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Sökning: WFRF:(PROCTOR S)

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1.
  • Thomas, HS, et al. (författare)
  • 2019
  • swepub:Mat__t
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  • Romagnoni, A, et al. (författare)
  • Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data
  • 2019
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10351-
  • Tidskriftsartikel (refereegranskat)abstract
    • Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers.
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4.
  • Momozawa, Y, et al. (författare)
  • IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes
  • 2018
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2427-
  • Tidskriftsartikel (refereegranskat)abstract
    • GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach.
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5.
  • Ademuyiwa, Adesoji O., et al. (författare)
  • Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
  • 2016
  • Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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  • Vaga, S., et al. (författare)
  • Compositional and functional differences of the mucosal microbiota along the intestine of healthy individuals
  • 2020
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Gut mucosal microbes evolved closest to the host, developing specialized local communities. There is, however, insufficient knowledge of these communities as most studies have employed sequencing technologies to investigate faecal microbiota only. This work used shotgun metagenomics of mucosal biopsies to explore the microbial communities' compositions of terminal ileum and large intestine in 5 healthy individuals. Functional annotations and genome-scale metabolic modelling of selected species were then employed to identify local functional enrichments. While faecal metagenomics provided a good approximation of the average gut mucosal microbiome composition, mucosal biopsies allowed detecting the subtle variations of local microbial communities. Given their significant enrichment in the mucosal microbiota, we highlight the roles of Bacteroides species and describe the antimicrobial resistance biogeography along the intestine. We also detail which species, at which locations, are involved with the tryptophan/indole pathway, whose malfunctioning has been linked to pathologies including inflammatory bowel disease. Our study thus provides invaluable resources for investigating mechanisms connecting gut microbiota and host pathophysiology.
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  • Proctor, D.N, et al. (författare)
  • Longitudinal changes in physical functional performance among the oldest old: insight from a study of Swedish twins
  • 2006
  • Ingår i: Aging Clinical and Experimental Research. ; 18:6, s. 517-530
  • Tidskriftsartikel (refereegranskat)abstract
    • The primary purpose was to characterize mean and individual-level patterns of change in physical functional performance over eight years (2 year intervals) in a community dwelling sample of Swedish twins (579 men and women aged 79-96 years at baseline). RESULTS: Mixed linear models revealed linear rates of decline for handgrip strength (grip) and time to complete five chair stands, and accelerating decline for peak expiratory flow rate (PEFR) for both sexes. Significant random effects were found for intercept and time for grip and PEFR tests, indicating differences between participants initially and over time. Individual differ-ences in chairstand performance were significant for initial status only. Age at baseline was predictive of initial status in grip, PEFR and chair performance (women only), but not rate of change. Measures of body size at baseline were predictive of individual variation in initial grip (height), PEFR (weight in men, height in women), and chair performance (height), but had less consistent associations with changes in test performance over time. In the deceased sub-sample (85% of participants), having been further from death was related to less steep de-clines in grip, but not PEFR or chair performance. Twins from the same pair were related in initial status (twin level variance ~30-70%), but they were not generally related in rate of change. CONCLUSIONS: These results indicate that changes in physical functional perform-ance in an elderly, community dwelling population vary across individuals in a test and sex-dependent manner. Constitutional variables (age, sex, body size) are predictive of baseline performance, but explain little variance in change over time. Initial status and rate of change in grip strength had the strongest association with proximity from death, indicating that while PEFR and repeated chair stand time are useful tests to assess function, grip strength appears to be a particularly useful biomarker in the oldest- old.
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13.
