SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "LAR1:uu ;mspu:(researchreview);lar1:(oru)"

Sökning: LAR1:uu > Forskningsöversikt > Örebro universitet

  • Resultat 1-10 av 34
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Alvarsson, Jonathan, 1981-, et al. (författare)
  • Predicting With Confidence : Using Conformal Prediction in Drug Discovery
  • 2021
  • Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier. - 0022-3549 .- 1520-6017. ; 110:1, s. 42-49
  • Forskningsöversikt (refereegranskat)abstract
    • One of the challenges with predictive modeling is how to quantify the reliability of the models' predictions on new objects. In this work we give an introduction to conformal prediction, a framework that sits on top of traditional machine learning algorithms and which outputs valid confidence estimates to predictions from QSAR models in the form of prediction intervals that are specific to each predicted object. For regression, a prediction interval consists of an upper and a lower bound. For classification, a prediction interval is a set that contains none, one, or many of the potential classes. The size of the prediction interval is affected by a user-specified confidence/significance level, and by the nonconformity of the predicted object; i.e., the strangeness as defined by a nonconformity function. Conformal prediction provides a rigorous and mathematically proven framework for in silico modeling with guarantees on error rates as well as a consistent handling of the models' applicability domain intrinsically linked to the underlying machine learning model. Apart from introducing the concepts and types of conformal prediction, we also provide an example application for modeling ABC transporters using conformal prediction, as well as a discussion on general implications for drug discovery.
  •  
2.
  • Bridel, Claire, et al. (författare)
  • Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
  • 2019
  • Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
  • Forskningsöversikt (refereegranskat)abstract
    • Importance  Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives  To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources  PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection  Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis  Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure  The cNfL levels adjusted for age and sex across diagnoses.Results  Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance  These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
  •  
3.
  • Bäcke, Pyrola, et al. (författare)
  • Interventions for the Management of Pain and Sedation in Newborns Undergoing Therapeutic Hypothermia for Hypoxic-Ischemic Encephalopathy : A Systematic Review
  • 2023
  • Ingår i: Pediatric Drugs. - : Springer. - 1174-5878 .- 1179-2019. ; 25:1, s. 27-41
  • Forskningsöversikt (refereegranskat)abstract
    • BACKGROUND: Newborn infants undergoing therapeutic hypothermia (TH) are exposed to multiple painful and stressful procedures. The aim of this systematic review was to assess benefits and harms of pharmacological and non-pharmacological interventions for the management of pain and sedation in newborn infants undergoing TH for hypoxic-ischemic encephalopathy.METHODS: We included randomized and observational studies reporting any intervention (either drugs or non-pharmacological interventions) to manage pain and sedation in newborn infants (> 33 weeks' gestational age) undergoing TH. We included any dose, duration and route of administration. We also included any type and duration of non-pharmacological interventions. Our prespecified primary outcomes were analgesia and sedation assessed using validated pain scales in the neonatal population; circulatory instability; mortality to discharge; and neurodevelopmental disability. A systematic literature search was conducted in the PubMed, Embase, CINAHL, Cochrane CENTRAL, Scopus, and Web of Science databases, with no language restrictions. Included studies underwent risk-of-bias assessment (Cochrane risk-of-bias tool and ROBINS-I) and data extraction performed by two authors independently. The plan had been to use effect measures such as mean difference for continuous outcomes and risk ratio for dichotomous outcomes, however the included studies are presented in a narrative synthesis due to their paucity and heterogeneity.RESULTS: Ten studies involving 3551 infants were included-one trial and nine observational studies. Most studies examined the use of phenobarbital or other antiepileptic drugs with primary outcomes related to seizure activity. The single trial that was included compared pentoxifylline with placebo. Among the primary outcomes, six studies reported circulatory instability and five reported mortality to discharge without relevant differences; two studies reported on neurodevelopmental disability and one study reported on pain scale. Three studies were ongoing. CONCLUSIONS: We found limited evidence to establish the benefits and harms of the interventions for the management of pain and sedation in newborn infants undergoing TH. Long-term outcomes were not reported. Given the very low certainty of evidence-due to imprecision of the estimates, inconsistency and limitations in study design (all nine observational studies with overall serious risk of bias)-for all outcomes, clinical trials are required to determine the most effective interventions in this population.SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD42020205755.
