQ) of 0.8 ng/L, and between-laboratory imprecision <10 % across 17 validation sites. All tested samples had measurable NfL concentrations well above the LLoQ. In matched pre-post treatment samples, decreases in NfL were observed in 26/29 RRMS patients three months after DMT start, with significant decreases detected in a majority of patients.Conclusions The sensitivity characteristics and reproducible performance across laboratories combined with full automation make this assay suitable for clinical use for NfL assessment, monitoring in individual patients, and cross-comparisons of results across multiple sites.
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