  • Thijssen, E. H., et al. (författare)
  • Diagnostic value of plasma phosphorylated tau181 in Alzheimer's disease and frontotemporal lobar degeneration
  • 2020
  • Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 26, s. 387-397
  • Tidskriftsartikel (refereegranskat)abstract
    • Plasma pTau181 concentrations are elevated specifically in patients diagnosed with Alzheimer's disease compared to those diagnosed with frontotemporal lobar degeneration or elderly controls, supporting its further development as a blood-based biomarker for AD. With the potential development of new disease-modifying Alzheimer's disease (AD) therapies, simple, widely available screening tests are needed to identify which individuals, who are experiencing symptoms of cognitive or behavioral decline, should be further evaluated for initiation of treatment. A blood-based test for AD would be a less invasive and less expensive screening tool than the currently approved cerebrospinal fluid or amyloid beta positron emission tomography (PET) diagnostic tests. We examined whether plasma tau phosphorylated at residue 181 (pTau181) could differentiate between clinically diagnosed or autopsy-confirmed AD and frontotemporal lobar degeneration. Plasma pTau181 concentrations were increased by 3.5-fold in AD compared to controls and differentiated AD from both clinically diagnosed (receiver operating characteristic area under the curve of 0.894) and autopsy-confirmed frontotemporal lobar degeneration (area under the curve of 0.878). Plasma pTau181 identified individuals who were amyloid beta-PET-positive regardless of clinical diagnosis and correlated with cortical tau protein deposition measured by F-18-flortaucipir PET. Plasma pTau181 may be useful to screen for tau pathology associated with AD.
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14.
  • Aliko, A., et al. (författare)
  • World Workshop on Oral Medicine VI: clinical implications of medication-induced salivary gland dysfunction
  • 2015
  • Ingår i: Oral Surgery Oral Medicine Oral Pathology Oral Radiology. - : Elsevier BV. - 2212-4403. ; 120:2, s. 185-206
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. This study aimed to systematically review the available literature on the clinical implications of medication-induced salivary gland dysfunction (MISGD). Study Design. The systematic review was performed using PubMed, Embase, and Web of Science (through June 2013). Studies were assessed for degree of relevance and strength of evidence, based on whether clinical implications of MISGD were the primary study outcomes, as well as on the appropriateness of study design and sample size. Results. For most purported xerogenic medications, xerostomia was the most frequent adverse effect. In the majority of the 129 reviewed papers, it was not documented whether xerostomia was accompanied by decreased salivary flow. Incidence and prevalence of medication-induced xerostomia varied widely and was often associated with number and dose of medications. Xerostomia was most frequently reported to be mild-to-moderate in severity. Its onset occurred usually in the first weeks of treatment. There was selected evidence that medication-induced xerostomia occurs more frequently in women and older adults and that MISGD may be associated with other clinical implications, such as caries or oral mucosal alterations. Conclusions. The systematic review showed that MISGD constitutes a significant burden in many patients and may be associated with important negative implications for oral health.
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15.
  • Dawes, C., et al. (författare)
  • The functions of human saliva: A review sponsored by the World Workshop on Oral Medicine VI
  • 2015
  • Ingår i: Archives of Oral Biology. - : Elsevier BV. - 0003-9969. ; 60:6, s. 863-874
  • Forskningsöversikt (refereegranskat)abstract
    • This narrative review of the functions of saliva was conducted in the PubMed, Embase and Web of Science databases. Additional references relevant to the topic were used, as our key words did not generate references which covered all known functions of saliva. These functions include maintaining a moist oral mucosa which is less susceptible to abrasion, and removal of micro-organisms, desquamated epithelial cells, leucocytes and food debris by swallowing. The mucins form a slimy coating on all surfaces in the mouth and act as a lubricant during such processes as mastication, formation of a food bolus, swallowing and speaking. Saliva provides the fluid in which solid tastants may dissolve and distributes tastants around the mouth to the locations of the taste buds. The hypotonic unstimulated saliva facilitates taste recognition. Salivary amylase is involved in digestion of starches. Saliva acts as a buffer to protect oral, pharyngeal and oesophageal mucosae from orally ingested acid or acid regurgitated from the stomach. Saliva protects the teeth against acid by contributing to the acquired enamel pellicle, which forms a renewable lubricant between opposing tooth surfaces, by being supersaturated with respect to tooth mineral, by containing bicarbonate as a buffer and urea and by facilitating clearance of acidic materials from the mouth. Saliva contains many antibacterial, antiviral and antifungal agents which modulate the oral microbial flora in different ways. Saliva also facilitates the healing of oral wounds. Clearly, saliva has many functions which are needed for proper protection and functioning of the human body. (C) 2015 Elsevier Ltd. All rights reserved. RAMS CK, 1988, GASTROENTEROLOGY, V95, P1460
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  • Franke, Andre, et al. (författare)
  • Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1118-1125
  • Tidskriftsartikel (refereegranskat)abstract
    • We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.