  •  
4.
  • Bäcke, Pyrola, et al. (författare)
  • Interventions for the management of Pain and Sedation in Newborns undergoing Therapeutic hypothermia for hypoxic-ischemic encephalopathy (IPSNUT) : protocol of a systematic review
  • 2022
  • Ingår i: Systematic Reviews. - : BioMed Central. - 2046-4053. ; 11:1
  • Forskningsöversikt (refereegranskat)abstract
    • BACKGROUND: Clinical research has shown that therapeutic hypothermia after neonatal hypoxic-ischemic injury improves survival without disability. There is no consensus regarding pain relief or sedation during therapeutic hypothermia in newborns; however, therapeutic hypothermia seems to be associated with pain and stress, and adequate analgesia and sedation are central to maximize the effect of therapeutic hypothermia. Pain needs to be adequately managed in all patients, especially the newborn infant due to the potential short- and long-term negative effects of inadequately treated pain in this population.METHODS: We will perform a systematic review of pharmacological and non-pharmacological interventions for the management of pain and sedation in newborn infants undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy. We will include randomized, quasi-randomized controlled trials and observational studies. The use of pharmacological or non-pharmacological interventions will be compared to other pharmacological and or non-pharmacological interventions or no intervention/placebo. The primary outcomes for this review will be analgesia and sedation assessed with validated pain scales, circulatory instability, mortality to discharge, and moderate-to-severe neurodevelopmental disability. We will search the following databases: CINAHL, ClinicalTrials.gov , Cochrane Library, Embase, PubMed, Scopus, and Web of Science. Two independent researchers will screen the records for inclusion, extract data using a data extraction form, and assess the risk of bias in the included trials.DISCUSSION: The result of this review will summarize the knowledge regarding the management of pain and sedation in infants treated with therapeutic hypothermia and potentially provide clinicians with guidance on the effective and safe methods.
  •  
5.
  • Bäcke, Pyrola, et al. (författare)
  • Pharmacological interventions for pain and sedation management in newborn infants undergoing therapeutic hypothermia
  • 2022
  • Ingår i: Cochrane Database of Systematic Reviews. - : John Wiley & Sons. - 1469-493X .- 1469-493X. ; 2022:11
  • Forskningsöversikt (refereegranskat)abstract
    • BACKGROUND: Newborn infants affected by hypoxic-ischemic encephalopathy (HIE) undergo therapeutic hypothermia. As this treatment seems to be associated with pain, and intensive and invasive care is needed, pharmacological interventions are often used. Moreover, painful procedures in the newborn period can affect pain responses later in life, impair brain development, and possibly have a long-term negative impact on neurodevelopment and quality of life.OBJECTIVES: To determine the effects of pharmacological interventions for pain and sedation management in newborn infants undergoing therapeutic hypothermia. Primary outcomes were analgesia and sedation, and all-cause mortality to discharge.SEARCH METHODS: We searched CENTRAL, PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and the trial register ISRCTN in August 2021. We also checked the reference lists of relevant articles to identify additional studies.SELECTION CRITERIA: We included randomized controlled trials (RCT), quasi-RCTs and cluster-randomized trials comparing drugs used for the management of pain or sedation, or both, during therapeutic hypothermia: any opioids (e.g. morphine, fentanyl), alpha-2 agonists (e.g. clonidine, dexmedetomidine), N-Methyl-D-aspartate (NMDA) receptor antagonist (e.g. ketamine), other analgesics (e.g. paracetamol), and sedatives (e.g. benzodiazepines such as midazolam) versus another drug, placebo, no intervention, or non-pharmacological interventions.  Primary outcomes were analgesia and sedation, and all-cause mortality to discharge.DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies identified by the search strategy for inclusion. We planned to use the GRADE approach to assess the certainty of evidence. We planned to assess the methodological quality of included trials using Cochrane Effective Practice and Organisation of Care Group (EPOC) criteria (assessing randomization, blinding, loss to follow-up, and handling of outcome data). We planned to evaluate treatment effects using a fixed-effect model with risk ratio (RR) for categorical data and mean, standard deviation (SD), and mean difference (MD) for continuous data.  MAIN RESULTS: We did not find any completed studies for inclusion. Amongst the four excluded studies, topiramate and atropine were used in two and one trial, respectively; one study used dexmedetomidine and was initially reported in 2019 to be a randomized trial. However, it was an observational study (correction in 2021). We identified one ongoing study comparing dexmedetomidine to morphine.AUTHORS' CONCLUSIONS: We found no studies that met our inclusion criteria and hence there is no evidence to recommend or refute the use of pharmacological interventions for pain and sedation management in newborn infants undergoing therapeutic hypothermia.
