| 1. |
- Ahmed, Laeeq, et al.
(författare)
-
Predicting target profiles with confidence as a service using docking scores
- 2020
-
Ingår i: Journal of Cheminformatics. - : Springer Nature. - 1758-2946. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Identifying and assessing ligand-target binding is a core component in early drug discovery as one or more unwanted interactions may be associated with safety issues. Contributions: We present an open-source, extendable web service for predicting target profiles with confidence using machine learning for a panel of 7 targets, where models are trained on molecular docking scores from a large virtual library. The method uses conformal prediction to produce valid measures of prediction efficiency for a particular confidence level. The service also offers the possibility to dock chemical structures to the panel of targets with QuickVina on individual compound basis. Results: The docking procedure and resulting models were validated by docking well-known inhibitors for each of the 7 targets using QuickVina. The model predictions showed comparable performance to molecular docking scores against an external validation set. The implementation as publicly available microservices on Kubernetes ensures resilience, scalability, and extensibility.
|
|
| 2. |
- Bodin, Ingrid, 1944-
(författare)
-
Impairment of intra-oral sensation, discrimination ability, and swallowing function following radiotherapy and surgery for oral and pharyngeal cancer
- 2004
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Oral and pharyngeal cancer is commonly treated with a combination of radiotherapy and surgery. It is a clinical knowledge that patients often experience severe swallowing disorders following treatment. Since surgical sequelae are instantaneous and obvious, little attention has been paid to other concurrent effects of the treatment. To shed light on this subject, the aim of this thesis was twofold (i) to make a retrospective inventory of the sequelae following treatment and (ii) to perform a prospective, inceptive examination at diagnosis, and to follow-up after radiotherapy, six months and 12 months after surgery. The files of ninety-nine patients revealed that following treatment one-third had to use gastric fistulas and more than nine of ten patients had restricted swallowing capacity. Every second patient could only swallow puréed or liquid food. Adequate intra-oral sensation and discrimination ability is essential for bolus preparation and bolus control, for appropriate elicitation of the swallowing reflex and, hence, for the oral phase of swallowing. At the inceptive examination, the prospective part of the study demonstrated intra-oral discrimination ability in patients was equal to that in healthy controls but was impaired six months after treatment and there was no significant improvement after 12 months. It had been expected that the patient’s healthy, non-tumor side would compensate but it did not. An explanation was found when it was revealed that radiotherapy induced a delayed decline in intra-oral sensation. Sensory decline was not demonstrated within a month after radiotherapy but was manifest six months later. Since the radiotherapy field includes the neck, because of the risk for metastasis, it is highly plausible that pharyngeal sensation declines in a manner corresponding to that found intra-orally when the healthy side is irradiated. In accord with this presumption, pharyngeal swallowing function deteriorated in patents with oral tumors. Cineradiographic evaluation of oral and pharyngeal swallowing function disclosed a significant association between the degree of swallowing dysfunction and the degree of sensory decline and with the degree of impairment of shape recognition. Conclusions: Delayed intra-oral sensory decline, found to be induced by radiotherapy, can be expected to appear in the entire radiation field, including the oral cavity and the pharynx, with adverse effect on swallowing. Testing intra-oral sensation close to the last radiotherapy session is not advisable, because sensory decline does not develop immediately after radiotherapy but manifests after six months. Spontaneous sensory rehabilitation cannot be expected after six months. The significant association between degree of swallowing dysfunction and degree of intra-oral sensory decline and impaired discrimination ability must be considered in the quest for functional rehabilitation of patients treated for oral or pharyngeal cancer.
|
|
| 3. |
- Capuccini, Marco, et al.
(författare)
-
On-demand virtual research environments using microservices
- 2019
-
Ingår i: PeerJ Computer Science. - : PeerJ. - 2376-5992. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- The computational demands for scientific applications are continuously increasing. The emergence of cloud computing has enabled on-demand resource allocation. However, relying solely on infrastructure as a service does not achieve the degree of flexibility required by the scientific community. Here we present a microservice-oriented methodology, where scientific applications run in a distributed orchestration platform as software containers, referred to as on-demand, virtual research environments. The methodology is vendor agnostic and we provide an open source implementation that supports the major cloud providers, offering scalable management of scientific pipelines. We demonstrate applicability and scalability of our methodology in life science applications, but the methodology is general and can be applied to other scientific domains.
|
|
| 4. |
- Emami Khoonsari, Payam, et al.