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  • Garshick, Eric, et al. (författare)
  • Respiratory Health after Military Service in Southwest Asia and Afghanistan An Official American Thoracic Society Workshop Report
  • 2019
  • Ingår i: Proceedings of the American Thoracic Society online. - : American Thoracic Society. - 1546-3222 .- 1943-5665. ; 16:8, s. E1-E16
  • Tidskriftsartikel (refereegranskat)abstract
    • Since 2001, more than 2.7 million U.S. military personnel have been deployed in support of operations in Southwest Asia and Afghanistan. Land-based personnel experienced elevated exposures to particulate matter and other inhalational exposures from multiple sources, including desert dust, burn pit combustion, and other industrial, mobile, or military sources. A workshop conducted at the 2018 American Thoracic Society International Conference had the goals of: 1) identifying key studies assessing postdeployment respiratory health, 2) describing emerging research, and 3) highlighting knowledge gaps. The workshop reviewed epidemiologic studies that demonstrated more frequent encounters for respiratory symptoms postdeployment compared with nondeployers and for airway disease, predominantly asthma, as well as case series describing postdeployment dyspnea, asthma, and a range of other respiratory tract findings. On the basis of particulate matter effects in other populations, it also is possible that deployers experienced reductions in pulmonary function as a result of such exposure. The workshop also gave particular attention to constrictive bronchiolitis, which has been reported in lung biopsies of selected deployers. Workshop participants had heterogeneous views regarding the definition and frequency of constrictive bronchiolitis and other small airway pathologic findings in deployed populations. The workshop concluded that the relationship of airway disease, including constrictive bronchiolitis, to exposures experienced during deployment remains to be better defined. Future clinical and epidemiologic research efforts should address better characterization of deployment exposures; carry out longitudinal assessment of potentially related adverse health conditions, including lung function and other physiologic changes; and use rigorous histologic, exposure, and clinical characterization of patients with respiratory tract abnormalities.
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18.
  • Han, Songfeng, et al. (författare)
  • Non-contact scanning diffuse correlation tomography system for three-dimensional blood flow imaging in a murine bone graft model.
  • 2015
  • Ingår i: Biomedical Optics Express. - 2156-7085. ; 6:7
  • Tidskriftsartikel (refereegranskat)abstract
    • A non-contact galvanometer-based optical scanning system for diffuse correlation tomography was developed for monitoring bone graft healing in a murine femur model. A linear image reconstruction algorithm for diffuse correlation tomography was tested using finite-element method based simulated data and experimental data from a femur or a tube suspended in a homogeneous liquid phantom. Finally, the non-contact system was utilized to monitor in vivo blood flow changes prior to and one week after bone graft transplantation within murine femurs. Localized blood flow changes were observed in three mice, demonstrating a potential for quantification of longitudinal blood flow associated with bone graft healing.
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19.