  •  
6.
  • Dernini, S., et al. (författare)
  • Med Diet 4.0 : the Mediterranean diet with four sustainable benefits
  • 2017
  • Ingår i: Public Health Nutrition. - : Cambridge University Press. - 1368-9800 .- 1475-2727. ; 20:7, s. 1322-1330
  • Forskningsöversikt (refereegranskat)abstract
    • Objective: To characterize the multiple dimensions and benefits of the Mediterranean diet as a sustainable diet, in order to revitalize this intangible food heritage at the country level; and to develop a multidimensional framework - the Med Diet 4.0 - in which four sustainability benefits of the Mediterranean diet are presented in parallel: major health and nutrition benefits, low environmental impacts and richness in biodiversity, high sociocultural food values, and positive local economic returns.Design: A narrative review was applied at the country level to highlight the multiple sustainable benefits of the Mediterranean diet into a single multidimensional framework: the Med Diet 4.0.Setting/subjects: We included studies published in English in peer-reviewed journals that contained data on the characterization of sustainable diets and of the Mediterranean diet. The methodological framework approach was finalized through a series of meetings, workshops and conferences where the framework was presented, discussed and ultimately refined.Results: The Med Diet 4.0 provides a conceptual multidimensional framework to characterize the Mediterranean diet as a sustainable diet model, by applying principles of sustainability to the Mediterranean diet.Conclusions: By providing a broader understanding of the many sustainable benefits of the Mediterranean diet, the Med Diet 4.0 can contribute to the revitalization of the Mediterranean diet by improving its current perception not only as a healthy diet but also a sustainable lifestyle model, with country-specific and culturally appropriate variations. It also takes into account the identity and diversity of food cultures and systems, expressed within the notion of the Mediterranean diet, across the Mediterranean region and in other parts of the world. Further multidisciplinary studies are needed for the assessment of the sustainability of the Mediterranean diet to include these new dimensions.
  •  
7.
  • Digkas, Evangelos, et al. (författare)
  • Randomized Versus Real-World Evidence on the Efficacy and Toxicity of Checkpoint Inhibitors in Cancer in Patients with Advanced Non-small Cell Lung Cancer or Melanoma : A Meta-analysis
  • 2022
  • Ingår i: Targeted oncology. - : Springer. - 1776-2596 .- 1776-260X. ; 17:5, s. 507-515
  • Forskningsöversikt (refereegranskat)abstract
    • BACKGROUND: Both randomized controlled trials (RCTs) and real-world evidence (RWE) studies provide results regarding the efficacy and toxicity of checkpoint inhibitors in cancer patients. The results from these two sources are considered complementary but whether they are comparable remains unknown.OBJECTIVE: The aim of this study was to compare the efficacy and toxicity of checkpoint inhibitors between RCTs and RWE studies in patients with advanced non-small cell lung cancer (NSCLC) or melanoma.PATIENTS AND METHODS: Two electronic databases were searched to identify eligible studies, either RCTs or RWE studies, investigating the efficacy or toxicity of checkpoint inhibitors given for indications that were approved by the European Medicines Agency (EMA) at the date of the last search. A meta-analysis was performed and the pooled estimates of objective response rates (ORR), progression-free survival (PFS), overall survival (OS), and toxicity and treatment discontinuation between RCTs and RWE studies were compared.RESULTS: In total, 43 RWE studies and 15 RCTs were eligible, with adequate data for pooled estimates for immunotherapy indications regarding NSCLC and melanoma. No statistically significant or clinically meaningful differences in terms of pooled PFS, OS, or rates of treatment discontinuation due to toxicity between RCTs and RWE studies were observed. In some indications, a higher rate of response rates and lower rate of toxicity in favor of RWE was observed.CONCLUSION: In patients with melanoma or NSCLC, the clinical value of checkpoint inhibitors is evident in both RCTs and real-world settings. Some differences in response or toxicity rates in favor of RWE mainly reflects the inherent difficulties in evaluating these outcomes in RWE studies.