(författare)
-
Interoperable and scalable data analysis with microservices : Applications in metabolomics
- 2019
-
Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 35:19, s. 3752-3760
-
Tidskriftsartikel (refereegranskat)abstract
- MotivationDeveloping a robust and performant data analysis workflow that integrates all necessary components whilst still being able to scale over multiple compute nodes is a challenging task. We introduce a generic method based on the microservice architecture, where software tools are encapsulated as Docker containers that can be connected into scientific workflows and executed using the Kubernetes container orchestrator.ResultsWe developed a Virtual Research Environment (VRE) which facilitates rapid integration of new tools and developing scalable and interoperable workflows for performing metabolomics data analysis. The environment can be launched on-demand on cloud resources and desktop computers. IT-expertise requirements on the user side are kept to a minimum, and workflows can be re-used effortlessly by any novice user. We validate our method in the field of metabolomics on two mass spectrometry, one nuclear magnetic resonance spectroscopy and one fluxomics study. We showed that the method scales dynamically with increasing availability of computational resources. We demonstrated that the method facilitates interoperability using integration of the major software suites resulting in a turn-key workflow encompassing all steps for mass-spectrometry-based metabolomics including preprocessing, statistics and identification. Microservices is a generic methodology that can serve any scientific discipline and opens up for new types of large-scale integrative science.
|
|
| 5. |
- Herman, Stephanie, et al.
(författare)
-
Integration of magnetic resonance imaging and protein and metabolite CSF measurements to enable early diagnosis of secondary progressive multiple sclerosis
- 2018
-
Ingår i: Theranostics. - : Ivyspring International Publisher. - 1838-7640. ; 8:16, s. 4477-4490
-
Tidskriftsartikel (refereegranskat)abstract
- Molecular networks in neurological diseases are complex. Despite this fact, contemporary biomarkers are in most cases interpreted in isolation, leading to a significant loss of information and power. We present an analytical approach to scrutinize and combine information from biomarkers originating from multiple sources with the aim of discovering a condensed set of biomarkers that in combination could distinguish the progressive degenerative phenotype of multiple sclerosis (SPMS) from the relapsing-remitting phenotype (RRMS). Methods: Clinical and magnetic resonance imaging (MRI) data were integrated with data from protein and metabolite measurements of cerebrospinal fluid, and a method was developed to sift through all the variables to establish a small set of highly informative measurements. This prospective study included 16 SPMS patients, 30 RRMS patients and 10 controls. Protein concentrations were quantitated with multiplexed fluorescent bead-based immunoassays and ELISA. The metabolome was recorded using liquid chromatography-mass spectrometry. Clinical follow-up data of the SPMS patients were used to assess disease progression and development of disability. Results: Eleven variables were in combination able to distinguish SPMS from RRMS patients with high confidence superior to any single measurement. The identified variables consisted of three MRI variables: the size of the spinal cord and the third ventricle and the total number of T1 hypointense lesions; six proteins: galectin-9, monocyte chemoattractant protein-1 (MCP-1), transforming growth factor alpha (TGF-alpha), tumor necrosis factor alpha (TNF-alpha), soluble CD40L (sCD40L) and platelet-derived growth factor AA (PDGF-AA); and two metabolites: 20 beta-dihydrocortisol (20 beta-DHF) and indolepyruvate. The proteins myelin basic protein (MBP) and macrophage-derived chemokine (MDC), as well as the metabolites 20 beta-DHF and 5,6-dihydroxyprostaglandin F1a (5,6-DH-PGF1), were identified as potential biomarkers of disability progression. Conclusion: Our study demonstrates, in a limited but well-defined and data-rich cohort, the importance and value of combining multiple biomarkers to aid diagnostics and track disease progression.
|
|
| 6. |
- Kåberg, Martin, et al.
(författare)
-
High risk of non-alcoholic liver disease mortality in patients with chronic hepatitis C with illicit substance use disorder
- 2020
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 55:5, s. 574-580
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: Hepatitis C virus (HCV) is a slowly progressive disease, often transmitted among people who inject drugs (PWID). Mortality in PWID is high, with an overrepresentation of drug-related causes. This study investigated the risk of death in patients with chronic hepatitis C virus (HCV) infection with or without illicit substance use disorder (ISUD).Methods: Patients with HCV were identified using the Swedish National Patient Registry according to the International Classification of Diseases-10 (ICD-10) code B18.2, with ≤5 matched comparators from the general population. Patients with ≥2 physician visits with ICD-10 codes F11, F12, F14, F15, F16, or F19 were considered to have ISUD. The underlying cause of death was analyzed for alcoholic liver disease, non-alcoholic liver disease, liver cancer, drug-related and external causes, non-liver cancers, or other causes. Mortality risks were assessed using the standardized mortality ratio (SMR) with 95% CIs and Cox regression analyses for cause-specific hazard ratios.Results: In total, 38,186 patients with HCV were included, with 31% meeting the ISUD definition. Non-alcoholic liver disease SMRs in patients with and without ISUD were 123.2 (95% CI, 103.7-145.2) and 69.4 (95% CI, 63.8-75.3), respectively. The significant independent factors associated with non-alcoholic liver disease mortality were older age, being unmarried, male sex, and having ISUD.Conclusions: The relative risks for non-alcoholic liver disease mortality were elevated for patients with ISUD. Having ISUD was a significant independent factor for non-alcoholic liver disease. Thus, patients with HCV with ISUD should be given HCV treatment to reduce the risk for liver disease.