  • Ivanics, Tommy, et al. (författare)
  • Evaluation of a Multidisciplinary Team Approach for Generating Survivorship Care Plan Treatment Summaries in Patients With Breast Cancer
  • 2019
  • Ingår i: J Oncol Pract. - : American Society of Clinical Oncology (ASCO). ; 15:5, s. e467-e474
  • Tidskriftsartikel (refereegranskat)abstract
    • The optimal structure for survivorship care plan (SCP) programs and methodology for generating treatment summaries (TSs) has not yet been defined, but the Commission on Cancer and the National Accreditation Program for Breast Centers both mandate that participating oncology programs implement SCP-TS processes for patients that have completed treatment. METHODS: We used the Institute for Healthcare Improvement’s Plan-Do-Study-Act model for conducting a quality improvement project evaluating two different SCP-TS programs implemented at the Henry Ford Health System/Henry Ford Cancer Institute’s Breast Oncology Program in Detroit, Michigan. System I involved TSs drafted by nonspecialist breast clinic staff; System II involved TSs vetted through a multidisciplinary breast specialist conference approach. Accuracy of basic documentation entries related to dates and components of treatment were compared for the two approaches. RESULTS: Seventy-one System I and 93 System II documents were reviewed. Documentation was accurate in at least 90% of documents for both systems regarding delivery of chemotherapy and/or endocrine therapy and for documenting the identity of the various members of the cancer treatment team. Both systems had notable inaccuracies in documenting type of surgery performed, but System II had fewer inaccuracies than System I (33.78% v 51.67%, respectively; P = .05). System II, compared with System I, had fewer inaccuracies in documenting date of diagnosis (9.68% v 25.35%, respectively; P = .01) and had less missing information for dose of radiation delivered (9.33% v 33.9%, respectively; P < .01). CONCLUSION: A multidisciplinary team approach to drafting and reviewing SCP-TS documents improved content accuracy for our program, but ongoing education regarding documentation of various surgical procedures is warranted.
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20.
  • Jovanović, Veljko, et al. (författare)
  • The Satisfaction with Life Scale in Adolescent Samples : Measurement Invariance across 24 Countries and Regions, Age, and Gender
  • 2022
  • Ingår i: Applied Research in Quality of Life. - : Springer Science and Business Media LLC. - 1871-2584 .- 1871-2576. ; 17:4, s. 2139-2161
  • Tidskriftsartikel (refereegranskat)abstract
    • Measurement of adolescent life satisfaction across cultures has not received much attention in previous empirical research. The present study evaluated measurement invariance of the Satisfaction with Life Scale (SWLS) among adolescents in 24 countries and regions (N = 22,710; age range = 13–19 years; 53% female). A single-factor model with residual covariance between a pair of items tapping past life satisfaction fitted well in 19 countries and regions and showed a partial metric invariance. In a subset of nine countries and regions, partial scalar invariance was supported. Partial metric invariance across all 24 countries and regions was achieved when custom model modifications in five countries and regions were included. Three SWLS items showed evidence of noninvariance across cultures. The measurement model was found to operate similarly across gender and age. Our findings suggest that caution is needed when using the SWLS for measuring life satisfaction among adolescents from different cultures.
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  • Li, Dalin, et al. (författare)
  • A Pleiotropic Missense Variant in SLC39A8 Is Associated With Crohn's Disease and Human Gut Microbiome Composition
  • 2016
  • Ingår i: Gastroenterology. - : Saunders Elsevier. - 0016-5085 .- 1528-0012. ; 151:4, s. 724-732
  • Tidskriftsartikel (refereegranskat)abstract
    • Background & Aims: Genome-wide association studies have identified 200 inflammatory bowel disease (IBD) loci, but the genetic architecture of Crohn's disease (CD) and ulcerative colitis remain incompletely defined. Here, we aimed to identify novel associations between IBD and functional genetic variants using the Illumina ExomeChip (San Diego, CA).Methods: Genotyping was performed in 10,523 IBD cases and 5726 non-IBD controls. There were 91,713 functional single-nucleotide polymorphism loci in coding regions analyzed. A novel identified association was replicated further in 2 independent cohorts. We further examined the association of the identified single-nucleotide polymorphism with microbiota from 338 mucosal lavage samples in the Mucosal Luminal Interface cohort measured using 16S sequencing.Results: We identified an association between CD and a missense variant encoding alanine or threonine at position 391 in the zinc transporter solute carrier family 39, member 8 protein (SLC39A8 alanine 391 threonine, rs13107325) and replicated the association with CD in 2 replication cohorts (combined meta-analysis P = 5.55 × 10(-13)). This variant has been associated previously with distinct phenotypes including obesity, lipid levels, blood pressure, and schizophrenia. We subsequently determined that the CD risk allele was associated with altered colonic mucosal microbiome composition in both healthy controls (P = .009) and CD cases (P = .0009). Moreover, microbes depleted in healthy carriers strongly overlap with those reduced in CD patients (P = 9.24 × 10(-16)) and overweight individuals (P = 6.73 × 10(-16)).Conclusions: Our results suggest that an SLC39A8-dependent shift in the gut microbiome could explain its pleiotropic effects on multiple complex diseases including CD.
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  • Michaloski, John, et al. (författare)
  • Push–Button Discrete Event Simulation for Analysis of Factory Floor Operations
  • 2010
  • Ingår i: ASME 2010 International Mechanical Engineering Congress and Exposition, IMECE 2010; Vancouver, BC; Canada; 12 November 2010 through 18 November 2010. - 9780791844274 ; 3:PARTS A AND B, s. 313-319
  • Konferensbidrag (refereegranskat)abstract
    • In manufacturing, Discrete Event Simulation (DES) can beeffectively used to model production and provide sustainability analysis of equipment and system operation by measuring throughput, capacity, and bottlenecks. DES allows analysis under different scenarios and conditions that can then be used to forecast more optimal system performance. For discrete parts production, DES is rarely used because of the difficulty in attaining timely and accurate statistical modeling of the equipment and process operation. In this paper we look at the use of the plant floor interoperability standard, MTConnect, as a means to improve the access to machine tool data. Given data access, we develop a Finite State Model in order to streamline Machine Tool and DES integration. A case study of a prototype Capacity Planning system using DES as a modeling back–end will be described to help in understanding resource allocation of shop floor machines to a batch of aerospace parts. Direct machine tool statistical parameterization into a Web–based DES leads to “Push–button” automated simulations.
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  • Ramanarayanan, Vikram, et al. (författare)
  • Analysis of speech production real-time MRI
  • 2018
  • Ingår i: Computer Speech and Language. - : Elsevier BV. - 0885-2308. ; 52, s. 1-22
  • Forskningsöversikt (refereegranskat)abstract
    • Recent advances in real-time magnetic resonance imaging (RT-MRI) have made it possible to study the anatomy and dynamic motion of the vocal tract during speech production with great detail. The abundance of rich data on speech articulation provided by medical imaging techniques affords new opportunities for speech science, linguistics, clinical and technological research and application development, but also presents new challenges in audio–video data analysis and data modeling. We review techniques used in analysis of articulatory data acquired using RT-MRI, and assess the utility of different approaches for different types of data and research goals.
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28.
  • van Leeuwen, S. J. M., et al. (författare)
  • Significant salivary changes in relation to oral mucositis following autologous hematopoietic stem cell transplantation
  • 2021
  • Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365.
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this multicentre, longitudinal study was to determine salivary changes in relation to oral mucositis (OM) in multiple myeloma patients following high-dose melphalan and autologous hematopoietic stem cell transplantation (ASCT). Unstimulated and stimulated whole-mouth saliva samples (UWS and SWS) were collected before ASCT, 1x/wk during the hospitalisation phase, and 3 and 12 months post-ASCT. During the hospitalisation period OM was scored 3x/wk (WHO system). Flow rate, pH, total protein concentration (Nanodrop), albumin, lactoferrin, neutrophil defensin-1 (HNP1), total IgA and S100A8/A9 (ELISA) were determined. Mixed models were used to evaluate differences between ulcerative (u)OM (>= 2 WHO, n = 20) and non-uOM (n = 31) groups. Until 18 days after ASCT, flow rate, pH, total IgA and HNP1 levels decreased in UWS and/or SWS, while log lactoferrin levels were significantly increased (UWS: p = 0.016 95% CI [0.36, 3.58], SWS: p < 0.001 95% CI [1.14, 3.29]). Twelve months post-ASCT, salivary protein levels were similar to baseline except for log total IgA, which was higher (UWS: p < 0.001 95% CI [0.49, 1.29], SWS: p < 0.001 95% CI [0.72, 1.45]). No differences between uOM and non-uOM groups were observed. Changes in salivary proteins indicated an inflammatory reaction in salivary glands coinciding with mucosal and systemic reactions in response to high-dose melphalan.
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29.
  • van Leeuwen, S. J. M., et al. (författare)
  • The salivary proteome in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients: a labelled and label-free proteomics approach
  • 2023
  • Ingår i: Bmc Oral Health. - 1472-6831. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundOral mucositis is a frequently seen complication in the first weeks after hematopoietic stem cell transplantation recipients which can severely affects patients quality of life. In this study, a labelled and label-free proteomics approach were used to identify differences between the salivary proteomes of autologous hematopoietic stem cell transplantation (ASCT) recipients developing ulcerative oral mucositis (ULC-OM; WHO score & GE; 2) or not (NON-OM).MethodsIn the TMT-labelled analysis we pooled saliva samples from 5 ULC-OM patients at each of 5 timepoints: baseline, 1, 2, 3 weeks and 3 months after ASCT and compared these with pooled samples from 5 NON-OM patients. For the label-free analysis we analyzed saliva samples from 9 ULC-OM and 10 NON-OM patients at 6 different timepoints (including 12 months after ASCT) with Data-Independent Acquisition (DIA). As spectral library, all samples were grouped (ULC-OM vs NON-OM) and analyzed with Data Dependent Analysis (DDA). PCA plots and a volcano plot were generated in RStudio and differently regulated proteins were analyzed using GO analysis with g:Profiler.ResultsA different clustering of ULC-OM pools was found at baseline, weeks 2 and 3 after ASCT with TMT-labelled analysis. Using label-free analysis, week 1-3 samples clustered distinctly from the other timepoints. Unique and up-regulated proteins in the NON-OM group (DDA analysis) were involved in immune system-related processes, while those proteins in the ULC-OM group were intracellular proteins indicating cell lysis.ConclusionsThe salivary proteome in ASCT recipients has a tissue protective or tissue-damage signature, that corresponded with the absence or presence of ulcerative oral mucositis, respectively.
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  • Villa, A., et al. (författare)
  • World Workshop on Oral Medicine VI: a systematic review of medication-induced salivary gland dysfunction
  • 2016
  • Ingår i: Oral Diseases. - : Wiley. - 1354-523X. ; 22:5, s. 365-382
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this paper was to perform a systematic review of the pathogenesis of medication-induced salivary gland dysfunction (MISGD). Review of the identified papers was based on the standards regarding the methodology for systematic reviews set forth by the World Workshop on Oral Medicine IV and the PRISMA statement. Eligible papers were assessed for both the degree and strength of relevance to the pathogenesis of MISGD as well as on the appropriateness of the study design and sample size. A total of 99 papers were retained for the final analysis. MISGD in human studies was generally reported as xerostomia (the sensation of oral dryness) without measurements of salivary secretion rate. Medications may act on the central nervous system (CNS) and/or at the neuroglandular junction on muscarinic, α-and β-adrenergic receptors and certain peptidergic receptors. The types of medications that were most commonly implicated for inducing salivary gland dysfunction were those acting onthe nervous, cardiovascular, genitourinary, musculoskeletal, respiratory, and alimentary systems. Although many medications may affect the salivary flow rate and composition, most of the studies considered only xerostomia. Thus, further human studies are necessary to improve our understanding of the association between MISGD and the underlying pathophysiology. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
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31.
  • Villa, A., et al. (författare)
  • World Workshop on Oral Medicine VI: a systematic review of medication-induced salivary gland dysfunction: prevalence, diagnosis, and treatment
  • 2015
  • Ingår i: Clinical Oral Investigations. - : Springer Science and Business Media LLC. - 1432-6981 .- 1436-3771. ; 19:7, s. 1563-1580
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Medication-induced salivary gland dysfunction (MISGD) causes significant morbidity resulting in decreased quality of life. This systematic review assessed the literature on the prevalence, diagnosis, treatment, and prevention of MISGD. Materials and methods Electronic databases were searched for articles related to MISGD through June 2013. Four independent reviewers extracted information regarding study design, study population, interventions, outcomes, and conclusions for each article. Only papers with acceptable degree of relevance, quality of methodology, and strength of evidence were retained for further analysis. Results There were limited data on the epidemiology of MISGD. Furthermore, various methods were used to assess salivary flow rate or xerostomia. Preventive and therapeutic strategies included substitution of medications, oral, or systemic therapy with sialogogues, use of saliva substitutes or of electro-stimulating devices. Although there are promising approaches to improve salivary gland function, most studies are characterized by small numbers and heterogeneous methods. Conclusions Physicians and dentists should identify the medications associated with xerostomia and salivary gland dysfunction through a thorough medical history. Preferably, health care providers should measure the unstimulated and stimulated whole salivary flow rates of all their patients so that these values can be used as a baseline to rate the complaints of patients who subsequently claim to experience xerostomia or salivary gland dysfunction as well as the possibilities of effectively treating this condition. Clinical relevance MISGD remains a major burden for the population. This systematic review provides a contemporary in-depth description of the diagnosis and treatment of MISGD.
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32.
  • Wolff, A., et al. (författare)
  • A Guide to Medications Inducing Salivary Gland Dysfunction, Xerostomia, and Subjective Sialorrhea: A Systematic Review Sponsored by the World Workshop on Oral Medicine VI
  • 2017
  • Ingår i: Drugs in R&D. - : Springer Science and Business Media LLC. - 1174-5886 .- 1179-6901. ; 17:1, s. 1-28
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Medication-induced salivary gland dysfunction (MISGD), xerostomia (sensation of oral dryness), and subjective sialorrhea cause significant morbidity and impair quality of life. However, no evidence-based lists of the medications that cause these disorders exist. Objective Our objective was to compile a list of medications affecting salivary gland function and inducing xerostomia or subjective sialorrhea. Data Sources Electronic databases were searched for relevant articles published until June 2013. Of 3867 screened records, 269 had an acceptable degree of relevance, quality of methodology, and strength of evidence. We found 56 chemical substances with a higher level of evidence and 50 with a moderate level of evidence of causing the abovementioned disorders. At the first level of the Anatomical Therapeutic Chemical (ATC) classification system, 9 of 14 anatomical groups were represented, mainly the alimentary, cardiovascular, genitourinary, nervous, and respiratory systems. Management strategies include substitution or discontinuation of medications whenever possible, oral or systemic therapy with sialogogues, administration of saliva substitutes, and use of electro-stimulating devices. Limitations While xerostomia was a commonly reported outcome, objectively measured salivary flow rate was rarely reported. Moreover, xerostomia was mostly assessed as an adverse effect rather than the primary outcome of medication use. This study may not include some medications that could cause xerostomia when administered in conjunction with others or for which xerostomia as an adverse reaction has not been reported in the literature or was not detected in our search. Conclusions We compiled a comprehensive list of medications with documented effects on salivary gland function or symptoms that may assist practitioners in assessing patients who complain of dry mouth while taking medications. The list may also prove useful in helping practitioners anticipate adverse effects and consider alternative medications.
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