  •  
8.
  • Ek, Weronica E, et al. (författare)
  • The history of genetics in inflammatory bowel disease
  • 2014
  • Ingår i: Annals of Gastroenterology. - Athens, Greece : Hellenic Society of Gastroenterology. - 1108-7471 .- 1792-7463. ; 27:4, s. 294-303
  • Forskningsöversikt (refereegranskat)abstract
    • The influence of genetics in the etiology of inflammatory bowel disease (IBD) was initially demonstrated by epidemiological data, including differences in prevalence among different ethnic groups, familial aggregation of IBD, concordance in twins, and association with genetic syndromes. These early observations paved the way to molecular genetics in IBD, and culminated in the identification of nucleotide-binding oligomerization domain containing 2 (NOD2) gene as an IBD risk gene in 2001. As in other complex diseases, the advent of Genome Wide Association studies has dramatically improved the resolution of the IBD genome and our understanding of the pathogenesis of IBD. However, the complexity of the genetic puzzle in IBD seems more pronounced today than ever previously. In total, 163 risk genes/loci have been identified, and the corresponding number of possible causal variants is challenging. The great majority of these loci are associated with both Crohn's disease and ulcerative colitis, suggesting that nearly all of the biological mechanisms involved in one disease play some role in the other. Interestingly, a large proportion of the IBD risk loci are also shared with other immune-mediated diseases, primary immunodeficiencies and mycobacterial diseases.
  •  
9.
  • Elfström, P., et al. (författare)
  • Systematic review with meta-analysis : associations between coeliac disease and type 1 diabetes
  • 2014
  • Ingår i: Alimentary Pharmacology and Therapeutics. - : Wiley-Blackwell. - 0269-2813 .- 1365-2036. ; 40:10, s. 1123-1132
  • Forskningsöversikt (refereegranskat)abstract
    • Background: In the past decade, a number of population-based studies have examined the prevalence of coeliac disease in individuals with type 1 diabetes but prevalences have differed considerably.Aim: To examine the prevalence of coeliac disease in individuals with type 1 diabetes.Methods: A systematic review of English-language articles published in PubMed Medline between 2000 and May 2014. Search terms included celiac disease' or coeliac disease' and diabetes mellitus'. Studies were selected with at least 100 individuals with type 1 diabetes being screened for coeliac disease where the coeliac diagnosis was later confirmed through small intestinal biopsy. Data synthesis used random-effects inverse variance-weighted models, and metaregression was used to examine heterogeneity in subgroups.Results: A pooled analysis, based on 26,605 patients with type 1 diabetes, found a prevalence of biopsy-confirmed coeliac disease of 6.0% (95% CI=5.0-6.9%). Heterogeneity was large (I-2=93.2%). The prevalence was lower in adults with type 1 diabetes (2.7%), and in mixed populations with both children and adults with type 1 diabetes (4.7%) than in children (6.2%) with type 1 diabetes (P<0.001). Additional subgroup analyses could not explain the large variation in coeliac disease prevalence between studies.Conclusion: More than one in twenty patients with type 1 diabetes have biopsy-verified coeliac disease. This prevalence is high enough to motivate screening for coeliac disease among patients with type 1 diabetes.