|
|
| 7. |
- Malm, Tobias, 1980-
(författare)
-
Konsten att hålla ihop : Om lärande och organisering i rockband
- 2020
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rock bands are foundational for modern day music life. These small groups provide well-being and self-fulfillment to its members, as well as fuel for the cultural life and the increasingly highlighted creative industries. Rock bands, however, are particularly difficult to organize. Bands face a range of challenges in keeping together and developing as a group.The aim of this doctoral thesis is to develop knowledge on rock band formation and development over time. Based in the discipline of education, the thesis mainly contributes to the fields of organization studies, social theories of learning, and music and cultural life research.The thesis uses the theory of situated learning to explore rock band formation and development. The methodology is qualitative and ethnographic, and the research design builds on three studies: an interview study with three rock bands and two case studies. All five bands are Swedish and have found different degrees of success and popularity.The thesis investigates band activities and courses of events, band members’ identities, and challenges faced. The findings indicate that a rock band’s activities shift between a production mode – i.e. highly productive times associated with public performances, record releases and marketing, and behind the scenes processes of creating, recording and planning – and a contrasting less active hibernation mode without bigger public projects or goals. The amount of time spent in production mode depends on the band’s degree of “membership” in the music industry. Moreover, a band member forms and actualizes identities of colleague, creator, entrepreneur, friend, hobbyist and professional, in differing combinations, situations and modes. Furthermore, the members’ most significant challenges relate to identity dilemmas.Based on these findings, the thesis formulates a model for a rock band’s learning trajectory and argues that a band may develop as it approaches, or becomes a more central member in, the music industry. This development demands increased public success and organizational ability: the band members’ ability to form business-oriented practices, to participate uniformly in an overarching community of practice, and to be flexible as they must identify with, and ascribe meaning to, a variety of activities in different and sometimes contradictory ways.The thesis concludes that the challenges of persistence as a rock band or similar group relates chiefly to group member difficulties in identifying with different activities and situations that are necessary to sustain and develop as a collective. Eventually, individual members tend to handle the experience of uncertainty and ambivalence by holding on to one singular identity, which may prevent group development, foster intra- and interpersonal tensions, and ultimately can lead to significant conflicts and/or a band’s breakup.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Söderholm, Jonas, et al.
(författare)
-
ELEVATED RISK FOR LIVER RELATED MORTALITY IN CHRONIC HEPATITIS C PATIENTS BOTH WITH OR WITHOUT ILLICIT SUBSTANCE USE DISORDER : A NATION-WIDE REGISTER STUDY
- 2019
-
Ingår i: Hepatology. - : John Wiley & Sons. - 0270-9139 .- 1527-3350. ; 70:Suppl. 1, s. 366A-366A
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Hepatitis C is a slowly progressive disease mainly transmitted in people who inject drugs . This cohort has a high mortality from drug related causes, such as overdoses or external causes. We investigated the relative risk for liver related death in chronic hepatitis C (CHC) patients with or without illicit substance use disorders (SUD) .Methods: Patients with CHC were identified using the Swedish National Patient Registry (contains all inpatient, day surgery, and outpatient non-primary care visits) according to the International Classification of Diseases-10 (ICD-10) code B18.2. The baseline observation was set to the first CHC visit from 2001, and person-time continued until death, emigration or December 31, 2013, whichever came first. Patients with ≥2 non-primary care visits with ICD-10 codes F11, F12, F14, F15, F16, or F19 were considered to have illicit SUD . The underlying cause of death was obtained from the Cause of Death Register . A six months lag-period between CHC diagnosis and death was introduced to reduce surveillance bias. Non-alcoholic liver disease was defined using ICD-10 codes K71–K77, B15–B19, B94.2, R17-R18, I85 .0, I98 .2, and I98 .3 . The relative risk for death was determined using standardized mortality ratio (SMR) where the observed number of deaths was divided by the expected number of deaths taken from five comparators from the general population (matched for age/sex/place of residency) .Results: In total 38,186 patients with CHC were included in the study whereof 11,818 (31%) were considered to have illicit SUD . The CHC patients with SUD were younger (37 .7 vs . 46 .9 years) with a greater proportion of men (72% vs . 62%) than CHC patients without SUD . The SMRs for CHC patients with SUD were 10 .5, 33 .8, 18 .1, 123 .2, 61 .6, and 13 .2, for all-causes, liver cancer, alcoholic or non-alcoholic liver disease, drug-related, or external causes, respectively (Table 1) . The corresponding SMRs for CHC patients without SUD were 4 .1, 52 .8, 18 .0, 69 .4, 11 .2, and 4 .9, respectively (Table 1) .Conclusion: The relative risks for all investigated parameters were elevated for CHC patients whether they had illicit SUD or not . Furthermore, although the CHC patients with SUD had a high relative risk to die from both drug-related and external causes, the relative risk to die from non-alcoholic liver disease was also greatly elevated .
|
|