  •  
10.
  • Fallet, Manon, 1992-, et al. (författare)
  • Present and future challenges for the investigation of transgenerational epigenetic inheritance
  • 2023
  • Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 172
  • Forskningsöversikt (refereegranskat)abstract
    • Epigenetic pathways are essential in different biological processes and in phenotype-environment interactions in response to different stressors and they can induce phenotypic plasticity. They encompass several processes that are mitotically and, in some cases, meiotically heritable, so they can be transferred to subsequent generations via the germline. Transgenerational Epigenetic Inheritance (TEI) describes the phenomenon that phenotypic traits, such as changes in fertility, metabolic function, or behavior, induced by environmental factors (e.g., parental care, pathogens, pollutants, climate change), can be transferred to offspring generations via epigenetic mecha-nisms. Investigations on TEI contribute to deciphering the role of epigenetic mechanisms in adaptation, adver-sity, and evolution. However, molecular mechanisms underlying the transmission of epigenetic changes between generations, and the downstream chain of events leading to persistent phenotypic changes, remain unclear. Therefore, inter-, (transmission of information between parental and offspring generation via direct exposure) and transgenerational (transmission of information through several generations with disappearance of the triggering factor) consequences of epigenetic modifications remain major issues in the field of modern biology.In this article, we review and describe the major gaps and issues still encountered in the TEI field: the general challenges faced in epigenetic research; deciphering the key epigenetic mechanisms in inheritance processes; identifying the relevant drivers for TEI and implement a collaborative and multi-disciplinary approach to study TEI. Finally, we provide suggestions on how to overcome these challenges and ultimately be able to identify the specific contribution of epigenetics in transgenerational inheritance and use the correct tools for environmental science investigation and biomarkers identification.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-10 av 34
Typ av publikation
Typ av innehåll
refereegranskat (33)
populärvet., debatt m.m. (1)
Författare/redaktör
Bruschettini, Matteo (3)
Ludvigsson, Jonas F. ... (3)
Thernström Blomqvist ... (3)
Sundström, Johan, Pr ... (2)
Ljungqvist, Olle, 19 ... (1)
Blennow, Kaj, 1958 (1)
visa fler...
Poortmans, Philip (1)
Aase, Audun (1)
La Vecchia, C (1)
Janson, Christer (1)
Zetterberg, Henrik, ... (1)
Kuhle, Jens (1)
Holmberg, Lars (1)
Wallin, Anders, 1950 (1)
Gisslén, Magnus, 196 ... (1)
Landén, Mikael, 1966 (1)
Liljegren, G (1)
Forsberg, Pia, 1949- (1)
Adami, Hans Olov (1)
Lycke, Jan, 1956 (1)
Halfvarson, Jonas, 1 ... (1)
Mucci, Lorelei A (1)
Jonsson Henningsson, ... (1)
Cederholm, Tommy (1)
Ekström, Magnus (1)
Khademi, Mohsen (1)
Olsson, Tomas (1)
Piehl, Fredrik (1)
Smedh, Kennet (1)
Chabok, Abbas (1)
Wikkelsö, Carsten, 1 ... (1)
Johannsson, Gudmundu ... (1)
Hansson, Oskar (1)
Janelidze, Shorena (1)
Björkholm, Magnus (1)
Norinder, Ulf (1)
Sundh, Josefin, 1972 ... (1)
Teunissen, Charlotte ... (1)
Alvarsson, Jonathan, ... (1)
Leinonen, Ville (1)
Ek, Weronica E (1)
Eggers, Kai M., 1962 ... (1)
Axelsson, Markus, 19 ... (1)
Forsgren, Lars (1)
Kaltsas, Gregory (1)
Kassi, Eva (1)
Daskalakis, Kosmas, ... (1)
Hedström, Margareta (1)
Trichopoulou, A (1)
Svenningsson, Anders (1)
visa färre...
Lärosäte
Uppsala universitet (34)
Språk
Engelska (34)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (30)
Naturvetenskap (3)
Humaniora (1)

År

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy